Data are limited on the management of atopic dermatitis (AD) in adolescents, particularly in patients with skin of color, making it important to identify factors that may improve AD management in this population. Comorbid conditions (eg, acne, postinflammatory hyperpigmentation [PIH]), extracurricular activities (eg, athletics), and experimentation with cosmetics in adolescents, all of which can undermine treatment efficacy and medication adherence, make it particularly challenging to devise a therapeutic regimen in this patient population. We review the management of AD in black adolescents, with special consideration of concomitant treatment of acne vulgaris (AV) as well as lifestyle and social choices (Table).

Prevalence and Epidemiology

Atopic dermatitis affects 13% to 25% of children and 2% to 10% of adults.^1,2 Population‐based studies in the United States show a higher prevalence of AD in black children (19.3%) compared to European American (EA) children (16.1%).^3,4

AD in Black Adolescents

Atopic dermatitis is a common skin condition that is defined as a chronic, pruritic, inflammatory dermatosis with recurrent scaling, papules, and plaques (Figure) that usually develop during infancy and early childhood.³ Although AD severity improves for some patients in adolescence, it can be a lifelong issue affecting performance in academic and occupational settings.⁵ One US study of 8015 children found that there are racial and ethnic disparities in school absences among children (age range, 2–17 years) with AD, with children with skin of color being absent more often than white children.⁶ The same study noted that black children had a 1.5-fold higher chance of being absent 6 days over a 6-month school period compared to white children. It is postulated that AD has a greater impact on quality of life (QOL) in children with skin of color, resulting in the increased number of school absences in this population.⁶

The origin of AD currently is thought to be complex and can involve skin barrier dysfunction, environmental factors, microbiome effects, genetic predisposition, and immune dysregulation.^1,4 Atopic dermatitis is a heterogeneous disease with variations in the prevalence, genetic background, and immune activation patterns across racial groups.⁴ It is now understood to be an immune-mediated disease with multiple inflammatory pathways, with type 2–associated inflammation being a primary pathway. Patients with AD have strong helper T cell (T_H2) activation, and black patients with AD have higher IgE serum levels as well as absent T_H17/T_H1 activation.⁴

Atopic dermatitis currently is seen as a defect of the epidermal barrier, with variable clinical manifestations and expressivity.⁷ Filaggrin is an epidermal barrier protein, encoded by the FLG gene, and plays a major role in barrier function by regulating pH and promoting hydration of the skin.⁴ Loss of function of the FLG gene is the most well-studied genetic risk factor for developing AD, and this mutation is seen in patients with more severe and persistent AD in addition to patients with more skin infections and allergic sensitizations.^3,4 However, in the skin of color population, FLG mutations are 6 times less common than in the EA population, despite the fact that AD is more prevalent in patients of African descent.⁴ Therefore, the role of the FLG loss-of-function mutation and AD is not as well defined in black patients, and some researchers have found no association.³ The FLG loss-of-function mutation seems to play a smaller role in black patients than in EA patients, and other genes may be involved in skin barrier dysfunction.^3,4 In a small study of patients with mild AD compared to nonaffected patients, those with AD had lower total ceramide levels in the stratum corneum of affected sites than normal skin sites in healthy individuals.⁸

Particular disturbances in the gut microbiome have the possibility of impacting the development of AD.⁹ Additionally, the development of AD may be influenced by the skin microbiome, which can change depending on body site, with fungal organisms thought to make up a large proportion of the microbiome of patients with AD. In patients with AD, there is a lack of microbial diversity and an overgrowth of Staphylococcus aureus.⁹

Diagnosis

Clinicians diagnose AD based on clinical characteristics, and the lack of objective criteria can hinder diagnosis.¹ Thus, diagnosing AD in children with dark skin can pose a particular challenge given the varied clinical presentation of AD across skin types. Severe cases of AD may not be diagnosed or treated adequately in deeply pigmented children because erythema, a defining characteristic of AD, may be hard to identify in darker skin types.¹⁰ Furthermore, clinical erythema scores among black children may be “strongly” underestimated using scoring systems such as Eczema Area and Severity Index and SCORing Atopic Dermatitis.⁴ It is estimated that the risk for severe AD may be 6 times higher in black children compared to white children.¹⁰ Additionally, patients with skin of color can present with more treatment-resistant AD.⁴

Treatment of AD

Current treatment is focused on restoring epidermal barrier function, often with topical agents, such as moisturizers containing different amounts of emollients, occlusives, and humectants; corticosteroids; calcineurin inhibitors; and antimicrobials. Emollients such as glycol stearate, glyceryl stearate, and soy sterols function as lubricants, softening the skin. Occlusive agents include petrolatum, dimethicone, and mineral oil; they act by forming a layer to slow evaporation of water. Humectants including glycerol, lactic acid, and urea function by promoting water retention.¹¹ For acute flares, mid- to high-potency topical corticosteroids are recommended. Also, topical calcineurin inhibitors such as tacrolimus and pimecrolimus may be used alone or in combination with topical steroids. Finally, bleach baths and topical mupirocin applied to the nares also have proved helpful in moderate to severe AD with secondary bacterial infections.¹¹ Phototherapy can be used in adult and pediatric patients with acute and chronic AD if traditional treatments have failed.²

Systemic agents are indicated and recommended for the subset of adult and pediatric patients in whom optimized topical regimens and/or phototherapy do not adequately provide disease control or when QOL is substantially impacted. The systemic agents effective in the pediatric population include cyclosporine, azathioprine, mycophenolate mofetil, and possibly methotrexate.¹¹ Dupilumab recently was approved by the US Food and Drug Administration for patients 12 years and older with moderate to severe AD whose disease is not well controlled with topical medications.

Patients with AD are predisposed to secondary bacterial and viral infections because of their dysfunctional skin barrier; these infections most commonly are caused by S aureus and herpes simplex virus, respectively.² Systemic antibiotics are only recommended for patients with AD when there is clinical evidence of bacterial infection. In patients with evidence of eczema herpeticum, systemic antiviral agents should be used to treat the underlying herpes simplex virus infection.² Atopic dermatitis typically has been studied in white patients; however, patients with skin of color have higher frequencies of treatment-resistant AD. Further research on treatment efficacy for AD in this patient population is needed, as data are limited.⁴

Treatment of AV in Patients With AD

Two of the most prevalent skin diseases affecting the pediatric population are AD and AV, and both can remarkably impact QOL.¹² Acne is one of the most common reasons for adolescent patients to seek dermatologic care, including patients with skin of color (Fitzpatrick skin types IV to VI).¹³ Thus, it is to be expected that many black adolescents with AD also will have AV. For mild to moderate acne in patients with skin of color, topical retinoids and benzoyl peroxide typically are first line.¹³ These medications can be problematic for patients with AD, as retinoids and many other acne treatments can cause dryness, which may exacerbate AD.

Moisturizers containing ceramide can be a helpful adjunctive therapy in treating acne,¹⁴ especially in patients with AD. Modifications to application of acne medications, such as using topical retinoids every other night or mixing them with moisturizers to minimize dryness, may be beneficial to these patients. Dapsone gel 7.5% used daily also may be an option for adolescents with AD and AV. A double-blind, vehicle-controlled study demonstrated that dapsone is safe and effective for patients 12 years and older with moderate acne, and patients with Fitzpatrick skin types IV to VI rated local scaling, erythema, dryness, and stinging/burning as “none” in the study.¹⁵ Another potentially helpful topical agent in patients with AD and AV is sulfacetamide, as it is not likely to cause dryness of the skin. In a small study, sodium sulfacetamide 10% and sulfur 5% in an emollient foam vehicle showed no residual film or sulfur smell and resulted in acne reduction of 50%.¹⁶

Patients with skin of color often experience PIH in AD and acne or hypopigmentation from inflammatory dermatoses including AD.^17,18 In addition to the dryness from AD and topical retinoid use, patients with skin of color may develop irritant contact dermatitis, thus leading to PIH.¹³ Dryness and irritant contact dermatitis also can be seen with the use of benzoyl peroxide in black patients. Because of these effects, gentle moisturizers are recommended, and both benzoyl peroxide and retinoids should be initiated at lower doses in patients with skin of color.¹³

For patients with severe nodulocystic acne, isotretinoin is the treatment of choice in patients with skin of color,¹³ but there is a dearth of clinical studies addressing complications seen in black adolescents on this treatment, especially with respect to those with AD. Of note, systemic antibiotics typically are initiated before isotretinoin; however, this strategy is falling out of favor due to concern for antibiotic resistance with long-term use.¹⁹

Impact of Athletics on AD in Black Adolescents

Because of the exacerbating effects of perspiration and heat causing itch and irritation in patients with AD, it is frequently advised that pediatric patients limit their participation in athletics because of the exacerbating effects of strenuous physical exercise on their disease.¹² In one study, 429 pediatric patients or their parents/guardians completed QOL questionnaires; 89% of patients 15 years and younger with severe AD reported that their disease was impacted by athletics and outdoor activities, and 86% of these pediatric patients with severe AD responded that their social lives and leisure activities were impacted.²⁰ Because adolescents often are involved in athletics or have mandatory physical education classes, AD may be isolating and may have a severe impact on self-esteem.

Aggressive treatment of AD with topical and systemic medications may be helpful in adolescents who may be reluctant to participate in sports because of teasing, bullying, or worsening of symptoms with heat or sweating.²¹ Now that dupilumab is available for adolescents, there is a chance that patients with severe and/or recalcitrant disease managed on this medication can achieve better control of their symptoms without the laboratory requirement of methotrexate and the difficulties of topical medication application, allowing them to engage in mandatory athletic classes as well as desired organized sports.

Use of Cosmetics for AD

Many adolescents experiment with cosmetics, and those with AD may use cosmetic products to cover hyperpigmented or hypopigmented lesions.¹⁸ In patients with active AD or increased sensitivity to allergens in cosmetic products, use of makeup can be a contributing factor for AD flares. Acne associated with cosmetics is especially important to consider in darker-skinned patients who may use makeup that is opaque and contains oil to conceal acne or PIH.

Allergens can be present in both cosmetics and pharmaceutical topical agents, and a Brazilian study found that approximately 89% of 813 prescription and nonprescription products (eg, topical drugs, sunscreens, moisturizers, soaps, cleansing lotions, shampoos, cosmeceuticals) contained allergens.²² Patients with AD have a higher prevalence of contact sensitization to fragrances, including balsam of Peru.²³ Some AD treatments that contain fragrances have caused further skin issues in a few patients. In one case series, 3 pediatric patients developed allergic contact dermatitis to Myroxylon pereirae (balsam of Peru) when using topical treatments for their AD, and their symptoms of scalp inflammation and alopecia resolved with discontinuation.²³

In a Dutch study, sensitization to Fragrance Mix I and M pereirae as well as other ingredients (eg, lanolin alcohol, Amerchol™ L 101 [a lanolin product]) was notably more common in pediatric patients with AD than in patients without AD; however, no data on patients with skin of color were included in this study.²⁴

Because of the increased risk of sensitization to fragrances and other ingredients in patients with AD as well as the high percentage of allergens in prescription and nonprescription products, it is important to discuss all personal care products that patients may be using, not just their cosmetic products. Also, patch testing may be helpful in determining true allergens in some patients. Patch testing is recommended for patients with treatment-resistant AD, and a recent study suggested it should be done prior to long-term use of immunosuppressive agents.²⁵ Increased steroid phobia and a push toward alternative medicines are leading both patients with AD and guardians of children with AD to look for other forms of moisturization, such as olive oil, coconut oil, sunflower seed oil, and shea butter, to decrease transepidermal water loss.^26,27 An important factor in AD treatment efficacy is patient acceptability in using what is recommended.²⁷ One study showed there was no difference in efficacy or acceptability in using a cream containing shea butter extract vs the ceramide-precursor product.²⁷ Current data show olive oil may exacerbate dry skin and AD,²⁶ and recommendation of any over-the-counter oils and butters in patients with AD should be made with great caution, as many of these products contain fragrances and other potential allergens.

Alternative Therapies for AD

Patients with AD often seek alternative or integrative treatment options, including dietary modifications and holistic remedies. Studies investigating the role of vitamins and supplements in treating AD are limited by sample size.²⁸ However, there is some evidence that may support supplementation with vitamins D and E in addressing AD symptoms. The use of probiotics in treating AD is controversial, but there are studies suggesting that the use of probiotics may prove beneficial in preventing infantile AD.²⁸ Additionally, findings from an ex vivo and in vitro study show that some conditions, including AD and acne, may benefit from the same probiotics, despite the differences in these two diseases. Both AD and acne have inflammatory and skin dysbiosis characteristics, which may be the common thread leading to both conditions potentially responding to treatment with probiotics.²⁹

Preliminary evidence indicates that supplements containing fatty acids such as docosahexaenoic acid, sea buckthorn oil, and hemp seed oil may decrease the severity of AD.²⁸ In a 20-week, randomized, single-blind, crossover study published in 2005, dietary hemp seed oil showed an improvement of clinical symptoms, including dry skin and itchiness, in patients with AD.³⁰

In light of recent legalization in several states, patients may turn to use of cannabinoid products to manage AD. In a systematic review, cannabinoid use was reportedly a therapeutic option in the treatment of AD and AV; however, the data are based on preclinical work, and there are no randomized, placebo-controlled studies to support the use of cannabinoids.³¹ Furthermore, there is great concern that use of these products in adolescents is an even larger unknown.

Final Thoughts

Eighty percent of children diagnosed with AD experience symptom improvement before their early teens³²; for those with AD during their preteen and teenage years, there can be psychological ramifications, as teenagers with AD report having fewer friends, are less socially involved, participate in fewer sports, and are absent from classes more often than their peers.⁵ In black patients with AD, school absences are even more common.⁶ Given the social and emotional impact of AD on patients with skin of color, it is imperative to treat the condition appropriately.³³ There are areas of opportunity for further research on alternate dosing of existing treatments for AV in patients with AD, further recommendations for adolescent athletes with AD, and which cosmetic and alternative medicine products may be beneficial for this population to improve their QOL.

Providers should discuss medical management in a broader context considering patients’ extracurricular activities, treatment vehicle preferences, expectations, and personal care habits. It also is important to address the many possible factors that may influence treatment adherence early on, particularly in adolescents, as these could be barriers to treatment. This article highlights considerations for treating AD and comorbid conditions that may further complicate treatment in adolescent patients with skin of color. The information provided should serve as a guide in initial counseling and management of AD in adolescents with skin of color.

Data are limited on the management of atopic dermatitis (AD) in adolescents, particularly in patients with skin of color, making it important to identify factors that may improve AD management in this population. Comorbid conditions (eg, acne, postinflammatory hyperpigmentation [PIH]), extracurricular activities (eg, athletics), and experimentation with cosmetics in adolescents, all of which can undermine treatment efficacy and medication adherence, make it particularly challenging to devise a therapeutic regimen in this patient population. We review the management of AD in black adolescents, with special consideration of concomitant treatment of acne vulgaris (AV) as well as lifestyle and social choices (Table).

Prevalence and Epidemiology

Atopic dermatitis affects 13% to 25% of children and 2% to 10% of adults.^1,2 Population‐based studies in the United States show a higher prevalence of AD in black children (19.3%) compared to European American (EA) children (16.1%).^3,4

AD in Black Adolescents

Atopic dermatitis is a common skin condition that is defined as a chronic, pruritic, inflammatory dermatosis with recurrent scaling, papules, and plaques (Figure) that usually develop during infancy and early childhood.³ Although AD severity improves for some patients in adolescence, it can be a lifelong issue affecting performance in academic and occupational settings.⁵ One US study of 8015 children found that there are racial and ethnic disparities in school absences among children (age range, 2–17 years) with AD, with children with skin of color being absent more often than white children.⁶ The same study noted that black children had a 1.5-fold higher chance of being absent 6 days over a 6-month school period compared to white children. It is postulated that AD has a greater impact on quality of life (QOL) in children with skin of color, resulting in the increased number of school absences in this population.⁶

The origin of AD currently is thought to be complex and can involve skin barrier dysfunction, environmental factors, microbiome effects, genetic predisposition, and immune dysregulation.^1,4 Atopic dermatitis is a heterogeneous disease with variations in the prevalence, genetic background, and immune activation patterns across racial groups.⁴ It is now understood to be an immune-mediated disease with multiple inflammatory pathways, with type 2–associated inflammation being a primary pathway. Patients with AD have strong helper T cell (T_H2) activation, and black patients with AD have higher IgE serum levels as well as absent T_H17/T_H1 activation.⁴

Atopic dermatitis currently is seen as a defect of the epidermal barrier, with variable clinical manifestations and expressivity.⁷ Filaggrin is an epidermal barrier protein, encoded by the FLG gene, and plays a major role in barrier function by regulating pH and promoting hydration of the skin.⁴ Loss of function of the FLG gene is the most well-studied genetic risk factor for developing AD, and this mutation is seen in patients with more severe and persistent AD in addition to patients with more skin infections and allergic sensitizations.^3,4 However, in the skin of color population, FLG mutations are 6 times less common than in the EA population, despite the fact that AD is more prevalent in patients of African descent.⁴ Therefore, the role of the FLG loss-of-function mutation and AD is not as well defined in black patients, and some researchers have found no association.³ The FLG loss-of-function mutation seems to play a smaller role in black patients than in EA patients, and other genes may be involved in skin barrier dysfunction.^3,4 In a small study of patients with mild AD compared to nonaffected patients, those with AD had lower total ceramide levels in the stratum corneum of affected sites than normal skin sites in healthy individuals.⁸

Particular disturbances in the gut microbiome have the possibility of impacting the development of AD.⁹ Additionally, the development of AD may be influenced by the skin microbiome, which can change depending on body site, with fungal organisms thought to make up a large proportion of the microbiome of patients with AD. In patients with AD, there is a lack of microbial diversity and an overgrowth of Staphylococcus aureus.⁹

Diagnosis

Clinicians diagnose AD based on clinical characteristics, and the lack of objective criteria can hinder diagnosis.¹ Thus, diagnosing AD in children with dark skin can pose a particular challenge given the varied clinical presentation of AD across skin types. Severe cases of AD may not be diagnosed or treated adequately in deeply pigmented children because erythema, a defining characteristic of AD, may be hard to identify in darker skin types.¹⁰ Furthermore, clinical erythema scores among black children may be “strongly” underestimated using scoring systems such as Eczema Area and Severity Index and SCORing Atopic Dermatitis.⁴ It is estimated that the risk for severe AD may be 6 times higher in black children compared to white children.¹⁰ Additionally, patients with skin of color can present with more treatment-resistant AD.⁴

Treatment of AD

Current treatment is focused on restoring epidermal barrier function, often with topical agents, such as moisturizers containing different amounts of emollients, occlusives, and humectants; corticosteroids; calcineurin inhibitors; and antimicrobials. Emollients such as glycol stearate, glyceryl stearate, and soy sterols function as lubricants, softening the skin. Occlusive agents include petrolatum, dimethicone, and mineral oil; they act by forming a layer to slow evaporation of water. Humectants including glycerol, lactic acid, and urea function by promoting water retention.¹¹ For acute flares, mid- to high-potency topical corticosteroids are recommended. Also, topical calcineurin inhibitors such as tacrolimus and pimecrolimus may be used alone or in combination with topical steroids. Finally, bleach baths and topical mupirocin applied to the nares also have proved helpful in moderate to severe AD with secondary bacterial infections.¹¹ Phototherapy can be used in adult and pediatric patients with acute and chronic AD if traditional treatments have failed.²

Systemic agents are indicated and recommended for the subset of adult and pediatric patients in whom optimized topical regimens and/or phototherapy do not adequately provide disease control or when QOL is substantially impacted. The systemic agents effective in the pediatric population include cyclosporine, azathioprine, mycophenolate mofetil, and possibly methotrexate.¹¹ Dupilumab recently was approved by the US Food and Drug Administration for patients 12 years and older with moderate to severe AD whose disease is not well controlled with topical medications.

Patients with AD are predisposed to secondary bacterial and viral infections because of their dysfunctional skin barrier; these infections most commonly are caused by S aureus and herpes simplex virus, respectively.² Systemic antibiotics are only recommended for patients with AD when there is clinical evidence of bacterial infection. In patients with evidence of eczema herpeticum, systemic antiviral agents should be used to treat the underlying herpes simplex virus infection.² Atopic dermatitis typically has been studied in white patients; however, patients with skin of color have higher frequencies of treatment-resistant AD. Further research on treatment efficacy for AD in this patient population is needed, as data are limited.⁴

Treatment of AV in Patients With AD

Two of the most prevalent skin diseases affecting the pediatric population are AD and AV, and both can remarkably impact QOL.¹² Acne is one of the most common reasons for adolescent patients to seek dermatologic care, including patients with skin of color (Fitzpatrick skin types IV to VI).¹³ Thus, it is to be expected that many black adolescents with AD also will have AV. For mild to moderate acne in patients with skin of color, topical retinoids and benzoyl peroxide typically are first line.¹³ These medications can be problematic for patients with AD, as retinoids and many other acne treatments can cause dryness, which may exacerbate AD.

Moisturizers containing ceramide can be a helpful adjunctive therapy in treating acne,¹⁴ especially in patients with AD. Modifications to application of acne medications, such as using topical retinoids every other night or mixing them with moisturizers to minimize dryness, may be beneficial to these patients. Dapsone gel 7.5% used daily also may be an option for adolescents with AD and AV. A double-blind, vehicle-controlled study demonstrated that dapsone is safe and effective for patients 12 years and older with moderate acne, and patients with Fitzpatrick skin types IV to VI rated local scaling, erythema, dryness, and stinging/burning as “none” in the study.¹⁵ Another potentially helpful topical agent in patients with AD and AV is sulfacetamide, as it is not likely to cause dryness of the skin. In a small study, sodium sulfacetamide 10% and sulfur 5% in an emollient foam vehicle showed no residual film or sulfur smell and resulted in acne reduction of 50%.¹⁶

Patients with skin of color often experience PIH in AD and acne or hypopigmentation from inflammatory dermatoses including AD.^17,18 In addition to the dryness from AD and topical retinoid use, patients with skin of color may develop irritant contact dermatitis, thus leading to PIH.¹³ Dryness and irritant contact dermatitis also can be seen with the use of benzoyl peroxide in black patients. Because of these effects, gentle moisturizers are recommended, and both benzoyl peroxide and retinoids should be initiated at lower doses in patients with skin of color.¹³

For patients with severe nodulocystic acne, isotretinoin is the treatment of choice in patients with skin of color,¹³ but there is a dearth of clinical studies addressing complications seen in black adolescents on this treatment, especially with respect to those with AD. Of note, systemic antibiotics typically are initiated before isotretinoin; however, this strategy is falling out of favor due to concern for antibiotic resistance with long-term use.¹⁹

Impact of Athletics on AD in Black Adolescents

Because of the exacerbating effects of perspiration and heat causing itch and irritation in patients with AD, it is frequently advised that pediatric patients limit their participation in athletics because of the exacerbating effects of strenuous physical exercise on their disease.¹² In one study, 429 pediatric patients or their parents/guardians completed QOL questionnaires; 89% of patients 15 years and younger with severe AD reported that their disease was impacted by athletics and outdoor activities, and 86% of these pediatric patients with severe AD responded that their social lives and leisure activities were impacted.²⁰ Because adolescents often are involved in athletics or have mandatory physical education classes, AD may be isolating and may have a severe impact on self-esteem.

Aggressive treatment of AD with topical and systemic medications may be helpful in adolescents who may be reluctant to participate in sports because of teasing, bullying, or worsening of symptoms with heat or sweating.²¹ Now that dupilumab is available for adolescents, there is a chance that patients with severe and/or recalcitrant disease managed on this medication can achieve better control of their symptoms without the laboratory requirement of methotrexate and the difficulties of topical medication application, allowing them to engage in mandatory athletic classes as well as desired organized sports.

Use of Cosmetics for AD

Many adolescents experiment with cosmetics, and those with AD may use cosmetic products to cover hyperpigmented or hypopigmented lesions.¹⁸ In patients with active AD or increased sensitivity to allergens in cosmetic products, use of makeup can be a contributing factor for AD flares. Acne associated with cosmetics is especially important to consider in darker-skinned patients who may use makeup that is opaque and contains oil to conceal acne or PIH.

Allergens can be present in both cosmetics and pharmaceutical topical agents, and a Brazilian study found that approximately 89% of 813 prescription and nonprescription products (eg, topical drugs, sunscreens, moisturizers, soaps, cleansing lotions, shampoos, cosmeceuticals) contained allergens.²² Patients with AD have a higher prevalence of contact sensitization to fragrances, including balsam of Peru.²³ Some AD treatments that contain fragrances have caused further skin issues in a few patients. In one case series, 3 pediatric patients developed allergic contact dermatitis to Myroxylon pereirae (balsam of Peru) when using topical treatments for their AD, and their symptoms of scalp inflammation and alopecia resolved with discontinuation.²³

In a Dutch study, sensitization to Fragrance Mix I and M pereirae as well as other ingredients (eg, lanolin alcohol, Amerchol™ L 101 [a lanolin product]) was notably more common in pediatric patients with AD than in patients without AD; however, no data on patients with skin of color were included in this study.²⁴

Because of the increased risk of sensitization to fragrances and other ingredients in patients with AD as well as the high percentage of allergens in prescription and nonprescription products, it is important to discuss all personal care products that patients may be using, not just their cosmetic products. Also, patch testing may be helpful in determining true allergens in some patients. Patch testing is recommended for patients with treatment-resistant AD, and a recent study suggested it should be done prior to long-term use of immunosuppressive agents.²⁵ Increased steroid phobia and a push toward alternative medicines are leading both patients with AD and guardians of children with AD to look for other forms of moisturization, such as olive oil, coconut oil, sunflower seed oil, and shea butter, to decrease transepidermal water loss.^26,27 An important factor in AD treatment efficacy is patient acceptability in using what is recommended.²⁷ One study showed there was no difference in efficacy or acceptability in using a cream containing shea butter extract vs the ceramide-precursor product.²⁷ Current data show olive oil may exacerbate dry skin and AD,²⁶ and recommendation of any over-the-counter oils and butters in patients with AD should be made with great caution, as many of these products contain fragrances and other potential allergens.

Alternative Therapies for AD

Patients with AD often seek alternative or integrative treatment options, including dietary modifications and holistic remedies. Studies investigating the role of vitamins and supplements in treating AD are limited by sample size.²⁸ However, there is some evidence that may support supplementation with vitamins D and E in addressing AD symptoms. The use of probiotics in treating AD is controversial, but there are studies suggesting that the use of probiotics may prove beneficial in preventing infantile AD.²⁸ Additionally, findings from an ex vivo and in vitro study show that some conditions, including AD and acne, may benefit from the same probiotics, despite the differences in these two diseases. Both AD and acne have inflammatory and skin dysbiosis characteristics, which may be the common thread leading to both conditions potentially responding to treatment with probiotics.²⁹

Preliminary evidence indicates that supplements containing fatty acids such as docosahexaenoic acid, sea buckthorn oil, and hemp seed oil may decrease the severity of AD.²⁸ In a 20-week, randomized, single-blind, crossover study published in 2005, dietary hemp seed oil showed an improvement of clinical symptoms, including dry skin and itchiness, in patients with AD.³⁰

In light of recent legalization in several states, patients may turn to use of cannabinoid products to manage AD. In a systematic review, cannabinoid use was reportedly a therapeutic option in the treatment of AD and AV; however, the data are based on preclinical work, and there are no randomized, placebo-controlled studies to support the use of cannabinoids.³¹ Furthermore, there is great concern that use of these products in adolescents is an even larger unknown.

Final Thoughts

Eighty percent of children diagnosed with AD experience symptom improvement before their early teens³²; for those with AD during their preteen and teenage years, there can be psychological ramifications, as teenagers with AD report having fewer friends, are less socially involved, participate in fewer sports, and are absent from classes more often than their peers.⁵ In black patients with AD, school absences are even more common.⁶ Given the social and emotional impact of AD on patients with skin of color, it is imperative to treat the condition appropriately.³³ There are areas of opportunity for further research on alternate dosing of existing treatments for AV in patients with AD, further recommendations for adolescent athletes with AD, and which cosmetic and alternative medicine products may be beneficial for this population to improve their QOL.

Providers should discuss medical management in a broader context considering patients’ extracurricular activities, treatment vehicle preferences, expectations, and personal care habits. It also is important to address the many possible factors that may influence treatment adherence early on, particularly in adolescents, as these could be barriers to treatment. This article highlights considerations for treating AD and comorbid conditions that may further complicate treatment in adolescent patients with skin of color. The information provided should serve as a guide in initial counseling and management of AD in adolescents with skin of color.

Data are limited on the management of atopic dermatitis (AD) in adolescents, particularly in patients with skin of color, making it important to identify factors that may improve AD management in this population. Comorbid conditions (eg, acne, postinflammatory hyperpigmentation [PIH]), extracurricular activities (eg, athletics), and experimentation with cosmetics in adolescents, all of which can undermine treatment efficacy and medication adherence, make it particularly challenging to devise a therapeutic regimen in this patient population. We review the management of AD in black adolescents, with special consideration of concomitant treatment of acne vulgaris (AV) as well as lifestyle and social choices (Table).

Prevalence and Epidemiology

Atopic dermatitis affects 13% to 25% of children and 2% to 10% of adults.^1,2 Population‐based studies in the United States show a higher prevalence of AD in black children (19.3%) compared to European American (EA) children (16.1%).^3,4

AD in Black Adolescents

Atopic dermatitis is a common skin condition that is defined as a chronic, pruritic, inflammatory dermatosis with recurrent scaling, papules, and plaques (Figure) that usually develop during infancy and early childhood.³ Although AD severity improves for some patients in adolescence, it can be a lifelong issue affecting performance in academic and occupational settings.⁵ One US study of 8015 children found that there are racial and ethnic disparities in school absences among children (age range, 2–17 years) with AD, with children with skin of color being absent more often than white children.⁶ The same study noted that black children had a 1.5-fold higher chance of being absent 6 days over a 6-month school period compared to white children. It is postulated that AD has a greater impact on quality of life (QOL) in children with skin of color, resulting in the increased number of school absences in this population.⁶

The origin of AD currently is thought to be complex and can involve skin barrier dysfunction, environmental factors, microbiome effects, genetic predisposition, and immune dysregulation.^1,4 Atopic dermatitis is a heterogeneous disease with variations in the prevalence, genetic background, and immune activation patterns across racial groups.⁴ It is now understood to be an immune-mediated disease with multiple inflammatory pathways, with type 2–associated inflammation being a primary pathway. Patients with AD have strong helper T cell (T_H2) activation, and black patients with AD have higher IgE serum levels as well as absent T_H17/T_H1 activation.⁴

Atopic dermatitis currently is seen as a defect of the epidermal barrier, with variable clinical manifestations and expressivity.⁷ Filaggrin is an epidermal barrier protein, encoded by the FLG gene, and plays a major role in barrier function by regulating pH and promoting hydration of the skin.⁴ Loss of function of the FLG gene is the most well-studied genetic risk factor for developing AD, and this mutation is seen in patients with more severe and persistent AD in addition to patients with more skin infections and allergic sensitizations.^3,4 However, in the skin of color population, FLG mutations are 6 times less common than in the EA population, despite the fact that AD is more prevalent in patients of African descent.⁴ Therefore, the role of the FLG loss-of-function mutation and AD is not as well defined in black patients, and some researchers have found no association.³ The FLG loss-of-function mutation seems to play a smaller role in black patients than in EA patients, and other genes may be involved in skin barrier dysfunction.^3,4 In a small study of patients with mild AD compared to nonaffected patients, those with AD had lower total ceramide levels in the stratum corneum of affected sites than normal skin sites in healthy individuals.⁸

Particular disturbances in the gut microbiome have the possibility of impacting the development of AD.⁹ Additionally, the development of AD may be influenced by the skin microbiome, which can change depending on body site, with fungal organisms thought to make up a large proportion of the microbiome of patients with AD. In patients with AD, there is a lack of microbial diversity and an overgrowth of Staphylococcus aureus.⁹

Diagnosis

Clinicians diagnose AD based on clinical characteristics, and the lack of objective criteria can hinder diagnosis.¹ Thus, diagnosing AD in children with dark skin can pose a particular challenge given the varied clinical presentation of AD across skin types. Severe cases of AD may not be diagnosed or treated adequately in deeply pigmented children because erythema, a defining characteristic of AD, may be hard to identify in darker skin types.¹⁰ Furthermore, clinical erythema scores among black children may be “strongly” underestimated using scoring systems such as Eczema Area and Severity Index and SCORing Atopic Dermatitis.⁴ It is estimated that the risk for severe AD may be 6 times higher in black children compared to white children.¹⁰ Additionally, patients with skin of color can present with more treatment-resistant AD.⁴

Treatment of AD

Current treatment is focused on restoring epidermal barrier function, often with topical agents, such as moisturizers containing different amounts of emollients, occlusives, and humectants; corticosteroids; calcineurin inhibitors; and antimicrobials. Emollients such as glycol stearate, glyceryl stearate, and soy sterols function as lubricants, softening the skin. Occlusive agents include petrolatum, dimethicone, and mineral oil; they act by forming a layer to slow evaporation of water. Humectants including glycerol, lactic acid, and urea function by promoting water retention.¹¹ For acute flares, mid- to high-potency topical corticosteroids are recommended. Also, topical calcineurin inhibitors such as tacrolimus and pimecrolimus may be used alone or in combination with topical steroids. Finally, bleach baths and topical mupirocin applied to the nares also have proved helpful in moderate to severe AD with secondary bacterial infections.¹¹ Phototherapy can be used in adult and pediatric patients with acute and chronic AD if traditional treatments have failed.²

Systemic agents are indicated and recommended for the subset of adult and pediatric patients in whom optimized topical regimens and/or phototherapy do not adequately provide disease control or when QOL is substantially impacted. The systemic agents effective in the pediatric population include cyclosporine, azathioprine, mycophenolate mofetil, and possibly methotrexate.¹¹ Dupilumab recently was approved by the US Food and Drug Administration for patients 12 years and older with moderate to severe AD whose disease is not well controlled with topical medications.

Patients with AD are predisposed to secondary bacterial and viral infections because of their dysfunctional skin barrier; these infections most commonly are caused by S aureus and herpes simplex virus, respectively.² Systemic antibiotics are only recommended for patients with AD when there is clinical evidence of bacterial infection. In patients with evidence of eczema herpeticum, systemic antiviral agents should be used to treat the underlying herpes simplex virus infection.² Atopic dermatitis typically has been studied in white patients; however, patients with skin of color have higher frequencies of treatment-resistant AD. Further research on treatment efficacy for AD in this patient population is needed, as data are limited.⁴

Treatment of AV in Patients With AD

Two of the most prevalent skin diseases affecting the pediatric population are AD and AV, and both can remarkably impact QOL.¹² Acne is one of the most common reasons for adolescent patients to seek dermatologic care, including patients with skin of color (Fitzpatrick skin types IV to VI).¹³ Thus, it is to be expected that many black adolescents with AD also will have AV. For mild to moderate acne in patients with skin of color, topical retinoids and benzoyl peroxide typically are first line.¹³ These medications can be problematic for patients with AD, as retinoids and many other acne treatments can cause dryness, which may exacerbate AD.

Moisturizers containing ceramide can be a helpful adjunctive therapy in treating acne,¹⁴ especially in patients with AD. Modifications to application of acne medications, such as using topical retinoids every other night or mixing them with moisturizers to minimize dryness, may be beneficial to these patients. Dapsone gel 7.5% used daily also may be an option for adolescents with AD and AV. A double-blind, vehicle-controlled study demonstrated that dapsone is safe and effective for patients 12 years and older with moderate acne, and patients with Fitzpatrick skin types IV to VI rated local scaling, erythema, dryness, and stinging/burning as “none” in the study.¹⁵ Another potentially helpful topical agent in patients with AD and AV is sulfacetamide, as it is not likely to cause dryness of the skin. In a small study, sodium sulfacetamide 10% and sulfur 5% in an emollient foam vehicle showed no residual film or sulfur smell and resulted in acne reduction of 50%.¹⁶

Patients with skin of color often experience PIH in AD and acne or hypopigmentation from inflammatory dermatoses including AD.^17,18 In addition to the dryness from AD and topical retinoid use, patients with skin of color may develop irritant contact dermatitis, thus leading to PIH.¹³ Dryness and irritant contact dermatitis also can be seen with the use of benzoyl peroxide in black patients. Because of these effects, gentle moisturizers are recommended, and both benzoyl peroxide and retinoids should be initiated at lower doses in patients with skin of color.¹³

For patients with severe nodulocystic acne, isotretinoin is the treatment of choice in patients with skin of color,¹³ but there is a dearth of clinical studies addressing complications seen in black adolescents on this treatment, especially with respect to those with AD. Of note, systemic antibiotics typically are initiated before isotretinoin; however, this strategy is falling out of favor due to concern for antibiotic resistance with long-term use.¹⁹

Impact of Athletics on AD in Black Adolescents

Because of the exacerbating effects of perspiration and heat causing itch and irritation in patients with AD, it is frequently advised that pediatric patients limit their participation in athletics because of the exacerbating effects of strenuous physical exercise on their disease.¹² In one study, 429 pediatric patients or their parents/guardians completed QOL questionnaires; 89% of patients 15 years and younger with severe AD reported that their disease was impacted by athletics and outdoor activities, and 86% of these pediatric patients with severe AD responded that their social lives and leisure activities were impacted.²⁰ Because adolescents often are involved in athletics or have mandatory physical education classes, AD may be isolating and may have a severe impact on self-esteem.

Aggressive treatment of AD with topical and systemic medications may be helpful in adolescents who may be reluctant to participate in sports because of teasing, bullying, or worsening of symptoms with heat or sweating.²¹ Now that dupilumab is available for adolescents, there is a chance that patients with severe and/or recalcitrant disease managed on this medication can achieve better control of their symptoms without the laboratory requirement of methotrexate and the difficulties of topical medication application, allowing them to engage in mandatory athletic classes as well as desired organized sports.

Use of Cosmetics for AD

Many adolescents experiment with cosmetics, and those with AD may use cosmetic products to cover hyperpigmented or hypopigmented lesions.¹⁸ In patients with active AD or increased sensitivity to allergens in cosmetic products, use of makeup can be a contributing factor for AD flares. Acne associated with cosmetics is especially important to consider in darker-skinned patients who may use makeup that is opaque and contains oil to conceal acne or PIH.

Allergens can be present in both cosmetics and pharmaceutical topical agents, and a Brazilian study found that approximately 89% of 813 prescription and nonprescription products (eg, topical drugs, sunscreens, moisturizers, soaps, cleansing lotions, shampoos, cosmeceuticals) contained allergens.²² Patients with AD have a higher prevalence of contact sensitization to fragrances, including balsam of Peru.²³ Some AD treatments that contain fragrances have caused further skin issues in a few patients. In one case series, 3 pediatric patients developed allergic contact dermatitis to Myroxylon pereirae (balsam of Peru) when using topical treatments for their AD, and their symptoms of scalp inflammation and alopecia resolved with discontinuation.²³

In a Dutch study, sensitization to Fragrance Mix I and M pereirae as well as other ingredients (eg, lanolin alcohol, Amerchol™ L 101 [a lanolin product]) was notably more common in pediatric patients with AD than in patients without AD; however, no data on patients with skin of color were included in this study.²⁴

Because of the increased risk of sensitization to fragrances and other ingredients in patients with AD as well as the high percentage of allergens in prescription and nonprescription products, it is important to discuss all personal care products that patients may be using, not just their cosmetic products. Also, patch testing may be helpful in determining true allergens in some patients. Patch testing is recommended for patients with treatment-resistant AD, and a recent study suggested it should be done prior to long-term use of immunosuppressive agents.²⁵ Increased steroid phobia and a push toward alternative medicines are leading both patients with AD and guardians of children with AD to look for other forms of moisturization, such as olive oil, coconut oil, sunflower seed oil, and shea butter, to decrease transepidermal water loss.^26,27 An important factor in AD treatment efficacy is patient acceptability in using what is recommended.²⁷ One study showed there was no difference in efficacy or acceptability in using a cream containing shea butter extract vs the ceramide-precursor product.²⁷ Current data show olive oil may exacerbate dry skin and AD,²⁶ and recommendation of any over-the-counter oils and butters in patients with AD should be made with great caution, as many of these products contain fragrances and other potential allergens.

