Sorbitan sesquioleate (SSO), sorbitan monooleate (SMO), and related compounds are increasingly recognized contact allergens. Sorbitan sesquioleate and SMO are nonionic emulsifying agents derived from sorbitol.¹

Sorbitan sesquioleate, SMO, and other sorbitol derivatives are used as emulsifiers and dispersing agents in cosmetics, topical medications, topical emollients, produce, and other commercial products. Related compounds also are found in foods such as apples, berries, cherries, and sucrose-free cakes and cookies.¹ We present a case of allergic contact dermatitis (ACD) with positive patch testing to sorbitans and clinical correlation with beer and bread exposure.

Case Report

A 62-year-old man presented with a persistent pruritic rash of 6 months’ duration. Erythematous eczematous papules and plaques were observed on the face, neck, chest, abdomen, back, and upper and lower extremities, affecting approximately 60% of the body surface area. His current list of medications was reviewed and included a multivitamin, fish oil, and vitamin C. A punch biopsy revealed spongiotic dermatitis with eosinophils. Patch testing using the North American Contact Dermatitis Group Standard Series with supplemental allergens found in toiletries revealed a positive reaction to SSO and SMO that was persistent at 48 and 96 hours. Notably, patch testing for sodium benzoate, nickel, potassium dichromate, and balsam of Peru were negative. Investigation into the personal care products the patient used identified the presence of sorbitol solution in Vanicream bar soap and Vanicream moisturizing cream (Pharmaceutical Specialties Inc). These products were started after the development of the rash and were discontinued after positive patch testing, but the patient continued to experience the eruption with no improvement.

Retrospectively, the patient was able to correlate exacerbations with drinking beer and eating sandwiches. He habitually ate a sandwich on the same type of bread every single day and enjoyed the same brand of beer 2 to 4 times per week without much variation. To limit allergens, the patient gave up the daily sandwich and avoided bread altogether, noting remarkable clinical improvement over a few weeks. Later, he described even more improvement while on a trip where he did not have access to his usual beer. The eruption recurred when he returned home and excessively indulged in his favorite beer. He also noted recurrence with exposure to certain breads. No new lesions developed with avoidance of beer and bread, and he had less than 1% body surface area involvement at 2-month follow-up and 0% involvement at 1 year. For educational purposes, follow-up patch testing was performed using Vanicream sorbitol solution and the specific beer and bread the patient consumed. The Vanicream solution was obtained from the manufacturer. The beer was placed directly onto a test disc. The bread was moistened with a drop of saline and then placed directly onto a test disc. All were negative at 48 and 96 hours.

Comment

Sorbitol Ingredients
We report a case of systemic ACD with a positive patch test to sorbitans that was exacerbated with consumption of beer and bread and resolved with avoidance of these products. Although it was determined that the patient used personal care products containing a sorbitol solution, discontinuation did not result in clinical improvement. Sorbitol, sorbitans, and sorbitol derivatives are not commonly reported in the ingredient lists of foods such as beer and bread. Both beer and bread are created with the addition of yeast cultures, for fermentation in beer and for leavening in bread. Sorbitol is used as an osmotic stabilizer in the preparation of yeast strains² and also is a by-product of fermentation by certain bacteria³ found in beer. Additionally, review of commercially available preparations of baker’s and brewer’s yeasts, such as Fleischmann’s and Red Star, list sorbitan monostearate in the ingredients.^4-7 We propose that trace amounts are present in the yeast preparations for brewing and baking.

In this case, the offending beer and bread were locally made products (Abita Beer, Covington, Louisiana; Leidenheimer Bread, New Orleans, Louisiana). Both companies were unable to share their yeast sources, limiting our ability to confirm the use of sorbitol in their preparation. We hypothesize that if sorbitol is commonly used in yeast culture preparation and can be a by-product of fermentation, then it is present in trace amounts in many beers and breads and is not specific to these two products.

Contact Allergy
There are few prior reports of ACD due to beer. A case series in 1969 described 4 patients with positive patch testing to ethanol and alcohol by-products and clinical resolution with avoidance of alcohol.⁸ Another case from 1985 described ACD to beer where patch testing was positive to the beer itself.⁹ Other published cases of cutaneous reactions to beer demonstrated immediate-type hypersensitivity resulting from both ingestion and skin contact, which is thought to be caused by IgE antibodies to malt and barley proteins.^10,11

It is important to distinguish between systemic ACD and oral allergy syndrome (OAS). Although the defining features and criteria for diagnosing OAS have not been officially established, OAS is an IgE-mediated immune reaction commonly described as itching, tingling, or swelling, usually confined to the oral cavity after recent consumption of foods such as raw fruits, vegetables, and nuts.¹² Oral allergy syndrome is treated with antihistamines and avoidance of known food allergens. In comparison, ACD is a type IV hypersensitivity, delayed cell-mediated reaction, commonly presenting with widespread rash.