Alternative Therapies for AD

Patients with AD often seek alternative or integrative treatment options, including dietary modifications and holistic remedies. Studies investigating the role of vitamins and supplements in treating AD are limited by sample size.²⁸ However, there is some evidence that may support supplementation with vitamins D and E in addressing AD symptoms. The use of probiotics in treating AD is controversial, but there are studies suggesting that the use of probiotics may prove beneficial in preventing infantile AD.²⁸ Additionally, findings from an ex vivo and in vitro study show that some conditions, including AD and acne, may benefit from the same probiotics, despite the differences in these two diseases. Both AD and acne have inflammatory and skin dysbiosis characteristics, which may be the common thread leading to both conditions potentially responding to treatment with probiotics.²⁹

Preliminary evidence indicates that supplements containing fatty acids such as docosahexaenoic acid, sea buckthorn oil, and hemp seed oil may decrease the severity of AD.²⁸ In a 20-week, randomized, single-blind, crossover study published in 2005, dietary hemp seed oil showed an improvement of clinical symptoms, including dry skin and itchiness, in patients with AD.³⁰

In light of recent legalization in several states, patients may turn to use of cannabinoid products to manage AD. In a systematic review, cannabinoid use was reportedly a therapeutic option in the treatment of AD and AV; however, the data are based on preclinical work, and there are no randomized, placebo-controlled studies to support the use of cannabinoids.³¹ Furthermore, there is great concern that use of these products in adolescents is an even larger unknown.

Final Thoughts

Eighty percent of children diagnosed with AD experience symptom improvement before their early teens³²; for those with AD during their preteen and teenage years, there can be psychological ramifications, as teenagers with AD report having fewer friends, are less socially involved, participate in fewer sports, and are absent from classes more often than their peers.⁵ In black patients with AD, school absences are even more common.⁶ Given the social and emotional impact of AD on patients with skin of color, it is imperative to treat the condition appropriately.³³ There are areas of opportunity for further research on alternate dosing of existing treatments for AV in patients with AD, further recommendations for adolescent athletes with AD, and which cosmetic and alternative medicine products may be beneficial for this population to improve their QOL.

Providers should discuss medical management in a broader context considering patients’ extracurricular activities, treatment vehicle preferences, expectations, and personal care habits. It also is important to address the many possible factors that may influence treatment adherence early on, particularly in adolescents, as these could be barriers to treatment. This article highlights considerations for treating AD and comorbid conditions that may further complicate treatment in adolescent patients with skin of color. The information provided should serve as a guide in initial counseling and management of AD in adolescents with skin of color.

Dermatologic conditions historically have affected military members’ ability to serve during times of peace and conflict. These conditions range from chronic dermatologic diseases to environment- or occupation-related dermatologic diseases. Mild to moderate atopic dermatitis (AD) typically is a manageable skin condition. However, in a deployed setting, a flare of AD can result in the inability of a member to perform their military duty, which directly compromises mission safety and effectiveness. The military developed and updates medical standards for entry and retention of service members. These standards are designed to ensure the greatest potential for a military member to successfully serve at home station and during combat operations.

Impact of Injuries in Military

Historically, disease and nonbattle injuries have resulted in notably more hospitalizations and time lost than injuries sustained on the battlefield.¹ A review of major conflicts dating from World War II shows approximately 10% of all dermatologic concerns were related to eczematous dermatitis, with 2% specifically related to AD. These numbers varied remarkably depending on the location and environment of the conflict, with eczema accounting for 25% of dermatologic concerns during the Gulf War.² During the initial phases of Operation Iraqi Freedom, approximately 75% of hospitalizations were from disease and nonbattle injuries, of which dermatologic disease accounted for 3%.¹ From 2003 to 2006 in Iraq, 35 service members were evacuated from combat zones specifically for uncontrolled AD.³ In a deployed environment, each member is critical to the unit’s success in completing their mission. A single member of a unit often is the only person qualified to perform a function for that team. There are rarely extra people with similar skills to replace a member unable to complete his/her duties. The loss of a single member compromises the effectiveness and safety of the team and can lead to mission failure. Therefore, AD can have a profound impact on military operations in a deployed environment.

Military Medical Standards for Accession and Retention

There are 2 main goals of the military medical standards. First, the individual health of the applicant or military member is of utmost importance. Applicants with medical conditions that will be exacerbated by military service or that limit the ability for successful military operations are not accepted for military service. Once an active-duty member is diagnosed with a medical condition, the military determines if limitations are needed for military assignments and deployments based on available medical care in those locations. Second, mission accomplishment in combat operations requires that healthy military members are able to complete their jobs in extreme environments and under notable stress. If an applicant has a medical condition unsuitable for military service, it is in the best interest of the applicant and the military to deny entry.

The Medical Standards for Appointment, Enlistment, or Induction Into the Military Services (DoD Instruction 6130.03) lists conditions that are disqualifying for military service.⁴ Section 5.21 lists the following as disqualifying for military service in relation to eczematous dermatitis:

d. History of AD or eczema after the 12th birthday. History of residual or recurrent lesions in characteristic areas (face, neck, antecubital or popliteal fossae, occasionally wrists and hands).

 

 

 

e. History of recurrent or chronic nonspecific dermatitis within the past 2 years to include contact (irritant or allergic) or dyshidrotic dermatitis requiring more than treatment with topical corticosteroid.⁴

Although cases of incorrect diagnosis or very mild AD can be considered for a waiver, the process can be laborious and consideration or approval is not guaranteed. For current military members with new chronic eczematous dermatitis, each service has a process for evaluation and treatment. Some special operational jobs, such as aircrew, missile operators, and divers, have more restrictive medical requirements that are monitored by physicians with special training in these populations.

Atopic dermatitis affects 25% of children and 2% to 3% of adults.⁵ Approximately 60% of patients with AD will develop their first eruption by 1 year of age, and 90% by 5 years of age. Although the majority of patients will have resolution of their disease during childhood, 10% to 30% will have persistent disease into adulthood.⁵ Because the majority of AD resolves in childhood, it is understandable that asymptomatic individuals with a history of AD before 12 years of age meet military entrance medical standards.

Provoking Factors

The US Military maintains stringent medical standards because of the nature of the dynamic, rapidly changing military environment and its demands. Whether training for readiness in an austere location, deploying to extreme climates, or being stationed overseas, service members must be prepared to encounter a myriad of environmental extremes, physical stress, and psychological stressors. Environmental factors commonly experienced in the military can provoke or exacerbate symptoms of AD (Figures 1 and 2). Ideally, an individual with AD lives in a stable climate, has access to moisturizers and topical steroids, bathes regularly to remove dust and debris, wears 100% cotton garments to avoid irritation, and avoids using gear that would cause exacerbations. Service members rarely have such accommodations in deployed settings. A recent article in Military Medicine explained quite well, “If someone wanted to design an experience with the explicit goal to flare a person with otherwise well controlled atopic dermatitis it would probably look like a military deployment.”³

The United States has a military presence in countries with extreme temperature and humidity variations all over the world. Uniforms are standardized, and members are required to wear prescribed clothing with no alternatives. Uniforms are made of durable sturdy material. If uniforms can be laundered, they often are grouped together, and sensitive detergent cannot be specified. Bathing is challenging in deployed locations, with troops often going weeks using baby wipes for self-hygiene. These conditions increase risk for development of contact allergens, and little access to proper hygiene practices also increases risk for secondary infections in members with AD.

In addition to environmental challenges, the military gear and equipment used can flare AD. Service members must wear protective gear such as body armor. These heavy hard pieces of material are bulky; difficult to wash; and cause friction, sweating, and irritation. The military prepares for operations in chemical, biological, radiological, or nuclear environments, which requires wearing a rubber mask, multiple layers of boots and gloves, and thick charcoal impregnated over garments for many hours. Such conditions may flare AD or make it intolerable.

Although stress is a part of any deployment experience, excessive or prolonged stress can lead to combat operational stress reactions that inhibit a service member’s ability to function.⁶ Stressors during deployment can accumulate and may be caused by the operational environment, loss of fellow service members to injury or death, illness, leadership demands, personal choices, issues on the home front, interpersonal conflicts, and sleep loss.⁷ Atopic dermatitis can be exacerbated by such stress, leading to increased pruritus and scratching.^7-9 Symptomatic AD also can play a role in worsening combat stress. Although severe pruritus may affect attentiveness to job duties during the day, these symptoms, if uncontrolled, also can negatively affect sleep. As many as 60% of patients with AD at baseline and 83% of patients with exacerbations experience sleep disturbance due to their disease.⁵ These stressors experienced by deployed military personnel can contribute to combat stress reactions, which may vary from simple inattentiveness to more serious behaviors such as suicidal ideation.⁶ Combat stress reactions inhibit a military member’s ability to function properly in the deployed environment and can lead to notable safety concerns and potential mission failure.

Vaccinations

Military members deploying overseas are required to receive specific vaccinations, including the smallpox vaccine. Although the virus was eradicated in 1980, the concern for smallpox to be used as a biological weapon in certain areas of the world necessitates continued vaccination of military populations. According to the Centers for Disease Control and Prevention, the only known reservoir for the virus is humans, and the disease has a mortality rate of 30%.¹⁰ A history of or present AD is a contraindication for primary smallpox vaccination and revaccination for nonemergency use because of the risk for eczema vaccinatum.¹¹ The risk also applies to close contacts of vaccinated members. For 30 days after vaccination, service members must avoid skin-to-skin contact with anyone who has active AD.¹² Eczema vaccinatum in vaccinated individuals is typically self-limited; however, eczema vaccinatum in nonvaccinated contacts can be severe. One case report described a 28-month-old child with refractory AD who developed severe eczema vaccinatum after contact with her recently vaccinated military parent. The child required a 48-day admission to the intensive care unit and multiple skin grafts; fortunately, the child did not develop any apparent long-term sequelae.¹³ This case highlights the importance of understanding the risks associated with smallpox vaccination in military members with AD and the responsibility of health care providers to properly screen and counsel individuals prior to administering smallpox vaccines.

Treatment

Treatment of mild to moderate AD is relatively straightforward in developed countries with good access to medical care. The most recent American Academy of Dermatology clinical guidelines for AD focus on minimizing irritants and triggers, regularly using moisturizers soon after bathing, and using topical steroids as needed.⁵ Military members face specific challenges regarding treatment of AD, particularly when deployed to remote locations without access to treatment facilities or medications. Military members are required to carry all necessary personal medications with them for at least 6 months and preferably the duration of the deployment, sometimes up to 1 year. Military members carry a large amount of gear for deployments, and it is not feasible to pack an additional 10 to 20 lb worth of emollients and topical steroids to last the entire deployment. Routine laboratory monitoring is limited or completely unavailable. Refrigeration typically is not available, making use of systemic medications nearly impossible during deployments. In the event of complications such as eczema herpeticum or secondary bacterial infection, service members could require evacuation from the deployed location to a larger field hospital or to the United States, which is costly and also removes a valuable team member from the deployed unit. These limitations in access to care, medications, and treatment options make AD a difficult condition to treat in the deployed setting.

Nonmilitary Medical Providers

Civilian providers play an important role in diagnosing and treating AD. It is vital to completely and accurately document treatment of all skin diseases; however, it is especially important for those who desire to or currently serve in the military. Military primary care providers or military dermatologists must review the information from civilian providers to aid in determining suitability for entry or retention in the military. Clearly documenting the morphology, extent of disease involvement (eg, body surface area), treatment plan, response to treatment, and exacerbating factors will aid in ensuring the patient’s medical record accurately reflects their skin disease. Ultimately, this record often is the only information available to make health determinations regarding military service.

Conclusion

A career in the military is challenging and rewarding for those who volunteer to serve. Because of the demanding and unpredictable lifestyle inherent with military service, the Department of Defense maintains strict medical standards for entrance and retention. These standards ensure members are capable of safely completing training and deploying anywhere in the world. Although AD is a relatively common and treatable skin disease in locations with well-established medical care, it can pose a notable problem for service members while deployed to austere locations with variable environments around the world. Environmental factors and gear requirements, coupled with limited access to treatment facilities and medications, render AD a potentially serious issue. Atopic dermatitis in military members can affect individual medical readiness and unit success. It is important that all providers understand the myriad effects that AD can have on an individual who wishes to join or continue service in the military.

Dermatologic conditions historically have affected military members’ ability to serve during times of peace and conflict. These conditions range from chronic dermatologic diseases to environment- or occupation-related dermatologic diseases. Mild to moderate atopic dermatitis (AD) typically is a manageable skin condition. However, in a deployed setting, a flare of AD can result in the inability of a member to perform their military duty, which directly compromises mission safety and effectiveness. The military developed and updates medical standards for entry and retention of service members. These standards are designed to ensure the greatest potential for a military member to successfully serve at home station and during combat operations.

Impact of Injuries in Military

Historically, disease and nonbattle injuries have resulted in notably more hospitalizations and time lost than injuries sustained on the battlefield.¹ A review of major conflicts dating from World War II shows approximately 10% of all dermatologic concerns were related to eczematous dermatitis, with 2% specifically related to AD. These numbers varied remarkably depending on the location and environment of the conflict, with eczema accounting for 25% of dermatologic concerns during the Gulf War.² During the initial phases of Operation Iraqi Freedom, approximately 75% of hospitalizations were from disease and nonbattle injuries, of which dermatologic disease accounted for 3%.¹ From 2003 to 2006 in Iraq, 35 service members were evacuated from combat zones specifically for uncontrolled AD.³ In a deployed environment, each member is critical to the unit’s success in completing their mission. A single member of a unit often is the only person qualified to perform a function for that team. There are rarely extra people with similar skills to replace a member unable to complete his/her duties. The loss of a single member compromises the effectiveness and safety of the team and can lead to mission failure. Therefore, AD can have a profound impact on military operations in a deployed environment.

Military Medical Standards for Accession and Retention

There are 2 main goals of the military medical standards. First, the individual health of the applicant or military member is of utmost importance. Applicants with medical conditions that will be exacerbated by military service or that limit the ability for successful military operations are not accepted for military service. Once an active-duty member is diagnosed with a medical condition, the military determines if limitations are needed for military assignments and deployments based on available medical care in those locations. Second, mission accomplishment in combat operations requires that healthy military members are able to complete their jobs in extreme environments and under notable stress. If an applicant has a medical condition unsuitable for military service, it is in the best interest of the applicant and the military to deny entry.

The Medical Standards for Appointment, Enlistment, or Induction Into the Military Services (DoD Instruction 6130.03) lists conditions that are disqualifying for military service.⁴ Section 5.21 lists the following as disqualifying for military service in relation to eczematous dermatitis:

d. History of AD or eczema after the 12th birthday. History of residual or recurrent lesions in characteristic areas (face, neck, antecubital or popliteal fossae, occasionally wrists and hands).

 

 

 

e. History of recurrent or chronic nonspecific dermatitis within the past 2 years to include contact (irritant or allergic) or dyshidrotic dermatitis requiring more than treatment with topical corticosteroid.⁴

Although cases of incorrect diagnosis or very mild AD can be considered for a waiver, the process can be laborious and consideration or approval is not guaranteed. For current military members with new chronic eczematous dermatitis, each service has a process for evaluation and treatment. Some special operational jobs, such as aircrew, missile operators, and divers, have more restrictive medical requirements that are monitored by physicians with special training in these populations.

Atopic dermatitis affects 25% of children and 2% to 3% of adults.⁵ Approximately 60% of patients with AD will develop their first eruption by 1 year of age, and 90% by 5 years of age. Although the majority of patients will have resolution of their disease during childhood, 10% to 30% will have persistent disease into adulthood.⁵ Because the majority of AD resolves in childhood, it is understandable that asymptomatic individuals with a history of AD before 12 years of age meet military entrance medical standards.

Provoking Factors

The US Military maintains stringent medical standards because of the nature of the dynamic, rapidly changing military environment and its demands. Whether training for readiness in an austere location, deploying to extreme climates, or being stationed overseas, service members must be prepared to encounter a myriad of environmental extremes, physical stress, and psychological stressors. Environmental factors commonly experienced in the military can provoke or exacerbate symptoms of AD (Figures 1 and 2). Ideally, an individual with AD lives in a stable climate, has access to moisturizers and topical steroids, bathes regularly to remove dust and debris, wears 100% cotton garments to avoid irritation, and avoids using gear that would cause exacerbations. Service members rarely have such accommodations in deployed settings. A recent article in Military Medicine explained quite well, “If someone wanted to design an experience with the explicit goal to flare a person with otherwise well controlled atopic dermatitis it would probably look like a military deployment.”³

The United States has a military presence in countries with extreme temperature and humidity variations all over the world. Uniforms are standardized, and members are required to wear prescribed clothing with no alternatives. Uniforms are made of durable sturdy material. If uniforms can be laundered, they often are grouped together, and sensitive detergent cannot be specified. Bathing is challenging in deployed locations, with troops often going weeks using baby wipes for self-hygiene. These conditions increase risk for development of contact allergens, and little access to proper hygiene practices also increases risk for secondary infections in members with AD.

In addition to environmental challenges, the military gear and equipment used can flare AD. Service members must wear protective gear such as body armor. These heavy hard pieces of material are bulky; difficult to wash; and cause friction, sweating, and irritation. The military prepares for operations in chemical, biological, radiological, or nuclear environments, which requires wearing a rubber mask, multiple layers of boots and gloves, and thick charcoal impregnated over garments for many hours. Such conditions may flare AD or make it intolerable.

Although stress is a part of any deployment experience, excessive or prolonged stress can lead to combat operational stress reactions that inhibit a service member’s ability to function.⁶ Stressors during deployment can accumulate and may be caused by the operational environment, loss of fellow service members to injury or death, illness, leadership demands, personal choices, issues on the home front, interpersonal conflicts, and sleep loss.⁷ Atopic dermatitis can be exacerbated by such stress, leading to increased pruritus and scratching.^7-9 Symptomatic AD also can play a role in worsening combat stress. Although severe pruritus may affect attentiveness to job duties during the day, these symptoms, if uncontrolled, also can negatively affect sleep. As many as 60% of patients with AD at baseline and 83% of patients with exacerbations experience sleep disturbance due to their disease.⁵ These stressors experienced by deployed military personnel can contribute to combat stress reactions, which may vary from simple inattentiveness to more serious behaviors such as suicidal ideation.⁶ Combat stress reactions inhibit a military member’s ability to function properly in the deployed environment and can lead to notable safety concerns and potential mission failure.

Vaccinations

Military members deploying overseas are required to receive specific vaccinations, including the smallpox vaccine. Although the virus was eradicated in 1980, the concern for smallpox to be used as a biological weapon in certain areas of the world necessitates continued vaccination of military populations. According to the Centers for Disease Control and Prevention, the only known reservoir for the virus is humans, and the disease has a mortality rate of 30%.¹⁰ A history of or present AD is a contraindication for primary smallpox vaccination and revaccination for nonemergency use because of the risk for eczema vaccinatum.¹¹ The risk also applies to close contacts of vaccinated members. For 30 days after vaccination, service members must avoid skin-to-skin contact with anyone who has active AD.¹² Eczema vaccinatum in vaccinated individuals is typically self-limited; however, eczema vaccinatum in nonvaccinated contacts can be severe. One case report described a 28-month-old child with refractory AD who developed severe eczema vaccinatum after contact with her recently vaccinated military parent. The child required a 48-day admission to the intensive care unit and multiple skin grafts; fortunately, the child did not develop any apparent long-term sequelae.¹³ This case highlights the importance of understanding the risks associated with smallpox vaccination in military members with AD and the responsibility of health care providers to properly screen and counsel individuals prior to administering smallpox vaccines.

Treatment

Treatment of mild to moderate AD is relatively straightforward in developed countries with good access to medical care. The most recent American Academy of Dermatology clinical guidelines for AD focus on minimizing irritants and triggers, regularly using moisturizers soon after bathing, and using topical steroids as needed.⁵ Military members face specific challenges regarding treatment of AD, particularly when deployed to remote locations without access to treatment facilities or medications. Military members are required to carry all necessary personal medications with them for at least 6 months and preferably the duration of the deployment, sometimes up to 1 year. Military members carry a large amount of gear for deployments, and it is not feasible to pack an additional 10 to 20 lb worth of emollients and topical steroids to last the entire deployment. Routine laboratory monitoring is limited or completely unavailable. Refrigeration typically is not available, making use of systemic medications nearly impossible during deployments. In the event of complications such as eczema herpeticum or secondary bacterial infection, service members could require evacuation from the deployed location to a larger field hospital or to the United States, which is costly and also removes a valuable team member from the deployed unit. These limitations in access to care, medications, and treatment options make AD a difficult condition to treat in the deployed setting.

Nonmilitary Medical Providers

Civilian providers play an important role in diagnosing and treating AD. It is vital to completely and accurately document treatment of all skin diseases; however, it is especially important for those who desire to or currently serve in the military. Military primary care providers or military dermatologists must review the information from civilian providers to aid in determining suitability for entry or retention in the military. Clearly documenting the morphology, extent of disease involvement (eg, body surface area), treatment plan, response to treatment, and exacerbating factors will aid in ensuring the patient’s medical record accurately reflects their skin disease. Ultimately, this record often is the only information available to make health determinations regarding military service.

Conclusion

A career in the military is challenging and rewarding for those who volunteer to serve. Because of the demanding and unpredictable lifestyle inherent with military service, the Department of Defense maintains strict medical standards for entrance and retention. These standards ensure members are capable of safely completing training and deploying anywhere in the world. Although AD is a relatively common and treatable skin disease in locations with well-established medical care, it can pose a notable problem for service members while deployed to austere locations with variable environments around the world. Environmental factors and gear requirements, coupled with limited access to treatment facilities and medications, render AD a potentially serious issue. Atopic dermatitis in military members can affect individual medical readiness and unit success. It is important that all providers understand the myriad effects that AD can have on an individual who wishes to join or continue service in the military.

Dermatologic conditions historically have affected military members’ ability to serve during times of peace and conflict. These conditions range from chronic dermatologic diseases to environment- or occupation-related dermatologic diseases. Mild to moderate atopic dermatitis (AD) typically is a manageable skin condition. However, in a deployed setting, a flare of AD can result in the inability of a member to perform their military duty, which directly compromises mission safety and effectiveness. The military developed and updates medical standards for entry and retention of service members. These standards are designed to ensure the greatest potential for a military member to successfully serve at home station and during combat operations.

Impact of Injuries in Military

Historically, disease and nonbattle injuries have resulted in notably more hospitalizations and time lost than injuries sustained on the battlefield.¹ A review of major conflicts dating from World War II shows approximately 10% of all dermatologic concerns were related to eczematous dermatitis, with 2% specifically related to AD. These numbers varied remarkably depending on the location and environment of the conflict, with eczema accounting for 25% of dermatologic concerns during the Gulf War.² During the initial phases of Operation Iraqi Freedom, approximately 75% of hospitalizations were from disease and nonbattle injuries, of which dermatologic disease accounted for 3%.¹ From 2003 to 2006 in Iraq, 35 service members were evacuated from combat zones specifically for uncontrolled AD.³ In a deployed environment, each member is critical to the unit’s success in completing their mission. A single member of a unit often is the only person qualified to perform a function for that team. There are rarely extra people with similar skills to replace a member unable to complete his/her duties. The loss of a single member compromises the effectiveness and safety of the team and can lead to mission failure. Therefore, AD can have a profound impact on military operations in a deployed environment.

Military Medical Standards for Accession and Retention

There are 2 main goals of the military medical standards. First, the individual health of the applicant or military member is of utmost importance. Applicants with medical conditions that will be exacerbated by military service or that limit the ability for successful military operations are not accepted for military service. Once an active-duty member is diagnosed with a medical condition, the military determines if limitations are needed for military assignments and deployments based on available medical care in those locations. Second, mission accomplishment in combat operations requires that healthy military members are able to complete their jobs in extreme environments and under notable stress. If an applicant has a medical condition unsuitable for military service, it is in the best interest of the applicant and the military to deny entry.

The Medical Standards for Appointment, Enlistment, or Induction Into the Military Services (DoD Instruction 6130.03) lists conditions that are disqualifying for military service.⁴ Section 5.21 lists the following as disqualifying for military service in relation to eczematous dermatitis:

d. History of AD or eczema after the 12th birthday. History of residual or recurrent lesions in characteristic areas (face, neck, antecubital or popliteal fossae, occasionally wrists and hands).

 

 

 

e. History of recurrent or chronic nonspecific dermatitis within the past 2 years to include contact (irritant or allergic) or dyshidrotic dermatitis requiring more than treatment with topical corticosteroid.⁴

Although cases of incorrect diagnosis or very mild AD can be considered for a waiver, the process can be laborious and consideration or approval is not guaranteed. For current military members with new chronic eczematous dermatitis, each service has a process for evaluation and treatment. Some special operational jobs, such as aircrew, missile operators, and divers, have more restrictive medical requirements that are monitored by physicians with special training in these populations.

Atopic dermatitis affects 25% of children and 2% to 3% of adults.⁵ Approximately 60% of patients with AD will develop their first eruption by 1 year of age, and 90% by 5 years of age. Although the majority of patients will have resolution of their disease during childhood, 10% to 30% will have persistent disease into adulthood.⁵ Because the majority of AD resolves in childhood, it is understandable that asymptomatic individuals with a history of AD before 12 years of age meet military entrance medical standards.

Provoking Factors

The US Military maintains stringent medical standards because of the nature of the dynamic, rapidly changing military environment and its demands. Whether training for readiness in an austere location, deploying to extreme climates, or being stationed overseas, service members must be prepared to encounter a myriad of environmental extremes, physical stress, and psychological stressors. Environmental factors commonly experienced in the military can provoke or exacerbate symptoms of AD (Figures 1 and 2). Ideally, an individual with AD lives in a stable climate, has access to moisturizers and topical steroids, bathes regularly to remove dust and debris, wears 100% cotton garments to avoid irritation, and avoids using gear that would cause exacerbations. Service members rarely have such accommodations in deployed settings. A recent article in Military Medicine explained quite well, “If someone wanted to design an experience with the explicit goal to flare a person with otherwise well controlled atopic dermatitis it would probably look like a military deployment.”³

The United States has a military presence in countries with extreme temperature and humidity variations all over the world. Uniforms are standardized, and members are required to wear prescribed clothing with no alternatives. Uniforms are made of durable sturdy material. If uniforms can be laundered, they often are grouped together, and sensitive detergent cannot be specified. Bathing is challenging in deployed locations, with troops often going weeks using baby wipes for self-hygiene. These conditions increase risk for development of contact allergens, and little access to proper hygiene practices also increases risk for secondary infections in members with AD.

In addition to environmental challenges, the military gear and equipment used can flare AD. Service members must wear protective gear such as body armor. These heavy hard pieces of material are bulky; difficult to wash; and cause friction, sweating, and irritation. The military prepares for operations in chemical, biological, radiological, or nuclear environments, which requires wearing a rubber mask, multiple layers of boots and gloves, and thick charcoal impregnated over garments for many hours. Such conditions may flare AD or make it intolerable.

Although stress is a part of any deployment experience, excessive or prolonged stress can lead to combat operational stress reactions that inhibit a service member’s ability to function.⁶ Stressors during deployment can accumulate and may be caused by the operational environment, loss of fellow service members to injury or death, illness, leadership demands, personal choices, issues on the home front, interpersonal conflicts, and sleep loss.⁷ Atopic dermatitis can be exacerbated by such stress, leading to increased pruritus and scratching.^7-9 Symptomatic AD also can play a role in worsening combat stress. Although severe pruritus may affect attentiveness to job duties during the day, these symptoms, if uncontrolled, also can negatively affect sleep. As many as 60% of patients with AD at baseline and 83% of patients with exacerbations experience sleep disturbance due to their disease.⁵ These stressors experienced by deployed military personnel can contribute to combat stress reactions, which may vary from simple inattentiveness to more serious behaviors such as suicidal ideation.⁶ Combat stress reactions inhibit a military member’s ability to function properly in the deployed environment and can lead to notable safety concerns and potential mission failure.

Vaccinations

Military members deploying overseas are required to receive specific vaccinations, including the smallpox vaccine. Although the virus was eradicated in 1980, the concern for smallpox to be used as a biological weapon in certain areas of the world necessitates continued vaccination of military populations. According to the Centers for Disease Control and Prevention, the only known reservoir for the virus is humans, and the disease has a mortality rate of 30%.¹⁰ A history of or present AD is a contraindication for primary smallpox vaccination and revaccination for nonemergency use because of the risk for eczema vaccinatum.¹¹ The risk also applies to close contacts of vaccinated members. For 30 days after vaccination, service members must avoid skin-to-skin contact with anyone who has active AD.¹² Eczema vaccinatum in vaccinated individuals is typically self-limited; however, eczema vaccinatum in nonvaccinated contacts can be severe. One case report described a 28-month-old child with refractory AD who developed severe eczema vaccinatum after contact with her recently vaccinated military parent. The child required a 48-day admission to the intensive care unit and multiple skin grafts; fortunately, the child did not develop any apparent long-term sequelae.¹³ This case highlights the importance of understanding the risks associated with smallpox vaccination in military members with AD and the responsibility of health care providers to properly screen and counsel individuals prior to administering smallpox vaccines.

Treatment

Treatment of mild to moderate AD is relatively straightforward in developed countries with good access to medical care. The most recent American Academy of Dermatology clinical guidelines for AD focus on minimizing irritants and triggers, regularly using moisturizers soon after bathing, and using topical steroids as needed.⁵ Military members face specific challenges regarding treatment of AD, particularly when deployed to remote locations without access to treatment facilities or medications. Military members are required to carry all necessary personal medications with them for at least 6 months and preferably the duration of the deployment, sometimes up to 1 year. Military members carry a large amount of gear for deployments, and it is not feasible to pack an additional 10 to 20 lb worth of emollients and topical steroids to last the entire deployment. Routine laboratory monitoring is limited or completely unavailable. Refrigeration typically is not available, making use of systemic medications nearly impossible during deployments. In the event of complications such as eczema herpeticum or secondary bacterial infection, service members could require evacuation from the deployed location to a larger field hospital or to the United States, which is costly and also removes a valuable team member from the deployed unit. These limitations in access to care, medications, and treatment options make AD a difficult condition to treat in the deployed setting.

Nonmilitary Medical Providers

Civilian providers play an important role in diagnosing and treating AD. It is vital to completely and accurately document treatment of all skin diseases; however, it is especially important for those who desire to or currently serve in the military. Military primary care providers or military dermatologists must review the information from civilian providers to aid in determining suitability for entry or retention in the military. Clearly documenting the morphology, extent of disease involvement (eg, body surface area), treatment plan, response to treatment, and exacerbating factors will aid in ensuring the patient’s medical record accurately reflects their skin disease. Ultimately, this record often is the only information available to make health determinations regarding military service.

Conclusion

A career in the military is challenging and rewarding for those who volunteer to serve. Because of the demanding and unpredictable lifestyle inherent with military service, the Department of Defense maintains strict medical standards for entrance and retention. These standards ensure members are capable of safely completing training and deploying anywhere in the world. Although AD is a relatively common and treatable skin disease in locations with well-established medical care, it can pose a notable problem for service members while deployed to austere locations with variable environments around the world. Environmental factors and gear requirements, coupled with limited access to treatment facilities and medications, render AD a potentially serious issue. Atopic dermatitis in military members can affect individual medical readiness and unit success. It is important that all providers understand the myriad effects that AD can have on an individual who wishes to join or continue service in the military.

The Great Pox, the French Disease, Cupid’s Disease – syphilis has had many names throughout history.

Michail Jungierek/Ausstellungsstück des Museum für Hamburgische Geschichte/Creative Commons

Why should we care about the history of syphilis? Surely syphilis has reached the status of a nonentity disease – in-and-out of the doctor’s office with a course of antibiotics and farewell to the problem. And on the surface, that is certainly true. For now. In the developed world. For those with access to reasonable health care.

But that is all the shiny surface of modern medical triumph. Despite successes in prevention throughout the late 20th and early 21st century, syphilis is making comeback. A growing reservoir of syphilis, often untreated, lies hidden by the invisibility of poorer nations and increasingly in the lower economic strata of the developed world. And the danger is increased by the rise of antibiotic-resistant strains of the disease.

Over the last decade, the European Union and several other high-income countries observed an increasing syphilis trend, according to a recent report by the European Centre for Disease Prevention and Control. And in the United States, the Centers for Disease Control and Prevention has expressed concern over “the rising tide of syphilis” and a “devastating surge in congenital syphilis.” Many reasons have been suggested for this resurgence of syphilis, including the prevalence of unprotected sex and the overall increase in multiple sexual partners in the sexually active population. This trend has been ascribed to a reduced fear of acquiring HIV from condomless sex because of the rise of antiretroviral therapies, which make HIV infection no longer a death sentence for those who have access to and can afford the drugs.

Men who have sex with men are the most affected population cited, which may in part be related to the trend in unprotected sex that has accompanied the decreasing fear of HIV. But in some countries, syphilis rates among heterosexual populations are on the increase as well. Even more troubling were the increases in syphilis diagnosed among pregnant women that were reported in high-income settings outside of the European Union, which led to increases in congenital syphilis infections.

According to a 2018 update on the global epidemiology of syphilis, each year an estimated 6 million new cases are diagnosed in people aged 15-49 years, with more than 300,000 fetal and neonatal deaths attributed to the disease. An additional 215,000 infants are at increased risk of early death because of prenatal infection.

For syphilis is indeed a nasty disease. But a remarkable one as well. It presents an almost textbook example of disease evolution and adaptation writ large. It is also a disease with equally remarkable properties – acute, systemic, latent, eruptive, and congenital in its various manifestations. As Sir William Osler, one of the brightest lights of medical education of his time, said in 1897: “I often tell my students that it [syphilis] is the only disease which they require to know thoroughly. Know syphilis in all its manifestations and relations, and all other things clinical will be added unto you.”

Syphilis is caused by the spirochete Treponema pallidum subspecies pallidum and is generally acquired by sexual contact. Congenital syphilis infection occurs by transplacental transmission.

In its modern manifestation, the disease evolves through several stages – primary, secondary, and tertiary. Primary, noncongenital infection is characterized by a lesion. This chancre, as it is called, occurs at the original site of infection, typically between 10 days and 3 months after exposure. The chancre usually appears on the genitals, but given the variety of sexual behaviors, chancres can also occur on the rectum, tongue, pharynx, breast, and so on. The myth of only choosing “a clean partner,” one without visible lesions, is misleading because vaginal and rectal lesions may not be easy to spot yet still remain profoundly infectious.

The secondary stage of an untreated infection occurs 2-3 months after the onset of chancre, and results in multisystem involvement as the spirochetes spread through the bloodstream. Symptoms include skin rash (involving the palms and the soles of the feet) and potentially a variety of other dermatologic manifestations. Fever and swollen lymph nodes may also be present before the disease moves into a latent stage, in which no clinical symptoms are evident. Following this, tertiary syphilis can occur 10-30 years after the initial infection in about 30% of the untreated population, resulting in neurosyphilis, cardiovascular syphilis, or late benign syphilis. Disease progression in tertiary syphilis can lead to dementia, disfigurement, and death.

Sounds bad, doesn’t it? But what we’ve just recounted is the relatively benign disease that modern syphilis has become. Syphilis began as a sweeping, lethal epidemic in the late 15th century spreading dread across the world from the Americas to Europe and then to Asia at a speed equal to the fastest sailing ships of the era.

Syphilis first appeared in Naples in its epidemic form in 1495. Recent anthropological and historical consensus has suggested that syphilis, as we know it today, like tobacco, potatoes, and maize is a product of the Americas that was brought to the Old World by the intrepid exploits of one Christopher Columbus in 1493. Just as the Spanish inadvertently brought smallpox to devastate the population of the New World, Christopher Columbus appears to have brought epidemic syphilis to the Old World in an ironic twist of fate.

Ruy Diaz de Isla, one of two Spanish physicians present when Christopher Columbus returned from his first voyage to America, wrote in a manuscript that Pinzon de Palos, the pilot of Columbus, and also other members of the crew already suffered from symptoms of what was likely syphilis on their return from the New World

Public domain

Although there has been some controversy regarding the origin of the syphilis epidemic, a recent molecular study using a large collection of pathogenic Treponema strains indicated that venereal syphilis arose relatively recently in human history, and that the closest related syphilis-causing strains were found in South America, providing support for the Columbian theory of syphilis’s origin.

Syphilis flamed across Europe like wildfire, lit by a series of small wars that started shortly after Columbus’s return. Soldiers throughout history have indulged themselves in activities well primed for the spread of venereal disease, and the doughty warriors of the late 15th century were no exception. And throughout the next 500-plus years, syphilis and war rode across the world in tandem, like the white and red horsemen of the Apocalypse.

In its initial launch, syphilis had the help of Charles VIII, the King of France, who had invaded Italy in early 1495 with an army of more than 30,000 mercenaries recruited from across Europe. His forces conquered Naples, which was primarily defended by Spanish mercenaries.

When Charles VIII broke up his army, “mercenaries, infected with a mysterious, serious disease, returned to their native lands or moved elsewhere to wage war, spreading the disease across Europe.” The “Great Pox” initially struck Italy, France, Germany, and Switzerland in 1495; then Holland and Greece in the following year, reaching England and Scotland by 1497; and then Hungary, Poland, and the Scandinavian countries by 1500.

As this period was the Age of Exploration, French, Dutch, and English sailors soon carried syphilis across the rest of an unsuspecting world, with the disease reaching India in 1498 before moving also to Africa and then throughout the rest of Asia in the early 16th century.

And yet, one of the most remarkable parts of the story is the rapid transformation of syphilis from a deadly virulent epidemic to a (comparatively) benign endemic status. Which will be the subject of my next posting.

Wellcome Library, London. Wellcome Images/Creative Commons

[email protected]

Mark Lesney is the managing editor of MDedge.com/IDPractioner . He has a PhD in Plant Virology and a PhD in the History of Science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor at the Georgetown University School of Medicine, Department of Biochemistry and Molecular & Cellular Biology, Washington, DC.

The Great Pox, the French Disease, Cupid’s Disease – syphilis has had many names throughout history.

Michail Jungierek/Ausstellungsstück des Museum für Hamburgische Geschichte/Creative Commons

Why should we care about the history of syphilis? Surely syphilis has reached the status of a nonentity disease – in-and-out of the doctor’s office with a course of antibiotics and farewell to the problem. And on the surface, that is certainly true. For now. In the developed world. For those with access to reasonable health care.

But that is all the shiny surface of modern medical triumph. Despite successes in prevention throughout the late 20th and early 21st century, syphilis is making comeback. A growing reservoir of syphilis, often untreated, lies hidden by the invisibility of poorer nations and increasingly in the lower economic strata of the developed world. And the danger is increased by the rise of antibiotic-resistant strains of the disease.

Over the last decade, the European Union and several other high-income countries observed an increasing syphilis trend, according to a recent report by the European Centre for Disease Prevention and Control. And in the United States, the Centers for Disease Control and Prevention has expressed concern over “the rising tide of syphilis” and a “devastating surge in congenital syphilis.” Many reasons have been suggested for this resurgence of syphilis, including the prevalence of unprotected sex and the overall increase in multiple sexual partners in the sexually active population. This trend has been ascribed to a reduced fear of acquiring HIV from condomless sex because of the rise of antiretroviral therapies, which make HIV infection no longer a death sentence for those who have access to and can afford the drugs.

Men who have sex with men are the most affected population cited, which may in part be related to the trend in unprotected sex that has accompanied the decreasing fear of HIV. But in some countries, syphilis rates among heterosexual populations are on the increase as well. Even more troubling were the increases in syphilis diagnosed among pregnant women that were reported in high-income settings outside of the European Union, which led to increases in congenital syphilis infections.

According to a 2018 update on the global epidemiology of syphilis, each year an estimated 6 million new cases are diagnosed in people aged 15-49 years, with more than 300,000 fetal and neonatal deaths attributed to the disease. An additional 215,000 infants are at increased risk of early death because of prenatal infection.

For syphilis is indeed a nasty disease. But a remarkable one as well. It presents an almost textbook example of disease evolution and adaptation writ large. It is also a disease with equally remarkable properties – acute, systemic, latent, eruptive, and congenital in its various manifestations. As Sir William Osler, one of the brightest lights of medical education of his time, said in 1897: “I often tell my students that it [syphilis] is the only disease which they require to know thoroughly. Know syphilis in all its manifestations and relations, and all other things clinical will be added unto you.”

Syphilis is caused by the spirochete Treponema pallidum subspecies pallidum and is generally acquired by sexual contact. Congenital syphilis infection occurs by transplacental transmission.

In its modern manifestation, the disease evolves through several stages – primary, secondary, and tertiary. Primary, noncongenital infection is characterized by a lesion. This chancre, as it is called, occurs at the original site of infection, typically between 10 days and 3 months after exposure. The chancre usually appears on the genitals, but given the variety of sexual behaviors, chancres can also occur on the rectum, tongue, pharynx, breast, and so on. The myth of only choosing “a clean partner,” one without visible lesions, is misleading because vaginal and rectal lesions may not be easy to spot yet still remain profoundly infectious.

The secondary stage of an untreated infection occurs 2-3 months after the onset of chancre, and results in multisystem involvement as the spirochetes spread through the bloodstream. Symptoms include skin rash (involving the palms and the soles of the feet) and potentially a variety of other dermatologic manifestations. Fever and swollen lymph nodes may also be present before the disease moves into a latent stage, in which no clinical symptoms are evident. Following this, tertiary syphilis can occur 10-30 years after the initial infection in about 30% of the untreated population, resulting in neurosyphilis, cardiovascular syphilis, or late benign syphilis. Disease progression in tertiary syphilis can lead to dementia, disfigurement, and death.

Sounds bad, doesn’t it? But what we’ve just recounted is the relatively benign disease that modern syphilis has become. Syphilis began as a sweeping, lethal epidemic in the late 15th century spreading dread across the world from the Americas to Europe and then to Asia at a speed equal to the fastest sailing ships of the era.

Syphilis first appeared in Naples in its epidemic form in 1495. Recent anthropological and historical consensus has suggested that syphilis, as we know it today, like tobacco, potatoes, and maize is a product of the Americas that was brought to the Old World by the intrepid exploits of one Christopher Columbus in 1493. Just as the Spanish inadvertently brought smallpox to devastate the population of the New World, Christopher Columbus appears to have brought epidemic syphilis to the Old World in an ironic twist of fate.

Ruy Diaz de Isla, one of two Spanish physicians present when Christopher Columbus returned from his first voyage to America, wrote in a manuscript that Pinzon de Palos, the pilot of Columbus, and also other members of the crew already suffered from symptoms of what was likely syphilis on their return from the New World

Public domain

Although there has been some controversy regarding the origin of the syphilis epidemic, a recent molecular study using a large collection of pathogenic Treponema strains indicated that venereal syphilis arose relatively recently in human history, and that the closest related syphilis-causing strains were found in South America, providing support for the Columbian theory of syphilis’s origin.

Syphilis flamed across Europe like wildfire, lit by a series of small wars that started shortly after Columbus’s return. Soldiers throughout history have indulged themselves in activities well primed for the spread of venereal disease, and the doughty warriors of the late 15th century were no exception. And throughout the next 500-plus years, syphilis and war rode across the world in tandem, like the white and red horsemen of the Apocalypse.

In its initial launch, syphilis had the help of Charles VIII, the King of France, who had invaded Italy in early 1495 with an army of more than 30,000 mercenaries recruited from across Europe. His forces conquered Naples, which was primarily defended by Spanish mercenaries.

When Charles VIII broke up his army, “mercenaries, infected with a mysterious, serious disease, returned to their native lands or moved elsewhere to wage war, spreading the disease across Europe.” The “Great Pox” initially struck Italy, France, Germany, and Switzerland in 1495; then Holland and Greece in the following year, reaching England and Scotland by 1497; and then Hungary, Poland, and the Scandinavian countries by 1500.

As this period was the Age of Exploration, French, Dutch, and English sailors soon carried syphilis across the rest of an unsuspecting world, with the disease reaching India in 1498 before moving also to Africa and then throughout the rest of Asia in the early 16th century.

And yet, one of the most remarkable parts of the story is the rapid transformation of syphilis from a deadly virulent epidemic to a (comparatively) benign endemic status. Which will be the subject of my next posting.

Wellcome Library, London. Wellcome Images/Creative Commons

[email protected]

Mark Lesney is the managing editor of MDedge.com/IDPractioner . He has a PhD in Plant Virology and a PhD in the History of Science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor at the Georgetown University School of Medicine, Department of Biochemistry and Molecular & Cellular Biology, Washington, DC.

The Great Pox, the French Disease, Cupid’s Disease – syphilis has had many names throughout history.

Michail Jungierek/Ausstellungsstück des Museum für Hamburgische Geschichte/Creative Commons

Why should we care about the history of syphilis? Surely syphilis has reached the status of a nonentity disease – in-and-out of the doctor’s office with a course of antibiotics and farewell to the problem. And on the surface, that is certainly true. For now. In the developed world. For those with access to reasonable health care.

But that is all the shiny surface of modern medical triumph. Despite successes in prevention throughout the late 20th and early 21st century, syphilis is making comeback. A growing reservoir of syphilis, often untreated, lies hidden by the invisibility of poorer nations and increasingly in the lower economic strata of the developed world. And the danger is increased by the rise of antibiotic-resistant strains of the disease.

Over the last decade, the European Union and several other high-income countries observed an increasing syphilis trend, according to a recent report by the European Centre for Disease Prevention and Control. And in the United States, the Centers for Disease Control and Prevention has expressed concern over “the rising tide of syphilis” and a “devastating surge in congenital syphilis.” Many reasons have been suggested for this resurgence of syphilis, including the prevalence of unprotected sex and the overall increase in multiple sexual partners in the sexually active population. This trend has been ascribed to a reduced fear of acquiring HIV from condomless sex because of the rise of antiretroviral therapies, which make HIV infection no longer a death sentence for those who have access to and can afford the drugs.

Men who have sex with men are the most affected population cited, which may in part be related to the trend in unprotected sex that has accompanied the decreasing fear of HIV. But in some countries, syphilis rates among heterosexual populations are on the increase as well. Even more troubling were the increases in syphilis diagnosed among pregnant women that were reported in high-income settings outside of the European Union, which led to increases in congenital syphilis infections.

According to a 2018 update on the global epidemiology of syphilis, each year an estimated 6 million new cases are diagnosed in people aged 15-49 years, with more than 300,000 fetal and neonatal deaths attributed to the disease. An additional 215,000 infants are at increased risk of early death because of prenatal infection.

For syphilis is indeed a nasty disease. But a remarkable one as well. It presents an almost textbook example of disease evolution and adaptation writ large. It is also a disease with equally remarkable properties – acute, systemic, latent, eruptive, and congenital in its various manifestations. As Sir William Osler, one of the brightest lights of medical education of his time, said in 1897: “I often tell my students that it [syphilis] is the only disease which they require to know thoroughly. Know syphilis in all its manifestations and relations, and all other things clinical will be added unto you.”

Syphilis is caused by the spirochete Treponema pallidum subspecies pallidum and is generally acquired by sexual contact. Congenital syphilis infection occurs by transplacental transmission.

In its modern manifestation, the disease evolves through several stages – primary, secondary, and tertiary. Primary, noncongenital infection is characterized by a lesion. This chancre, as it is called, occurs at the original site of infection, typically between 10 days and 3 months after exposure. The chancre usually appears on the genitals, but given the variety of sexual behaviors, chancres can also occur on the rectum, tongue, pharynx, breast, and so on. The myth of only choosing “a clean partner,” one without visible lesions, is misleading because vaginal and rectal lesions may not be easy to spot yet still remain profoundly infectious.

The secondary stage of an untreated infection occurs 2-3 months after the onset of chancre, and results in multisystem involvement as the spirochetes spread through the bloodstream. Symptoms include skin rash (involving the palms and the soles of the feet) and potentially a variety of other dermatologic manifestations. Fever and swollen lymph nodes may also be present before the disease moves into a latent stage, in which no clinical symptoms are evident. Following this, tertiary syphilis can occur 10-30 years after the initial infection in about 30% of the untreated population, resulting in neurosyphilis, cardiovascular syphilis, or late benign syphilis. Disease progression in tertiary syphilis can lead to dementia, disfigurement, and death.

Sounds bad, doesn’t it? But what we’ve just recounted is the relatively benign disease that modern syphilis has become. Syphilis began as a sweeping, lethal epidemic in the late 15th century spreading dread across the world from the Americas to Europe and then to Asia at a speed equal to the fastest sailing ships of the era.

Syphilis first appeared in Naples in its epidemic form in 1495. Recent anthropological and historical consensus has suggested that syphilis, as we know it today, like tobacco, potatoes, and maize is a product of the Americas that was brought to the Old World by the intrepid exploits of one Christopher Columbus in 1493. Just as the Spanish inadvertently brought smallpox to devastate the population of the New World, Christopher Columbus appears to have brought epidemic syphilis to the Old World in an ironic twist of fate.

Ruy Diaz de Isla, one of two Spanish physicians present when Christopher Columbus returned from his first voyage to America, wrote in a manuscript that Pinzon de Palos, the pilot of Columbus, and also other members of the crew already suffered from symptoms of what was likely syphilis on their return from the New World

Public domain

Although there has been some controversy regarding the origin of the syphilis epidemic, a recent molecular study using a large collection of pathogenic Treponema strains indicated that venereal syphilis arose relatively recently in human history, and that the closest related syphilis-causing strains were found in South America, providing support for the Columbian theory of syphilis’s origin.

Syphilis flamed across Europe like wildfire, lit by a series of small wars that started shortly after Columbus’s return. Soldiers throughout history have indulged themselves in activities well primed for the spread of venereal disease, and the doughty warriors of the late 15th century were no exception. And throughout the next 500-plus years, syphilis and war rode across the world in tandem, like the white and red horsemen of the Apocalypse.

In its initial launch, syphilis had the help of Charles VIII, the King of France, who had invaded Italy in early 1495 with an army of more than 30,000 mercenaries recruited from across Europe. His forces conquered Naples, which was primarily defended by Spanish mercenaries.

When Charles VIII broke up his army, “mercenaries, infected with a mysterious, serious disease, returned to their native lands or moved elsewhere to wage war, spreading the disease across Europe.” The “Great Pox” initially struck Italy, France, Germany, and Switzerland in 1495; then Holland and Greece in the following year, reaching England and Scotland by 1497; and then Hungary, Poland, and the Scandinavian countries by 1500.

As this period was the Age of Exploration, French, Dutch, and English sailors soon carried syphilis across the rest of an unsuspecting world, with the disease reaching India in 1498 before moving also to Africa and then throughout the rest of Asia in the early 16th century.

And yet, one of the most remarkable parts of the story is the rapid transformation of syphilis from a deadly virulent epidemic to a (comparatively) benign endemic status. Which will be the subject of my next posting.

Wellcome Library, London. Wellcome Images/Creative Commons

[email protected]

Mark Lesney is the managing editor of MDedge.com/IDPractioner . He has a PhD in Plant Virology and a PhD in the History of Science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor at the Georgetown University School of Medicine, Department of Biochemistry and Molecular & Cellular Biology, Washington, DC.

According to World Health Organization estimates, 65 million people have moderate-to-severe chronic obstructive pulmonary disease (COPD) globally, and > 20 million patients with COPD are living in the US.¹ COPD is a progressive respiratory disease with a poor prognosis and a significant cause of morbidity and mortality in the US, especially within the Veterans Health Administration (VHA).² The prevalence of COPD is higher in veterans than it is in the general population. COPD prevalence in the adult US population has been estimated to be between 5% and 15%, whereas in veterans, prevalence estimates have ranged from about 5% to 43%.^3-5

COPD is associated with disabling dyspnea, muscle weakness, exercise intolerance, morbidity, and mortality. These symptoms and complications gradually and progressively compromise mobility, ability to perform daily functions, and decrease quality of life (QOL). Dyspnea, fatigue, and discomfort are the principal symptoms that negatively impact exercise tolerance.^6,7 Therefore, patients often intentionally limit their activities to avoid these uncomfortable feelings and adopt a more sedentary behavior. As the disease progresses, individuals with COPD will gradually need assistance in performing activities of daily living, which eventually leads to functional dependence.

Pulmonary rehabilitation (PR) is an essential component of the management of symptomatic patients with COPD. PR is an evidence-based, multidisciplinary, comprehensive intervention that includes exercise and education for patients with chronic respiratory disease.⁸ The key benefits of PR are clinical improvements in dyspnea, physical capacity, QOL, and reduced disability in patients with COPD and other respiratory diseases.^9-11 PR was found to improve respiratory health in veterans with COPD and decrease respiratory-related health care utilization.¹²

Despite the known benefits of PR, many patients with chronic respiratory diseases are not referred or do not have access to rehabilitation. Also, uptake of PR is low due to patient frailty, transportation issues, and other health care access problems.^13-15 Unfortunately, in the US health care system, access to PR and other nonpharmacologic treatments can be challenging due to a shortage of available PR programs, limited physician referral to existing programs, and lack of family and social support.¹⁶

There are only a few accredited PR programs in VHA facilities, and they tend to be located in urban areas.^12,17 Many patients have limited access to the PR programs due to geographic distance to the programs and transportation challenges (eg, limited ability to drive, cost of transportation). Moreover, veterans with COPD are likely to have limited mobility or are homebound due to experiencing shortness of breath with minimal exertion. Given the clear benefits of PR and the increasing impact of COPD on morbidity and mortality of the patients with COPD, strategies to improve the access and capacity of PR are needed. VA telehealth services allow for distribution of health care services in different geographic locations by providing access for the veterans who live in rural and highly rural areas. The most recent implementation of VA Video Connect (VVC) by the VHA provides a new avenue for clinicians to deliver much needed medical care into the veterans’ home.

COPD Telehealth Program

In this article, we describe the processes for developing and delivering an in-home, interactive, supervised PR program for veterans with severe COPD through VA telehealth service. The program consists of 18 sessions delivered over 6 weeks by a licensed physical therapist (PT) and a respiratory therapist (RT). The aims of the telehealth PR are to improve exercise tolerance, reduce dyspnea and fatigue, improve QOL, improve accessibility, and decrease costs and transportation burdens for patients with COPD. The program was developed, implemented and delivered by an interdisciplinary team, including a pulmonologist, PT, RT, physiatrist, and nonclinical supporting staff.

To be eligible to participate in the program the patient must: (1) have a forced expiratory volume (FEV₁) < 60%; ( 2) be medically stable and be receiving optimal medical management; (3) have no severe cognitive impairments; (4) be able to use a computer and e-mail; (5) be able to ambulate with or without a walking device; (6) be willing to enroll in a smoking cessation program or to stop smoking; (7) be willing to participate without prolonged interruption; and (8) have all visual and auditory impairments corrected with medical devices.

After referral and enrollment, patients receive medical and physical examinations by the PR team, including a pulmonologist, a PT, and a RT, to ensure that the patients are medically stable to undergo rehabilitation and to develop a tailored exercise program while being mindful of the comorbidities, limitations, and precautions, (eg, loss of balance, risk of fall, limited range of motion). The preprogram assessment includes a pulmonary function test, arterial blood gas test, Montreal Cognitive Assessment, Modified Medical Research Council Scale, St. George Respiratory Questionnaire, the COPD Assessment Test, Patient Health Questionnaire-9,Generalized Anxiety Disorder Assessment-7, Epworth Sleepiness Scale, Katz Index of Independence of Activities of Daily Living, medications and inhaler use, oxygen use, breathing pattern, coughing, 6-minute walk test, Modified Borg Dyspnea Scale, grip strength, 5 Times Sit to Stand Test, manual muscle test, gait measure, Timed Up & Go test, clinical balance tests, range of motion, flexibility, sensation, pain, and fall history.^18-32 Educational needs (eg, respiratory hygiene, nutrition, infection control, sleep, disease/symptom management) also are evaluated.

This thorough assessment is performed in a face-to-face outpatient visit. During the program participation, a physiatrist may be consulted for additional needs (eg, wheelchair assessment, home safety evaluation/ modifications, and mobility/disability issues). After completing the 6-week program, patients are scheduled for the postprogram evaluation in a face-to-face outpatient visit with the clinicians.

Equipment

Both clinician and the patient are equipped with a computer with Wi-Fi connectivity, a webcam, and a microphone. Patients are provided an exercise pictorial booklet, an exercise compact disk (audio and video), small exercise apparatuses (eg, assorted colors of resistance bands, hand grip exerciser, hand putty, ergometer, harmonica, and pedometer), incentive spirometer, pulse oximeter, cough assistive device (as needed), blood pressure monitor, COPD information booklets, and a diary to use at home during the program.³³

Technology Preparation

Prior to starting the telehealth program, the patient is contacted 1 or 2 days before the first session for technical preparation and familiarization of the VA telehealth connection process. Either the PT or RT provides step-by-step instructions for the patient to practice connecting through VVC during this preparatory phone call. The patient also practices using the computer webcam, speaker, and microphone; checks the telehealth scheduling e-mail; and learns how to solve possible common technical issues (eg, adjusting volume and position of webcam). The patient is asked to set up a table close to the computer and to place all exercise apparatuses and respiratory devices on the table surface.

Program Delivery

A secure online VVC is used for connection during the telehealth session. The patient received an e-mail from the telehealth scheduling system with a link for VVC before each session. During the 6-week program, each telehealth session is conducted by a PT and a RT concurrently for 120 minutes, 3 days per week. The PT provides exercises for the patient to attempt, and the RT provides breathing training and monitoring during the session. After a successful connection to VVC, the therapist verifies the patient’s identity and confirms patient consent for the telehealth session.

After this check-in process, the patient performs a self-measure of resting blood pressure (BP), heart rate, respiratory rate, and blood oxygen saturation and reports to the therapists. During the exercise session, fatigue/exertion, dyspnea (Modified Borg Dyspnea Scale; Borg CR10 Scale), BP, heart rate, oxygen saturation, and other clinical symptoms and responses to exercise are monitored by the therapists, using both patient-reported measures and clinical observation by the therapists.^34,35 Any medical emergency during the session is reported immediately to the pulmonologist for further management.

Structure

Prior to each exercise session, exercise precautions, fall prevention, good posture, pursed-lip breathing, pacing, and coordinated breathing are discussed with the patient. The PT demonstrates stretching and warm-up exercises in front of the webcam for the patient to follow. Then the patient performs all exercises in view of the webcam during the session (Figure 1). A RT monitors breathing patterns and corrects with verbal instructions if not properly performed.

Loss of skeletal muscle mass and cachexia are highly prevalent comorbidities of COPD and have been associated with breathlessness, functional limitation, and poor prognosis.³⁶ To address these comorbidities, our program consists of progressive strengthening, aerobic, balance, and flexibility exercises. Resistance bands and tubes are used for strengthening exercises. Callisthenic exercises (eg, chair squat, chair stand, knee marching, bridging, single limb stances, and lunge) are used for progressive strengthening and balance exercises. Progression of strengthening and balance exercises are done through increasing the volume of exercise (ie, numbers of sets and repetitions) and increased load and level of difficulty based on the patient’s progress and comorbidity. The exercise program focuses on strengthening muscles, especially large muscle groups, to improve overall muscle strength and performance of functional activities.³⁷

Arm/pedal ergometer and daily walking are used for daily aerobic exercise. In a study of patients with COPD by the PAC-COPD Study Group, step counter use was found to increase physical activity and improve exercise capacity, which supports its use in COPD management.³⁸ During program participation, the patient is asked to wear a pedometer to monitor the number of steps taken per day and to report step data to the therapists during the telehealth session. The pedometer stores the previous 41 calendar days of data and displays the most recent 7 calendar days of data.

The patient is encouraged to set a realistic daily step goal. The general program goal is to increase at least 1000 steps per day. However, this goal can be adjusted depending on the patient’s health status and comorbid conditions. The PAC-COPD Study Group found that for every additional 1000 daily steps at low intensity, COPD hospitalization risk decreased by 20%.³⁹ A magnitude of 2000 steps or about 1 mile of walking per day was found to be associated with increased physical activity and health benefits in the general population.⁴⁰

Respiratory muscle training and breathing exercise are provided by the RT, using breathing and incentive spirometer techniques (Figure 2). Huff coughing, diaphragmatic deep breathing, and pursed-lip breathing are instructed by the RT during the session. Effective coughing technique with a cough assistive device is also provided during breathing training if needed.

Patient Education

In patients with COPD, there are numerous positive health benefits associated with education, including assisting the patients to become active participants in the PR program leading to satisfying outcomes; assisting the patients to better understand the lung health, disease processes, physical and psychological changes that occur with COPD; assisting the patients to explore coping strategies for those changes; building lifelong behavioral changes; and developing the self-management skills for sustainability. Through the educational process, patients with COPD can become more skilled at collaborative self-management and improve adherence to their treatment plan, which in turn can result in a reduction in hospital admissions and reduced health care costs.^8,41

Education is provided with every session after the patient completes the exercise. Patients are required to record their COPD symptoms, daily activity, home exercise program, sleep, food intake, and additional physical or social activity in their COPD diary and to report during the session (Figure 3). A COPD diary assists patients in self-monitoring their COPD symptoms and provides the therapists with information about clinical changes, behavioral changes, and/or specific unmet needs for education. Several topics related to COPD are included in the education session: lung or respiratory disease/condition and self-management; smoking cessation; physical activity; energy-conserving techniques; breathing and coughing techniques; smoking cessation; nutrition/healthy eating and weight counseling; sex and intimacy; psychological counseling and/or group support; emergency planning (eg, medical, travel, and inclement weather); correct use of inhaler and medications; home oxygen; sleep and sleep hygiene; palliative care and advanced directive; infection control; and sputum clearance.^42,43

Program Maintenance

After successfully completing the 6-week program, patients are referred to the VA TeleMOVE! Program or MOVE! Weight Management Program for continuous, long-term management of weight, nutrition, physical activity/exercise, and social activity needs or goals. The patients are scheduled for monthly follow-up phone visits for 6 months with the telerehabilitation team for enforcing sustainability. The phone call visit consists of reviewing breathing techniques, exercise program, physical activity, education, encouragement, and addressing any issues that arise during the self-maintained period.

Limitations

There are several issues of concern and precautions when delivering PR through telehealth into the home. First, the patient performs exercises independently without being manually guarded by the therapists. Risk of falls are a major concern due to impaired balance, poor vision, and other possible unusual physiologic responses to exercise (eg, drop in BP, dizziness, loss of balance). The area in front of the computer needs to be cleared of fall hazards (ie, area rug, wires, objects on the floor). The patient also needs to be educated on self-measurements of BP and oxygen saturation and reports to the therapists. The therapists provide detailed instructions on how to obtain these measures correctly; otherwise, the values may not be valid for a clinical judgment during the exercise session or for other clinical management. In a home environment, there is a limited use of exercise apparatuses. For this program, we only used resistance bands/tubes, small arm/leg ergometer, hand grip, and hand putty for the exercise program. We feel that dumbbell and weight plates are not suitable due to a possible risk of injury if the patient accidently drops them.

Advanced balance training is not suitable due to an increased risk for falls. Without the presence of the PT, level of challenge/difficulty is somewhat limited for this telehealth supervision exercise program. In addition, visual and audio quality are necessary for the session. The patient and the therapists need to see each other clearly to ensure correct methods and forms of each exercise. Furthermore, rehearsal of technical skills with the therapists is very important because this population is older and often has limited computer skills. Any technical difficulty or failure can lead to undesirable situations (eg, anxiety episodes, worries, shortness of breath, upset), which compromise exercise performance during the session. Finally, a phone is needed as an alternative in case of a poor VVC connection.

Conclusion

COPD symptoms and complications greatly affect patients’ ability to perform daily activities, decrease QOL and functional ability, and result in extensive use of health services. Many patients have limited access to a PR program at hospitals or rehabilitation centers due to health conditions, lack of transportation, and/or family support. This home-based, interactive telehealth PR program can break down the geographic barriers, solve poor program accessibility, potentially increase the utilization of PR, and reduce the cost and travel required by the patients.

Acknowledgments
The Telehealth Pulmonary Rehabilitation Program was originally funded by the Veterans Health Administration VA ACCESS Program (AS, CL, HKH). We thank all the veterans for their time and effort in participating in this newly developed rehabilitation program.

According to World Health Organization estimates, 65 million people have moderate-to-severe chronic obstructive pulmonary disease (COPD) globally, and > 20 million patients with COPD are living in the US.¹ COPD is a progressive respiratory disease with a poor prognosis and a significant cause of morbidity and mortality in the US, especially within the Veterans Health Administration (VHA).² The prevalence of COPD is higher in veterans than it is in the general population. COPD prevalence in the adult US population has been estimated to be between 5% and 15%, whereas in veterans, prevalence estimates have ranged from about 5% to 43%.^3-5

COPD is associated with disabling dyspnea, muscle weakness, exercise intolerance, morbidity, and mortality. These symptoms and complications gradually and progressively compromise mobility, ability to perform daily functions, and decrease quality of life (QOL). Dyspnea, fatigue, and discomfort are the principal symptoms that negatively impact exercise tolerance.^6,7 Therefore, patients often intentionally limit their activities to avoid these uncomfortable feelings and adopt a more sedentary behavior. As the disease progresses, individuals with COPD will gradually need assistance in performing activities of daily living, which eventually leads to functional dependence.

Pulmonary rehabilitation (PR) is an essential component of the management of symptomatic patients with COPD. PR is an evidence-based, multidisciplinary, comprehensive intervention that includes exercise and education for patients with chronic respiratory disease.⁸ The key benefits of PR are clinical improvements in dyspnea, physical capacity, QOL, and reduced disability in patients with COPD and other respiratory diseases.^9-11 PR was found to improve respiratory health in veterans with COPD and decrease respiratory-related health care utilization.¹²

Despite the known benefits of PR, many patients with chronic respiratory diseases are not referred or do not have access to rehabilitation. Also, uptake of PR is low due to patient frailty, transportation issues, and other health care access problems.^13-15 Unfortunately, in the US health care system, access to PR and other nonpharmacologic treatments can be challenging due to a shortage of available PR programs, limited physician referral to existing programs, and lack of family and social support.¹⁶

There are only a few accredited PR programs in VHA facilities, and they tend to be located in urban areas.^12,17 Many patients have limited access to the PR programs due to geographic distance to the programs and transportation challenges (eg, limited ability to drive, cost of transportation). Moreover, veterans with COPD are likely to have limited mobility or are homebound due to experiencing shortness of breath with minimal exertion. Given the clear benefits of PR and the increasing impact of COPD on morbidity and mortality of the patients with COPD, strategies to improve the access and capacity of PR are needed. VA telehealth services allow for distribution of health care services in different geographic locations by providing access for the veterans who live in rural and highly rural areas. The most recent implementation of VA Video Connect (VVC) by the VHA provides a new avenue for clinicians to deliver much needed medical care into the veterans’ home.

COPD Telehealth Program

In this article, we describe the processes for developing and delivering an in-home, interactive, supervised PR program for veterans with severe COPD through VA telehealth service. The program consists of 18 sessions delivered over 6 weeks by a licensed physical therapist (PT) and a respiratory therapist (RT). The aims of the telehealth PR are to improve exercise tolerance, reduce dyspnea and fatigue, improve QOL, improve accessibility, and decrease costs and transportation burdens for patients with COPD. The program was developed, implemented and delivered by an interdisciplinary team, including a pulmonologist, PT, RT, physiatrist, and nonclinical supporting staff.

To be eligible to participate in the program the patient must: (1) have a forced expiratory volume (FEV₁) < 60%; ( 2) be medically stable and be receiving optimal medical management; (3) have no severe cognitive impairments; (4) be able to use a computer and e-mail; (5) be able to ambulate with or without a walking device; (6) be willing to enroll in a smoking cessation program or to stop smoking; (7) be willing to participate without prolonged interruption; and (8) have all visual and auditory impairments corrected with medical devices.

After referral and enrollment, patients receive medical and physical examinations by the PR team, including a pulmonologist, a PT, and a RT, to ensure that the patients are medically stable to undergo rehabilitation and to develop a tailored exercise program while being mindful of the comorbidities, limitations, and precautions, (eg, loss of balance, risk of fall, limited range of motion). The preprogram assessment includes a pulmonary function test, arterial blood gas test, Montreal Cognitive Assessment, Modified Medical Research Council Scale, St. George Respiratory Questionnaire, the COPD Assessment Test, Patient Health Questionnaire-9,Generalized Anxiety Disorder Assessment-7, Epworth Sleepiness Scale, Katz Index of Independence of Activities of Daily Living, medications and inhaler use, oxygen use, breathing pattern, coughing, 6-minute walk test, Modified Borg Dyspnea Scale, grip strength, 5 Times Sit to Stand Test, manual muscle test, gait measure, Timed Up & Go test, clinical balance tests, range of motion, flexibility, sensation, pain, and fall history.^18-32 Educational needs (eg, respiratory hygiene, nutrition, infection control, sleep, disease/symptom management) also are evaluated.

This thorough assessment is performed in a face-to-face outpatient visit. During the program participation, a physiatrist may be consulted for additional needs (eg, wheelchair assessment, home safety evaluation/ modifications, and mobility/disability issues). After completing the 6-week program, patients are scheduled for the postprogram evaluation in a face-to-face outpatient visit with the clinicians.

Equipment

Both clinician and the patient are equipped with a computer with Wi-Fi connectivity, a webcam, and a microphone. Patients are provided an exercise pictorial booklet, an exercise compact disk (audio and video), small exercise apparatuses (eg, assorted colors of resistance bands, hand grip exerciser, hand putty, ergometer, harmonica, and pedometer), incentive spirometer, pulse oximeter, cough assistive device (as needed), blood pressure monitor, COPD information booklets, and a diary to use at home during the program.³³

Technology Preparation

Prior to starting the telehealth program, the patient is contacted 1 or 2 days before the first session for technical preparation and familiarization of the VA telehealth connection process. Either the PT or RT provides step-by-step instructions for the patient to practice connecting through VVC during this preparatory phone call. The patient also practices using the computer webcam, speaker, and microphone; checks the telehealth scheduling e-mail; and learns how to solve possible common technical issues (eg, adjusting volume and position of webcam). The patient is asked to set up a table close to the computer and to place all exercise apparatuses and respiratory devices on the table surface.

Program Delivery

A secure online VVC is used for connection during the telehealth session. The patient received an e-mail from the telehealth scheduling system with a link for VVC before each session. During the 6-week program, each telehealth session is conducted by a PT and a RT concurrently for 120 minutes, 3 days per week. The PT provides exercises for the patient to attempt, and the RT provides breathing training and monitoring during the session. After a successful connection to VVC, the therapist verifies the patient’s identity and confirms patient consent for the telehealth session.

After this check-in process, the patient performs a self-measure of resting blood pressure (BP), heart rate, respiratory rate, and blood oxygen saturation and reports to the therapists. During the exercise session, fatigue/exertion, dyspnea (Modified Borg Dyspnea Scale; Borg CR10 Scale), BP, heart rate, oxygen saturation, and other clinical symptoms and responses to exercise are monitored by the therapists, using both patient-reported measures and clinical observation by the therapists.^34,35 Any medical emergency during the session is reported immediately to the pulmonologist for further management.

Structure

Prior to each exercise session, exercise precautions, fall prevention, good posture, pursed-lip breathing, pacing, and coordinated breathing are discussed with the patient. The PT demonstrates stretching and warm-up exercises in front of the webcam for the patient to follow. Then the patient performs all exercises in view of the webcam during the session (Figure 1). A RT monitors breathing patterns and corrects with verbal instructions if not properly performed.

Loss of skeletal muscle mass and cachexia are highly prevalent comorbidities of COPD and have been associated with breathlessness, functional limitation, and poor prognosis.³⁶ To address these comorbidities, our program consists of progressive strengthening, aerobic, balance, and flexibility exercises. Resistance bands and tubes are used for strengthening exercises. Callisthenic exercises (eg, chair squat, chair stand, knee marching, bridging, single limb stances, and lunge) are used for progressive strengthening and balance exercises. Progression of strengthening and balance exercises are done through increasing the volume of exercise (ie, numbers of sets and repetitions) and increased load and level of difficulty based on the patient’s progress and comorbidity. The exercise program focuses on strengthening muscles, especially large muscle groups, to improve overall muscle strength and performance of functional activities.³⁷

Arm/pedal ergometer and daily walking are used for daily aerobic exercise. In a study of patients with COPD by the PAC-COPD Study Group, step counter use was found to increase physical activity and improve exercise capacity, which supports its use in COPD management.³⁸ During program participation, the patient is asked to wear a pedometer to monitor the number of steps taken per day and to report step data to the therapists during the telehealth session. The pedometer stores the previous 41 calendar days of data and displays the most recent 7 calendar days of data.

The patient is encouraged to set a realistic daily step goal. The general program goal is to increase at least 1000 steps per day. However, this goal can be adjusted depending on the patient’s health status and comorbid conditions. The PAC-COPD Study Group found that for every additional 1000 daily steps at low intensity, COPD hospitalization risk decreased by 20%.³⁹ A magnitude of 2000 steps or about 1 mile of walking per day was found to be associated with increased physical activity and health benefits in the general population.⁴⁰

Respiratory muscle training and breathing exercise are provided by the RT, using breathing and incentive spirometer techniques (Figure 2). Huff coughing, diaphragmatic deep breathing, and pursed-lip breathing are instructed by the RT during the session. Effective coughing technique with a cough assistive device is also provided during breathing training if needed.

Patient Education

In patients with COPD, there are numerous positive health benefits associated with education, including assisting the patients to become active participants in the PR program leading to satisfying outcomes; assisting the patients to better understand the lung health, disease processes, physical and psychological changes that occur with COPD; assisting the patients to explore coping strategies for those changes; building lifelong behavioral changes; and developing the self-management skills for sustainability. Through the educational process, patients with COPD can become more skilled at collaborative self-management and improve adherence to their treatment plan, which in turn can result in a reduction in hospital admissions and reduced health care costs.^8,41

Education is provided with every session after the patient completes the exercise. Patients are required to record their COPD symptoms, daily activity, home exercise program, sleep, food intake, and additional physical or social activity in their COPD diary and to report during the session (Figure 3). A COPD diary assists patients in self-monitoring their COPD symptoms and provides the therapists with information about clinical changes, behavioral changes, and/or specific unmet needs for education. Several topics related to COPD are included in the education session: lung or respiratory disease/condition and self-management; smoking cessation; physical activity; energy-conserving techniques; breathing and coughing techniques; smoking cessation; nutrition/healthy eating and weight counseling; sex and intimacy; psychological counseling and/or group support; emergency planning (eg, medical, travel, and inclement weather); correct use of inhaler and medications; home oxygen; sleep and sleep hygiene; palliative care and advanced directive; infection control; and sputum clearance.^42,43

Program Maintenance

After successfully completing the 6-week program, patients are referred to the VA TeleMOVE! Program or MOVE! Weight Management Program for continuous, long-term management of weight, nutrition, physical activity/exercise, and social activity needs or goals. The patients are scheduled for monthly follow-up phone visits for 6 months with the telerehabilitation team for enforcing sustainability. The phone call visit consists of reviewing breathing techniques, exercise program, physical activity, education, encouragement, and addressing any issues that arise during the self-maintained period.

Limitations

There are several issues of concern and precautions when delivering PR through telehealth into the home. First, the patient performs exercises independently without being manually guarded by the therapists. Risk of falls are a major concern due to impaired balance, poor vision, and other possible unusual physiologic responses to exercise (eg, drop in BP, dizziness, loss of balance). The area in front of the computer needs to be cleared of fall hazards (ie, area rug, wires, objects on the floor). The patient also needs to be educated on self-measurements of BP and oxygen saturation and reports to the therapists. The therapists provide detailed instructions on how to obtain these measures correctly; otherwise, the values may not be valid for a clinical judgment during the exercise session or for other clinical management. In a home environment, there is a limited use of exercise apparatuses. For this program, we only used resistance bands/tubes, small arm/leg ergometer, hand grip, and hand putty for the exercise program. We feel that dumbbell and weight plates are not suitable due to a possible risk of injury if the patient accidently drops them.

Advanced balance training is not suitable due to an increased risk for falls. Without the presence of the PT, level of challenge/difficulty is somewhat limited for this telehealth supervision exercise program. In addition, visual and audio quality are necessary for the session. The patient and the therapists need to see each other clearly to ensure correct methods and forms of each exercise. Furthermore, rehearsal of technical skills with the therapists is very important because this population is older and often has limited computer skills. Any technical difficulty or failure can lead to undesirable situations (eg, anxiety episodes, worries, shortness of breath, upset), which compromise exercise performance during the session. Finally, a phone is needed as an alternative in case of a poor VVC connection.

Conclusion

COPD symptoms and complications greatly affect patients’ ability to perform daily activities, decrease QOL and functional ability, and result in extensive use of health services. Many patients have limited access to a PR program at hospitals or rehabilitation centers due to health conditions, lack of transportation, and/or family support. This home-based, interactive telehealth PR program can break down the geographic barriers, solve poor program accessibility, potentially increase the utilization of PR, and reduce the cost and travel required by the patients.

Acknowledgments
The Telehealth Pulmonary Rehabilitation Program was originally funded by the Veterans Health Administration VA ACCESS Program (AS, CL, HKH). We thank all the veterans for their time and effort in participating in this newly developed rehabilitation program.

According to World Health Organization estimates, 65 million people have moderate-to-severe chronic obstructive pulmonary disease (COPD) globally, and > 20 million patients with COPD are living in the US.¹ COPD is a progressive respiratory disease with a poor prognosis and a significant cause of morbidity and mortality in the US, especially within the Veterans Health Administration (VHA).² The prevalence of COPD is higher in veterans than it is in the general population. COPD prevalence in the adult US population has been estimated to be between 5% and 15%, whereas in veterans, prevalence estimates have ranged from about 5% to 43%.^3-5

COPD is associated with disabling dyspnea, muscle weakness, exercise intolerance, morbidity, and mortality. These symptoms and complications gradually and progressively compromise mobility, ability to perform daily functions, and decrease quality of life (QOL). Dyspnea, fatigue, and discomfort are the principal symptoms that negatively impact exercise tolerance.^6,7 Therefore, patients often intentionally limit their activities to avoid these uncomfortable feelings and adopt a more sedentary behavior. As the disease progresses, individuals with COPD will gradually need assistance in performing activities of daily living, which eventually leads to functional dependence.