Occupational contact dermatitis is common in bakers and food handlers and is more often irritant than allergic. Several relevant allergens have been identified in these groups^13,14 and do not include sorbitans; our patient tested positive to both SSO and SMO. Sorbitan sesquioleate and SMO have been increasingly recognized as contact allergens over the last several years, both as standalone allergens and as potential cross-reactors.¹ Sorbitan sesquioleate, SMO, and other sorbitol derivatives are found in cosmetics, topical and oral medications, topical emollients, produce, and other commercial products, including but not limited to topical clindamycin, topical metronidazole, topical ketoconazole, tazarotene cream 0.05% and 0.1%, toothpastes, acetaminophen maximum strength liquid, apples, berries, and sucrose-free cakes and cookies.^1,15,16

In 2014, a study evaluated 12 oral antihistamines as potential sources for systemic contact allergens; 55% of these 12 oral antihistamine preparations included at least 1 of 10 allergen groups specifically identified. The sorbitans and sorbitol derivatives group ranked highest among the group of allergens found listed in these oral medications.¹⁷

Most patients found to have a contact allergy to the products containing SSO, SMO, or sorbitol derivatives reported notable improvement with discontinuation and change to sorbitol-free product use.^1,18 It should be noted that SSO is added as an emulsifier to many of the fragrances used for patch testing. A positive patch test to fragrance mix without concomitant sorbitan testing may incorrectly diagnose the allergen.¹⁹

Patients with atopic dermatitis, particularly those with a filaggrin mutation, are at increased risk for ACD to sorbitans due to a compromised skin barrier and frequent use of topical steroids. In one study, 75% of patients (n=12) with a positive patch test to SSO were using a topical steroid emulsified with sorbitol or sorbitan derivatives.¹⁹

Conclusion

Sorbitan sesquioleate and SMO are increasingly relevant contact allergens. Sorbitol and related substances have been identified in numerous products and may be present in yeast-fermented and leavened goods. When patch testing is positive to SSO and SMO, the dermatologist should inquire about dietary habits with specific attention to beer and bread, in addition to inventorying other dietary preferences, prescription and over-the-counter medications, and personal care products. We suggest dietary considerations only if topical exposures have been eliminated and the rash has not improved.

Sorbitan sesquioleate (SSO), sorbitan monooleate (SMO), and related compounds are increasingly recognized contact allergens. Sorbitan sesquioleate and SMO are nonionic emulsifying agents derived from sorbitol.¹

Sorbitan sesquioleate, SMO, and other sorbitol derivatives are used as emulsifiers and dispersing agents in cosmetics, topical medications, topical emollients, produce, and other commercial products. Related compounds also are found in foods such as apples, berries, cherries, and sucrose-free cakes and cookies.¹ We present a case of allergic contact dermatitis (ACD) with positive patch testing to sorbitans and clinical correlation with beer and bread exposure.

Case Report

A 62-year-old man presented with a persistent pruritic rash of 6 months’ duration. Erythematous eczematous papules and plaques were observed on the face, neck, chest, abdomen, back, and upper and lower extremities, affecting approximately 60% of the body surface area. His current list of medications was reviewed and included a multivitamin, fish oil, and vitamin C. A punch biopsy revealed spongiotic dermatitis with eosinophils. Patch testing using the North American Contact Dermatitis Group Standard Series with supplemental allergens found in toiletries revealed a positive reaction to SSO and SMO that was persistent at 48 and 96 hours. Notably, patch testing for sodium benzoate, nickel, potassium dichromate, and balsam of Peru were negative. Investigation into the personal care products the patient used identified the presence of sorbitol solution in Vanicream bar soap and Vanicream moisturizing cream (Pharmaceutical Specialties Inc). These products were started after the development of the rash and were discontinued after positive patch testing, but the patient continued to experience the eruption with no improvement.

Retrospectively, the patient was able to correlate exacerbations with drinking beer and eating sandwiches. He habitually ate a sandwich on the same type of bread every single day and enjoyed the same brand of beer 2 to 4 times per week without much variation. To limit allergens, the patient gave up the daily sandwich and avoided bread altogether, noting remarkable clinical improvement over a few weeks. Later, he described even more improvement while on a trip where he did not have access to his usual beer. The eruption recurred when he returned home and excessively indulged in his favorite beer. He also noted recurrence with exposure to certain breads. No new lesions developed with avoidance of beer and bread, and he had less than 1% body surface area involvement at 2-month follow-up and 0% involvement at 1 year. For educational purposes, follow-up patch testing was performed using Vanicream sorbitol solution and the specific beer and bread the patient consumed. The Vanicream solution was obtained from the manufacturer. The beer was placed directly onto a test disc. The bread was moistened with a drop of saline and then placed directly onto a test disc. All were negative at 48 and 96 hours.