Pulmonary rehabilitation (PR) is an essential component of the management of symptomatic patients with COPD. PR is an evidence-based, multidisciplinary, comprehensive intervention that includes exercise and education for patients with chronic respiratory disease.⁸ The key benefits of PR are clinical improvements in dyspnea, physical capacity, QOL, and reduced disability in patients with COPD and other respiratory diseases.^9-11 PR was found to improve respiratory health in veterans with COPD and decrease respiratory-related health care utilization.¹²

Despite the known benefits of PR, many patients with chronic respiratory diseases are not referred or do not have access to rehabilitation. Also, uptake of PR is low due to patient frailty, transportation issues, and other health care access problems.^13-15 Unfortunately, in the US health care system, access to PR and other nonpharmacologic treatments can be challenging due to a shortage of available PR programs, limited physician referral to existing programs, and lack of family and social support.¹⁶

There are only a few accredited PR programs in VHA facilities, and they tend to be located in urban areas.^12,17 Many patients have limited access to the PR programs due to geographic distance to the programs and transportation challenges (eg, limited ability to drive, cost of transportation). Moreover, veterans with COPD are likely to have limited mobility or are homebound due to experiencing shortness of breath with minimal exertion. Given the clear benefits of PR and the increasing impact of COPD on morbidity and mortality of the patients with COPD, strategies to improve the access and capacity of PR are needed. VA telehealth services allow for distribution of health care services in different geographic locations by providing access for the veterans who live in rural and highly rural areas. The most recent implementation of VA Video Connect (VVC) by the VHA provides a new avenue for clinicians to deliver much needed medical care into the veterans’ home.

COPD Telehealth Program

In this article, we describe the processes for developing and delivering an in-home, interactive, supervised PR program for veterans with severe COPD through VA telehealth service. The program consists of 18 sessions delivered over 6 weeks by a licensed physical therapist (PT) and a respiratory therapist (RT). The aims of the telehealth PR are to improve exercise tolerance, reduce dyspnea and fatigue, improve QOL, improve accessibility, and decrease costs and transportation burdens for patients with COPD. The program was developed, implemented and delivered by an interdisciplinary team, including a pulmonologist, PT, RT, physiatrist, and nonclinical supporting staff.

To be eligible to participate in the program the patient must: (1) have a forced expiratory volume (FEV₁) < 60%; ( 2) be medically stable and be receiving optimal medical management; (3) have no severe cognitive impairments; (4) be able to use a computer and e-mail; (5) be able to ambulate with or without a walking device; (6) be willing to enroll in a smoking cessation program or to stop smoking; (7) be willing to participate without prolonged interruption; and (8) have all visual and auditory impairments corrected with medical devices.

After referral and enrollment, patients receive medical and physical examinations by the PR team, including a pulmonologist, a PT, and a RT, to ensure that the patients are medically stable to undergo rehabilitation and to develop a tailored exercise program while being mindful of the comorbidities, limitations, and precautions, (eg, loss of balance, risk of fall, limited range of motion). The preprogram assessment includes a pulmonary function test, arterial blood gas test, Montreal Cognitive Assessment, Modified Medical Research Council Scale, St. George Respiratory Questionnaire, the COPD Assessment Test, Patient Health Questionnaire-9,Generalized Anxiety Disorder Assessment-7, Epworth Sleepiness Scale, Katz Index of Independence of Activities of Daily Living, medications and inhaler use, oxygen use, breathing pattern, coughing, 6-minute walk test, Modified Borg Dyspnea Scale, grip strength, 5 Times Sit to Stand Test, manual muscle test, gait measure, Timed Up & Go test, clinical balance tests, range of motion, flexibility, sensation, pain, and fall history.^18-32 Educational needs (eg, respiratory hygiene, nutrition, infection control, sleep, disease/symptom management) also are evaluated.

This thorough assessment is performed in a face-to-face outpatient visit. During the program participation, a physiatrist may be consulted for additional needs (eg, wheelchair assessment, home safety evaluation/ modifications, and mobility/disability issues). After completing the 6-week program, patients are scheduled for the postprogram evaluation in a face-to-face outpatient visit with the clinicians.

Equipment

Both clinician and the patient are equipped with a computer with Wi-Fi connectivity, a webcam, and a microphone. Patients are provided an exercise pictorial booklet, an exercise compact disk (audio and video), small exercise apparatuses (eg, assorted colors of resistance bands, hand grip exerciser, hand putty, ergometer, harmonica, and pedometer), incentive spirometer, pulse oximeter, cough assistive device (as needed), blood pressure monitor, COPD information booklets, and a diary to use at home during the program.³³

Technology Preparation

Prior to starting the telehealth program, the patient is contacted 1 or 2 days before the first session for technical preparation and familiarization of the VA telehealth connection process. Either the PT or RT provides step-by-step instructions for the patient to practice connecting through VVC during this preparatory phone call. The patient also practices using the computer webcam, speaker, and microphone; checks the telehealth scheduling e-mail; and learns how to solve possible common technical issues (eg, adjusting volume and position of webcam). The patient is asked to set up a table close to the computer and to place all exercise apparatuses and respiratory devices on the table surface.

Program Delivery

A secure online VVC is used for connection during the telehealth session. The patient received an e-mail from the telehealth scheduling system with a link for VVC before each session. During the 6-week program, each telehealth session is conducted by a PT and a RT concurrently for 120 minutes, 3 days per week. The PT provides exercises for the patient to attempt, and the RT provides breathing training and monitoring during the session. After a successful connection to VVC, the therapist verifies the patient’s identity and confirms patient consent for the telehealth session.

After this check-in process, the patient performs a self-measure of resting blood pressure (BP), heart rate, respiratory rate, and blood oxygen saturation and reports to the therapists. During the exercise session, fatigue/exertion, dyspnea (Modified Borg Dyspnea Scale; Borg CR10 Scale), BP, heart rate, oxygen saturation, and other clinical symptoms and responses to exercise are monitored by the therapists, using both patient-reported measures and clinical observation by the therapists.^34,35 Any medical emergency during the session is reported immediately to the pulmonologist for further management.

Structure

Prior to each exercise session, exercise precautions, fall prevention, good posture, pursed-lip breathing, pacing, and coordinated breathing are discussed with the patient. The PT demonstrates stretching and warm-up exercises in front of the webcam for the patient to follow. Then the patient performs all exercises in view of the webcam during the session (Figure 1). A RT monitors breathing patterns and corrects with verbal instructions if not properly performed.

Loss of skeletal muscle mass and cachexia are highly prevalent comorbidities of COPD and have been associated with breathlessness, functional limitation, and poor prognosis.³⁶ To address these comorbidities, our program consists of progressive strengthening, aerobic, balance, and flexibility exercises. Resistance bands and tubes are used for strengthening exercises. Callisthenic exercises (eg, chair squat, chair stand, knee marching, bridging, single limb stances, and lunge) are used for progressive strengthening and balance exercises. Progression of strengthening and balance exercises are done through increasing the volume of exercise (ie, numbers of sets and repetitions) and increased load and level of difficulty based on the patient’s progress and comorbidity. The exercise program focuses on strengthening muscles, especially large muscle groups, to improve overall muscle strength and performance of functional activities.³⁷

Arm/pedal ergometer and daily walking are used for daily aerobic exercise. In a study of patients with COPD by the PAC-COPD Study Group, step counter use was found to increase physical activity and improve exercise capacity, which supports its use in COPD management.³⁸ During program participation, the patient is asked to wear a pedometer to monitor the number of steps taken per day and to report step data to the therapists during the telehealth session. The pedometer stores the previous 41 calendar days of data and displays the most recent 7 calendar days of data.

The patient is encouraged to set a realistic daily step goal. The general program goal is to increase at least 1000 steps per day. However, this goal can be adjusted depending on the patient’s health status and comorbid conditions. The PAC-COPD Study Group found that for every additional 1000 daily steps at low intensity, COPD hospitalization risk decreased by 20%.³⁹ A magnitude of 2000 steps or about 1 mile of walking per day was found to be associated with increased physical activity and health benefits in the general population.⁴⁰

Respiratory muscle training and breathing exercise are provided by the RT, using breathing and incentive spirometer techniques (Figure 2). Huff coughing, diaphragmatic deep breathing, and pursed-lip breathing are instructed by the RT during the session. Effective coughing technique with a cough assistive device is also provided during breathing training if needed.

Patient Education

In patients with COPD, there are numerous positive health benefits associated with education, including assisting the patients to become active participants in the PR program leading to satisfying outcomes; assisting the patients to better understand the lung health, disease processes, physical and psychological changes that occur with COPD; assisting the patients to explore coping strategies for those changes; building lifelong behavioral changes; and developing the self-management skills for sustainability. Through the educational process, patients with COPD can become more skilled at collaborative self-management and improve adherence to their treatment plan, which in turn can result in a reduction in hospital admissions and reduced health care costs.^8,41

Education is provided with every session after the patient completes the exercise. Patients are required to record their COPD symptoms, daily activity, home exercise program, sleep, food intake, and additional physical or social activity in their COPD diary and to report during the session (Figure 3). A COPD diary assists patients in self-monitoring their COPD symptoms and provides the therapists with information about clinical changes, behavioral changes, and/or specific unmet needs for education. Several topics related to COPD are included in the education session: lung or respiratory disease/condition and self-management; smoking cessation; physical activity; energy-conserving techniques; breathing and coughing techniques; smoking cessation; nutrition/healthy eating and weight counseling; sex and intimacy; psychological counseling and/or group support; emergency planning (eg, medical, travel, and inclement weather); correct use of inhaler and medications; home oxygen; sleep and sleep hygiene; palliative care and advanced directive; infection control; and sputum clearance.^42,43

Program Maintenance

After successfully completing the 6-week program, patients are referred to the VA TeleMOVE! Program or MOVE! Weight Management Program for continuous, long-term management of weight, nutrition, physical activity/exercise, and social activity needs or goals. The patients are scheduled for monthly follow-up phone visits for 6 months with the telerehabilitation team for enforcing sustainability. The phone call visit consists of reviewing breathing techniques, exercise program, physical activity, education, encouragement, and addressing any issues that arise during the self-maintained period.

Limitations

There are several issues of concern and precautions when delivering PR through telehealth into the home. First, the patient performs exercises independently without being manually guarded by the therapists. Risk of falls are a major concern due to impaired balance, poor vision, and other possible unusual physiologic responses to exercise (eg, drop in BP, dizziness, loss of balance). The area in front of the computer needs to be cleared of fall hazards (ie, area rug, wires, objects on the floor). The patient also needs to be educated on self-measurements of BP and oxygen saturation and reports to the therapists. The therapists provide detailed instructions on how to obtain these measures correctly; otherwise, the values may not be valid for a clinical judgment during the exercise session or for other clinical management. In a home environment, there is a limited use of exercise apparatuses. For this program, we only used resistance bands/tubes, small arm/leg ergometer, hand grip, and hand putty for the exercise program. We feel that dumbbell and weight plates are not suitable due to a possible risk of injury if the patient accidently drops them.

Advanced balance training is not suitable due to an increased risk for falls. Without the presence of the PT, level of challenge/difficulty is somewhat limited for this telehealth supervision exercise program. In addition, visual and audio quality are necessary for the session. The patient and the therapists need to see each other clearly to ensure correct methods and forms of each exercise. Furthermore, rehearsal of technical skills with the therapists is very important because this population is older and often has limited computer skills. Any technical difficulty or failure can lead to undesirable situations (eg, anxiety episodes, worries, shortness of breath, upset), which compromise exercise performance during the session. Finally, a phone is needed as an alternative in case of a poor VVC connection.

Conclusion

COPD symptoms and complications greatly affect patients’ ability to perform daily activities, decrease QOL and functional ability, and result in extensive use of health services. Many patients have limited access to a PR program at hospitals or rehabilitation centers due to health conditions, lack of transportation, and/or family support. This home-based, interactive telehealth PR program can break down the geographic barriers, solve poor program accessibility, potentially increase the utilization of PR, and reduce the cost and travel required by the patients.

Acknowledgments
The Telehealth Pulmonary Rehabilitation Program was originally funded by the Veterans Health Administration VA ACCESS Program (AS, CL, HKH). We thank all the veterans for their time and effort in participating in this newly developed rehabilitation program.

Candida albicans (C albicans) is a normal commensal in the human gastrointestinal (GI) tract. In addition to localized infections in healthy human beings, dissemination with fatal outcome can occur in immunocompromised individuals.¹

Invasive candidiasis (IC) due to C albicans is the most common nosocomial mycosis in the world and has 2 forms, candidemia and deep-seated tissue candidiasis, which can lead to multisystem organ failure.² The deep-seated form may originate from nonhematogenous routes, such as introduction through a peritoneal catheter or ascending infection from cystitis.² In addition, about 50% of primary candidemia cases lead to secondary deep-seated candidiasis; however, only about 40% of these cases show positive blood cultures. Since the window of opportunity for a positive culture is narrow, active candidemia may be missed.^3,4

Once developed, the prognosis for IC is grim: Mortality is 40% regardless of therapy.² IC typically occurs in immunocompromised hosts; IC in immunocompetent persons has rarely been reported.^5,6 It is challenging to diagnose IC in the immunocompetent patients as 50% to 70% of the general population is naturally colonized by this organism, and when found, it is assumed to be mostly innocuous. Neutrophil-driven cell-mediated immunity associated with IL-1 and IL-17 response prevent fungal growth and dissemination, protecting the immunocompetent host.⁷

We report on a patient who showed no neutropenia or leukocytopenia but developed disseminated candidiasis. This report is one of the rare cases of full-blown disseminated candidiasis with lesions related to C albicans found in almost all of the important organs.

Case Presentation

A 67-year-old male patient with a history of hypertension, peripheral vascular disease, daily heavy alcohol consumption, and a 50-pack-year history of smoking developed gangrene of the left fifth toe. He underwent vascular surgery consultation with an aortogram/left lower extremity angiography that showed occlusion of the left external iliac artery as well as the left common femoral artery. It was decided to improve inflow in the common iliac artery by placing a bare metal stent and subsequent balloon dilatation before a right to left femoral to femoral artery bypass. The patient tolerated the procedure well and was discharged home.

Two days later, the patient was admitted to a US Department of Veterans Affairs (VA) complexity level 1a hospital with weakness and worsening pain in the left lower extremities. Examination revealed chronic ischemic changes in the feet bilaterally and evidence of dry gangrene in the left fifth toe requiring femoral bypass surgery. But poor nutritional status and cardiac status prevented pursuing a permanent solution.

Following completion of a stress echocardiogram, the patient developed shock with systolic blood pressure of 60 mm Hg, and atrial fibrillation (AF) with rapid ventricular rate (RVR). He was initially treated with IV fluid supplementation, vasopressor therapy, synchronized cardioversion, and IV amiodarone/anticoagulation therapy, due to his persistent AF with RVR. The patient was transferred to a tertiary care center for persistent hypothermia and received treatment with warm saline. After initial recovery with warm saline resuscitation, he had a prolonged, complicated hospital course in which he developed progressive respiratory failure requiring intubation and critical care support. He developed a right internal jugular deep venous thrombosis, heparin-induced thrombocytopenia, lower GI bleeding requiring emergent embolization by interventional radiology, inferior vena cava filter placement, renal failure requiring dialysis, small bowel obstruction secondary to right lower quadrant phlegmon and perforation requiring small bowel resection and end ileostomy. His antibiotic regimen included therapy with vancomycin and piperacillin-tazobactam.

He eventually recovered and was extubated and subsequently transferred back to the VA hospital where cefepime was initiated because of suspicion of a urinary tract infection and septicemia (urine cultures eventually grew C albicans). Over the subsequent 3 days, the patient’s renal output and hyperkalemia worsened, he also developed increased anion gap metabolic acidosis and was intubated again and placed on full mechanical ventilatory support. His blood cultures were negative, and sputum cultures revealed normal respiratory flora and 1+ C albicans. Infectious diseases consultation recommended an abdominal ultrasound, which revealed nonspecific findings. The antibiotic regimen was changed to daptomycin and piperacillin-tazobactam. A follow-up chest X-ray revealed a developing right lower lobe pneumonia and hilar prominence suggestive of lymphadenopathy. The patient’s clinical condition deteriorated, and he subsequently developed cardiac arrest; resuscitation was not successful and he expired.

Outcome and Follow-up

An autopsy disclosed the cause of death to be bilateral candida pneumonia, part of a disseminated (invasive) candidiasis, in a patient rendered vulnerable to such infection by peripheral vascular disease and renal insufficiency. Purulent inflammation was noted at the site of disarticulation of the left foot and confluent consolidation of the lower lobes of both lungs as well as focal consolidation of the middle lobe of the right lung. Examination of histologic sections, with staining both by routine method (hematoxylin and eosin) and the Grocott-Gömöri methenamine silver method for fungus, disclosed fungal forms (yeast and filamentous) in most tissues, including the lungs (Figure 1 A and B) and kidneys (Figure 1 C and D). The pulmonary sections in addition to massive inflammation showed macrophages with engulfed yeast (Figure 2 A) and a lymphatic channel, stuffed with yeast in an alveolar septum (Figure 2 B). These findings confirmed the antemortem presence of the fungus and the body’s response to it. Inflammation was noted around glomeruli overgrown by candida (Figure 1 C and D); fungi also were seen in capsular regions (not depicted). C albicans was present in the myocardium (Figure 1 E and F), brain, thyroid, and adrenal glands (Figure 3); the only organ without C albicans was the liver, either because invasion was truly absent here or because sampling had not managed to retrieve it.

Paraffin-embedded blocks of lung tissue, sent to the University of Washington Molecular Diagnosis Microbiology Laboratory for broad-range polymerase chain reaction (PCR) identification, were positive for C albicans after extraction of gDNA and conduction of PCR using internal transcribed spacer 1 and 2 specific primers.

Discussion

IC is rare among immunocompetent individuals, but C albicans can evolve into a fatal disseminated infection. We report an atypical case of IC, with profound pulmonary infection in a patient who died 1 month after hospitalization for lower extremity pain.

Cell-mediated immunity involving neutrophils and macrophages plays a major role in protection against candidiasis, while cytokines and chemokines involve regulating balanced immunity.^1,2 A series of recent studies show that alcohol impairs neutrophil-mediated killing and phagocytic-mediated uptake of a pathogen in this process.^8,9 As the patient chronically misused alcohol, his immune system may have experienced a subclinical immunosuppression, which would have become clinically relevant once C albicans was introduced systemically. Recent studies of bacterial pathogenesis and alcoholism strongly support this hypothesis.^10,11

Most patients with the unusual diagnosis of candida pneumonia have had a background of malignancy or immunosuppressive factors (eg, administration of corticosteroids).¹² In a series of 20 cases, 14 had sputum cultures positive for the organism, 6 had positive urine cultures, and 6 had positive blood cultures. Chest radiographs usually showed confluent bronchopneumonia. Five patients were diagnosed antemortem and treated with amphotericin B, but none survived.¹³ In the literature a positive blood culture or demonstration of yeast within pulmonary histiocytes has been considered proof of the pathogenicity of the fungus, as opposed to noninvasive colonization of the airways, a common occurrence in patients receiving mechanical ventilation.²

The C albicans in this case may have been introduced hematogenously from the amputation site or through an ascending cystitis, or possibly have been derived from commensal flora in the GI tract. The iron supplementation provided to the patient may have promoted the growth and virulence of the candida; studies have shown that the kidneys assimilate increased levels of iron during disseminated candidiasis thus providing a more favorable site for colonization.¹⁷The presence of C albicans in a single collection of sputum or urine does not ordinarily indicate infection in an immunocompetent individual. Estimation of serum procalcitonin, a biomarker for bacterial infection and sepsis, might be useful if negative, for turning attention to a nonbacterial (such as, candida) source as the causative agent.¹⁸

Conclusion

C albicans can rarely cause disseminated disease in nonimmunocompromised critically ill patients. Low serum procalcitonin levels in a septic patient might indicate nonbacterial cause such as candidiasis. Even with disseminated candidiasis, blood cultures may remain negative.

Candida albicans (C albicans) is a normal commensal in the human gastrointestinal (GI) tract. In addition to localized infections in healthy human beings, dissemination with fatal outcome can occur in immunocompromised individuals.¹

Invasive candidiasis (IC) due to C albicans is the most common nosocomial mycosis in the world and has 2 forms, candidemia and deep-seated tissue candidiasis, which can lead to multisystem organ failure.² The deep-seated form may originate from nonhematogenous routes, such as introduction through a peritoneal catheter or ascending infection from cystitis.² In addition, about 50% of primary candidemia cases lead to secondary deep-seated candidiasis; however, only about 40% of these cases show positive blood cultures. Since the window of opportunity for a positive culture is narrow, active candidemia may be missed.^3,4

Once developed, the prognosis for IC is grim: Mortality is 40% regardless of therapy.² IC typically occurs in immunocompromised hosts; IC in immunocompetent persons has rarely been reported.^5,6 It is challenging to diagnose IC in the immunocompetent patients as 50% to 70% of the general population is naturally colonized by this organism, and when found, it is assumed to be mostly innocuous. Neutrophil-driven cell-mediated immunity associated with IL-1 and IL-17 response prevent fungal growth and dissemination, protecting the immunocompetent host.⁷

We report on a patient who showed no neutropenia or leukocytopenia but developed disseminated candidiasis. This report is one of the rare cases of full-blown disseminated candidiasis with lesions related to C albicans found in almost all of the important organs.

Case Presentation

A 67-year-old male patient with a history of hypertension, peripheral vascular disease, daily heavy alcohol consumption, and a 50-pack-year history of smoking developed gangrene of the left fifth toe. He underwent vascular surgery consultation with an aortogram/left lower extremity angiography that showed occlusion of the left external iliac artery as well as the left common femoral artery. It was decided to improve inflow in the common iliac artery by placing a bare metal stent and subsequent balloon dilatation before a right to left femoral to femoral artery bypass. The patient tolerated the procedure well and was discharged home.

Two days later, the patient was admitted to a US Department of Veterans Affairs (VA) complexity level 1a hospital with weakness and worsening pain in the left lower extremities. Examination revealed chronic ischemic changes in the feet bilaterally and evidence of dry gangrene in the left fifth toe requiring femoral bypass surgery. But poor nutritional status and cardiac status prevented pursuing a permanent solution.

Following completion of a stress echocardiogram, the patient developed shock with systolic blood pressure of 60 mm Hg, and atrial fibrillation (AF) with rapid ventricular rate (RVR). He was initially treated with IV fluid supplementation, vasopressor therapy, synchronized cardioversion, and IV amiodarone/anticoagulation therapy, due to his persistent AF with RVR. The patient was transferred to a tertiary care center for persistent hypothermia and received treatment with warm saline. After initial recovery with warm saline resuscitation, he had a prolonged, complicated hospital course in which he developed progressive respiratory failure requiring intubation and critical care support. He developed a right internal jugular deep venous thrombosis, heparin-induced thrombocytopenia, lower GI bleeding requiring emergent embolization by interventional radiology, inferior vena cava filter placement, renal failure requiring dialysis, small bowel obstruction secondary to right lower quadrant phlegmon and perforation requiring small bowel resection and end ileostomy. His antibiotic regimen included therapy with vancomycin and piperacillin-tazobactam.

He eventually recovered and was extubated and subsequently transferred back to the VA hospital where cefepime was initiated because of suspicion of a urinary tract infection and septicemia (urine cultures eventually grew C albicans). Over the subsequent 3 days, the patient’s renal output and hyperkalemia worsened, he also developed increased anion gap metabolic acidosis and was intubated again and placed on full mechanical ventilatory support. His blood cultures were negative, and sputum cultures revealed normal respiratory flora and 1+ C albicans. Infectious diseases consultation recommended an abdominal ultrasound, which revealed nonspecific findings. The antibiotic regimen was changed to daptomycin and piperacillin-tazobactam. A follow-up chest X-ray revealed a developing right lower lobe pneumonia and hilar prominence suggestive of lymphadenopathy. The patient’s clinical condition deteriorated, and he subsequently developed cardiac arrest; resuscitation was not successful and he expired.

Outcome and Follow-up

An autopsy disclosed the cause of death to be bilateral candida pneumonia, part of a disseminated (invasive) candidiasis, in a patient rendered vulnerable to such infection by peripheral vascular disease and renal insufficiency. Purulent inflammation was noted at the site of disarticulation of the left foot and confluent consolidation of the lower lobes of both lungs as well as focal consolidation of the middle lobe of the right lung. Examination of histologic sections, with staining both by routine method (hematoxylin and eosin) and the Grocott-Gömöri methenamine silver method for fungus, disclosed fungal forms (yeast and filamentous) in most tissues, including the lungs (Figure 1 A and B) and kidneys (Figure 1 C and D). The pulmonary sections in addition to massive inflammation showed macrophages with engulfed yeast (Figure 2 A) and a lymphatic channel, stuffed with yeast in an alveolar septum (Figure 2 B). These findings confirmed the antemortem presence of the fungus and the body’s response to it. Inflammation was noted around glomeruli overgrown by candida (Figure 1 C and D); fungi also were seen in capsular regions (not depicted). C albicans was present in the myocardium (Figure 1 E and F), brain, thyroid, and adrenal glands (Figure 3); the only organ without C albicans was the liver, either because invasion was truly absent here or because sampling had not managed to retrieve it.

Paraffin-embedded blocks of lung tissue, sent to the University of Washington Molecular Diagnosis Microbiology Laboratory for broad-range polymerase chain reaction (PCR) identification, were positive for C albicans after extraction of gDNA and conduction of PCR using internal transcribed spacer 1 and 2 specific primers.

Discussion

IC is rare among immunocompetent individuals, but C albicans can evolve into a fatal disseminated infection. We report an atypical case of IC, with profound pulmonary infection in a patient who died 1 month after hospitalization for lower extremity pain.

Cell-mediated immunity involving neutrophils and macrophages plays a major role in protection against candidiasis, while cytokines and chemokines involve regulating balanced immunity.^1,2 A series of recent studies show that alcohol impairs neutrophil-mediated killing and phagocytic-mediated uptake of a pathogen in this process.^8,9 As the patient chronically misused alcohol, his immune system may have experienced a subclinical immunosuppression, which would have become clinically relevant once C albicans was introduced systemically. Recent studies of bacterial pathogenesis and alcoholism strongly support this hypothesis.^10,11

Most patients with the unusual diagnosis of candida pneumonia have had a background of malignancy or immunosuppressive factors (eg, administration of corticosteroids).¹² In a series of 20 cases, 14 had sputum cultures positive for the organism, 6 had positive urine cultures, and 6 had positive blood cultures. Chest radiographs usually showed confluent bronchopneumonia. Five patients were diagnosed antemortem and treated with amphotericin B, but none survived.¹³ In the literature a positive blood culture or demonstration of yeast within pulmonary histiocytes has been considered proof of the pathogenicity of the fungus, as opposed to noninvasive colonization of the airways, a common occurrence in patients receiving mechanical ventilation.²

The C albicans in this case may have been introduced hematogenously from the amputation site or through an ascending cystitis, or possibly have been derived from commensal flora in the GI tract. The iron supplementation provided to the patient may have promoted the growth and virulence of the candida; studies have shown that the kidneys assimilate increased levels of iron during disseminated candidiasis thus providing a more favorable site for colonization.¹⁷The presence of C albicans in a single collection of sputum or urine does not ordinarily indicate infection in an immunocompetent individual. Estimation of serum procalcitonin, a biomarker for bacterial infection and sepsis, might be useful if negative, for turning attention to a nonbacterial (such as, candida) source as the causative agent.¹⁸

Conclusion

C albicans can rarely cause disseminated disease in nonimmunocompromised critically ill patients. Low serum procalcitonin levels in a septic patient might indicate nonbacterial cause such as candidiasis. Even with disseminated candidiasis, blood cultures may remain negative.

Candida albicans (C albicans) is a normal commensal in the human gastrointestinal (GI) tract. In addition to localized infections in healthy human beings, dissemination with fatal outcome can occur in immunocompromised individuals.¹

Invasive candidiasis (IC) due to C albicans is the most common nosocomial mycosis in the world and has 2 forms, candidemia and deep-seated tissue candidiasis, which can lead to multisystem organ failure.² The deep-seated form may originate from nonhematogenous routes, such as introduction through a peritoneal catheter or ascending infection from cystitis.² In addition, about 50% of primary candidemia cases lead to secondary deep-seated candidiasis; however, only about 40% of these cases show positive blood cultures. Since the window of opportunity for a positive culture is narrow, active candidemia may be missed.^3,4

Once developed, the prognosis for IC is grim: Mortality is 40% regardless of therapy.² IC typically occurs in immunocompromised hosts; IC in immunocompetent persons has rarely been reported.^5,6 It is challenging to diagnose IC in the immunocompetent patients as 50% to 70% of the general population is naturally colonized by this organism, and when found, it is assumed to be mostly innocuous. Neutrophil-driven cell-mediated immunity associated with IL-1 and IL-17 response prevent fungal growth and dissemination, protecting the immunocompetent host.⁷

We report on a patient who showed no neutropenia or leukocytopenia but developed disseminated candidiasis. This report is one of the rare cases of full-blown disseminated candidiasis with lesions related to C albicans found in almost all of the important organs.

Case Presentation

A 67-year-old male patient with a history of hypertension, peripheral vascular disease, daily heavy alcohol consumption, and a 50-pack-year history of smoking developed gangrene of the left fifth toe. He underwent vascular surgery consultation with an aortogram/left lower extremity angiography that showed occlusion of the left external iliac artery as well as the left common femoral artery. It was decided to improve inflow in the common iliac artery by placing a bare metal stent and subsequent balloon dilatation before a right to left femoral to femoral artery bypass. The patient tolerated the procedure well and was discharged home.

Two days later, the patient was admitted to a US Department of Veterans Affairs (VA) complexity level 1a hospital with weakness and worsening pain in the left lower extremities. Examination revealed chronic ischemic changes in the feet bilaterally and evidence of dry gangrene in the left fifth toe requiring femoral bypass surgery. But poor nutritional status and cardiac status prevented pursuing a permanent solution.

Following completion of a stress echocardiogram, the patient developed shock with systolic blood pressure of 60 mm Hg, and atrial fibrillation (AF) with rapid ventricular rate (RVR). He was initially treated with IV fluid supplementation, vasopressor therapy, synchronized cardioversion, and IV amiodarone/anticoagulation therapy, due to his persistent AF with RVR. The patient was transferred to a tertiary care center for persistent hypothermia and received treatment with warm saline. After initial recovery with warm saline resuscitation, he had a prolonged, complicated hospital course in which he developed progressive respiratory failure requiring intubation and critical care support. He developed a right internal jugular deep venous thrombosis, heparin-induced thrombocytopenia, lower GI bleeding requiring emergent embolization by interventional radiology, inferior vena cava filter placement, renal failure requiring dialysis, small bowel obstruction secondary to right lower quadrant phlegmon and perforation requiring small bowel resection and end ileostomy. His antibiotic regimen included therapy with vancomycin and piperacillin-tazobactam.

He eventually recovered and was extubated and subsequently transferred back to the VA hospital where cefepime was initiated because of suspicion of a urinary tract infection and septicemia (urine cultures eventually grew C albicans). Over the subsequent 3 days, the patient’s renal output and hyperkalemia worsened, he also developed increased anion gap metabolic acidosis and was intubated again and placed on full mechanical ventilatory support. His blood cultures were negative, and sputum cultures revealed normal respiratory flora and 1+ C albicans. Infectious diseases consultation recommended an abdominal ultrasound, which revealed nonspecific findings. The antibiotic regimen was changed to daptomycin and piperacillin-tazobactam. A follow-up chest X-ray revealed a developing right lower lobe pneumonia and hilar prominence suggestive of lymphadenopathy. The patient’s clinical condition deteriorated, and he subsequently developed cardiac arrest; resuscitation was not successful and he expired.

Outcome and Follow-up

An autopsy disclosed the cause of death to be bilateral candida pneumonia, part of a disseminated (invasive) candidiasis, in a patient rendered vulnerable to such infection by peripheral vascular disease and renal insufficiency. Purulent inflammation was noted at the site of disarticulation of the left foot and confluent consolidation of the lower lobes of both lungs as well as focal consolidation of the middle lobe of the right lung. Examination of histologic sections, with staining both by routine method (hematoxylin and eosin) and the Grocott-Gömöri methenamine silver method for fungus, disclosed fungal forms (yeast and filamentous) in most tissues, including the lungs (Figure 1 A and B) and kidneys (Figure 1 C and D). The pulmonary sections in addition to massive inflammation showed macrophages with engulfed yeast (Figure 2 A) and a lymphatic channel, stuffed with yeast in an alveolar septum (Figure 2 B). These findings confirmed the antemortem presence of the fungus and the body’s response to it. Inflammation was noted around glomeruli overgrown by candida (Figure 1 C and D); fungi also were seen in capsular regions (not depicted). C albicans was present in the myocardium (Figure 1 E and F), brain, thyroid, and adrenal glands (Figure 3); the only organ without C albicans was the liver, either because invasion was truly absent here or because sampling had not managed to retrieve it.

Paraffin-embedded blocks of lung tissue, sent to the University of Washington Molecular Diagnosis Microbiology Laboratory for broad-range polymerase chain reaction (PCR) identification, were positive for C albicans after extraction of gDNA and conduction of PCR using internal transcribed spacer 1 and 2 specific primers.

Discussion

IC is rare among immunocompetent individuals, but C albicans can evolve into a fatal disseminated infection. We report an atypical case of IC, with profound pulmonary infection in a patient who died 1 month after hospitalization for lower extremity pain.

Cell-mediated immunity involving neutrophils and macrophages plays a major role in protection against candidiasis, while cytokines and chemokines involve regulating balanced immunity.^1,2 A series of recent studies show that alcohol impairs neutrophil-mediated killing and phagocytic-mediated uptake of a pathogen in this process.^8,9 As the patient chronically misused alcohol, his immune system may have experienced a subclinical immunosuppression, which would have become clinically relevant once C albicans was introduced systemically. Recent studies of bacterial pathogenesis and alcoholism strongly support this hypothesis.^10,11

Most patients with the unusual diagnosis of candida pneumonia have had a background of malignancy or immunosuppressive factors (eg, administration of corticosteroids).¹² In a series of 20 cases, 14 had sputum cultures positive for the organism, 6 had positive urine cultures, and 6 had positive blood cultures. Chest radiographs usually showed confluent bronchopneumonia. Five patients were diagnosed antemortem and treated with amphotericin B, but none survived.¹³ In the literature a positive blood culture or demonstration of yeast within pulmonary histiocytes has been considered proof of the pathogenicity of the fungus, as opposed to noninvasive colonization of the airways, a common occurrence in patients receiving mechanical ventilation.²

The C albicans in this case may have been introduced hematogenously from the amputation site or through an ascending cystitis, or possibly have been derived from commensal flora in the GI tract. The iron supplementation provided to the patient may have promoted the growth and virulence of the candida; studies have shown that the kidneys assimilate increased levels of iron during disseminated candidiasis thus providing a more favorable site for colonization.¹⁷The presence of C albicans in a single collection of sputum or urine does not ordinarily indicate infection in an immunocompetent individual. Estimation of serum procalcitonin, a biomarker for bacterial infection and sepsis, might be useful if negative, for turning attention to a nonbacterial (such as, candida) source as the causative agent.¹⁸

Conclusion

C albicans can rarely cause disseminated disease in nonimmunocompromised critically ill patients. Low serum procalcitonin levels in a septic patient might indicate nonbacterial cause such as candidiasis. Even with disseminated candidiasis, blood cultures may remain negative.

Impressive progress has been made in recent years in the management and treatment of atopic dermatitis (AD) and its comorbidities; however, there is a major need for state-of-the-art, evidence-based, multidisciplinary education for AD management. To address this need, the first Revolutionizing Atopic Dermatitis (RAD) Conference was held in April 2019 in Chicago, Illinois, featuring cutting-edge research presented by globally recognized experts in dermatology, allergy and immunology, sleep medicine, ophthalmology, and nursing care. The following is a recap of the latest topics in AD research presented at the conference.

Diagnosis and Assessment of AD: Jonathan I. Silverberg, MD, PhD, MPH

Although diagnosis of AD typically is straightforward in children, it can be challenging in adults, even for expert clinicians. These challenges stem from the different lesional distribution and morphology of AD in adults vs children.^1,2 Additionally, the conditions included in the differential diagnosis of AD (eg, allergic contact dermatitis, cutaneous T-cell lymphoma, psoriasis) are far more common in adults than in children. Formal diagnostic criteria can be useful to improve the diagnosis of AD in clinical practice.³ It is important to note that flexural lesions and early disease onset are diagnostic criteria in AD; nevertheless, neither are essential nor sufficient on their own to make the diagnosis.

Patch Testing: Jacob P. Thyssen, MD, PhD, DmSci, and Noreen Heer Nicol, PhD, RN, FNP, NEA-BC

Patch testing can be used in AD patients to rule out contact dermatitis as an alternative or comorbid diagnosis.^4-6 Because contact dermatitis can mimic AD, patch testing is recommended for all patients with adolescent and adult-onset AD.⁵ Additionally, refractory cases of AD across all ages, especially prior to initiation of systemic therapy, warrant patch testing. The unique challenges of patch testing in AD patients were reviewed.

Patient Panel

Atopic dermatitis can be a considerable disease burden on both patients and society in general. At the 2019 RAD Conference, a panel of patients bravely shared their AD journeys. Their eye-opening stories highlighted opportunities for improving real-world assessment and management of AD. Some key takeaways included the importance of adequately assessing the symptom burden of AD and not merely relying on visual inspection of the skin. The need for long-term treatment approaches beyond quick fixes with steroids also was discussed.

Pathogenesis of AD: Mark Boguniewicz, MD

There have been many advances in our understanding of the complex pathogenesis of AD,^7-11 which is characterized by an altered skin barrier and immune dysregulation. Filaggrin deficiency in the skin has structural and biophysical consequences. A subset of patients with AD has filaggrin loss-of-function genetic polymorphisms inherited in an autosomal-semidominant pattern; however, many other genetic polymorphisms have been identified that affect different components of the skin architecture and immune system. Many cytokine pathways have been found to be upregulated in AD lesions, including IL-13, IL-4, IL-31, and IL-5 in acute and chronic lesions, and IFN-γ and other helper T cell (T_H1) cytokines in chronic lesions. IL-4 and IL-13 (T_H2 cytokines) have been shown to decrease epidermal expression of filaggrin and lead to lipid abnormalities in the skin of patients with AD. Even normal-appearing, nonlesional skin has substantial immune activation and barrier abnormalities in patients with moderate to severe AD. Activation of different immune pathways may contribute to the heterogeneous clinical presentation of AD. There also is an increasingly recognized role of superantigen-producing Staphylococcus aureus and decreased microbial diversity in AD.

Therapies for AD

The advances in our understanding of AD pathophysiology have led to the development of 2 recently approved therapeutic agents.^7-10 Crisaborole ointment 2% is a topical phosphodiesterase 4 inhibitor that was approved by the US Food and Drug Administration in 2016 for treatment of mild to moderate AD. Treatment with crisaborole ointment 2% demonstrated improvement in lesion severity, itch, and quality of life in children and adults with AD. Dupilumab, an injectable biologic therapy that inhibits IL-4 and IL-13 signaling, was approved by the US Food and Drug Administration in 2017 for adults and in 2019 for adolescents aged 12 to 17 years with moderate to severe AD. The expert panel of speakers at the 2019 RAD Conference discussed many practical clinical pearls regarding patient education, optimization of both short- and long-term efficacy, and prevention and management of treatment-related adverse events. The discussion included evidence-based guidelines for bathing practices and topical therapy in AD, as well as practical pearls for patient and provider education in AD, reviewed by Dr. Nicol. Evidence-based guidelines for use of phototherapy and systemic and biologic therapy for AD also were highlighted by Dr. Silverberg.

After decades of limited therapeutic options, there is a large therapeutic pipeline of topical, oral, and biologic agents in development for the treatment AD.^7-9 Dr. Boguniewicz reviewed the state-of-the-art treatments that are the furthest advanced in development. Many of these agents may be approved within the next couple of years and look promising in terms of their potential to improve the care of patients with AD.

Comorbidities of AD

The impact of AD is not just skin deep. Atopic dermatitis is associated with myriad comorbid health conditions.^12-16 Dr. Boguniewicz reviewed the relationship between AD and atopic comorbidities, including asthma, hay fever, and food allergies, which are common across all AD patients. In addition, a subset of children with AD demonstrated the atopic march, in which AD first appears early in life followed by the development of other atopic comorbidities in later childhood or adulthood. In particular, children with filaggrin null mutations were found to be at increased risk of early-onset, severe, persistent AD with asthma and allergic sensitization.¹⁷ More recently, eosinophilic esophagitis was demonstrated to be a late-onset comorbidity of the atopic march.¹⁸ The allergy guidelines for which patients are appropriate candidates for food and/or aeroallergen testing were discussed,¹⁹ and it was emphasized that patients with AD should not routinely receive this testing.

Atopic dermatitis is associated with many other comorbidities, including sleep disturbances. Phyllis C. Zee, MD, PhD, provided a brilliant review of circadian regulation of physiology and the immune system. Sleep is one of the most important determinants of patients’ health and well-being. Atopic dermatitis is associated with disturbances of sleep and circadian rhythms. Sleep disturbances are gaining recognition as an important end point to assess for improvement in clinical practice and trials.

Patients with AD have long been recognized to have increased ophthalmic comorbidities, including allergic conjunctivitis, atopic keratoconjunctivitis, and cataracts. More recently, conjunctivitis has emerged as an important adverse event with dupilumab treatment.²⁰ Jeanine Baqai, MD, reviewed the various ophthalmic comorbidities and shared numerous clinical signs of ophthalmic comorbidities that dermatologists can assess with the naked eye (no slit-lamp examination needed). Pearls to manage dupilumab-related conjunctivitis shared by Dr. Baqai and the speaker panel included elimination of eye rubbing, cold compresses, avoidance of exacerbating factors, artificial tears, and timely referral to an ophthalmologist. Medications discussed were mast cell stabilizers, antihistamines, and corticosteroids and calcineurin inhibitors.

Final Thoughts

There has been an explosion of new research that has increased our understanding of all aspects of AD, and the standard of care is truly being revolutionized. Clinicians should stay tuned to a wealth of new evidence-based recommendations coming down the pike.

Impressive progress has been made in recent years in the management and treatment of atopic dermatitis (AD) and its comorbidities; however, there is a major need for state-of-the-art, evidence-based, multidisciplinary education for AD management. To address this need, the first Revolutionizing Atopic Dermatitis (RAD) Conference was held in April 2019 in Chicago, Illinois, featuring cutting-edge research presented by globally recognized experts in dermatology, allergy and immunology, sleep medicine, ophthalmology, and nursing care. The following is a recap of the latest topics in AD research presented at the conference.

Diagnosis and Assessment of AD: Jonathan I. Silverberg, MD, PhD, MPH

Although diagnosis of AD typically is straightforward in children, it can be challenging in adults, even for expert clinicians. These challenges stem from the different lesional distribution and morphology of AD in adults vs children.^1,2 Additionally, the conditions included in the differential diagnosis of AD (eg, allergic contact dermatitis, cutaneous T-cell lymphoma, psoriasis) are far more common in adults than in children. Formal diagnostic criteria can be useful to improve the diagnosis of AD in clinical practice.³ It is important to note that flexural lesions and early disease onset are diagnostic criteria in AD; nevertheless, neither are essential nor sufficient on their own to make the diagnosis.

Patch Testing: Jacob P. Thyssen, MD, PhD, DmSci, and Noreen Heer Nicol, PhD, RN, FNP, NEA-BC

Patch testing can be used in AD patients to rule out contact dermatitis as an alternative or comorbid diagnosis.^4-6 Because contact dermatitis can mimic AD, patch testing is recommended for all patients with adolescent and adult-onset AD.⁵ Additionally, refractory cases of AD across all ages, especially prior to initiation of systemic therapy, warrant patch testing. The unique challenges of patch testing in AD patients were reviewed.

Patient Panel

Atopic dermatitis can be a considerable disease burden on both patients and society in general. At the 2019 RAD Conference, a panel of patients bravely shared their AD journeys. Their eye-opening stories highlighted opportunities for improving real-world assessment and management of AD. Some key takeaways included the importance of adequately assessing the symptom burden of AD and not merely relying on visual inspection of the skin. The need for long-term treatment approaches beyond quick fixes with steroids also was discussed.

Pathogenesis of AD: Mark Boguniewicz, MD

There have been many advances in our understanding of the complex pathogenesis of AD,^7-11 which is characterized by an altered skin barrier and immune dysregulation. Filaggrin deficiency in the skin has structural and biophysical consequences. A subset of patients with AD has filaggrin loss-of-function genetic polymorphisms inherited in an autosomal-semidominant pattern; however, many other genetic polymorphisms have been identified that affect different components of the skin architecture and immune system. Many cytokine pathways have been found to be upregulated in AD lesions, including IL-13, IL-4, IL-31, and IL-5 in acute and chronic lesions, and IFN-γ and other helper T cell (T_H1) cytokines in chronic lesions. IL-4 and IL-13 (T_H2 cytokines) have been shown to decrease epidermal expression of filaggrin and lead to lipid abnormalities in the skin of patients with AD. Even normal-appearing, nonlesional skin has substantial immune activation and barrier abnormalities in patients with moderate to severe AD. Activation of different immune pathways may contribute to the heterogeneous clinical presentation of AD. There also is an increasingly recognized role of superantigen-producing Staphylococcus aureus and decreased microbial diversity in AD.

Therapies for AD

The advances in our understanding of AD pathophysiology have led to the development of 2 recently approved therapeutic agents.^7-10 Crisaborole ointment 2% is a topical phosphodiesterase 4 inhibitor that was approved by the US Food and Drug Administration in 2016 for treatment of mild to moderate AD. Treatment with crisaborole ointment 2% demonstrated improvement in lesion severity, itch, and quality of life in children and adults with AD. Dupilumab, an injectable biologic therapy that inhibits IL-4 and IL-13 signaling, was approved by the US Food and Drug Administration in 2017 for adults and in 2019 for adolescents aged 12 to 17 years with moderate to severe AD. The expert panel of speakers at the 2019 RAD Conference discussed many practical clinical pearls regarding patient education, optimization of both short- and long-term efficacy, and prevention and management of treatment-related adverse events. The discussion included evidence-based guidelines for bathing practices and topical therapy in AD, as well as practical pearls for patient and provider education in AD, reviewed by Dr. Nicol. Evidence-based guidelines for use of phototherapy and systemic and biologic therapy for AD also were highlighted by Dr. Silverberg.

After decades of limited therapeutic options, there is a large therapeutic pipeline of topical, oral, and biologic agents in development for the treatment AD.^7-9 Dr. Boguniewicz reviewed the state-of-the-art treatments that are the furthest advanced in development. Many of these agents may be approved within the next couple of years and look promising in terms of their potential to improve the care of patients with AD.

Comorbidities of AD

The impact of AD is not just skin deep. Atopic dermatitis is associated with myriad comorbid health conditions.^12-16 Dr. Boguniewicz reviewed the relationship between AD and atopic comorbidities, including asthma, hay fever, and food allergies, which are common across all AD patients. In addition, a subset of children with AD demonstrated the atopic march, in which AD first appears early in life followed by the development of other atopic comorbidities in later childhood or adulthood. In particular, children with filaggrin null mutations were found to be at increased risk of early-onset, severe, persistent AD with asthma and allergic sensitization.¹⁷ More recently, eosinophilic esophagitis was demonstrated to be a late-onset comorbidity of the atopic march.¹⁸ The allergy guidelines for which patients are appropriate candidates for food and/or aeroallergen testing were discussed,¹⁹ and it was emphasized that patients with AD should not routinely receive this testing.

Atopic dermatitis is associated with many other comorbidities, including sleep disturbances. Phyllis C. Zee, MD, PhD, provided a brilliant review of circadian regulation of physiology and the immune system. Sleep is one of the most important determinants of patients’ health and well-being. Atopic dermatitis is associated with disturbances of sleep and circadian rhythms. Sleep disturbances are gaining recognition as an important end point to assess for improvement in clinical practice and trials.

Patients with AD have long been recognized to have increased ophthalmic comorbidities, including allergic conjunctivitis, atopic keratoconjunctivitis, and cataracts. More recently, conjunctivitis has emerged as an important adverse event with dupilumab treatment.²⁰ Jeanine Baqai, MD, reviewed the various ophthalmic comorbidities and shared numerous clinical signs of ophthalmic comorbidities that dermatologists can assess with the naked eye (no slit-lamp examination needed). Pearls to manage dupilumab-related conjunctivitis shared by Dr. Baqai and the speaker panel included elimination of eye rubbing, cold compresses, avoidance of exacerbating factors, artificial tears, and timely referral to an ophthalmologist. Medications discussed were mast cell stabilizers, antihistamines, and corticosteroids and calcineurin inhibitors.

Final Thoughts

There has been an explosion of new research that has increased our understanding of all aspects of AD, and the standard of care is truly being revolutionized. Clinicians should stay tuned to a wealth of new evidence-based recommendations coming down the pike.

Impressive progress has been made in recent years in the management and treatment of atopic dermatitis (AD) and its comorbidities; however, there is a major need for state-of-the-art, evidence-based, multidisciplinary education for AD management. To address this need, the first Revolutionizing Atopic Dermatitis (RAD) Conference was held in April 2019 in Chicago, Illinois, featuring cutting-edge research presented by globally recognized experts in dermatology, allergy and immunology, sleep medicine, ophthalmology, and nursing care. The following is a recap of the latest topics in AD research presented at the conference.

Diagnosis and Assessment of AD: Jonathan I. Silverberg, MD, PhD, MPH

Although diagnosis of AD typically is straightforward in children, it can be challenging in adults, even for expert clinicians. These challenges stem from the different lesional distribution and morphology of AD in adults vs children.^1,2 Additionally, the conditions included in the differential diagnosis of AD (eg, allergic contact dermatitis, cutaneous T-cell lymphoma, psoriasis) are far more common in adults than in children. Formal diagnostic criteria can be useful to improve the diagnosis of AD in clinical practice.³ It is important to note that flexural lesions and early disease onset are diagnostic criteria in AD; nevertheless, neither are essential nor sufficient on their own to make the diagnosis.

Patch Testing: Jacob P. Thyssen, MD, PhD, DmSci, and Noreen Heer Nicol, PhD, RN, FNP, NEA-BC

Patch testing can be used in AD patients to rule out contact dermatitis as an alternative or comorbid diagnosis.^4-6 Because contact dermatitis can mimic AD, patch testing is recommended for all patients with adolescent and adult-onset AD.⁵ Additionally, refractory cases of AD across all ages, especially prior to initiation of systemic therapy, warrant patch testing. The unique challenges of patch testing in AD patients were reviewed.

Patient Panel

Atopic dermatitis can be a considerable disease burden on both patients and society in general. At the 2019 RAD Conference, a panel of patients bravely shared their AD journeys. Their eye-opening stories highlighted opportunities for improving real-world assessment and management of AD. Some key takeaways included the importance of adequately assessing the symptom burden of AD and not merely relying on visual inspection of the skin. The need for long-term treatment approaches beyond quick fixes with steroids also was discussed.

Pathogenesis of AD: Mark Boguniewicz, MD

There have been many advances in our understanding of the complex pathogenesis of AD,^7-11 which is characterized by an altered skin barrier and immune dysregulation. Filaggrin deficiency in the skin has structural and biophysical consequences. A subset of patients with AD has filaggrin loss-of-function genetic polymorphisms inherited in an autosomal-semidominant pattern; however, many other genetic polymorphisms have been identified that affect different components of the skin architecture and immune system. Many cytokine pathways have been found to be upregulated in AD lesions, including IL-13, IL-4, IL-31, and IL-5 in acute and chronic lesions, and IFN-γ and other helper T cell (T_H1) cytokines in chronic lesions. IL-4 and IL-13 (T_H2 cytokines) have been shown to decrease epidermal expression of filaggrin and lead to lipid abnormalities in the skin of patients with AD. Even normal-appearing, nonlesional skin has substantial immune activation and barrier abnormalities in patients with moderate to severe AD. Activation of different immune pathways may contribute to the heterogeneous clinical presentation of AD. There also is an increasingly recognized role of superantigen-producing Staphylococcus aureus and decreased microbial diversity in AD.

Therapies for AD

The advances in our understanding of AD pathophysiology have led to the development of 2 recently approved therapeutic agents.^7-10 Crisaborole ointment 2% is a topical phosphodiesterase 4 inhibitor that was approved by the US Food and Drug Administration in 2016 for treatment of mild to moderate AD. Treatment with crisaborole ointment 2% demonstrated improvement in lesion severity, itch, and quality of life in children and adults with AD. Dupilumab, an injectable biologic therapy that inhibits IL-4 and IL-13 signaling, was approved by the US Food and Drug Administration in 2017 for adults and in 2019 for adolescents aged 12 to 17 years with moderate to severe AD. The expert panel of speakers at the 2019 RAD Conference discussed many practical clinical pearls regarding patient education, optimization of both short- and long-term efficacy, and prevention and management of treatment-related adverse events. The discussion included evidence-based guidelines for bathing practices and topical therapy in AD, as well as practical pearls for patient and provider education in AD, reviewed by Dr. Nicol. Evidence-based guidelines for use of phototherapy and systemic and biologic therapy for AD also were highlighted by Dr. Silverberg.

After decades of limited therapeutic options, there is a large therapeutic pipeline of topical, oral, and biologic agents in development for the treatment AD.^7-9 Dr. Boguniewicz reviewed the state-of-the-art treatments that are the furthest advanced in development. Many of these agents may be approved within the next couple of years and look promising in terms of their potential to improve the care of patients with AD.

Comorbidities of AD

The impact of AD is not just skin deep. Atopic dermatitis is associated with myriad comorbid health conditions.^12-16 Dr. Boguniewicz reviewed the relationship between AD and atopic comorbidities, including asthma, hay fever, and food allergies, which are common across all AD patients. In addition, a subset of children with AD demonstrated the atopic march, in which AD first appears early in life followed by the development of other atopic comorbidities in later childhood or adulthood. In particular, children with filaggrin null mutations were found to be at increased risk of early-onset, severe, persistent AD with asthma and allergic sensitization.¹⁷ More recently, eosinophilic esophagitis was demonstrated to be a late-onset comorbidity of the atopic march.¹⁸ The allergy guidelines for which patients are appropriate candidates for food and/or aeroallergen testing were discussed,¹⁹ and it was emphasized that patients with AD should not routinely receive this testing.

Atopic dermatitis is associated with many other comorbidities, including sleep disturbances. Phyllis C. Zee, MD, PhD, provided a brilliant review of circadian regulation of physiology and the immune system. Sleep is one of the most important determinants of patients’ health and well-being. Atopic dermatitis is associated with disturbances of sleep and circadian rhythms. Sleep disturbances are gaining recognition as an important end point to assess for improvement in clinical practice and trials.

Patients with AD have long been recognized to have increased ophthalmic comorbidities, including allergic conjunctivitis, atopic keratoconjunctivitis, and cataracts. More recently, conjunctivitis has emerged as an important adverse event with dupilumab treatment.²⁰ Jeanine Baqai, MD, reviewed the various ophthalmic comorbidities and shared numerous clinical signs of ophthalmic comorbidities that dermatologists can assess with the naked eye (no slit-lamp examination needed). Pearls to manage dupilumab-related conjunctivitis shared by Dr. Baqai and the speaker panel included elimination of eye rubbing, cold compresses, avoidance of exacerbating factors, artificial tears, and timely referral to an ophthalmologist. Medications discussed were mast cell stabilizers, antihistamines, and corticosteroids and calcineurin inhibitors.

Final Thoughts

There has been an explosion of new research that has increased our understanding of all aspects of AD, and the standard of care is truly being revolutionized. Clinicians should stay tuned to a wealth of new evidence-based recommendations coming down the pike.

The Federal Bureau of Labor Statistics projects 37% job growth for physician assistants (PAs) from 2016 to 2026, much greater than the average for all other occupations as well as for other medical professions.¹ This growth has been accompanied by increased enrollment in medical (doctor of medicine [MD], doctor of osteopathic medicine) and nurse practitioner (NP) schools.² Clinical teaching sites serve a crucial function in the training of all clinical disciplines. These sites provide hands-on and experiential learning in medical settings, necessary components for learners practicing to become clinicians. Significant PA program expansion has led to increased demand for clinical training, creating competition for sites and a shortage of willing and well-trained preceptors.³

This challenge has been recognized by PA program directors. In the Joint Report of the 2013 Multi-Discipline Clerkship/Clinical Training Site Survey, PA program directors expressed concern about the adequacy of clinical opportunities for students, increased difficulty developing new core sites, and preserving existing core sites. In addition, they noted that a shortage of clinical sites was one of the greatest barriers to the PA programs’ sustained growth and success.⁴

Program directors also indicated difficulty securing clinical training sites in internal medicine (IM) and high rates of attrition of medicine clinical preceptors for their students.⁵ The reasons are multifold: increasing clinical demands, time, teaching competence, lack of experience, academic affiliation, lack of reimbursement, or compensation. Moreover, there is a declining number of PAs who work in primary care compared with specialty and subspecialty care, limiting the availability of clinical training preceptors in medicine and primary care.^6-8 According to the American Academy of PAs (AAPA) census and salary survey data, the percentage of PAs working in the primary care specialties (ie, family medicine, IM, and general pediatrics) has decreased from > 47% in 1995 to 24% in 2017.⁹ As such, there is a need to broaden the educational landscape to provide more high-quality training sites in IM.

The postacute health care setting may address this training need. It offers a unique clinical opportunity to expose learners to a broad range of disease complexity and clinical acuity, as the percentage of patients discharged from hospitals to postacute care (PAC) has increased and care shifts from the hospital to the PAC setting.^10,11 The longer PAC length of stay also enables learners to follow patients longitudinally over several weeks and experience interprofessional team-based care. In addition, the PAC setting offers learners the ability to acquire the necessary skills for smooth and effective transitions of care. This setting has been extensively used for trainees of nursing, pharmacy, physical therapy (PT) and occupational therapy (OT), speech-language pathology, psychology, and social work (SW), but few programs have used the PAC setting as clerkship sites for IM rotations for PA students. To address this need for IM sites, the VA Boston Healthcare System (VABHS), in conjunction with the Boston University School of Medicine Physician Assistant Program, developed a novel medicine clinical clerkship site for physician assistants in the PAC unit of the community living center (CLC) at VABHS. This report describes the program structure, curriculum, and participant evaluation results.

Clinical Clerkship Program

VABHS CLC is a 110-bed facility comprising 3 units: a 65-bed PAC unit, a 15-bed closed hospice/palliative care unit, and a 30-bed long-term care unit. The service is staffed continuously with physicians, PAs, and NPs. A majority of patients are admitted from the acute care hospital of VABHS (West Roxbury campus) and other regional VA facilities. The CLC offers dynamic services, including phlebotomy, general radiology, IV diuretics and antibiotics, wound care, and subacute PT, OT, and speech-language pathology rehabilitation. The CLC serves as a venue for transitioning patients from acute inpatient care to home. The patient population is often elderly, with multiple active comorbidities and variable medical literacy, adherence, and follow-up.

The CLC provides a diverse interprofessional learning environment, offering core IM rotations for first-year psychiatry residents, oral and maxillofacial surgery residents, and PA students. The CLC also has expanded as a clinical site both for transitions-in-care IM resident curricula and electives as well as a geriatrics fellowship. In addition, the site offers rotations for NPs, nursing, pharmacy, physical and occupational therapies, speech-language pathology, psychology, and SW.

The Boston University School of Medicine Physician Assistant Program was founded in 2015 as a master’s degree program completed over 28 months. The first 12 months are didactic, and the following 16 months are clinical training with 14 months of rotations (2 IM, family medicine, pediatrics, emergency medicine, general surgery, obstetrics and gynecology, psychiatry, neurology, and 5 elective rotations), and 2 months for a thesis. The program has about 30 students per year and 4 clerkship sites for IM.

Program Description

The VABHS medicine clerkship hosts 1 to 2 PA students for 4-week blocks in the PAC unit of the CLC. Each student rotates on both PA and MD teams. Students follow 3 to 4 patients and participate fully in their care from admission to discharge; they prepare daily presentations and participate in medical management, family meetings, chart documentation, and care coordination with the interprofessional team. Students are provided a physical examination checklist and feedback form, and they are expected to track findings and record feedback and goals with their supervising preceptor weekly. They also make formal case presentations and participate in monthly medicine didactic rounds available to all VABHS IM students and trainees via videoconference.

In addition, beginning in July 2017, all PA students in the CLC began to participate in a 4-week Interprofessional Curriculum in Transitional Care. The curriculum includes 14 didactic lectures taught by 16 interprofessional faculty, including medicine, geriatric, and palliative care physicians; PAs; social workers; physical and occupational therapists; pharmacists; and a geriatric psychologist. The didactics include topics on the interprofessional team, the care continuum, teams and teamwork, interdisciplinary coordination of care, components of effective transitions in care, medication reconciliation, approaching difficult conversations, advance care planning, and quality improvement. The goal of the curriculum is to provide learners the knowledge, skills, and dispositions necessary for high-quality transitional care and interprofessional practice as well as specific training for effective and safe transfers of care between clinical settings. Although PA students are the main participants in this curriculum, all other learners in the PAC unit are also invited to attend the lectures.

The unique attributes of this training site include direct interaction with supervising PAs and physicians, rather than experiencing the traditional teaching hierarchy (with interns, residents, fellows); observation of the natural progression of disease of both acute care and primary care issues due to the longer length of stay (2 to 6 weeks, where the typical student will see the same patient 7 to 10 times during their rotation); exposure to a host of medically complex patients offering a multitude of clinical scenarios and abnormal physical exam findings; exposure to a hospice/palliative care ward and end-of-life care; and interaction within an interprofessional training environment of nursing, pharmacy, PT, OT, speech-language pathology, psychology, and SW trainees.

Program Evaluation

At the end of rotations continuously through the year, PA students electronically complete a site evaluation from the Boston University School of Medicine Physician Assistant Program. The evaluation consists of 14 questions: 6 about site quality and 8 about instruction quality. The questions are answered on a 5-point Likert scale. Also included are 2 open-ended response questions that ask what they liked about the rotation and what they felt could be improved. Results are anonymous, de-identified and blinded both to the program as well as the clerkship site. Results are aggregated and provided to program sites annually. Responses are converted to a dichotomous variable, where any good or excellent response (4 or 5) is considered positive and any neutral or below (3, 2, 1) is considered a nonpositive response.

Results

The clerkship site has been operational since June 22, 2015. There have been 59 students who participated in the rotation. A different scale in these evaluations was used between June 22, 2015, and September 13, 2015. Therefore, 7 responses were excluded from the analysis, leaving 52 usable evaluations. The responses were analyzed both in total (for the CLC as well as other IM rotation sites) and by individual clerkship year to look for any trends over time: September 14, 2015, through April 24, 2016; April 25, 2016, through April 28, 2017; and May 1, 2017, through March 1, 2018 (Table).

Site evaluations showed high satisfaction regarding the quality of the physical environment as well as the learning environment. Students endorsed the PAC unit having resources and physical space for them, such as a desk and computer, opportunity for participation in patient care, and parking (100%; n = 52). Site evaluations revealed high satisfaction with the quality of teaching and faculty encouragement and support of their learning (100%; n = 52). The evaluations revealed that bedside teaching was strong (94%; n = 49). The students reported high satisfaction with the volume of patients provided (92%; n = 48) as well as the diversity of diagnoses (92%; n = 48).

There were fewer positive responses in the first 2 years of the rotation with regard to formal lectures (50% and 67%; 7/14 and 16/24, respectively). In the third year of the rotation, students had a much higher satisfaction rate (93%; 13/14). This increased satisfaction was associated with the development and incorporation of the Interprofessional Curriculum in Transitional Care in 2017.

Discussion

Access to high-quality PA student clerkship sites has become a pressing issue in recent years because of increased competition for sites and a shortage of willing and well-trained preceptors. There has been marked growth in schools and enrollment across all medical professions. The Accreditation Review Commission on Education for the PA (ARC-PA) reported that the total number of accredited entry-level PA programs in 2018 was 246, with 58 new accredited programs projected by 2022.¹² The Joint Report of the 2013 Multi-Discipline Clerkship/Clinical Training Site Survey reported a 66% increase in first-year enrollment in PA programs from 2002 to 2012.⁵ Programs must implement alternative strategies to attract clinical sites (eg, academic appointments, increased clinical resources to training sites) or face continued challenges with recruiting training sites for their students. Postacute care may be a natural extension to expand the footprint for clinical sites for these programs, augmenting acute inpatient and outpatient rotations. This implementation would increase the pool of clinical training sites and preceptors.

The experience with this novel training site, based on PA student feedback and evaluations, has been positive, and the postacute setting can provide students with high-quality IM clinical experiences. Students report adequate patient volume and diversity. In addition, evaluations are comparable with that of other IM site rotations the students experience. Qualitative feedback has emphasized the value of following patients over longer periods; eg, weeks vs days (as in acute care) enabling students to build relationships with patients as well as observe a richer clinical spectrum of disease over a less compressed period. “Patients have complex issues, so from a medical standpoint it challenges you to think of new ways to manage their care,” commented a representative student. “It is really beneficial that you can follow them over time.”

Furthermore, in response to student feedback on didactics, an interprofessional curriculum was developed to add formal structure as well as to create a curriculum in care transitions. This curriculum provided a unique opportunity for PA students to receive formal instruction on areas of particular relevance for transitional care (eg, care continuum, end of life issues, and care transitions). The curriculum also allows the interprofessional faculty a unique and enjoyable opportunity for interprofessional collaboration.

The 1 month PAC rotation is augmented with inpatient IM and outpatient family medicine rotations, consequently giving exposure to the full continuum of care. The PAC setting provides learners multifaceted benefits: the opportunity to strengthen and develop the knowledge, attitudes, and skills necessary for IM; increased understanding of other professions by observing and interacting as a team caring for a patient over a longer period as opposed to the acute care setting; the ability to perform effective, efficient, and safe transfer between clinical settings; and broad exposure to transitional care. As a result, the PAC rotation enhances but does not replace the necessary and essential rotations of inpatient and outpatient medicine.

Moreover, this rotation provides unique and core IM training for PA students. Our site focuses on interprofessional collaboration, emphasizing the importance of team-based care, an essential concept in modern day medicine. Formal exposure to other care specialties, such as PT and OT, SW, and mental health, is essential for students to appreciate clinical medicine and a patient’s physical and mental experience over the course of a disease and clinical state. In addition, the physical exam checklist ensures that students are exposed to the full spectrum of IM examination findings during their rotation. Finally, weekly feedback forms require students to ask and receive concrete feedback from their supervising providers.

Limitations

The generalizability of this model requires careful consideration. VABHS is a tertiary care integrated health care system, enabling students to learn from patients moving through multiple care transitions in a single health care system. In addition, other settings may not have the staffing or clinical volume to sustain such a model. All PAC clinical faculty teach voluntarily, and local leadership has set expectations for all clinicians to participate in teaching of trainees and PA students. Evaluations also note less diversity in the patient population, a challenge that some VA facilities face. This issue could be addressed by ensuring that students also have IM rotations at other inpatient medical facilities. A more balanced experience, where students reap the positive benefits of PAC but do not lose exposure to a diverse patient pool, could result. Furthermore, some of the perceived positive impacts also may be related to professional and personal attributes of the teaching clinicians rather than to the PAC setting.

Conclusion

PAC settings can be effective training sites for medicine clerkships for PA students and can provide high-quality training in IM as PA programs continue to expand. This setting offers students exposure to interprofessional, team-based care and the opportunity to care for patients with a broad range of disease complexity. Learning is further enhanced by the ability to follow patients longitudinally over their disease course as well as to work directly with teaching faculty and other interprofessional health care professionals. Evaluations of this novel clerkship experience have shown high levels of student satisfaction in knowledge growth, clinical skills, bedside teaching, and mentorship.

Acknowledgments
We thank Juman Hijab for her critical role in establishing and maintaining the clerkship. We thank Steven Simon, Matt Russell, and Thomas Parrino for their leadership and guidance in establishing and maintaining the clerkship. We thank the Boston University School of Medicine Physician Assistant Program Director Mary Warner for her support and guidance in creating and supporting the clerkship. In addition, we thank the interprofessional education faculty for their dedicated involvement in teaching, including Stephanie Saunders, Lindsay Lefers, Jessica Rawlins, Lindsay Brennan, Angela Viani, Eric Charette, Nicole O’Neil, Susan Nathan, Jordana Meyerson, Shivani Jindal, Wei Shen, Amy Hanson, Gilda Cain, and Kate Hinrichs.

The Federal Bureau of Labor Statistics projects 37% job growth for physician assistants (PAs) from 2016 to 2026, much greater than the average for all other occupations as well as for other medical professions.¹ This growth has been accompanied by increased enrollment in medical (doctor of medicine [MD], doctor of osteopathic medicine) and nurse practitioner (NP) schools.² Clinical teaching sites serve a crucial function in the training of all clinical disciplines. These sites provide hands-on and experiential learning in medical settings, necessary components for learners practicing to become clinicians. Significant PA program expansion has led to increased demand for clinical training, creating competition for sites and a shortage of willing and well-trained preceptors.³

This challenge has been recognized by PA program directors. In the Joint Report of the 2013 Multi-Discipline Clerkship/Clinical Training Site Survey, PA program directors expressed concern about the adequacy of clinical opportunities for students, increased difficulty developing new core sites, and preserving existing core sites. In addition, they noted that a shortage of clinical sites was one of the greatest barriers to the PA programs’ sustained growth and success.⁴

Program directors also indicated difficulty securing clinical training sites in internal medicine (IM) and high rates of attrition of medicine clinical preceptors for their students.⁵ The reasons are multifold: increasing clinical demands, time, teaching competence, lack of experience, academic affiliation, lack of reimbursement, or compensation. Moreover, there is a declining number of PAs who work in primary care compared with specialty and subspecialty care, limiting the availability of clinical training preceptors in medicine and primary care.^6-8 According to the American Academy of PAs (AAPA) census and salary survey data, the percentage of PAs working in the primary care specialties (ie, family medicine, IM, and general pediatrics) has decreased from > 47% in 1995 to 24% in 2017.⁹ As such, there is a need to broaden the educational landscape to provide more high-quality training sites in IM.

The postacute health care setting may address this training need. It offers a unique clinical opportunity to expose learners to a broad range of disease complexity and clinical acuity, as the percentage of patients discharged from hospitals to postacute care (PAC) has increased and care shifts from the hospital to the PAC setting.^10,11 The longer PAC length of stay also enables learners to follow patients longitudinally over several weeks and experience interprofessional team-based care. In addition, the PAC setting offers learners the ability to acquire the necessary skills for smooth and effective transitions of care. This setting has been extensively used for trainees of nursing, pharmacy, physical therapy (PT) and occupational therapy (OT), speech-language pathology, psychology, and social work (SW), but few programs have used the PAC setting as clerkship sites for IM rotations for PA students. To address this need for IM sites, the VA Boston Healthcare System (VABHS), in conjunction with the Boston University School of Medicine Physician Assistant Program, developed a novel medicine clinical clerkship site for physician assistants in the PAC unit of the community living center (CLC) at VABHS. This report describes the program structure, curriculum, and participant evaluation results.

Clinical Clerkship Program

VABHS CLC is a 110-bed facility comprising 3 units: a 65-bed PAC unit, a 15-bed closed hospice/palliative care unit, and a 30-bed long-term care unit. The service is staffed continuously with physicians, PAs, and NPs. A majority of patients are admitted from the acute care hospital of VABHS (West Roxbury campus) and other regional VA facilities. The CLC offers dynamic services, including phlebotomy, general radiology, IV diuretics and antibiotics, wound care, and subacute PT, OT, and speech-language pathology rehabilitation. The CLC serves as a venue for transitioning patients from acute inpatient care to home. The patient population is often elderly, with multiple active comorbidities and variable medical literacy, adherence, and follow-up.

The CLC provides a diverse interprofessional learning environment, offering core IM rotations for first-year psychiatry residents, oral and maxillofacial surgery residents, and PA students. The CLC also has expanded as a clinical site both for transitions-in-care IM resident curricula and electives as well as a geriatrics fellowship. In addition, the site offers rotations for NPs, nursing, pharmacy, physical and occupational therapies, speech-language pathology, psychology, and SW.

The Boston University School of Medicine Physician Assistant Program was founded in 2015 as a master’s degree program completed over 28 months. The first 12 months are didactic, and the following 16 months are clinical training with 14 months of rotations (2 IM, family medicine, pediatrics, emergency medicine, general surgery, obstetrics and gynecology, psychiatry, neurology, and 5 elective rotations), and 2 months for a thesis. The program has about 30 students per year and 4 clerkship sites for IM.

Program Description

The VABHS medicine clerkship hosts 1 to 2 PA students for 4-week blocks in the PAC unit of the CLC. Each student rotates on both PA and MD teams. Students follow 3 to 4 patients and participate fully in their care from admission to discharge; they prepare daily presentations and participate in medical management, family meetings, chart documentation, and care coordination with the interprofessional team. Students are provided a physical examination checklist and feedback form, and they are expected to track findings and record feedback and goals with their supervising preceptor weekly. They also make formal case presentations and participate in monthly medicine didactic rounds available to all VABHS IM students and trainees via videoconference.

In addition, beginning in July 2017, all PA students in the CLC began to participate in a 4-week Interprofessional Curriculum in Transitional Care. The curriculum includes 14 didactic lectures taught by 16 interprofessional faculty, including medicine, geriatric, and palliative care physicians; PAs; social workers; physical and occupational therapists; pharmacists; and a geriatric psychologist. The didactics include topics on the interprofessional team, the care continuum, teams and teamwork, interdisciplinary coordination of care, components of effective transitions in care, medication reconciliation, approaching difficult conversations, advance care planning, and quality improvement. The goal of the curriculum is to provide learners the knowledge, skills, and dispositions necessary for high-quality transitional care and interprofessional practice as well as specific training for effective and safe transfers of care between clinical settings. Although PA students are the main participants in this curriculum, all other learners in the PAC unit are also invited to attend the lectures.

The unique attributes of this training site include direct interaction with supervising PAs and physicians, rather than experiencing the traditional teaching hierarchy (with interns, residents, fellows); observation of the natural progression of disease of both acute care and primary care issues due to the longer length of stay (2 to 6 weeks, where the typical student will see the same patient 7 to 10 times during their rotation); exposure to a host of medically complex patients offering a multitude of clinical scenarios and abnormal physical exam findings; exposure to a hospice/palliative care ward and end-of-life care; and interaction within an interprofessional training environment of nursing, pharmacy, PT, OT, speech-language pathology, psychology, and SW trainees.

Program Evaluation

At the end of rotations continuously through the year, PA students electronically complete a site evaluation from the Boston University School of Medicine Physician Assistant Program. The evaluation consists of 14 questions: 6 about site quality and 8 about instruction quality. The questions are answered on a 5-point Likert scale. Also included are 2 open-ended response questions that ask what they liked about the rotation and what they felt could be improved. Results are anonymous, de-identified and blinded both to the program as well as the clerkship site. Results are aggregated and provided to program sites annually. Responses are converted to a dichotomous variable, where any good or excellent response (4 or 5) is considered positive and any neutral or below (3, 2, 1) is considered a nonpositive response.

Results

The clerkship site has been operational since June 22, 2015. There have been 59 students who participated in the rotation. A different scale in these evaluations was used between June 22, 2015, and September 13, 2015. Therefore, 7 responses were excluded from the analysis, leaving 52 usable evaluations. The responses were analyzed both in total (for the CLC as well as other IM rotation sites) and by individual clerkship year to look for any trends over time: September 14, 2015, through April 24, 2016; April 25, 2016, through April 28, 2017; and May 1, 2017, through March 1, 2018 (Table).

Site evaluations showed high satisfaction regarding the quality of the physical environment as well as the learning environment. Students endorsed the PAC unit having resources and physical space for them, such as a desk and computer, opportunity for participation in patient care, and parking (100%; n = 52). Site evaluations revealed high satisfaction with the quality of teaching and faculty encouragement and support of their learning (100%; n = 52). The evaluations revealed that bedside teaching was strong (94%; n = 49). The students reported high satisfaction with the volume of patients provided (92%; n = 48) as well as the diversity of diagnoses (92%; n = 48).

There were fewer positive responses in the first 2 years of the rotation with regard to formal lectures (50% and 67%; 7/14 and 16/24, respectively). In the third year of the rotation, students had a much higher satisfaction rate (93%; 13/14). This increased satisfaction was associated with the development and incorporation of the Interprofessional Curriculum in Transitional Care in 2017.

Discussion

Access to high-quality PA student clerkship sites has become a pressing issue in recent years because of increased competition for sites and a shortage of willing and well-trained preceptors. There has been marked growth in schools and enrollment across all medical professions. The Accreditation Review Commission on Education for the PA (ARC-PA) reported that the total number of accredited entry-level PA programs in 2018 was 246, with 58 new accredited programs projected by 2022.¹² The Joint Report of the 2013 Multi-Discipline Clerkship/Clinical Training Site Survey reported a 66% increase in first-year enrollment in PA programs from 2002 to 2012.⁵ Programs must implement alternative strategies to attract clinical sites (eg, academic appointments, increased clinical resources to training sites) or face continued challenges with recruiting training sites for their students. Postacute care may be a natural extension to expand the footprint for clinical sites for these programs, augmenting acute inpatient and outpatient rotations. This implementation would increase the pool of clinical training sites and preceptors.

The experience with this novel training site, based on PA student feedback and evaluations, has been positive, and the postacute setting can provide students with high-quality IM clinical experiences. Students report adequate patient volume and diversity. In addition, evaluations are comparable with that of other IM site rotations the students experience. Qualitative feedback has emphasized the value of following patients over longer periods; eg, weeks vs days (as in acute care) enabling students to build relationships with patients as well as observe a richer clinical spectrum of disease over a less compressed period. “Patients have complex issues, so from a medical standpoint it challenges you to think of new ways to manage their care,” commented a representative student. “It is really beneficial that you can follow them over time.”

Furthermore, in response to student feedback on didactics, an interprofessional curriculum was developed to add formal structure as well as to create a curriculum in care transitions. This curriculum provided a unique opportunity for PA students to receive formal instruction on areas of particular relevance for transitional care (eg, care continuum, end of life issues, and care transitions). The curriculum also allows the interprofessional faculty a unique and enjoyable opportunity for interprofessional collaboration.

The 1 month PAC rotation is augmented with inpatient IM and outpatient family medicine rotations, consequently giving exposure to the full continuum of care. The PAC setting provides learners multifaceted benefits: the opportunity to strengthen and develop the knowledge, attitudes, and skills necessary for IM; increased understanding of other professions by observing and interacting as a team caring for a patient over a longer period as opposed to the acute care setting; the ability to perform effective, efficient, and safe transfer between clinical settings; and broad exposure to transitional care. As a result, the PAC rotation enhances but does not replace the necessary and essential rotations of inpatient and outpatient medicine.

Moreover, this rotation provides unique and core IM training for PA students. Our site focuses on interprofessional collaboration, emphasizing the importance of team-based care, an essential concept in modern day medicine. Formal exposure to other care specialties, such as PT and OT, SW, and mental health, is essential for students to appreciate clinical medicine and a patient’s physical and mental experience over the course of a disease and clinical state. In addition, the physical exam checklist ensures that students are exposed to the full spectrum of IM examination findings during their rotation. Finally, weekly feedback forms require students to ask and receive concrete feedback from their supervising providers.

Limitations

The generalizability of this model requires careful consideration. VABHS is a tertiary care integrated health care system, enabling students to learn from patients moving through multiple care transitions in a single health care system. In addition, other settings may not have the staffing or clinical volume to sustain such a model. All PAC clinical faculty teach voluntarily, and local leadership has set expectations for all clinicians to participate in teaching of trainees and PA students. Evaluations also note less diversity in the patient population, a challenge that some VA facilities face. This issue could be addressed by ensuring that students also have IM rotations at other inpatient medical facilities. A more balanced experience, where students reap the positive benefits of PAC but do not lose exposure to a diverse patient pool, could result. Furthermore, some of the perceived positive impacts also may be related to professional and personal attributes of the teaching clinicians rather than to the PAC setting.

Conclusion

PAC settings can be effective training sites for medicine clerkships for PA students and can provide high-quality training in IM as PA programs continue to expand. This setting offers students exposure to interprofessional, team-based care and the opportunity to care for patients with a broad range of disease complexity. Learning is further enhanced by the ability to follow patients longitudinally over their disease course as well as to work directly with teaching faculty and other interprofessional health care professionals. Evaluations of this novel clerkship experience have shown high levels of student satisfaction in knowledge growth, clinical skills, bedside teaching, and mentorship.

Acknowledgments
We thank Juman Hijab for her critical role in establishing and maintaining the clerkship. We thank Steven Simon, Matt Russell, and Thomas Parrino for their leadership and guidance in establishing and maintaining the clerkship. We thank the Boston University School of Medicine Physician Assistant Program Director Mary Warner for her support and guidance in creating and supporting the clerkship. In addition, we thank the interprofessional education faculty for their dedicated involvement in teaching, including Stephanie Saunders, Lindsay Lefers, Jessica Rawlins, Lindsay Brennan, Angela Viani, Eric Charette, Nicole O’Neil, Susan Nathan, Jordana Meyerson, Shivani Jindal, Wei Shen, Amy Hanson, Gilda Cain, and Kate Hinrichs.

The Federal Bureau of Labor Statistics projects 37% job growth for physician assistants (PAs) from 2016 to 2026, much greater than the average for all other occupations as well as for other medical professions.¹ This growth has been accompanied by increased enrollment in medical (doctor of medicine [MD], doctor of osteopathic medicine) and nurse practitioner (NP) schools.² Clinical teaching sites serve a crucial function in the training of all clinical disciplines. These sites provide hands-on and experiential learning in medical settings, necessary components for learners practicing to become clinicians. Significant PA program expansion has led to increased demand for clinical training, creating competition for sites and a shortage of willing and well-trained preceptors.³

This challenge has been recognized by PA program directors. In the Joint Report of the 2013 Multi-Discipline Clerkship/Clinical Training Site Survey, PA program directors expressed concern about the adequacy of clinical opportunities for students, increased difficulty developing new core sites, and preserving existing core sites. In addition, they noted that a shortage of clinical sites was one of the greatest barriers to the PA programs’ sustained growth and success.⁴

Program directors also indicated difficulty securing clinical training sites in internal medicine (IM) and high rates of attrition of medicine clinical preceptors for their students.⁵ The reasons are multifold: increasing clinical demands, time, teaching competence, lack of experience, academic affiliation, lack of reimbursement, or compensation. Moreover, there is a declining number of PAs who work in primary care compared with specialty and subspecialty care, limiting the availability of clinical training preceptors in medicine and primary care.^6-8 According to the American Academy of PAs (AAPA) census and salary survey data, the percentage of PAs working in the primary care specialties (ie, family medicine, IM, and general pediatrics) has decreased from > 47% in 1995 to 24% in 2017.⁹ As such, there is a need to broaden the educational landscape to provide more high-quality training sites in IM.

The postacute health care setting may address this training need. It offers a unique clinical opportunity to expose learners to a broad range of disease complexity and clinical acuity, as the percentage of patients discharged from hospitals to postacute care (PAC) has increased and care shifts from the hospital to the PAC setting.^10,11 The longer PAC length of stay also enables learners to follow patients longitudinally over several weeks and experience interprofessional team-based care. In addition, the PAC setting offers learners the ability to acquire the necessary skills for smooth and effective transitions of care. This setting has been extensively used for trainees of nursing, pharmacy, physical therapy (PT) and occupational therapy (OT), speech-language pathology, psychology, and social work (SW), but few programs have used the PAC setting as clerkship sites for IM rotations for PA students. To address this need for IM sites, the VA Boston Healthcare System (VABHS), in conjunction with the Boston University School of Medicine Physician Assistant Program, developed a novel medicine clinical clerkship site for physician assistants in the PAC unit of the community living center (CLC) at VABHS. This report describes the program structure, curriculum, and participant evaluation results.

Clinical Clerkship Program

VABHS CLC is a 110-bed facility comprising 3 units: a 65-bed PAC unit, a 15-bed closed hospice/palliative care unit, and a 30-bed long-term care unit. The service is staffed continuously with physicians, PAs, and NPs. A majority of patients are admitted from the acute care hospital of VABHS (West Roxbury campus) and other regional VA facilities. The CLC offers dynamic services, including phlebotomy, general radiology, IV diuretics and antibiotics, wound care, and subacute PT, OT, and speech-language pathology rehabilitation. The CLC serves as a venue for transitioning patients from acute inpatient care to home. The patient population is often elderly, with multiple active comorbidities and variable medical literacy, adherence, and follow-up.

The CLC provides a diverse interprofessional learning environment, offering core IM rotations for first-year psychiatry residents, oral and maxillofacial surgery residents, and PA students. The CLC also has expanded as a clinical site both for transitions-in-care IM resident curricula and electives as well as a geriatrics fellowship. In addition, the site offers rotations for NPs, nursing, pharmacy, physical and occupational therapies, speech-language pathology, psychology, and SW.

The Boston University School of Medicine Physician Assistant Program was founded in 2015 as a master’s degree program completed over 28 months. The first 12 months are didactic, and the following 16 months are clinical training with 14 months of rotations (2 IM, family medicine, pediatrics, emergency medicine, general surgery, obstetrics and gynecology, psychiatry, neurology, and 5 elective rotations), and 2 months for a thesis. The program has about 30 students per year and 4 clerkship sites for IM.

Program Description

The VABHS medicine clerkship hosts 1 to 2 PA students for 4-week blocks in the PAC unit of the CLC. Each student rotates on both PA and MD teams. Students follow 3 to 4 patients and participate fully in their care from admission to discharge; they prepare daily presentations and participate in medical management, family meetings, chart documentation, and care coordination with the interprofessional team. Students are provided a physical examination checklist and feedback form, and they are expected to track findings and record feedback and goals with their supervising preceptor weekly. They also make formal case presentations and participate in monthly medicine didactic rounds available to all VABHS IM students and trainees via videoconference.

In addition, beginning in July 2017, all PA students in the CLC began to participate in a 4-week Interprofessional Curriculum in Transitional Care. The curriculum includes 14 didactic lectures taught by 16 interprofessional faculty, including medicine, geriatric, and palliative care physicians; PAs; social workers; physical and occupational therapists; pharmacists; and a geriatric psychologist. The didactics include topics on the interprofessional team, the care continuum, teams and teamwork, interdisciplinary coordination of care, components of effective transitions in care, medication reconciliation, approaching difficult conversations, advance care planning, and quality improvement. The goal of the curriculum is to provide learners the knowledge, skills, and dispositions necessary for high-quality transitional care and interprofessional practice as well as specific training for effective and safe transfers of care between clinical settings. Although PA students are the main participants in this curriculum, all other learners in the PAC unit are also invited to attend the lectures.

The unique attributes of this training site include direct interaction with supervising PAs and physicians, rather than experiencing the traditional teaching hierarchy (with interns, residents, fellows); observation of the natural progression of disease of both acute care and primary care issues due to the longer length of stay (2 to 6 weeks, where the typical student will see the same patient 7 to 10 times during their rotation); exposure to a host of medically complex patients offering a multitude of clinical scenarios and abnormal physical exam findings; exposure to a hospice/palliative care ward and end-of-life care; and interaction within an interprofessional training environment of nursing, pharmacy, PT, OT, speech-language pathology, psychology, and SW trainees.

Program Evaluation

At the end of rotations continuously through the year, PA students electronically complete a site evaluation from the Boston University School of Medicine Physician Assistant Program. The evaluation consists of 14 questions: 6 about site quality and 8 about instruction quality. The questions are answered on a 5-point Likert scale. Also included are 2 open-ended response questions that ask what they liked about the rotation and what they felt could be improved. Results are anonymous, de-identified and blinded both to the program as well as the clerkship site. Results are aggregated and provided to program sites annually. Responses are converted to a dichotomous variable, where any good or excellent response (4 or 5) is considered positive and any neutral or below (3, 2, 1) is considered a nonpositive response.

Results

The clerkship site has been operational since June 22, 2015. There have been 59 students who participated in the rotation. A different scale in these evaluations was used between June 22, 2015, and September 13, 2015. Therefore, 7 responses were excluded from the analysis, leaving 52 usable evaluations. The responses were analyzed both in total (for the CLC as well as other IM rotation sites) and by individual clerkship year to look for any trends over time: September 14, 2015, through April 24, 2016; April 25, 2016, through April 28, 2017; and May 1, 2017, through March 1, 2018 (Table).

Site evaluations showed high satisfaction regarding the quality of the physical environment as well as the learning environment. Students endorsed the PAC unit having resources and physical space for them, such as a desk and computer, opportunity for participation in patient care, and parking (100%; n = 52). Site evaluations revealed high satisfaction with the quality of teaching and faculty encouragement and support of their learning (100%; n = 52). The evaluations revealed that bedside teaching was strong (94%; n = 49). The students reported high satisfaction with the volume of patients provided (92%; n = 48) as well as the diversity of diagnoses (92%; n = 48).

There were fewer positive responses in the first 2 years of the rotation with regard to formal lectures (50% and 67%; 7/14 and 16/24, respectively). In the third year of the rotation, students had a much higher satisfaction rate (93%; 13/14). This increased satisfaction was associated with the development and incorporation of the Interprofessional Curriculum in Transitional Care in 2017.

Discussion

Access to high-quality PA student clerkship sites has become a pressing issue in recent years because of increased competition for sites and a shortage of willing and well-trained preceptors. There has been marked growth in schools and enrollment across all medical professions. The Accreditation Review Commission on Education for the PA (ARC-PA) reported that the total number of accredited entry-level PA programs in 2018 was 246, with 58 new accredited programs projected by 2022.¹² The Joint Report of the 2013 Multi-Discipline Clerkship/Clinical Training Site Survey reported a 66% increase in first-year enrollment in PA programs from 2002 to 2012.⁵ Programs must implement alternative strategies to attract clinical sites (eg, academic appointments, increased clinical resources to training sites) or face continued challenges with recruiting training sites for their students. Postacute care may be a natural extension to expand the footprint for clinical sites for these programs, augmenting acute inpatient and outpatient rotations. This implementation would increase the pool of clinical training sites and preceptors.

The experience with this novel training site, based on PA student feedback and evaluations, has been positive, and the postacute setting can provide students with high-quality IM clinical experiences. Students report adequate patient volume and diversity. In addition, evaluations are comparable with that of other IM site rotations the students experience. Qualitative feedback has emphasized the value of following patients over longer periods; eg, weeks vs days (as in acute care) enabling students to build relationships with patients as well as observe a richer clinical spectrum of disease over a less compressed period. “Patients have complex issues, so from a medical standpoint it challenges you to think of new ways to manage their care,” commented a representative student. “It is really beneficial that you can follow them over time.”

Furthermore, in response to student feedback on didactics, an interprofessional curriculum was developed to add formal structure as well as to create a curriculum in care transitions. This curriculum provided a unique opportunity for PA students to receive formal instruction on areas of particular relevance for transitional care (eg, care continuum, end of life issues, and care transitions). The curriculum also allows the interprofessional faculty a unique and enjoyable opportunity for interprofessional collaboration.

The 1 month PAC rotation is augmented with inpatient IM and outpatient family medicine rotations, consequently giving exposure to the full continuum of care. The PAC setting provides learners multifaceted benefits: the opportunity to strengthen and develop the knowledge, attitudes, and skills necessary for IM; increased understanding of other professions by observing and interacting as a team caring for a patient over a longer period as opposed to the acute care setting; the ability to perform effective, efficient, and safe transfer between clinical settings; and broad exposure to transitional care. As a result, the PAC rotation enhances but does not replace the necessary and essential rotations of inpatient and outpatient medicine.

Moreover, this rotation provides unique and core IM training for PA students. Our site focuses on interprofessional collaboration, emphasizing the importance of team-based care, an essential concept in modern day medicine. Formal exposure to other care specialties, such as PT and OT, SW, and mental health, is essential for students to appreciate clinical medicine and a patient’s physical and mental experience over the course of a disease and clinical state. In addition, the physical exam checklist ensures that students are exposed to the full spectrum of IM examination findings during their rotation. Finally, weekly feedback forms require students to ask and receive concrete feedback from their supervising providers.

Limitations

The generalizability of this model requires careful consideration. VABHS is a tertiary care integrated health care system, enabling students to learn from patients moving through multiple care transitions in a single health care system. In addition, other settings may not have the staffing or clinical volume to sustain such a model. All PAC clinical faculty teach voluntarily, and local leadership has set expectations for all clinicians to participate in teaching of trainees and PA students. Evaluations also note less diversity in the patient population, a challenge that some VA facilities face. This issue could be addressed by ensuring that students also have IM rotations at other inpatient medical facilities. A more balanced experience, where students reap the positive benefits of PAC but do not lose exposure to a diverse patient pool, could result. Furthermore, some of the perceived positive impacts also may be related to professional and personal attributes of the teaching clinicians rather than to the PAC setting.

Conclusion

PAC settings can be effective training sites for medicine clerkships for PA students and can provide high-quality training in IM as PA programs continue to expand. This setting offers students exposure to interprofessional, team-based care and the opportunity to care for patients with a broad range of disease complexity. Learning is further enhanced by the ability to follow patients longitudinally over their disease course as well as to work directly with teaching faculty and other interprofessional health care professionals. Evaluations of this novel clerkship experience have shown high levels of student satisfaction in knowledge growth, clinical skills, bedside teaching, and mentorship.

Acknowledgments
We thank Juman Hijab for her critical role in establishing and maintaining the clerkship. We thank Steven Simon, Matt Russell, and Thomas Parrino for their leadership and guidance in establishing and maintaining the clerkship. We thank the Boston University School of Medicine Physician Assistant Program Director Mary Warner for her support and guidance in creating and supporting the clerkship. In addition, we thank the interprofessional education faculty for their dedicated involvement in teaching, including Stephanie Saunders, Lindsay Lefers, Jessica Rawlins, Lindsay Brennan, Angela Viani, Eric Charette, Nicole O’Neil, Susan Nathan, Jordana Meyerson, Shivani Jindal, Wei Shen, Amy Hanson, Gilda Cain, and Kate Hinrichs.

*This article has been corrected to include a missing author.

Case Presentation. A 63-year-old male with well-controlled HIV (CD4 count 757, undetectable viral load), epilepsy, and hypertension presented to the VA Boston Healthcare System (VABHS) emergency department with 1 week of bilateral leg swelling and exertional shortness of breath. He reported having no fever, cough, chest pain, pain with inspiration and orthopnea. There was no personal or family history of pulmonary embolism. He reported weight gain but was unable to quantify how much. He also reported flare up of chronic knee pain, without swelling for which he had taken up to 4 tablets of naproxen daily for several weeks. His physical examination was notable for a heart rate of 105 beats per minute and bilateral pitting edema to his knees. Laboratory testing revealed a creatinine level of 2.5 mg/dL, which was increased from a baseline of 1.0 mg/dL (Table 1), and a urine protein-to-creatinine ratio of 7.8 mg/mg (Table 2). A renal ultrasound showed normal-sized kidneys without hydronephrosis or obstructing renal calculi. The patient was admitted for further workup of his dyspnea and acute kidney injury.

► Jonathan Li, MD, Chief Medical Resident, VABHS and Beth Israel Deaconess Medical Center (BIDMC). Dr. William, based on the degree of proteinuria and edema, a diagnosis of nephrotic syndrome was made. How is nephrotic syndrome defined, and how is it distinguished from glomerulonephritis?

► Jeffrey William, MD, Nephrologist, BIDMC, Assistant Professor of Medicine, Harvard Medical School. The pathophysiology of nephrotic disease and glomerulonephritis are quite distinct, resulting in symptoms and systemic manifestations that only slightly overlap. Glomerulonephritis is characterized by inflammation of the endothelial cells of the trilayered glomerular capillary, with a resulting active urine sediment with red blood cells, white blood cells, and casts. Nephrotic syndrome mostly affects the visceral epithelial cells of the glomerular capillary, commonly referred to as podocytes, and hence, the urine sediment in nephrotic disease is often inactive. Patients with nephrotic syndrome have nephrotic-range proteinuria (excretion of > 3.5 g per 24 h or a spot urine protein-creatinine ratio > 3.5 g in the steady state) and both hypoalbuminemia (< 3 g/dL) and peripheral edema. Lipiduria and hyperlipidemia are common findings in nephrotic syndrome but are not required for a clinical diagnosis.¹ In contrast, glomerulonephritis is defined by a constellation of findings that include renal insufficiency (often indicated by an elevation in blood urea nitrogen and creatinine), hypertension, hematuria, and subnephrotic range proteinuria. In practice, patients may fulfill criteria of both nephrotic and nephritic syndromes, but the preponderance of clinical evidence often points one way or the other. In this case, nephrotic syndrome was diagnosed based on the urine protein-to-creatinine ratio of 7.8 mg/mg, hypoalbuminemia, and edema.

► Dr. Li. What would be your first-line workup for evaluation of the etiology of this patient’s nephrotic syndrome?

► Dr. William. Rather than memorizing a list of etiologies of nephrotic syndrome, it is essential to consider the pathophysiology of heavy proteinuria. Though the glomerular filtration barrier is extremely complex and defects in any component can cause proteinuria, disruption of the podocyte is often involved. Common disease processes that chiefly target the podocyte include minimal change disease, primary focal and segmental glomerulosclerosis (FSGS), and membranous nephropathy, all by differing mechanisms. Minimal change disease and idiopathic/primary FSGS are increasingly thought to be at differing points on a spectrum of the same disease.² Secondary FSGS, on the other hand, is a progressive disease, commonly resulting from longstanding hypertension, diabetes mellitus, and obesity in adults. Membranous nephropathy can also be either primary or secondary. Primary membranous nephropathy is chiefly caused by a circulating IgG4 antibody to the podocyte membrane antigen PLA2R (M-type phospholipase A2 receptor), whereas secondary membranous nephropathy can be caused by a variety of systemic etiologies, including autoimmune disease (eg, systemic lupus erythematosus), certain malignancies, chronic infections (eg, hepatitis B and C), and many medications, including nonsteroidal anti-inflammatory drugs (NSAIDs).^3-5 Paraprotein deposition diseases can also cause glomerular damage leading to nephrotic-range proteinuria.

Given these potential diagnoses, a careful history should be taken to assess exposures and recent medication use. Urine sediment evaluation is essential in the evaluation of nephrotic syndrome to determine if there is an underlying nephritic process. Select serologies may be sent to look for autoimmune disease, such as systemic lupus erythematosus and common viral exposures like hepatitis B or C. Serum and urine protein electrophoreses would be appropriate initial tests of suspected paraprotein-related diseases. Other serologies, such as antineutrophil cytoplasmic antibodies or antiglomerular basement membrane antibodies, would not necessarily be indicated here given the lack of hematuria and presence of nephrotic-range proteinuria.

► Dr. Li. The initial evaluation was notable for an erythrocyte sedimentation rate > 120 (mm/h) and a weakly positive antinuclear antibody (ANA) titer of 1:40. The remainder of his initial workup did not reveal an etiology for his nephrotic syndrome (Table 3).

Dr. William, is there a role for starting urgent empiric steroids in nephrotic syndrome while workup is ongoing? If so, do the severity of proteinuria and/or symptoms play a role or is this determination based on something else?

► Dr. William. Edema is a primary symptom of nephrotic syndrome and can often be managed with diuretics alone. If a clear medication-mediated cause is suspected, discontinuation of this agent may result in spontaneous improvement without steroid treatment. However,in cases where an etiology is unclear and there are serious thrombotic complications requiring anticoagulation, and a renal biopsy is deemed to be too risky, then empiric steroid therapy may be necessary. Children with new-onset nephrotic syndrome are presumed to have minimal change disease, given its prevalence in this patient population, and are often given empiric steroids without obtaining a renal biopsy. However, in the adult population, a renal biopsy can typically be performed quickly and safely, with pathology results interpreted within days. In this patient, since a diagnosis was unclear and there was no contraindication to renal biopsy, a biopsy should be obtained before consideration of steroids.

► Dr. Li. Steroids were deferred in anticipation of renal biopsy, which showed stage I membranous nephropathy, suggestive of membranous lupus nephritis Class V. The deposits were strongly reactive for immunoglobuline G (IgG), IgA, and complement 1q (C1q), showed co-dominant staining for IgG1, IgG2, and IgG3, and were weakly positive for the PLA2 receptor. Focal intimal arteritis in a small interlobular vessel was seen.

Dr. William, the pathology returned suggestive of lupus nephritis. Does the overall clinical picture fit with lupus nephritis?

► Dr. William. Given the history and a rather low ANA, the diagnosis of lupus nephritis seems unlikely. The lack of IgG4 and PLA2R staining in the biopsy suggests that this membranous pattern on the biopsy is likely to be secondary to a systemic etiology, but further investigation should be pursued.

► Dr. Li. The patient was discharged after the biopsy with a planned outpatient nephrology follow-up to discuss results and treatment. He was prescribed an oral diuretic, and his symptoms improved. Several days after discharge, he developed blurry vision and was evaluated in the Ophthalmology clinic. On fundoscopy, he was found to have acute papillitis, a form of optic neuritis. As part of initial evaluation of infectious etiologies of papillitis, ophthalmology recommended testing for syphilis.

Dr. Strymish, when we are considering secondary syphilis, what is the recommended approach to diagnostic testing?

► Judith Strymish, MD, Infectious Diseases, BIDMC, Assistant Professor of Medicine, Harvard Medical School. The diagnosis of syphilis is usually made through serologic testing of blood specimens. Methods that detect the spirochete directly like dark-field smears are not readily available. Serologic tests include treponemal tests (eg, Treponema pallidum particle agglutination assay [TPPA]) and nontreponemal tests (eg, rapid plasma reagin [RPR]). One needs a confirmatory test because either test is associated with false positives. Either test can be done first. Most laboratories, including those at VABHS are now performing treponemal tests first as these have become more cost-effective.⁶ The TPPA treponemal test was found to have a lower false negative rate in primary syphilis compared with that of nontreponemal tests.⁷ Nontreponemal tests can be followed for response to therapy. If a patient has a history of treated syphilis, a nontreponemal test should be sent, since the treponemal test will remain positive for life.

If there is clinical concern for neurosyphilis, cerebrospinal fluid fluorescent (CSF) treponemal antibody needs to be sampled and sent for the nontreponemal venereal disease research laboratory (VDRL) test. The VDRL is highly specific for neurosyphilis but not as sensitive. Cerebrospinal fluid fluorescent treponemal antibody (CSF FTA) may also be sent; it is very sensitive but not very specific for neurosyphilis.

► Dr. Li. An RPR returned positive at 1:512 (was negative 14 months prior on a routine screening test), with positive reflex TPPA (Table 4). A diagnosis of secondary syphilis was made. Dr. Strymish, at this point, what additional testing and treatment is necessary?

► Dr. Strymish. With papillitis and a very high RPR, we need to assume that he has ophthalmic syphilis. This can occur in any stage of syphilis, but his eye findings and high RPR are consistent with secondary syphilis. Ophthalmic syphilis has been on the upswing, even more than is expected with recent increases in syphilis cases.⁸ Ophthalmic syphilis is considered a form of neurosyphilis. A lumbar puncture and treatment for neurosyphilis is recommended.^9,10

► Dr. Li. A lumbar puncture was performed, and his CSF was VDRL positive. This confirmed a diagnosis of neurosyphilis (Table 4). The patient was treated for neurosyphilis with IV penicillin. The patient shared that he had episodes of unprotected oral sexual activity within the past year and approximately 1 year ago, he came in close contact (but no sexual activity) with a person who had a rash consistent with syphilis.Dr. William, syphilis would be a potential unifying diagnosis of his renal and ophthalmologic manifestations. Is syphilis known to cause membranous nephropathy?

► Dr. William. Though it is uncommon, the nephrotic syndrome is a well-described complication of secondary syphilis.^11,12 Syphilis has been shown to cause nephrotic syndrome in a variety of ways. Case reports abound linking syphilis to minimal change disease and other glomerular diseases.^13,14 A case report from 1993 shows a membranous pattern of glomerular disease similar to this case.¹⁵ As a form of secondary membranous nephropathy, the immunofluorescence pattern can demonstrate staining similar to the “full house” seen in lupus nephritis (IgA, IgM, and C1q, in addition to IgG and C3).¹⁶ This explains the initial interpretation of this patient’s biopsy, as lupus nephritis would be a much more common etiology of secondary membranous nephropathy than is acute syphilis with this immunofluorescence pattern. However, the data in this case are highly suggestive of a causal relationship between secondary syphilis and membranous nephropathy.

► Dr. Li. Dr. Strymish, how should this patient be screened for syphilis reinfection, and at what intervals would you recommend?

► Dr. Strymish. He will need follow-up testing to make sure that his syphilis is effectively treated. If CSF pleocytosis was present initially, a CSF examination should be repeated every 6 months until the cell count is normal. He will also need follow-up for normalization of his RPR. Persons with HIV infection and primary or secondary syphilis should be evaluated clinically and serologically for treatment failure at 3, 6, 9, 12, and 24 months after therapy according to US Centers for Disease Control and Prevention guidelines.⁹

His treponemal test for syphilis will likely stay positive for life. His RPR should decrease significantly with effective treatment. It makes sense to screen with RPR alone as long as he continues to have risk factors for acquiring syphilis. Routine syphilis testing is recommended for pregnant women, sexually active men who have sex with men, sexually active persons with HIV, and persons taking PrEP (pre-exposure prophylaxis) for HIV prevention. He should be screened at least yearly for syphilis.

► Dr. Li. Over the next several months, the patient’s creatinine normalized and his proteinuria resolved. His vision recovered, and he has had no further ophthalmologic complications.

Dr. William, what is his long-term renal prognosis? Do you expect that his acute episode of membranous nephropathy will have permanent effects on his renal function?

► Dr. William. His rapid response to therapy for neurosyphilis provides evidence for this etiology of his renal dysfunction and glomerulonephritis. His long-term prognosis is quite good if the syphilis is the only reason for him to have renal disease. The renal damage is often reversible in these cases. However, given his prior extensive NSAID exposure and history of hypertension, he may be at higher risk for chronic kidney disease than an otherwise healthy patient, especially after an episode of acute kidney injury. Therefore, his renal function should continue to be monitored as an outpatient.

Acknowledgments

The authors thank this veteran for sharing his story and allowing us to learn from this unusual case for the benefit of our future patients.

*This article has been corrected to include a missing author.

Case Presentation. A 63-year-old male with well-controlled HIV (CD4 count 757, undetectable viral load), epilepsy, and hypertension presented to the VA Boston Healthcare System (VABHS) emergency department with 1 week of bilateral leg swelling and exertional shortness of breath. He reported having no fever, cough, chest pain, pain with inspiration and orthopnea. There was no personal or family history of pulmonary embolism. He reported weight gain but was unable to quantify how much. He also reported flare up of chronic knee pain, without swelling for which he had taken up to 4 tablets of naproxen daily for several weeks. His physical examination was notable for a heart rate of 105 beats per minute and bilateral pitting edema to his knees. Laboratory testing revealed a creatinine level of 2.5 mg/dL, which was increased from a baseline of 1.0 mg/dL (Table 1), and a urine protein-to-creatinine ratio of 7.8 mg/mg (Table 2). A renal ultrasound showed normal-sized kidneys without hydronephrosis or obstructing renal calculi. The patient was admitted for further workup of his dyspnea and acute kidney injury.

► Jonathan Li, MD, Chief Medical Resident, VABHS and Beth Israel Deaconess Medical Center (BIDMC). Dr. William, based on the degree of proteinuria and edema, a diagnosis of nephrotic syndrome was made. How is nephrotic syndrome defined, and how is it distinguished from glomerulonephritis?

► Jeffrey William, MD, Nephrologist, BIDMC, Assistant Professor of Medicine, Harvard Medical School. The pathophysiology of nephrotic disease and glomerulonephritis are quite distinct, resulting in symptoms and systemic manifestations that only slightly overlap. Glomerulonephritis is characterized by inflammation of the endothelial cells of the trilayered glomerular capillary, with a resulting active urine sediment with red blood cells, white blood cells, and casts. Nephrotic syndrome mostly affects the visceral epithelial cells of the glomerular capillary, commonly referred to as podocytes, and hence, the urine sediment in nephrotic disease is often inactive. Patients with nephrotic syndrome have nephrotic-range proteinuria (excretion of > 3.5 g per 24 h or a spot urine protein-creatinine ratio > 3.5 g in the steady state) and both hypoalbuminemia (< 3 g/dL) and peripheral edema. Lipiduria and hyperlipidemia are common findings in nephrotic syndrome but are not required for a clinical diagnosis.¹ In contrast, glomerulonephritis is defined by a constellation of findings that include renal insufficiency (often indicated by an elevation in blood urea nitrogen and creatinine), hypertension, hematuria, and subnephrotic range proteinuria. In practice, patients may fulfill criteria of both nephrotic and nephritic syndromes, but the preponderance of clinical evidence often points one way or the other. In this case, nephrotic syndrome was diagnosed based on the urine protein-to-creatinine ratio of 7.8 mg/mg, hypoalbuminemia, and edema.

► Dr. Li. What would be your first-line workup for evaluation of the etiology of this patient’s nephrotic syndrome?

► Dr. William. Rather than memorizing a list of etiologies of nephrotic syndrome, it is essential to consider the pathophysiology of heavy proteinuria. Though the glomerular filtration barrier is extremely complex and defects in any component can cause proteinuria, disruption of the podocyte is often involved. Common disease processes that chiefly target the podocyte include minimal change disease, primary focal and segmental glomerulosclerosis (FSGS), and membranous nephropathy, all by differing mechanisms. Minimal change disease and idiopathic/primary FSGS are increasingly thought to be at differing points on a spectrum of the same disease.² Secondary FSGS, on the other hand, is a progressive disease, commonly resulting from longstanding hypertension, diabetes mellitus, and obesity in adults. Membranous nephropathy can also be either primary or secondary. Primary membranous nephropathy is chiefly caused by a circulating IgG4 antibody to the podocyte membrane antigen PLA2R (M-type phospholipase A2 receptor), whereas secondary membranous nephropathy can be caused by a variety of systemic etiologies, including autoimmune disease (eg, systemic lupus erythematosus), certain malignancies, chronic infections (eg, hepatitis B and C), and many medications, including nonsteroidal anti-inflammatory drugs (NSAIDs).^3-5 Paraprotein deposition diseases can also cause glomerular damage leading to nephrotic-range proteinuria.

Given these potential diagnoses, a careful history should be taken to assess exposures and recent medication use. Urine sediment evaluation is essential in the evaluation of nephrotic syndrome to determine if there is an underlying nephritic process. Select serologies may be sent to look for autoimmune disease, such as systemic lupus erythematosus and common viral exposures like hepatitis B or C. Serum and urine protein electrophoreses would be appropriate initial tests of suspected paraprotein-related diseases. Other serologies, such as antineutrophil cytoplasmic antibodies or antiglomerular basement membrane antibodies, would not necessarily be indicated here given the lack of hematuria and presence of nephrotic-range proteinuria.

► Dr. Li. The initial evaluation was notable for an erythrocyte sedimentation rate > 120 (mm/h) and a weakly positive antinuclear antibody (ANA) titer of 1:40. The remainder of his initial workup did not reveal an etiology for his nephrotic syndrome (Table 3).

Dr. William, is there a role for starting urgent empiric steroids in nephrotic syndrome while workup is ongoing? If so, do the severity of proteinuria and/or symptoms play a role or is this determination based on something else?

► Dr. William. Edema is a primary symptom of nephrotic syndrome and can often be managed with diuretics alone. If a clear medication-mediated cause is suspected, discontinuation of this agent may result in spontaneous improvement without steroid treatment. However,in cases where an etiology is unclear and there are serious thrombotic complications requiring anticoagulation, and a renal biopsy is deemed to be too risky, then empiric steroid therapy may be necessary. Children with new-onset nephrotic syndrome are presumed to have minimal change disease, given its prevalence in this patient population, and are often given empiric steroids without obtaining a renal biopsy. However, in the adult population, a renal biopsy can typically be performed quickly and safely, with pathology results interpreted within days. In this patient, since a diagnosis was unclear and there was no contraindication to renal biopsy, a biopsy should be obtained before consideration of steroids.

► Dr. Li. Steroids were deferred in anticipation of renal biopsy, which showed stage I membranous nephropathy, suggestive of membranous lupus nephritis Class V. The deposits were strongly reactive for immunoglobuline G (IgG), IgA, and complement 1q (C1q), showed co-dominant staining for IgG1, IgG2, and IgG3, and were weakly positive for the PLA2 receptor. Focal intimal arteritis in a small interlobular vessel was seen.

Dr. William, the pathology returned suggestive of lupus nephritis. Does the overall clinical picture fit with lupus nephritis?

► Dr. William. Given the history and a rather low ANA, the diagnosis of lupus nephritis seems unlikely. The lack of IgG4 and PLA2R staining in the biopsy suggests that this membranous pattern on the biopsy is likely to be secondary to a systemic etiology, but further investigation should be pursued.

► Dr. Li. The patient was discharged after the biopsy with a planned outpatient nephrology follow-up to discuss results and treatment. He was prescribed an oral diuretic, and his symptoms improved. Several days after discharge, he developed blurry vision and was evaluated in the Ophthalmology clinic. On fundoscopy, he was found to have acute papillitis, a form of optic neuritis. As part of initial evaluation of infectious etiologies of papillitis, ophthalmology recommended testing for syphilis.

Dr. Strymish, when we are considering secondary syphilis, what is the recommended approach to diagnostic testing?

► Judith Strymish, MD, Infectious Diseases, BIDMC, Assistant Professor of Medicine, Harvard Medical School. The diagnosis of syphilis is usually made through serologic testing of blood specimens. Methods that detect the spirochete directly like dark-field smears are not readily available. Serologic tests include treponemal tests (eg, Treponema pallidum particle agglutination assay [TPPA]) and nontreponemal tests (eg, rapid plasma reagin [RPR]). One needs a confirmatory test because either test is associated with false positives. Either test can be done first. Most laboratories, including those at VABHS are now performing treponemal tests first as these have become more cost-effective.⁶ The TPPA treponemal test was found to have a lower false negative rate in primary syphilis compared with that of nontreponemal tests.⁷ Nontreponemal tests can be followed for response to therapy. If a patient has a history of treated syphilis, a nontreponemal test should be sent, since the treponemal test will remain positive for life.

If there is clinical concern for neurosyphilis, cerebrospinal fluid fluorescent (CSF) treponemal antibody needs to be sampled and sent for the nontreponemal venereal disease research laboratory (VDRL) test. The VDRL is highly specific for neurosyphilis but not as sensitive. Cerebrospinal fluid fluorescent treponemal antibody (CSF FTA) may also be sent; it is very sensitive but not very specific for neurosyphilis.

► Dr. Li. An RPR returned positive at 1:512 (was negative 14 months prior on a routine screening test), with positive reflex TPPA (Table 4). A diagnosis of secondary syphilis was made. Dr. Strymish, at this point, what additional testing and treatment is necessary?

► Dr. Strymish. With papillitis and a very high RPR, we need to assume that he has ophthalmic syphilis. This can occur in any stage of syphilis, but his eye findings and high RPR are consistent with secondary syphilis. Ophthalmic syphilis has been on the upswing, even more than is expected with recent increases in syphilis cases.⁸ Ophthalmic syphilis is considered a form of neurosyphilis. A lumbar puncture and treatment for neurosyphilis is recommended.^9,10

► Dr. Li. A lumbar puncture was performed, and his CSF was VDRL positive. This confirmed a diagnosis of neurosyphilis (Table 4). The patient was treated for neurosyphilis with IV penicillin. The patient shared that he had episodes of unprotected oral sexual activity within the past year and approximately 1 year ago, he came in close contact (but no sexual activity) with a person who had a rash consistent with syphilis.Dr. William, syphilis would be a potential unifying diagnosis of his renal and ophthalmologic manifestations. Is syphilis known to cause membranous nephropathy?

► Dr. William. Though it is uncommon, the nephrotic syndrome is a well-described complication of secondary syphilis.^11,12 Syphilis has been shown to cause nephrotic syndrome in a variety of ways. Case reports abound linking syphilis to minimal change disease and other glomerular diseases.^13,14 A case report from 1993 shows a membranous pattern of glomerular disease similar to this case.¹⁵ As a form of secondary membranous nephropathy, the immunofluorescence pattern can demonstrate staining similar to the “full house” seen in lupus nephritis (IgA, IgM, and C1q, in addition to IgG and C3).¹⁶ This explains the initial interpretation of this patient’s biopsy, as lupus nephritis would be a much more common etiology of secondary membranous nephropathy than is acute syphilis with this immunofluorescence pattern. However, the data in this case are highly suggestive of a causal relationship between secondary syphilis and membranous nephropathy.

► Dr. Li. Dr. Strymish, how should this patient be screened for syphilis reinfection, and at what intervals would you recommend?

► Dr. Strymish. He will need follow-up testing to make sure that his syphilis is effectively treated. If CSF pleocytosis was present initially, a CSF examination should be repeated every 6 months until the cell count is normal. He will also need follow-up for normalization of his RPR. Persons with HIV infection and primary or secondary syphilis should be evaluated clinically and serologically for treatment failure at 3, 6, 9, 12, and 24 months after therapy according to US Centers for Disease Control and Prevention guidelines.⁹

His treponemal test for syphilis will likely stay positive for life. His RPR should decrease significantly with effective treatment. It makes sense to screen with RPR alone as long as he continues to have risk factors for acquiring syphilis. Routine syphilis testing is recommended for pregnant women, sexually active men who have sex with men, sexually active persons with HIV, and persons taking PrEP (pre-exposure prophylaxis) for HIV prevention. He should be screened at least yearly for syphilis.

► Dr. Li. Over the next several months, the patient’s creatinine normalized and his proteinuria resolved. His vision recovered, and he has had no further ophthalmologic complications.

Dr. William, what is his long-term renal prognosis? Do you expect that his acute episode of membranous nephropathy will have permanent effects on his renal function?

► Dr. William. His rapid response to therapy for neurosyphilis provides evidence for this etiology of his renal dysfunction and glomerulonephritis. His long-term prognosis is quite good if the syphilis is the only reason for him to have renal disease. The renal damage is often reversible in these cases. However, given his prior extensive NSAID exposure and history of hypertension, he may be at higher risk for chronic kidney disease than an otherwise healthy patient, especially after an episode of acute kidney injury. Therefore, his renal function should continue to be monitored as an outpatient.

Acknowledgments

The authors thank this veteran for sharing his story and allowing us to learn from this unusual case for the benefit of our future patients.

*This article has been corrected to include a missing author.

Case Presentation. A 63-year-old male with well-controlled HIV (CD4 count 757, undetectable viral load), epilepsy, and hypertension presented to the VA Boston Healthcare System (VABHS) emergency department with 1 week of bilateral leg swelling and exertional shortness of breath. He reported having no fever, cough, chest pain, pain with inspiration and orthopnea. There was no personal or family history of pulmonary embolism. He reported weight gain but was unable to quantify how much. He also reported flare up of chronic knee pain, without swelling for which he had taken up to 4 tablets of naproxen daily for several weeks. His physical examination was notable for a heart rate of 105 beats per minute and bilateral pitting edema to his knees. Laboratory testing revealed a creatinine level of 2.5 mg/dL, which was increased from a baseline of 1.0 mg/dL (Table 1), and a urine protein-to-creatinine ratio of 7.8 mg/mg (Table 2). A renal ultrasound showed normal-sized kidneys without hydronephrosis or obstructing renal calculi. The patient was admitted for further workup of his dyspnea and acute kidney injury.

► Jonathan Li, MD, Chief Medical Resident, VABHS and Beth Israel Deaconess Medical Center (BIDMC). Dr. William, based on the degree of proteinuria and edema, a diagnosis of nephrotic syndrome was made. How is nephrotic syndrome defined, and how is it distinguished from glomerulonephritis?

► Jeffrey William, MD, Nephrologist, BIDMC, Assistant Professor of Medicine, Harvard Medical School. The pathophysiology of nephrotic disease and glomerulonephritis are quite distinct, resulting in symptoms and systemic manifestations that only slightly overlap. Glomerulonephritis is characterized by inflammation of the endothelial cells of the trilayered glomerular capillary, with a resulting active urine sediment with red blood cells, white blood cells, and casts. Nephrotic syndrome mostly affects the visceral epithelial cells of the glomerular capillary, commonly referred to as podocytes, and hence, the urine sediment in nephrotic disease is often inactive. Patients with nephrotic syndrome have nephrotic-range proteinuria (excretion of > 3.5 g per 24 h or a spot urine protein-creatinine ratio > 3.5 g in the steady state) and both hypoalbuminemia (< 3 g/dL) and peripheral edema. Lipiduria and hyperlipidemia are common findings in nephrotic syndrome but are not required for a clinical diagnosis.¹ In contrast, glomerulonephritis is defined by a constellation of findings that include renal insufficiency (often indicated by an elevation in blood urea nitrogen and creatinine), hypertension, hematuria, and subnephrotic range proteinuria. In practice, patients may fulfill criteria of both nephrotic and nephritic syndromes, but the preponderance of clinical evidence often points one way or the other. In this case, nephrotic syndrome was diagnosed based on the urine protein-to-creatinine ratio of 7.8 mg/mg, hypoalbuminemia, and edema.

► Dr. Li. What would be your first-line workup for evaluation of the etiology of this patient’s nephrotic syndrome?

► Dr. William. Rather than memorizing a list of etiologies of nephrotic syndrome, it is essential to consider the pathophysiology of heavy proteinuria. Though the glomerular filtration barrier is extremely complex and defects in any component can cause proteinuria, disruption of the podocyte is often involved. Common disease processes that chiefly target the podocyte include minimal change disease, primary focal and segmental glomerulosclerosis (FSGS), and membranous nephropathy, all by differing mechanisms. Minimal change disease and idiopathic/primary FSGS are increasingly thought to be at differing points on a spectrum of the same disease.² Secondary FSGS, on the other hand, is a progressive disease, commonly resulting from longstanding hypertension, diabetes mellitus, and obesity in adults. Membranous nephropathy can also be either primary or secondary. Primary membranous nephropathy is chiefly caused by a circulating IgG4 antibody to the podocyte membrane antigen PLA2R (M-type phospholipase A2 receptor), whereas secondary membranous nephropathy can be caused by a variety of systemic etiologies, including autoimmune disease (eg, systemic lupus erythematosus), certain malignancies, chronic infections (eg, hepatitis B and C), and many medications, including nonsteroidal anti-inflammatory drugs (NSAIDs).^3-5 Paraprotein deposition diseases can also cause glomerular damage leading to nephrotic-range proteinuria.

Given these potential diagnoses, a careful history should be taken to assess exposures and recent medication use. Urine sediment evaluation is essential in the evaluation of nephrotic syndrome to determine if there is an underlying nephritic process. Select serologies may be sent to look for autoimmune disease, such as systemic lupus erythematosus and common viral exposures like hepatitis B or C. Serum and urine protein electrophoreses would be appropriate initial tests of suspected paraprotein-related diseases. Other serologies, such as antineutrophil cytoplasmic antibodies or antiglomerular basement membrane antibodies, would not necessarily be indicated here given the lack of hematuria and presence of nephrotic-range proteinuria.

► Dr. Li. The initial evaluation was notable for an erythrocyte sedimentation rate > 120 (mm/h) and a weakly positive antinuclear antibody (ANA) titer of 1:40. The remainder of his initial workup did not reveal an etiology for his nephrotic syndrome (Table 3).

Dr. William, is there a role for starting urgent empiric steroids in nephrotic syndrome while workup is ongoing? If so, do the severity of proteinuria and/or symptoms play a role or is this determination based on something else?

► Dr. William. Edema is a primary symptom of nephrotic syndrome and can often be managed with diuretics alone. If a clear medication-mediated cause is suspected, discontinuation of this agent may result in spontaneous improvement without steroid treatment. However,in cases where an etiology is unclear and there are serious thrombotic complications requiring anticoagulation, and a renal biopsy is deemed to be too risky, then empiric steroid therapy may be necessary. Children with new-onset nephrotic syndrome are presumed to have minimal change disease, given its prevalence in this patient population, and are often given empiric steroids without obtaining a renal biopsy. However, in the adult population, a renal biopsy can typically be performed quickly and safely, with pathology results interpreted within days. In this patient, since a diagnosis was unclear and there was no contraindication to renal biopsy, a biopsy should be obtained before consideration of steroids.

► Dr. Li. Steroids were deferred in anticipation of renal biopsy, which showed stage I membranous nephropathy, suggestive of membranous lupus nephritis Class V. The deposits were strongly reactive for immunoglobuline G (IgG), IgA, and complement 1q (C1q), showed co-dominant staining for IgG1, IgG2, and IgG3, and were weakly positive for the PLA2 receptor. Focal intimal arteritis in a small interlobular vessel was seen.

Dr. William, the pathology returned suggestive of lupus nephritis. Does the overall clinical picture fit with lupus nephritis?

► Dr. William. Given the history and a rather low ANA, the diagnosis of lupus nephritis seems unlikely. The lack of IgG4 and PLA2R staining in the biopsy suggests that this membranous pattern on the biopsy is likely to be secondary to a systemic etiology, but further investigation should be pursued.

► Dr. Li. The patient was discharged after the biopsy with a planned outpatient nephrology follow-up to discuss results and treatment. He was prescribed an oral diuretic, and his symptoms improved. Several days after discharge, he developed blurry vision and was evaluated in the Ophthalmology clinic. On fundoscopy, he was found to have acute papillitis, a form of optic neuritis. As part of initial evaluation of infectious etiologies of papillitis, ophthalmology recommended testing for syphilis.

Dr. Strymish, when we are considering secondary syphilis, what is the recommended approach to diagnostic testing?

► Judith Strymish, MD, Infectious Diseases, BIDMC, Assistant Professor of Medicine, Harvard Medical School. The diagnosis of syphilis is usually made through serologic testing of blood specimens. Methods that detect the spirochete directly like dark-field smears are not readily available. Serologic tests include treponemal tests (eg, Treponema pallidum particle agglutination assay [TPPA]) and nontreponemal tests (eg, rapid plasma reagin [RPR]). One needs a confirmatory test because either test is associated with false positives. Either test can be done first. Most laboratories, including those at VABHS are now performing treponemal tests first as these have become more cost-effective.⁶ The TPPA treponemal test was found to have a lower false negative rate in primary syphilis compared with that of nontreponemal tests.⁷ Nontreponemal tests can be followed for response to therapy. If a patient has a history of treated syphilis, a nontreponemal test should be sent, since the treponemal test will remain positive for life.

If there is clinical concern for neurosyphilis, cerebrospinal fluid fluorescent (CSF) treponemal antibody needs to be sampled and sent for the nontreponemal venereal disease research laboratory (VDRL) test. The VDRL is highly specific for neurosyphilis but not as sensitive. Cerebrospinal fluid fluorescent treponemal antibody (CSF FTA) may also be sent; it is very sensitive but not very specific for neurosyphilis.

► Dr. Li. An RPR returned positive at 1:512 (was negative 14 months prior on a routine screening test), with positive reflex TPPA (Table 4). A diagnosis of secondary syphilis was made. Dr. Strymish, at this point, what additional testing and treatment is necessary?

► Dr. Strymish. With papillitis and a very high RPR, we need to assume that he has ophthalmic syphilis. This can occur in any stage of syphilis, but his eye findings and high RPR are consistent with secondary syphilis. Ophthalmic syphilis has been on the upswing, even more than is expected with recent increases in syphilis cases.⁸ Ophthalmic syphilis is considered a form of neurosyphilis. A lumbar puncture and treatment for neurosyphilis is recommended.^9,10

► Dr. Li. A lumbar puncture was performed, and his CSF was VDRL positive. This confirmed a diagnosis of neurosyphilis (Table 4). The patient was treated for neurosyphilis with IV penicillin. The patient shared that he had episodes of unprotected oral sexual activity within the past year and approximately 1 year ago, he came in close contact (but no sexual activity) with a person who had a rash consistent with syphilis.Dr. William, syphilis would be a potential unifying diagnosis of his renal and ophthalmologic manifestations. Is syphilis known to cause membranous nephropathy?

► Dr. William. Though it is uncommon, the nephrotic syndrome is a well-described complication of secondary syphilis.^11,12 Syphilis has been shown to cause nephrotic syndrome in a variety of ways. Case reports abound linking syphilis to minimal change disease and other glomerular diseases.^13,14 A case report from 1993 shows a membranous pattern of glomerular disease similar to this case.¹⁵ As a form of secondary membranous nephropathy, the immunofluorescence pattern can demonstrate staining similar to the “full house” seen in lupus nephritis (IgA, IgM, and C1q, in addition to IgG and C3).¹⁶ This explains the initial interpretation of this patient’s biopsy, as lupus nephritis would be a much more common etiology of secondary membranous nephropathy than is acute syphilis with this immunofluorescence pattern. However, the data in this case are highly suggestive of a causal relationship between secondary syphilis and membranous nephropathy.

► Dr. Li. Dr. Strymish, how should this patient be screened for syphilis reinfection, and at what intervals would you recommend?

► Dr. Strymish. He will need follow-up testing to make sure that his syphilis is effectively treated. If CSF pleocytosis was present initially, a CSF examination should be repeated every 6 months until the cell count is normal. He will also need follow-up for normalization of his RPR. Persons with HIV infection and primary or secondary syphilis should be evaluated clinically and serologically for treatment failure at 3, 6, 9, 12, and 24 months after therapy according to US Centers for Disease Control and Prevention guidelines.⁹

His treponemal test for syphilis will likely stay positive for life. His RPR should decrease significantly with effective treatment. It makes sense to screen with RPR alone as long as he continues to have risk factors for acquiring syphilis. Routine syphilis testing is recommended for pregnant women, sexually active men who have sex with men, sexually active persons with HIV, and persons taking PrEP (pre-exposure prophylaxis) for HIV prevention. He should be screened at least yearly for syphilis.

► Dr. Li. Over the next several months, the patient’s creatinine normalized and his proteinuria resolved. His vision recovered, and he has had no further ophthalmologic complications.

Dr. William, what is his long-term renal prognosis? Do you expect that his acute episode of membranous nephropathy will have permanent effects on his renal function?

► Dr. William. His rapid response to therapy for neurosyphilis provides evidence for this etiology of his renal dysfunction and glomerulonephritis. His long-term prognosis is quite good if the syphilis is the only reason for him to have renal disease. The renal damage is often reversible in these cases. However, given his prior extensive NSAID exposure and history of hypertension, he may be at higher risk for chronic kidney disease than an otherwise healthy patient, especially after an episode of acute kidney injury. Therefore, his renal function should continue to be monitored as an outpatient.

Acknowledgments

The authors thank this veteran for sharing his story and allowing us to learn from this unusual case for the benefit of our future patients.

Chronic pain significantly affects 100 million Americans.^1,2 Pain accounts for $560 to $635 billion in annual financial costs to society, including health care costs and loss of productivity (ie, days missed from work, hours of work lost, and lower wages).^2,3 Although pain prevalence exceeds other chronic diseases, such as diabetes mellitus, cancer, and heart disease, it lacks a sufficient body of evidence-based research and guidelines on the underlying mechanisms, valid methods of assessment, and comparative effectiveness of treatments to effectively implement into clinical practice.^2,4 Prevention and treatment of pain are often delayed, inaccessible, or inadequate.² Primary care providers (PCPs) are most often sought for pain management and treat about 52% of chronic pain patients.^2,3,5 Veterans are especially vulnerable to chronic pain and are at risk for inadequate treatment.²

Background

There is an epidemic of drug abuse and mortality from opioid prescription medication.⁶ In the US, rates of overdose deaths from prescription opioids were 6.1 per 100,000 for men and 4.2 per 100,000 for women in 2017. Opioids were involved in 47,600 overdose deaths in 2017, accounting for 67.8% of all drug overdose deaths.⁷

A large number of patients on long-term opioids have preexisting substance use disorders and/or psychiatric disease, further complicating chronic pain management.^8-10 Prescription opioid use has been the precursor for about 80% of people who are now heroin addicts.¹¹ Iatrogenic addiction from prescription medications isn’t easily captured by standard addiction criteria. Consequently, in patients who are on opioid therapy for prolonged periods, separating complex opioid dependence from addiction is difficult.¹² Improved addiction screening and risk mitigation strategies are needed along with aggressive treatment monitoring to curb the opioid epidemic.

Opioid Management in Primary Care

The majority of opioid medications are prescribed by PCPs, which is magnified in the US Department of Veterans Affairs (VA) health care system due to the high prevalence of service-related injuries.^3,13 The VA is at the forefront of addressing the complexities of opioid addiction through several initiatives.¹⁴ The ability to offer the frequent visits needed to safely manage patients prescribed opioids and the integration of mental health and addiction treatment are often lacking in non-VA primary care clinics. Therefore, a key to solving the opioid crisis is developing these capabilities so they can be delivered within the primary care setting. There is substantial evidence in support of nonopioid alternatives to chronic pain management, including other pharmacologic approaches, exercise, physical therapy, acupuncture, weight loss, smoking cessation, chiropractic care, cognitive behavioral therapy (CBT), and other integrative health modalities.

A 2009 VA directive mandated the development of a comprehensive, integrated, systemwide approach to pain management.¹⁵ The VA Stepped-Care Biopsychosocial Model for Pain Management is dependent on timely access to secondary consultation from pain medicine, behavioral health, physical medicine, and other specialty consultation.¹⁵

History of VHA SCAN-ECHO Model

The Specialty Care Access Network–Extension for Community Health Outcomes (SCAN-ECHO) is a Veterans Health Administration (VHA) adaptation of a program that originated at the University of Mexico.^16,17 The SCAN-ECHO model uses a multisite videoconferencing network to provide specialty care consultations to PCPs and patient aligned care teams (PACTs). During the 60- to 90-minute weekly sessions, case presentations are analyzed in real time so that over time, the PCPs gain knowledge, competency, and confidence in learning how to handle complex chronic conditions.

Since its implementation, the SCAN-ECHO program has been adopted across the VHA in a variety of specialties. One program, the SCAN-ECHO for Pain Management (SCAN-ECHO-PM) was implemented in 7 VHA networks in 31 states, spanning 47 medical centers and 148 community-based outpatient clinics (CBOCs).¹⁸ The SCAN-ECHO-PM program successfully conducted 257 multidisciplinary pain consultations between 2011 and 2013, resulting in increased initiation of nonopioid medications.¹⁸

The aim of this article is to describe the implementation of a multicomponent primary care-based pain clinic with a fully integrated mental health service and addiction service at the North Florida/South Georgia Veterans Health System (NF/SGVHS). A practiced-based intervention of the biopsychosocial model with robust patient engagement has guided the development of the NF/SGVHS pain clinic (Figure 1).^4,19

Pain CLinic

NF/SGVHS comprises the Malcom Randall and Lake City VA medical centers (VAMCs) hospitals, 3 satellite outpatient clinics, and 8 CBOCs. Spanning 33 counties in North Florida and 19 counties in South Georgia, the NF/SGVHS serves more than 140,000 patients. In 2010, the Malcom Randall VAMC established a multidisciplinary primary care pain clinic to manage veterans at high-risk for noncancer chronic pain and addiction. The noncancer pain policy was revised after garnering support from stakeholders who treat chronic pain, including the chiefs of psychiatry, rehabilitation medicine, neurosurgery, psychology, interventional pain, pharmacy, nursing, addiction medicine, and primary care. The clinic is staffed by primary care physicians trained in internal medicine and family medicine and is structured with 1-hour first visits, and 30-minute follow-up visits to allow enough time for comprehensive evaluation while meeting the needs for close follow-up support.

All physicians in the clinic have buprenorphine prescribing credentials to aid in the management of opioid addiction, as some patients feel more comfortable receiving addiction treatment in a primary care setting. The multimodal care model consists of several services that include addiction psychiatrists, interventional pain specialists, pain psychologists, and pain pharmacologists who coordinate the care to the veterans. The addiction psychiatrists offer a full range of services with inpatient residential and outpatient programs. Through recurring meetings with primary care pain clinic staff, the addiction psychiatrists are available to discuss use of buprenorphine and arrange follow-up for patients with complex pain addiction. There is ongoing collaboration to develop the best care plan that meets the patient’s needs for chronic pain, addiction, and/or mental health issues. The interventional pain service has 3 fellowship-trained pain care providers who deliver comprehensive evaluation, pharmacologic recommendations, and a full range of interventional and complementary therapies with an emphasis on objective functional improvement. Pain care providers offer alternatives to patients who are being weaned from opioids and support the multidisciplinary patient engagement model.

The pain psychology program, established in 2011, delivers CBT to 5 onsite locations and 5 telehealth locations. The service includes an advanced CBT program and a couples CBT program. The pharmacy pain fellowship program provides staff for an outpatient e-consult pain management service and an inpatient pharmacy consult service. Harnessing pain specialty pharmacists, the pharmacy service addresses pharmacokinetic issues, urine drug screen (UDS) results, opioid tapering and discharge planning for pain, addiction and mental health needs. The NF/SGVHS Primary Care Pain Clinic was established to support PCPs who did not feel comfortable managing chronic pain patients. These patients were typically on high-dose opioid therapy (> 100-mg morphine equivalent daily doses [MEDDs]); patients with a history of opioid addiction; patients with an addiction to opioids combined with benzodiazepines; and patients with comorbid medical issues (eg, sleep apnea), which complicated their management. The process of addressing opioid safety in these complex pain patients can be labor intensive and generally cannot be accomplished in a brief visit in a primary care setting where many other medical problems often need to be addressed.

Most patients on high-dose opioids are fearful of any changes in their medications. The difficult conversation regarding opioid safety is a lengthy one and frequently will occur over multiple visits. In addition, safely tapering opioids requires frequent follow-up to provide psychological support and to address withdrawal and mental health issues that may arise. As opioids are tapered, the clinic reinforces improved pain care through a multimodal biopsychosocial model. All veterans receiving pain care outside the VA are monitored annually to assure they are receiving evidence-based pain care as defined by the biopsychosocial model.

Education

Since 2011, the NF/SGVHS SCAN-ECHO pain and addiction educational forum has created > 50 hours of approved annual continuing medical education (CME) on pain management and addiction for PCPs. Initially, the 1-hour weekly educational audioconferences presented a pain management case along with related topics and involved specialists from interventional pain, physical therapy, psychiatry, nursing, neurology, and psychology departments. In 2013, in conjunction with the VA SCAN-ECHO program of Hunter Holmes McGuire VAMC in Richmond, Virginia, and Walter Reed National Military Medical Center in Bethesda, Maryland, the audioconference was expanded to 2 days each week with additional topics on addiction management. Residency and fellowship rotations were developed that specifically targeted fellows from psychiatry, pharmacology, and interventional pain departments.

Currently, an 8-session pain school is delivered onsite and at 7 telehealth locations. The school is a collaborative effort involving interventional pain, psychology, pharmacy, nutrition, and the primary care pain clinic staff. As the cornerstone of the program, the pain school stresses the biopsychosocial patient engagement model.

Program Evaluation

The VA is equipped with multiple telehealth service networks that allow for the delivery of programs, such as the pain school, a pain psychology program, and a yoga program, onsite or offsite. The VA Computerized Patient Record System (CPRS) manages electronic health records, allowing for rapid chart review and e-consults. The NF/SGVHS Pain Management Program provides about 1500 e-consults yearly. The CPRS includes templates with pain metrics to help PCPs deliver pain care more efficiently and evaluate performance measures. This system also allows for the capture of data to track improvements in the care of the veterans served.

From 2012 to 2017, more than 5000 NF/SGVHS patients were weaned from opioids. Overall, there was an 87% reduction in patients receiving opioids ( ≥ 100-mg MEDDs) within the NF/SGVHS, which is significantly more than the 49% seen nationally across the VHA (Figure 2). Percent reduction was calculated by taking the difference in number of patients receiving opioids in 2012 and 2017, dividing by the number of patients receiving opioids in 2012 and multiplying by 100. The largest proportion of opioid dose reductions for NF/SGVHS and VHA patients, respectively, were seen in 300-mg to 399-mg MEDDs (95% vs 67%, respectively); followed by ≥ 400-mg MEDDs (94% vs 71%, respectively); 200-mg to 299-mg MEDDs (91% vs 58%, respectively); and 100-mg to 199-mg MEDDs (84% vs 40%, respectively). When examining NF/SGVHS trends over time, there has been a consistent decline in patients prescribed opioids (18 223 in 2012 compared with 12 877 in 2017) with similar trends in benzodiazepine-opioid combination therapy (2694 in 2012 compared with 833 in 2017) (Figure 3).

Similar declines are seen when patients are stratified by the MEDD (Figure 4). From 2012 to 2017, 92% of the patients were successfully tapered off doses ≥ 400-mg MEDD (2012, n = 72; 2017, n = 6), and tapered off 300-mg to 399-mg MEDD (2012, n = 107; 2017, n = 5); 95% were tapered off 200-mg to 299-mg MEDD (2012, n = 262; 2017, n = 22); and 86% were tapered off 100-mg to 199-mg MEDD (2012, n = 876; 2017; n = 127).

Conclusion

Successful integration of primary care with mental health and addiction services is paramount to aggressively taper patients with chronic pain from opioids. There is evidence that drug dependence and chronic pain should be treated like other chronic illness.²⁰ Both chronic pain and addiction can be treated with a multidimensional self-management approach. In view of the high incidence of mental health and addiction associated with opioid use, it makes sense that an integrated, 1-stop pain and addiction clinic that understands and addresses both issues is more likely to improve patient outcomes.

Acknowledgments

This material is the result of work supported by the resources and facilities at the North Florida/South Georgia Veterans Health System, Geriatric Research Education Clinical Center in Gainesville, Florida.

Chronic pain significantly affects 100 million Americans.^1,2 Pain accounts for $560 to $635 billion in annual financial costs to society, including health care costs and loss of productivity (ie, days missed from work, hours of work lost, and lower wages).^2,3 Although pain prevalence exceeds other chronic diseases, such as diabetes mellitus, cancer, and heart disease, it lacks a sufficient body of evidence-based research and guidelines on the underlying mechanisms, valid methods of assessment, and comparative effectiveness of treatments to effectively implement into clinical practice.^2,4 Prevention and treatment of pain are often delayed, inaccessible, or inadequate.² Primary care providers (PCPs) are most often sought for pain management and treat about 52% of chronic pain patients.^2,3,5 Veterans are especially vulnerable to chronic pain and are at risk for inadequate treatment.²

Background

There is an epidemic of drug abuse and mortality from opioid prescription medication.⁶ In the US, rates of overdose deaths from prescription opioids were 6.1 per 100,000 for men and 4.2 per 100,000 for women in 2017. Opioids were involved in 47,600 overdose deaths in 2017, accounting for 67.8% of all drug overdose deaths.⁷

A large number of patients on long-term opioids have preexisting substance use disorders and/or psychiatric disease, further complicating chronic pain management.^8-10 Prescription opioid use has been the precursor for about 80% of people who are now heroin addicts.¹¹ Iatrogenic addiction from prescription medications isn’t easily captured by standard addiction criteria. Consequently, in patients who are on opioid therapy for prolonged periods, separating complex opioid dependence from addiction is difficult.¹² Improved addiction screening and risk mitigation strategies are needed along with aggressive treatment monitoring to curb the opioid epidemic.

Opioid Management in Primary Care

The majority of opioid medications are prescribed by PCPs, which is magnified in the US Department of Veterans Affairs (VA) health care system due to the high prevalence of service-related injuries.^3,13 The VA is at the forefront of addressing the complexities of opioid addiction through several initiatives.¹⁴ The ability to offer the frequent visits needed to safely manage patients prescribed opioids and the integration of mental health and addiction treatment are often lacking in non-VA primary care clinics. Therefore, a key to solving the opioid crisis is developing these capabilities so they can be delivered within the primary care setting. There is substantial evidence in support of nonopioid alternatives to chronic pain management, including other pharmacologic approaches, exercise, physical therapy, acupuncture, weight loss, smoking cessation, chiropractic care, cognitive behavioral therapy (CBT), and other integrative health modalities.

A 2009 VA directive mandated the development of a comprehensive, integrated, systemwide approach to pain management.¹⁵ The VA Stepped-Care Biopsychosocial Model for Pain Management is dependent on timely access to secondary consultation from pain medicine, behavioral health, physical medicine, and other specialty consultation.¹⁵

History of VHA SCAN-ECHO Model

The Specialty Care Access Network–Extension for Community Health Outcomes (SCAN-ECHO) is a Veterans Health Administration (VHA) adaptation of a program that originated at the University of Mexico.^16,17 The SCAN-ECHO model uses a multisite videoconferencing network to provide specialty care consultations to PCPs and patient aligned care teams (PACTs). During the 60- to 90-minute weekly sessions, case presentations are analyzed in real time so that over time, the PCPs gain knowledge, competency, and confidence in learning how to handle complex chronic conditions.

Since its implementation, the SCAN-ECHO program has been adopted across the VHA in a variety of specialties. One program, the SCAN-ECHO for Pain Management (SCAN-ECHO-PM) was implemented in 7 VHA networks in 31 states, spanning 47 medical centers and 148 community-based outpatient clinics (CBOCs).¹⁸ The SCAN-ECHO-PM program successfully conducted 257 multidisciplinary pain consultations between 2011 and 2013, resulting in increased initiation of nonopioid medications.¹⁸

The aim of this article is to describe the implementation of a multicomponent primary care-based pain clinic with a fully integrated mental health service and addiction service at the North Florida/South Georgia Veterans Health System (NF/SGVHS). A practiced-based intervention of the biopsychosocial model with robust patient engagement has guided the development of the NF/SGVHS pain clinic (Figure 1).^4,19

Pain CLinic

NF/SGVHS comprises the Malcom Randall and Lake City VA medical centers (VAMCs) hospitals, 3 satellite outpatient clinics, and 8 CBOCs. Spanning 33 counties in North Florida and 19 counties in South Georgia, the NF/SGVHS serves more than 140,000 patients. In 2010, the Malcom Randall VAMC established a multidisciplinary primary care pain clinic to manage veterans at high-risk for noncancer chronic pain and addiction. The noncancer pain policy was revised after garnering support from stakeholders who treat chronic pain, including the chiefs of psychiatry, rehabilitation medicine, neurosurgery, psychology, interventional pain, pharmacy, nursing, addiction medicine, and primary care. The clinic is staffed by primary care physicians trained in internal medicine and family medicine and is structured with 1-hour first visits, and 30-minute follow-up visits to allow enough time for comprehensive evaluation while meeting the needs for close follow-up support.

All physicians in the clinic have buprenorphine prescribing credentials to aid in the management of opioid addiction, as some patients feel more comfortable receiving addiction treatment in a primary care setting. The multimodal care model consists of several services that include addiction psychiatrists, interventional pain specialists, pain psychologists, and pain pharmacologists who coordinate the care to the veterans. The addiction psychiatrists offer a full range of services with inpatient residential and outpatient programs. Through recurring meetings with primary care pain clinic staff, the addiction psychiatrists are available to discuss use of buprenorphine and arrange follow-up for patients with complex pain addiction. There is ongoing collaboration to develop the best care plan that meets the patient’s needs for chronic pain, addiction, and/or mental health issues. The interventional pain service has 3 fellowship-trained pain care providers who deliver comprehensive evaluation, pharmacologic recommendations, and a full range of interventional and complementary therapies with an emphasis on objective functional improvement. Pain care providers offer alternatives to patients who are being weaned from opioids and support the multidisciplinary patient engagement model.

The pain psychology program, established in 2011, delivers CBT to 5 onsite locations and 5 telehealth locations. The service includes an advanced CBT program and a couples CBT program. The pharmacy pain fellowship program provides staff for an outpatient e-consult pain management service and an inpatient pharmacy consult service. Harnessing pain specialty pharmacists, the pharmacy service addresses pharmacokinetic issues, urine drug screen (UDS) results, opioid tapering and discharge planning for pain, addiction and mental health needs. The NF/SGVHS Primary Care Pain Clinic was established to support PCPs who did not feel comfortable managing chronic pain patients. These patients were typically on high-dose opioid therapy (> 100-mg morphine equivalent daily doses [MEDDs]); patients with a history of opioid addiction; patients with an addiction to opioids combined with benzodiazepines; and patients with comorbid medical issues (eg, sleep apnea), which complicated their management. The process of addressing opioid safety in these complex pain patients can be labor intensive and generally cannot be accomplished in a brief visit in a primary care setting where many other medical problems often need to be addressed.

Most patients on high-dose opioids are fearful of any changes in their medications. The difficult conversation regarding opioid safety is a lengthy one and frequently will occur over multiple visits. In addition, safely tapering opioids requires frequent follow-up to provide psychological support and to address withdrawal and mental health issues that may arise. As opioids are tapered, the clinic reinforces improved pain care through a multimodal biopsychosocial model. All veterans receiving pain care outside the VA are monitored annually to assure they are receiving evidence-based pain care as defined by the biopsychosocial model.

Education

Since 2011, the NF/SGVHS SCAN-ECHO pain and addiction educational forum has created > 50 hours of approved annual continuing medical education (CME) on pain management and addiction for PCPs. Initially, the 1-hour weekly educational audioconferences presented a pain management case along with related topics and involved specialists from interventional pain, physical therapy, psychiatry, nursing, neurology, and psychology departments. In 2013, in conjunction with the VA SCAN-ECHO program of Hunter Holmes McGuire VAMC in Richmond, Virginia, and Walter Reed National Military Medical Center in Bethesda, Maryland, the audioconference was expanded to 2 days each week with additional topics on addiction management. Residency and fellowship rotations were developed that specifically targeted fellows from psychiatry, pharmacology, and interventional pain departments.

Currently, an 8-session pain school is delivered onsite and at 7 telehealth locations. The school is a collaborative effort involving interventional pain, psychology, pharmacy, nutrition, and the primary care pain clinic staff. As the cornerstone of the program, the pain school stresses the biopsychosocial patient engagement model.

Program Evaluation

The VA is equipped with multiple telehealth service networks that allow for the delivery of programs, such as the pain school, a pain psychology program, and a yoga program, onsite or offsite. The VA Computerized Patient Record System (CPRS) manages electronic health records, allowing for rapid chart review and e-consults. The NF/SGVHS Pain Management Program provides about 1500 e-consults yearly. The CPRS includes templates with pain metrics to help PCPs deliver pain care more efficiently and evaluate performance measures. This system also allows for the capture of data to track improvements in the care of the veterans served.

From 2012 to 2017, more than 5000 NF/SGVHS patients were weaned from opioids. Overall, there was an 87% reduction in patients receiving opioids ( ≥ 100-mg MEDDs) within the NF/SGVHS, which is significantly more than the 49% seen nationally across the VHA (Figure 2). Percent reduction was calculated by taking the difference in number of patients receiving opioids in 2012 and 2017, dividing by the number of patients receiving opioids in 2012 and multiplying by 100. The largest proportion of opioid dose reductions for NF/SGVHS and VHA patients, respectively, were seen in 300-mg to 399-mg MEDDs (95% vs 67%, respectively); followed by ≥ 400-mg MEDDs (94% vs 71%, respectively); 200-mg to 299-mg MEDDs (91% vs 58%, respectively); and 100-mg to 199-mg MEDDs (84% vs 40%, respectively). When examining NF/SGVHS trends over time, there has been a consistent decline in patients prescribed opioids (18 223 in 2012 compared with 12 877 in 2017) with similar trends in benzodiazepine-opioid combination therapy (2694 in 2012 compared with 833 in 2017) (Figure 3).

Similar declines are seen when patients are stratified by the MEDD (Figure 4). From 2012 to 2017, 92% of the patients were successfully tapered off doses ≥ 400-mg MEDD (2012, n = 72; 2017, n = 6), and tapered off 300-mg to 399-mg MEDD (2012, n = 107; 2017, n = 5); 95% were tapered off 200-mg to 299-mg MEDD (2012, n = 262; 2017, n = 22); and 86% were tapered off 100-mg to 199-mg MEDD (2012, n = 876; 2017; n = 127).

Conclusion

Successful integration of primary care with mental health and addiction services is paramount to aggressively taper patients with chronic pain from opioids. There is evidence that drug dependence and chronic pain should be treated like other chronic illness.²⁰ Both chronic pain and addiction can be treated with a multidimensional self-management approach. In view of the high incidence of mental health and addiction associated with opioid use, it makes sense that an integrated, 1-stop pain and addiction clinic that understands and addresses both issues is more likely to improve patient outcomes.

Acknowledgments

This material is the result of work supported by the resources and facilities at the North Florida/South Georgia Veterans Health System, Geriatric Research Education Clinical Center in Gainesville, Florida.

Chronic pain significantly affects 100 million Americans.^1,2 Pain accounts for $560 to $635 billion in annual financial costs to society, including health care costs and loss of productivity (ie, days missed from work, hours of work lost, and lower wages).^2,3 Although pain prevalence exceeds other chronic diseases, such as diabetes mellitus, cancer, and heart disease, it lacks a sufficient body of evidence-based research and guidelines on the underlying mechanisms, valid methods of assessment, and comparative effectiveness of treatments to effectively implement into clinical practice.^2,4 Prevention and treatment of pain are often delayed, inaccessible, or inadequate.² Primary care providers (PCPs) are most often sought for pain management and treat about 52% of chronic pain patients.^2,3,5 Veterans are especially vulnerable to chronic pain and are at risk for inadequate treatment.²

Background

There is an epidemic of drug abuse and mortality from opioid prescription medication.⁶ In the US, rates of overdose deaths from prescription opioids were 6.1 per 100,000 for men and 4.2 per 100,000 for women in 2017. Opioids were involved in 47,600 overdose deaths in 2017, accounting for 67.8% of all drug overdose deaths.⁷

A large number of patients on long-term opioids have preexisting substance use disorders and/or psychiatric disease, further complicating chronic pain management.^8-10 Prescription opioid use has been the precursor for about 80% of people who are now heroin addicts.¹¹ Iatrogenic addiction from prescription medications isn’t easily captured by standard addiction criteria. Consequently, in patients who are on opioid therapy for prolonged periods, separating complex opioid dependence from addiction is difficult.¹² Improved addiction screening and risk mitigation strategies are needed along with aggressive treatment monitoring to curb the opioid epidemic.

Opioid Management in Primary Care

The majority of opioid medications are prescribed by PCPs, which is magnified in the US Department of Veterans Affairs (VA) health care system due to the high prevalence of service-related injuries.^3,13 The VA is at the forefront of addressing the complexities of opioid addiction through several initiatives.¹⁴ The ability to offer the frequent visits needed to safely manage patients prescribed opioids and the integration of mental health and addiction treatment are often lacking in non-VA primary care clinics. Therefore, a key to solving the opioid crisis is developing these capabilities so they can be delivered within the primary care setting. There is substantial evidence in support of nonopioid alternatives to chronic pain management, including other pharmacologic approaches, exercise, physical therapy, acupuncture, weight loss, smoking cessation, chiropractic care, cognitive behavioral therapy (CBT), and other integrative health modalities.

A 2009 VA directive mandated the development of a comprehensive, integrated, systemwide approach to pain management.¹⁵ The VA Stepped-Care Biopsychosocial Model for Pain Management is dependent on timely access to secondary consultation from pain medicine, behavioral health, physical medicine, and other specialty consultation.¹⁵

History of VHA SCAN-ECHO Model

The Specialty Care Access Network–Extension for Community Health Outcomes (SCAN-ECHO) is a Veterans Health Administration (VHA) adaptation of a program that originated at the University of Mexico.^16,17 The SCAN-ECHO model uses a multisite videoconferencing network to provide specialty care consultations to PCPs and patient aligned care teams (PACTs). During the 60- to 90-minute weekly sessions, case presentations are analyzed in real time so that over time, the PCPs gain knowledge, competency, and confidence in learning how to handle complex chronic conditions.

Since its implementation, the SCAN-ECHO program has been adopted across the VHA in a variety of specialties. One program, the SCAN-ECHO for Pain Management (SCAN-ECHO-PM) was implemented in 7 VHA networks in 31 states, spanning 47 medical centers and 148 community-based outpatient clinics (CBOCs).¹⁸ The SCAN-ECHO-PM program successfully conducted 257 multidisciplinary pain consultations between 2011 and 2013, resulting in increased initiation of nonopioid medications.¹⁸

The aim of this article is to describe the implementation of a multicomponent primary care-based pain clinic with a fully integrated mental health service and addiction service at the North Florida/South Georgia Veterans Health System (NF/SGVHS). A practiced-based intervention of the biopsychosocial model with robust patient engagement has guided the development of the NF/SGVHS pain clinic (Figure 1).^4,19

Pain CLinic

NF/SGVHS comprises the Malcom Randall and Lake City VA medical centers (VAMCs) hospitals, 3 satellite outpatient clinics, and 8 CBOCs. Spanning 33 counties in North Florida and 19 counties in South Georgia, the NF/SGVHS serves more than 140,000 patients. In 2010, the Malcom Randall VAMC established a multidisciplinary primary care pain clinic to manage veterans at high-risk for noncancer chronic pain and addiction. The noncancer pain policy was revised after garnering support from stakeholders who treat chronic pain, including the chiefs of psychiatry, rehabilitation medicine, neurosurgery, psychology, interventional pain, pharmacy, nursing, addiction medicine, and primary care. The clinic is staffed by primary care physicians trained in internal medicine and family medicine and is structured with 1-hour first visits, and 30-minute follow-up visits to allow enough time for comprehensive evaluation while meeting the needs for close follow-up support.

All physicians in the clinic have buprenorphine prescribing credentials to aid in the management of opioid addiction, as some patients feel more comfortable receiving addiction treatment in a primary care setting. The multimodal care model consists of several services that include addiction psychiatrists, interventional pain specialists, pain psychologists, and pain pharmacologists who coordinate the care to the veterans. The addiction psychiatrists offer a full range of services with inpatient residential and outpatient programs. Through recurring meetings with primary care pain clinic staff, the addiction psychiatrists are available to discuss use of buprenorphine and arrange follow-up for patients with complex pain addiction. There is ongoing collaboration to develop the best care plan that meets the patient’s needs for chronic pain, addiction, and/or mental health issues. The interventional pain service has 3 fellowship-trained pain care providers who deliver comprehensive evaluation, pharmacologic recommendations, and a full range of interventional and complementary therapies with an emphasis on objective functional improvement. Pain care providers offer alternatives to patients who are being weaned from opioids and support the multidisciplinary patient engagement model.

The pain psychology program, established in 2011, delivers CBT to 5 onsite locations and 5 telehealth locations. The service includes an advanced CBT program and a couples CBT program. The pharmacy pain fellowship program provides staff for an outpatient e-consult pain management service and an inpatient pharmacy consult service. Harnessing pain specialty pharmacists, the pharmacy service addresses pharmacokinetic issues, urine drug screen (UDS) results, opioid tapering and discharge planning for pain, addiction and mental health needs. The NF/SGVHS Primary Care Pain Clinic was established to support PCPs who did not feel comfortable managing chronic pain patients. These patients were typically on high-dose opioid therapy (> 100-mg morphine equivalent daily doses [MEDDs]); patients with a history of opioid addiction; patients with an addiction to opioids combined with benzodiazepines; and patients with comorbid medical issues (eg, sleep apnea), which complicated their management. The process of addressing opioid safety in these complex pain patients can be labor intensive and generally cannot be accomplished in a brief visit in a primary care setting where many other medical problems often need to be addressed.

Most patients on high-dose opioids are fearful of any changes in their medications. The difficult conversation regarding opioid safety is a lengthy one and frequently will occur over multiple visits. In addition, safely tapering opioids requires frequent follow-up to provide psychological support and to address withdrawal and mental health issues that may arise. As opioids are tapered, the clinic reinforces improved pain care through a multimodal biopsychosocial model. All veterans receiving pain care outside the VA are monitored annually to assure they are receiving evidence-based pain care as defined by the biopsychosocial model.

Education

Since 2011, the NF/SGVHS SCAN-ECHO pain and addiction educational forum has created > 50 hours of approved annual continuing medical education (CME) on pain management and addiction for PCPs. Initially, the 1-hour weekly educational audioconferences presented a pain management case along with related topics and involved specialists from interventional pain, physical therapy, psychiatry, nursing, neurology, and psychology departments. In 2013, in conjunction with the VA SCAN-ECHO program of Hunter Holmes McGuire VAMC in Richmond, Virginia, and Walter Reed National Military Medical Center in Bethesda, Maryland, the audioconference was expanded to 2 days each week with additional topics on addiction management. Residency and fellowship rotations were developed that specifically targeted fellows from psychiatry, pharmacology, and interventional pain departments.

Currently, an 8-session pain school is delivered onsite and at 7 telehealth locations. The school is a collaborative effort involving interventional pain, psychology, pharmacy, nutrition, and the primary care pain clinic staff. As the cornerstone of the program, the pain school stresses the biopsychosocial patient engagement model.

Program Evaluation

The VA is equipped with multiple telehealth service networks that allow for the delivery of programs, such as the pain school, a pain psychology program, and a yoga program, onsite or offsite. The VA Computerized Patient Record System (CPRS) manages electronic health records, allowing for rapid chart review and e-consults. The NF/SGVHS Pain Management Program provides about 1500 e-consults yearly. The CPRS includes templates with pain metrics to help PCPs deliver pain care more efficiently and evaluate performance measures. This system also allows for the capture of data to track improvements in the care of the veterans served.

From 2012 to 2017, more than 5000 NF/SGVHS patients were weaned from opioids. Overall, there was an 87% reduction in patients receiving opioids ( ≥ 100-mg MEDDs) within the NF/SGVHS, which is significantly more than the 49% seen nationally across the VHA (Figure 2). Percent reduction was calculated by taking the difference in number of patients receiving opioids in 2012 and 2017, dividing by the number of patients receiving opioids in 2012 and multiplying by 100. The largest proportion of opioid dose reductions for NF/SGVHS and VHA patients, respectively, were seen in 300-mg to 399-mg MEDDs (95% vs 67%, respectively); followed by ≥ 400-mg MEDDs (94% vs 71%, respectively); 200-mg to 299-mg MEDDs (91% vs 58%, respectively); and 100-mg to 199-mg MEDDs (84% vs 40%, respectively). When examining NF/SGVHS trends over time, there has been a consistent decline in patients prescribed opioids (18 223 in 2012 compared with 12 877 in 2017) with similar trends in benzodiazepine-opioid combination therapy (2694 in 2012 compared with 833 in 2017) (Figure 3).

Similar declines are seen when patients are stratified by the MEDD (Figure 4). From 2012 to 2017, 92% of the patients were successfully tapered off doses ≥ 400-mg MEDD (2012, n = 72; 2017, n = 6), and tapered off 300-mg to 399-mg MEDD (2012, n = 107; 2017, n = 5); 95% were tapered off 200-mg to 299-mg MEDD (2012, n = 262; 2017, n = 22); and 86% were tapered off 100-mg to 199-mg MEDD (2012, n = 876; 2017; n = 127).

Conclusion

Successful integration of primary care with mental health and addiction services is paramount to aggressively taper patients with chronic pain from opioids. There is evidence that drug dependence and chronic pain should be treated like other chronic illness.²⁰ Both chronic pain and addiction can be treated with a multidimensional self-management approach. In view of the high incidence of mental health and addiction associated with opioid use, it makes sense that an integrated, 1-stop pain and addiction clinic that understands and addresses both issues is more likely to improve patient outcomes.

Acknowledgments

This material is the result of work supported by the resources and facilities at the North Florida/South Georgia Veterans Health System, Geriatric Research Education Clinical Center in Gainesville, Florida.

Fecal incontinence (FI), also known as accidental bowel leakage, is the involuntary loss of feces, which includes both liquid and solid stool as defined by the International Continence Society (ICS) and the International Urogynecological Association (IUGA).^1,2 Fecal incontinence is common, occurring in 7% to 25% of community-dwelling women, and it increases with age.^2-6 The condition is rarely addressed, with only 30% of women seeking care.^6-8 This is due to patient embarrassment and the lack of a reliable screening tool. However, FI affects quality of life and mental health, and the associated economic burden likely will rise given the increased prevalence of FI among older women.^2,4,7,9

Fecal incontinence occurs due to poor stool consistency, anal and pelvic muscle weakness, reduced rectal compliance, reduced or increased rectal sensation, or bowel inflammation or dysfunction. Many conditions can cause FI (TABLE 1).^5,10,11 It is therefore important to elicit a full medical history with a focus on specific bowel symptoms, such as stool consistency type (TABLE 2),¹² FI frequency, and duration of symptoms, as well as to perform a complete examination to identify any readily reversible or malignant causes. A colonoscopy is recommended for individuals who meet screening criteria or present with a change in bowel symptoms, such as diarrhea, bleeding, or obstruction.^13,14

Fecal incontinence treatments include a range of approaches categorized from conservative, or first-line therapy, to fourth-line surgical managements (FIGURE 1).^1,10,13,14 In this Update, we review the results of 3 well-designed trials that enrolled women with frequent nonneurogenic FI. 

Common first- and second-line treatments produce equivalent improvements in FI symptoms at
6 months 

Jelovsek JE, Markland AD, Whitehead WE, et al; National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Controlling faecal incontinence in women by performing anal exercises with biofeedback or loperamide: a randomized clinical trial. Lancet Gastroenterol Hepatol. 2019;4:698-710. 

In a multicenter, randomized trial of first- and second-line treatments for FI, Jelovsek and colleagues evaluated the efficacy of oral placebo, loperamide, pelvic floor physical therapy (PFPT) with biofeedback using anorectal manometry, or combination therapy over a 24-week period. 

Continue to: Four treatments compared...

Three hundred women with FI occurring monthly for 3 months were included in the trial. Women were excluded if they had a stool classification of type 1 or type 7 on the Bristol Stool Scale, inflammatory bowel disease (IBD), history of rectovaginal fistula or cloacal defect, rectal prolapse, prior bowel diversion, fecal impaction, neurologic disorder leading to incontinence, use of loperamide or diphenoxylate within the last 30 days, childbirth within the last 3 months, need for antiretroviral drugs, hepatic impairment, or chronic abdominal pain without diarrhea. 

Baseline characteristics and symptoms severity were similar among participants. The average age of the women was 63 years, with 79% white and 85% postmenopausal. Participants had a mean (SD) of 1.6 (1.8) leaks per day. 

Participants were randomly assigned in a 0.5:1:1:1 fashion to receive oral placebo, loperamide, oral placebo with PFPT/biofeedback, or loperamide with PFPT/biofeedback. All participants received a standardized educational pamphlet that outlined dietary and behavioral recommendations. 

Women assigned to PFPT/biofeedback received 6 sessions every other week. Loperamide was started at a dosage of 2 mg per day with the possibility of dose maintenance, escalation, reduction, or discontinuation. 

Study outcomes. The primary outcome was a change from baseline to 24 weeks in the Vaizey FI symptom severity score, which assesses fecal frequency, urgency, and use of pads and medications. Secondary outcomes included assessment of a 7-day bowel diary and other quality-of-life measures. Data at 24 weeks were available for 89% of the women. 

All treatment groups experienced improved FI symptoms 

Based on changes in Vaizey scores after 24 weeks of treatment, women in all treatment groups had similar improvement in symptoms severity. However, those who received loperamide and PFPT/biofeedback had decreased pad changes per week and more accident-free days compared with women treated with placebo and biofeedback. Quality of life at 24 weeks was not statistically different between treatment groups as improvement was seen in all groups, including those who received oral placebo and patient education. 

Adverse events. The proportion of gastrointestinal adverse effects was similar between treatment groups, ranging from 45% to 63%. Constipation was the most common adverse event overall and was more common in those taking loperamide, occurring in 51% of the loperamide plus PFPT/biofeedback group, 38% of those who received loperamide alone, 23% of the biofeedback with placebo group, and 12% of the placebo-alone group. 

Strengths and limitations. Strengths of this study include its multisite, large sample size, low dropout rate, and sufficiently powered design to compare various combinations of first- and second-line therapies in women with a mean baseline FI of 1.6 leaks per day. Another strength is the robustness of the PFPT/biofeedback sessions that used anorectal manometry. This may, however, limit the study's external validity given that clinical use of this device is likely rare. Additionally, the population was comprised largely of postmenopausal and white women, which may make the findings less generalizable to other populations. 

Continue to: Novel vaginal bowel control system...

Novel vaginal bowel control system is effective, durable over 12 months for FI treatment 

Richter HE, Dunivan G, Brown HW, et al. A 12-month clinical durability of effectiveness and safety evaluation of a vaginal bowel control system for the nonsurgical treatment of fecal incontinence. Female Pelvic Med Reconstr Surg. 2019;25:113-119. 

Richter and colleagues characterized clinical success, effect on quality of life, and durability over 12 months of a novel vaginal bowel control device (Eclipse System; Pelvalon) for FI in a prospective cohort study. The device is a silicone-coated vaginal insert with a detachable pump and balloon that deflects the rectovaginal septum posteriorly, thus impeding the passage of stool in the rectum (FIGURE 2). 

Study eligibility criteria and treatment protocol 

Women were eligible for the study if they had 4 or more episodes of fecal soiling on a 2-week bowel diary and had FI for at least 6 months. Participants were excluded if they had prolapse outside the hymen, rectovaginal fistula, IBD, congenital anorectal malformation, urinary or colorectal infection, chronic pelvic or anorectal pain, pregnancy or planning pregnancy in the next 5 months, unmanaged chronic watery diarrhea, presence of an open wound or tear in the vagina, significant urogenital atrophy, or any psychiatric or neurologic disorder that would hinder the ability to participate. 

Participants successfully fitted with the device (3 attempts were allowed) were entered into the study's run-in phase. Those who were successfully fitted and had a 50% or greater reduction in FI continued into the treatment phase with 12 months of follow-up. 

Of the 137 women eligible for device fitting, 62% were successfully fitted. The 73 (86%) women who had a 50% or greater reduction in FI during the run-in period comprised the intent-to-treat study population. On average, these women were 61.3 years of age, with 70% white and 82% postmenopausal. At baseline, they had a mean of 14.1 episodes of FI over 2 weeks. (Prior to enrollment, 97.3% of women attempted self-management strategies, 17.8% to 23% failed conservative therapy, and 7.8% to 13.7% failed surgical therapy.) The follow-up rate at 12 months was 74%. 

Study outcomes. The primary outcome was treatment success, defined as proportion of subjects with a 50% or greater reduction in FI episodes at 3 months; this outcome also was evaluated at 6 and 12 months. Secondary outcomes were the number of FI episodes and quality-of-life measures at 3, 6, and 12 months. 

Treatment success, patient satisfaction high 

In the treatment phase, women had sustained improvements in symptom severity and quality-of-life measures over 12 months. Treatment success was 73% at 3 months, 71% at 6 months, and 70% at 12 months. Complete continence was achieved in 46% of participants at 12 months, and major FI episodes (requiring immediate change of undergarments) decreased from 5.0 at baseline to 0.5 at 12 months. Quality-of-life measures were improved at 3 months, and improvement was sustained over 12 months. Satisfaction was 94% at 12 months. 

Adverse events. No serious device-related adverse events occurred. Mild device-related adverse events were experienced by 45% of women during the fitting process and by 38% during treatment period. These included vaginal wall injury such as hyperemia and erosion; vaginal or pelvic discomfort; vaginal infection; constipation; and lower urinary tract issues such as urinary tract infection, urinary incontinence, and voiding dysfunction. No adverse events led to treatment discontinuation. 

Strengths and limitations. Strengths of this study include that it was conducted at multiple clinical sites, had a large sample size, and had a 1-year follow-up period in a population with daily FI. A limitation was that only women who had a 50% or greater reduction in FI episodes during the run-in period were followed for 12 months; however, this was 86% of the original cohort. The use of a comparative group using other devices, such as anal plugs, would have strengthened this study. 

Continue to: Sacroneuromodulation for FI…

Sacral neuromodulation for FI is effective long-term 

Hull T, Giese C, Wexner SD, et al; for the SNS Study Group. Long-term durability of sacral nerve stimulation therapy for chronic fecal incontinence. Dis Colon Rectum. 2013;56:234-245. 

In this multicenter, prospective cohort study, Hull and colleagues evaluated the 5-year efficacy of sacral neuromodulation (SNM), also known as sacral nerve stimulation, for treatment of FI. This study followed an earlier investigation by Wexner and colleagues, which reported that 83% of 120 patients treated with SNM had a 50% or greater improvement in FI episodes at 12 months.¹⁶ 

Details of the study 

The investigators enrolled 133 participants (92% female) who had more than 2 episodes of FI per week for longer than 6 months (12 months after vaginal delivery). Participants were excluded if they had congenital anorectal malformations, prior rectal surgery within the past 12 months (or 24 months if due to cancer), defects greater than 120° of the external anal sphincter (EAS), IBD, unmanaged chronic watery diarrhea, stool consistency type 6 or type 7 on the Bristol Stool Scale, sequela of pelvic radiation, active anal abscess or fistula, pregnancy, or planned pregnancy. 

Eligible participants underwent a 2-stage procedure with the InterStim bowel control device (Medtronic). If participants experienced a 50% or greater reduction in incontinence episodes with a wearable external SNM device in the test stimulation (stage 1), they received the chronic SNM implant device (stage 2). 

Participants who underwent device implantation were followed at 1, 3, and 6 months and annually for 5 years or until they exited the study. Bowel diaries and quality of life assessments were completed at baseline and at follow-up. 

The primary outcome was therapeutic success, defined as 50% or greater improvement in FI episodes per week. 

A total of 120 participants (90%) underwent implantation of the chronic lead and neuromodulator, and 76 (63%) were followed for 5 years. Baseline characteristics available in the initial study of 133 participants showed that the mean age was 60.5 years; 25% had undergone a prior anal sphincteroplasty; and 16.5% and 10.5% had EAS or internal anal sphincter (IAS) defects, respectively, on endoanal ultrasonography.¹⁶ 

Therapeutic success was high at 5 years 

At the 5-year follow-up, 89% (64/72) of participants met therapeutic success, with a reduction in weekly FI episodes from 9.1 at baseline to 1.7 at 5 years. The number of incontinence pads required decreased, and more participants wore no pads at 5 years. In the intention-to-treat analysis, carrying forward the baseline FI rate in participants who lacked follow-up data, the therapeutic success rate was 69%. Quality-of-life measures improved at 5 years, both statistically and by minimal clinical difference. 

Adverse events. Sixty-eight percent of participants experienced device-related adverse events, including implant site pain, change in sensation of stimulation, change in efficacy, implant site infection, or neurostimulator battery depletion (neurostimulator use commonly expires after 3 to 5 years). Of these events, 80% were successfully treated with medications, reprogramming, or no intervention. The 5-year probability of device revision or replacement was 24.4%, and the 5-year probability of device explant was 19.0%. 

Strengths and limitations. Overall, this study was a well-designed, multicenter trial with long-term follow-up that showed significant improvement in FI with the use of SNM. Its strengths include the enrollment of postmenopausal women who had current defects in EAS and/or IAS on endoanal ultrasonography and 25% who had a prior sphincteroplasty. The findings therefore are relevant to the gynecologic population in whom anal sphincteroplasty would not be recommended. The study also accounted for dropouts and reported the adjusted success rate of 69% at 5 years in that group. 

The lack of a control arm to rule out the placebo effect is a limitation of this study, although randomized trials comparing the effect of SNM "on" versus "off" showed greater improvement with the device "on."¹⁷ 

Fecal incontinence (FI), also known as accidental bowel leakage, is the involuntary loss of feces, which includes both liquid and solid stool as defined by the International Continence Society (ICS) and the International Urogynecological Association (IUGA).^1,2 Fecal incontinence is common, occurring in 7% to 25% of community-dwelling women, and it increases with age.^2-6 The condition is rarely addressed, with only 30% of women seeking care.^6-8 This is due to patient embarrassment and the lack of a reliable screening tool. However, FI affects quality of life and mental health, and the associated economic burden likely will rise given the increased prevalence of FI among older women.^2,4,7,9

Fecal incontinence occurs due to poor stool consistency, anal and pelvic muscle weakness, reduced rectal compliance, reduced or increased rectal sensation, or bowel inflammation or dysfunction. Many conditions can cause FI (TABLE 1).^5,10,11 It is therefore important to elicit a full medical history with a focus on specific bowel symptoms, such as stool consistency type (TABLE 2),¹² FI frequency, and duration of symptoms, as well as to perform a complete examination to identify any readily reversible or malignant causes. A colonoscopy is recommended for individuals who meet screening criteria or present with a change in bowel symptoms, such as diarrhea, bleeding, or obstruction.^13,14

Fecal incontinence treatments include a range of approaches categorized from conservative, or first-line therapy, to fourth-line surgical managements (FIGURE 1).^1,10,13,14 In this Update, we review the results of 3 well-designed trials that enrolled women with frequent nonneurogenic FI. 

Common first- and second-line treatments produce equivalent improvements in FI symptoms at
6 months 

Jelovsek JE, Markland AD, Whitehead WE, et al; National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Controlling faecal incontinence in women by performing anal exercises with biofeedback or loperamide: a randomized clinical trial. Lancet Gastroenterol Hepatol. 2019;4:698-710. 

In a multicenter, randomized trial of first- and second-line treatments for FI, Jelovsek and colleagues evaluated the efficacy of oral placebo, loperamide, pelvic floor physical therapy (PFPT) with biofeedback using anorectal manometry, or combination therapy over a 24-week period. 

Continue to: Four treatments compared...

Three hundred women with FI occurring monthly for 3 months were included in the trial. Women were excluded if they had a stool classification of type 1 or type 7 on the Bristol Stool Scale, inflammatory bowel disease (IBD), history of rectovaginal fistula or cloacal defect, rectal prolapse, prior bowel diversion, fecal impaction, neurologic disorder leading to incontinence, use of loperamide or diphenoxylate within the last 30 days, childbirth within the last 3 months, need for antiretroviral drugs, hepatic impairment, or chronic abdominal pain without diarrhea. 

Baseline characteristics and symptoms severity were similar among participants. The average age of the women was 63 years, with 79% white and 85% postmenopausal. Participants had a mean (SD) of 1.6 (1.8) leaks per day. 

Participants were randomly assigned in a 0.5:1:1:1 fashion to receive oral placebo, loperamide, oral placebo with PFPT/biofeedback, or loperamide with PFPT/biofeedback. All participants received a standardized educational pamphlet that outlined dietary and behavioral recommendations. 

Women assigned to PFPT/biofeedback received 6 sessions every other week. Loperamide was started at a dosage of 2 mg per day with the possibility of dose maintenance, escalation, reduction, or discontinuation. 

Study outcomes. The primary outcome was a change from baseline to 24 weeks in the Vaizey FI symptom severity score, which assesses fecal frequency, urgency, and use of pads and medications. Secondary outcomes included assessment of a 7-day bowel diary and other quality-of-life measures. Data at 24 weeks were available for 89% of the women. 

All treatment groups experienced improved FI symptoms 

Based on changes in Vaizey scores after 24 weeks of treatment, women in all treatment groups had similar improvement in symptoms severity. However, those who received loperamide and PFPT/biofeedback had decreased pad changes per week and more accident-free days compared with women treated with placebo and biofeedback. Quality of life at 24 weeks was not statistically different between treatment groups as improvement was seen in all groups, including those who received oral placebo and patient education. 

Adverse events. The proportion of gastrointestinal adverse effects was similar between treatment groups, ranging from 45% to 63%. Constipation was the most common adverse event overall and was more common in those taking loperamide, occurring in 51% of the loperamide plus PFPT/biofeedback group, 38% of those who received loperamide alone, 23% of the biofeedback with placebo group, and 12% of the placebo-alone group. 

Strengths and limitations. Strengths of this study include its multisite, large sample size, low dropout rate, and sufficiently powered design to compare various combinations of first- and second-line therapies in women with a mean baseline FI of 1.6 leaks per day. Another strength is the robustness of the PFPT/biofeedback sessions that used anorectal manometry. This may, however, limit the study's external validity given that clinical use of this device is likely rare. Additionally, the population was comprised largely of postmenopausal and white women, which may make the findings less generalizable to other populations. 

Continue to: Novel vaginal bowel control system...

Novel vaginal bowel control system is effective, durable over 12 months for FI treatment 

Richter HE, Dunivan G, Brown HW, et al. A 12-month clinical durability of effectiveness and safety evaluation of a vaginal bowel control system for the nonsurgical treatment of fecal incontinence. Female Pelvic Med Reconstr Surg. 2019;25:113-119. 

Richter and colleagues characterized clinical success, effect on quality of life, and durability over 12 months of a novel vaginal bowel control device (Eclipse System; Pelvalon) for FI in a prospective cohort study. The device is a silicone-coated vaginal insert with a detachable pump and balloon that deflects the rectovaginal septum posteriorly, thus impeding the passage of stool in the rectum (FIGURE 2). 

Study eligibility criteria and treatment protocol 

Women were eligible for the study if they had 4 or more episodes of fecal soiling on a 2-week bowel diary and had FI for at least 6 months. Participants were excluded if they had prolapse outside the hymen, rectovaginal fistula, IBD, congenital anorectal malformation, urinary or colorectal infection, chronic pelvic or anorectal pain, pregnancy or planning pregnancy in the next 5 months, unmanaged chronic watery diarrhea, presence of an open wound or tear in the vagina, significant urogenital atrophy, or any psychiatric or neurologic disorder that would hinder the ability to participate. 

Participants successfully fitted with the device (3 attempts were allowed) were entered into the study's run-in phase. Those who were successfully fitted and had a 50% or greater reduction in FI continued into the treatment phase with 12 months of follow-up. 

Of the 137 women eligible for device fitting, 62% were successfully fitted. The 73 (86%) women who had a 50% or greater reduction in FI during the run-in period comprised the intent-to-treat study population. On average, these women were 61.3 years of age, with 70% white and 82% postmenopausal. At baseline, they had a mean of 14.1 episodes of FI over 2 weeks. (Prior to enrollment, 97.3% of women attempted self-management strategies, 17.8% to 23% failed conservative therapy, and 7.8% to 13.7% failed surgical therapy.) The follow-up rate at 12 months was 74%. 

Study outcomes. The primary outcome was treatment success, defined as proportion of subjects with a 50% or greater reduction in FI episodes at 3 months; this outcome also was evaluated at 6 and 12 months. Secondary outcomes were the number of FI episodes and quality-of-life measures at 3, 6, and 12 months. 

Treatment success, patient satisfaction high 

In the treatment phase, women had sustained improvements in symptom severity and quality-of-life measures over 12 months. Treatment success was 73% at 3 months, 71% at 6 months, and 70% at 12 months. Complete continence was achieved in 46% of participants at 12 months, and major FI episodes (requiring immediate change of undergarments) decreased from 5.0 at baseline to 0.5 at 12 months. Quality-of-life measures were improved at 3 months, and improvement was sustained over 12 months. Satisfaction was 94% at 12 months. 

Adverse events. No serious device-related adverse events occurred. Mild device-related adverse events were experienced by 45% of women during the fitting process and by 38% during treatment period. These included vaginal wall injury such as hyperemia and erosion; vaginal or pelvic discomfort; vaginal infection; constipation; and lower urinary tract issues such as urinary tract infection, urinary incontinence, and voiding dysfunction. No adverse events led to treatment discontinuation. 

Strengths and limitations. Strengths of this study include that it was conducted at multiple clinical sites, had a large sample size, and had a 1-year follow-up period in a population with daily FI. A limitation was that only women who had a 50% or greater reduction in FI episodes during the run-in period were followed for 12 months; however, this was 86% of the original cohort. The use of a comparative group using other devices, such as anal plugs, would have strengthened this study. 

Continue to: Sacroneuromodulation for FI…

Sacral neuromodulation for FI is effective long-term 

Hull T, Giese C, Wexner SD, et al; for the SNS Study Group. Long-term durability of sacral nerve stimulation therapy for chronic fecal incontinence. Dis Colon Rectum. 2013;56:234-245. 

In this multicenter, prospective cohort study, Hull and colleagues evaluated the 5-year efficacy of sacral neuromodulation (SNM), also known as sacral nerve stimulation, for treatment of FI. This study followed an earlier investigation by Wexner and colleagues, which reported that 83% of 120 patients treated with SNM had a 50% or greater improvement in FI episodes at 12 months.¹⁶ 

Details of the study 

The investigators enrolled 133 participants (92% female) who had more than 2 episodes of FI per week for longer than 6 months (12 months after vaginal delivery). Participants were excluded if they had congenital anorectal malformations, prior rectal surgery within the past 12 months (or 24 months if due to cancer), defects greater than 120° of the external anal sphincter (EAS), IBD, unmanaged chronic watery diarrhea, stool consistency type 6 or type 7 on the Bristol Stool Scale, sequela of pelvic radiation, active anal abscess or fistula, pregnancy, or planned pregnancy. 

Eligible participants underwent a 2-stage procedure with the InterStim bowel control device (Medtronic). If participants experienced a 50% or greater reduction in incontinence episodes with a wearable external SNM device in the test stimulation (stage 1), they received the chronic SNM implant device (stage 2). 

Participants who underwent device implantation were followed at 1, 3, and 6 months and annually for 5 years or until they exited the study. Bowel diaries and quality of life assessments were completed at baseline and at follow-up. 

The primary outcome was therapeutic success, defined as 50% or greater improvement in FI episodes per week. 

A total of 120 participants (90%) underwent implantation of the chronic lead and neuromodulator, and 76 (63%) were followed for 5 years. Baseline characteristics available in the initial study of 133 participants showed that the mean age was 60.5 years; 25% had undergone a prior anal sphincteroplasty; and 16.5% and 10.5% had EAS or internal anal sphincter (IAS) defects, respectively, on endoanal ultrasonography.¹⁶ 

Therapeutic success was high at 5 years 

At the 5-year follow-up, 89% (64/72) of participants met therapeutic success, with a reduction in weekly FI episodes from 9.1 at baseline to 1.7 at 5 years. The number of incontinence pads required decreased, and more participants wore no pads at 5 years. In the intention-to-treat analysis, carrying forward the baseline FI rate in participants who lacked follow-up data, the therapeutic success rate was 69%. Quality-of-life measures improved at 5 years, both statistically and by minimal clinical difference. 

Adverse events. Sixty-eight percent of participants experienced device-related adverse events, including implant site pain, change in sensation of stimulation, change in efficacy, implant site infection, or neurostimulator battery depletion (neurostimulator use commonly expires after 3 to 5 years). Of these events, 80% were successfully treated with medications, reprogramming, or no intervention. The 5-year probability of device revision or replacement was 24.4%, and the 5-year probability of device explant was 19.0%. 

Strengths and limitations. Overall, this study was a well-designed, multicenter trial with long-term follow-up that showed significant improvement in FI with the use of SNM. Its strengths include the enrollment of postmenopausal women who had current defects in EAS and/or IAS on endoanal ultrasonography and 25% who had a prior sphincteroplasty. The findings therefore are relevant to the gynecologic population in whom anal sphincteroplasty would not be recommended. The study also accounted for dropouts and reported the adjusted success rate of 69% at 5 years in that group. 

The lack of a control arm to rule out the placebo effect is a limitation of this study, although randomized trials comparing the effect of SNM "on" versus "off" showed greater improvement with the device "on."¹⁷ 

Fecal incontinence (FI), also known as accidental bowel leakage, is the involuntary loss of feces, which includes both liquid and solid stool as defined by the International Continence Society (ICS) and the International Urogynecological Association (IUGA).^1,2 Fecal incontinence is common, occurring in 7% to 25% of community-dwelling women, and it increases with age.^2-6 The condition is rarely addressed, with only 30% of women seeking care.^6-8 This is due to patient embarrassment and the lack of a reliable screening tool. However, FI affects quality of life and mental health, and the associated economic burden likely will rise given the increased prevalence of FI among older women.^2,4,7,9

Fecal incontinence occurs due to poor stool consistency, anal and pelvic muscle weakness, reduced rectal compliance, reduced or increased rectal sensation, or bowel inflammation or dysfunction. Many conditions can cause FI (TABLE 1).^5,10,11 It is therefore important to elicit a full medical history with a focus on specific bowel symptoms, such as stool consistency type (TABLE 2),¹² FI frequency, and duration of symptoms, as well as to perform a complete examination to identify any readily reversible or malignant causes. A colonoscopy is recommended for individuals who meet screening criteria or present with a change in bowel symptoms, such as diarrhea, bleeding, or obstruction.^13,14

Fecal incontinence treatments include a range of approaches categorized from conservative, or first-line therapy, to fourth-line surgical managements (FIGURE 1).^1,10,13,14 In this Update, we review the results of 3 well-designed trials that enrolled women with frequent nonneurogenic FI. 

Common first- and second-line treatments produce equivalent improvements in FI symptoms at
6 months 

Jelovsek JE, Markland AD, Whitehead WE, et al; National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Controlling faecal incontinence in women by performing anal exercises with biofeedback or loperamide: a randomized clinical trial. Lancet Gastroenterol Hepatol. 2019;4:698-710. 

In a multicenter, randomized trial of first- and second-line treatments for FI, Jelovsek and colleagues evaluated the efficacy of oral placebo, loperamide, pelvic floor physical therapy (PFPT) with biofeedback using anorectal manometry, or combination therapy over a 24-week period. 

Continue to: Four treatments compared...

Three hundred women with FI occurring monthly for 3 months were included in the trial. Women were excluded if they had a stool classification of type 1 or type 7 on the Bristol Stool Scale, inflammatory bowel disease (IBD), history of rectovaginal fistula or cloacal defect, rectal prolapse, prior bowel diversion, fecal impaction, neurologic disorder leading to incontinence, use of loperamide or diphenoxylate within the last 30 days, childbirth within the last 3 months, need for antiretroviral drugs, hepatic impairment, or chronic abdominal pain without diarrhea. 

Baseline characteristics and symptoms severity were similar among participants. The average age of the women was 63 years, with 79% white and 85% postmenopausal. Participants had a mean (SD) of 1.6 (1.8) leaks per day. 

Participants were randomly assigned in a 0.5:1:1:1 fashion to receive oral placebo, loperamide, oral placebo with PFPT/biofeedback, or loperamide with PFPT/biofeedback. All participants received a standardized educational pamphlet that outlined dietary and behavioral recommendations. 

Women assigned to PFPT/biofeedback received 6 sessions every other week. Loperamide was started at a dosage of 2 mg per day with the possibility of dose maintenance, escalation, reduction, or discontinuation. 

Study outcomes. The primary outcome was a change from baseline to 24 weeks in the Vaizey FI symptom severity score, which assesses fecal frequency, urgency, and use of pads and medications. Secondary outcomes included assessment of a 7-day bowel diary and other quality-of-life measures. Data at 24 weeks were available for 89% of the women. 

All treatment groups experienced improved FI symptoms 

Based on changes in Vaizey scores after 24 weeks of treatment, women in all treatment groups had similar improvement in symptoms severity. However, those who received loperamide and PFPT/biofeedback had decreased pad changes per week and more accident-free days compared with women treated with placebo and biofeedback. Quality of life at 24 weeks was not statistically different between treatment groups as improvement was seen in all groups, including those who received oral placebo and patient education. 

Adverse events. The proportion of gastrointestinal adverse effects was similar between treatment groups, ranging from 45% to 63%. Constipation was the most common adverse event overall and was more common in those taking loperamide, occurring in 51% of the loperamide plus PFPT/biofeedback group, 38% of those who received loperamide alone, 23% of the biofeedback with placebo group, and 12% of the placebo-alone group. 

Strengths and limitations. Strengths of this study include its multisite, large sample size, low dropout rate, and sufficiently powered design to compare various combinations of first- and second-line therapies in women with a mean baseline FI of 1.6 leaks per day. Another strength is the robustness of the PFPT/biofeedback sessions that used anorectal manometry. This may, however, limit the study's external validity given that clinical use of this device is likely rare. Additionally, the population was comprised largely of postmenopausal and white women, which may make the findings less generalizable to other populations. 

Continue to: Novel vaginal bowel control system...

Novel vaginal bowel control system is effective, durable over 12 months for FI treatment 

Richter HE, Dunivan G, Brown HW, et al. A 12-month clinical durability of effectiveness and safety evaluation of a vaginal bowel control system for the nonsurgical treatment of fecal incontinence. Female Pelvic Med Reconstr Surg. 2019;25:113-119. 

Richter and colleagues characterized clinical success, effect on quality of life, and durability over 12 months of a novel vaginal bowel control device (Eclipse System; Pelvalon) for FI in a prospective cohort study. The device is a silicone-coated vaginal insert with a detachable pump and balloon that deflects the rectovaginal septum posteriorly, thus impeding the passage of stool in the rectum (FIGURE 2). 

Study eligibility criteria and treatment protocol 

Women were eligible for the study if they had 4 or more episodes of fecal soiling on a 2-week bowel diary and had FI for at least 6 months. Participants were excluded if they had prolapse outside the hymen, rectovaginal fistula, IBD, congenital anorectal malformation, urinary or colorectal infection, chronic pelvic or anorectal pain, pregnancy or planning pregnancy in the next 5 months, unmanaged chronic watery diarrhea, presence of an open wound or tear in the vagina, significant urogenital atrophy, or any psychiatric or neurologic disorder that would hinder the ability to participate. 

Participants successfully fitted with the device (3 attempts were allowed) were entered into the study's run-in phase. Those who were successfully fitted and had a 50% or greater reduction in FI continued into the treatment phase with 12 months of follow-up. 

Of the 137 women eligible for device fitting, 62% were successfully fitted. The 73 (86%) women who had a 50% or greater reduction in FI during the run-in period comprised the intent-to-treat study population. On average, these women were 61.3 years of age, with 70% white and 82% postmenopausal. At baseline, they had a mean of 14.1 episodes of FI over 2 weeks. (Prior to enrollment, 97.3% of women attempted self-management strategies, 17.8% to 23% failed conservative therapy, and 7.8% to 13.7% failed surgical therapy.) The follow-up rate at 12 months was 74%. 

Study outcomes. The primary outcome was treatment success, defined as proportion of subjects with a 50% or greater reduction in FI episodes at 3 months; this outcome also was evaluated at 6 and 12 months. Secondary outcomes were the number of FI episodes and quality-of-life measures at 3, 6, and 12 months. 

Treatment success, patient satisfaction high 

In the treatment phase, women had sustained improvements in symptom severity and quality-of-life measures over 12 months. Treatment success was 73% at 3 months, 71% at 6 months, and 70% at 12 months. Complete continence was achieved in 46% of participants at 12 months, and major FI episodes (requiring immediate change of undergarments) decreased from 5.0 at baseline to 0.5 at 12 months. Quality-of-life measures were improved at 3 months, and improvement was sustained over 12 months. Satisfaction was 94% at 12 months. 

Adverse events. No serious device-related adverse events occurred. Mild device-related adverse events were experienced by 45% of women during the fitting process and by 38% during treatment period. These included vaginal wall injury such as hyperemia and erosion; vaginal or pelvic discomfort; vaginal infection; constipation; and lower urinary tract issues such as urinary tract infection, urinary incontinence, and voiding dysfunction. No adverse events led to treatment discontinuation. 

Strengths and limitations. Strengths of this study include that it was conducted at multiple clinical sites, had a large sample size, and had a 1-year follow-up period in a population with daily FI. A limitation was that only women who had a 50% or greater reduction in FI episodes during the run-in period were followed for 12 months; however, this was 86% of the original cohort. The use of a comparative group using other devices, such as anal plugs, would have strengthened this study. 

Continue to: Sacroneuromodulation for FI…

Sacral neuromodulation for FI is effective long-term 

Hull T, Giese C, Wexner SD, et al; for the SNS Study Group. Long-term durability of sacral nerve stimulation therapy for chronic fecal incontinence. Dis Colon Rectum. 2013;56:234-245. 

In this multicenter, prospective cohort study, Hull and colleagues evaluated the 5-year efficacy of sacral neuromodulation (SNM), also known as sacral nerve stimulation, for treatment of FI. This study followed an earlier investigation by Wexner and colleagues, which reported that 83% of 120 patients treated with SNM had a 50% or greater improvement in FI episodes at 12 months.¹⁶ 

Details of the study 

The investigators enrolled 133 participants (92% female) who had more than 2 episodes of FI per week for longer than 6 months (12 months after vaginal delivery). Participants were excluded if they had congenital anorectal malformations, prior rectal surgery within the past 12 months (or 24 months if due to cancer), defects greater than 120° of the external anal sphincter (EAS), IBD, unmanaged chronic watery diarrhea, stool consistency type 6 or type 7 on the Bristol Stool Scale, sequela of pelvic radiation, active anal abscess or fistula, pregnancy, or planned pregnancy. 

Eligible participants underwent a 2-stage procedure with the InterStim bowel control device (Medtronic). If participants experienced a 50% or greater reduction in incontinence episodes with a wearable external SNM device in the test stimulation (stage 1), they received the chronic SNM implant device (stage 2). 

Participants who underwent device implantation were followed at 1, 3, and 6 months and annually for 5 years or until they exited the study. Bowel diaries and quality of life assessments were completed at baseline and at follow-up. 

The primary outcome was therapeutic success, defined as 50% or greater improvement in FI episodes per week. 

A total of 120 participants (90%) underwent implantation of the chronic lead and neuromodulator, and 76 (63%) were followed for 5 years. Baseline characteristics available in the initial study of 133 participants showed that the mean age was 60.5 years; 25% had undergone a prior anal sphincteroplasty; and 16.5% and 10.5% had EAS or internal anal sphincter (IAS) defects, respectively, on endoanal ultrasonography.¹⁶ 

Therapeutic success was high at 5 years 

At the 5-year follow-up, 89% (64/72) of participants met therapeutic success, with a reduction in weekly FI episodes from 9.1 at baseline to 1.7 at 5 years. The number of incontinence pads required decreased, and more participants wore no pads at 5 years. In the intention-to-treat analysis, carrying forward the baseline FI rate in participants who lacked follow-up data, the therapeutic success rate was 69%. Quality-of-life measures improved at 5 years, both statistically and by minimal clinical difference. 

Adverse events. Sixty-eight percent of participants experienced device-related adverse events, including implant site pain, change in sensation of stimulation, change in efficacy, implant site infection, or neurostimulator battery depletion (neurostimulator use commonly expires after 3 to 5 years). Of these events, 80% were successfully treated with medications, reprogramming, or no intervention. The 5-year probability of device revision or replacement was 24.4%, and the 5-year probability of device explant was 19.0%. 

Strengths and limitations. Overall, this study was a well-designed, multicenter trial with long-term follow-up that showed significant improvement in FI with the use of SNM. Its strengths include the enrollment of postmenopausal women who had current defects in EAS and/or IAS on endoanal ultrasonography and 25% who had a prior sphincteroplasty. The findings therefore are relevant to the gynecologic population in whom anal sphincteroplasty would not be recommended. The study also accounted for dropouts and reported the adjusted success rate of 69% at 5 years in that group. 

The lack of a control arm to rule out the placebo effect is a limitation of this study, although randomized trials comparing the effect of SNM "on" versus "off" showed greater improvement with the device "on."¹⁷