Comment

Sorbitol Ingredients
We report a case of systemic ACD with a positive patch test to sorbitans that was exacerbated with consumption of beer and bread and resolved with avoidance of these products. Although it was determined that the patient used personal care products containing a sorbitol solution, discontinuation did not result in clinical improvement. Sorbitol, sorbitans, and sorbitol derivatives are not commonly reported in the ingredient lists of foods such as beer and bread. Both beer and bread are created with the addition of yeast cultures, for fermentation in beer and for leavening in bread. Sorbitol is used as an osmotic stabilizer in the preparation of yeast strains² and also is a by-product of fermentation by certain bacteria³ found in beer. Additionally, review of commercially available preparations of baker’s and brewer’s yeasts, such as Fleischmann’s and Red Star, list sorbitan monostearate in the ingredients.^4-7 We propose that trace amounts are present in the yeast preparations for brewing and baking.

In this case, the offending beer and bread were locally made products (Abita Beer, Covington, Louisiana; Leidenheimer Bread, New Orleans, Louisiana). Both companies were unable to share their yeast sources, limiting our ability to confirm the use of sorbitol in their preparation. We hypothesize that if sorbitol is commonly used in yeast culture preparation and can be a by-product of fermentation, then it is present in trace amounts in many beers and breads and is not specific to these two products.

Contact Allergy
There are few prior reports of ACD due to beer. A case series in 1969 described 4 patients with positive patch testing to ethanol and alcohol by-products and clinical resolution with avoidance of alcohol.⁸ Another case from 1985 described ACD to beer where patch testing was positive to the beer itself.⁹ Other published cases of cutaneous reactions to beer demonstrated immediate-type hypersensitivity resulting from both ingestion and skin contact, which is thought to be caused by IgE antibodies to malt and barley proteins.^10,11

It is important to distinguish between systemic ACD and oral allergy syndrome (OAS). Although the defining features and criteria for diagnosing OAS have not been officially established, OAS is an IgE-mediated immune reaction commonly described as itching, tingling, or swelling, usually confined to the oral cavity after recent consumption of foods such as raw fruits, vegetables, and nuts.¹² Oral allergy syndrome is treated with antihistamines and avoidance of known food allergens. In comparison, ACD is a type IV hypersensitivity, delayed cell-mediated reaction, commonly presenting with widespread rash.

Occupational contact dermatitis is common in bakers and food handlers and is more often irritant than allergic. Several relevant allergens have been identified in these groups^13,14 and do not include sorbitans; our patient tested positive to both SSO and SMO. Sorbitan sesquioleate and SMO have been increasingly recognized as contact allergens over the last several years, both as standalone allergens and as potential cross-reactors.¹ Sorbitan sesquioleate, SMO, and other sorbitol derivatives are found in cosmetics, topical and oral medications, topical emollients, produce, and other commercial products, including but not limited to topical clindamycin, topical metronidazole, topical ketoconazole, tazarotene cream 0.05% and 0.1%, toothpastes, acetaminophen maximum strength liquid, apples, berries, and sucrose-free cakes and cookies.^1,15,16

In 2014, a study evaluated 12 oral antihistamines as potential sources for systemic contact allergens; 55% of these 12 oral antihistamine preparations included at least 1 of 10 allergen groups specifically identified. The sorbitans and sorbitol derivatives group ranked highest among the group of allergens found listed in these oral medications.¹⁷

Most patients found to have a contact allergy to the products containing SSO, SMO, or sorbitol derivatives reported notable improvement with discontinuation and change to sorbitol-free product use.^1,18 It should be noted that SSO is added as an emulsifier to many of the fragrances used for patch testing. A positive patch test to fragrance mix without concomitant sorbitan testing may incorrectly diagnose the allergen.¹⁹

Patients with atopic dermatitis, particularly those with a filaggrin mutation, are at increased risk for ACD to sorbitans due to a compromised skin barrier and frequent use of topical steroids. In one study, 75% of patients (n=12) with a positive patch test to SSO were using a topical steroid emulsified with sorbitol or sorbitan derivatives.¹⁹

Conclusion

Sorbitan sesquioleate and SMO are increasingly relevant contact allergens. Sorbitol and related substances have been identified in numerous products and may be present in yeast-fermented and leavened goods. When patch testing is positive to SSO and SMO, the dermatologist should inquire about dietary habits with specific attention to beer and bread, in addition to inventorying other dietary preferences, prescription and over-the-counter medications, and personal care products. We suggest dietary considerations only if topical exposures have been eliminated and the rash has not improved.

Sorbitan sesquioleate (SSO), sorbitan monooleate (SMO), and related compounds are increasingly recognized contact allergens. Sorbitan sesquioleate and SMO are nonionic emulsifying agents derived from sorbitol.¹

Sorbitan sesquioleate, SMO, and other sorbitol derivatives are used as emulsifiers and dispersing agents in cosmetics, topical medications, topical emollients, produce, and other commercial products. Related compounds also are found in foods such as apples, berries, cherries, and sucrose-free cakes and cookies.¹ We present a case of allergic contact dermatitis (ACD) with positive patch testing to sorbitans and clinical correlation with beer and bread exposure.

Case Report

A 62-year-old man presented with a persistent pruritic rash of 6 months’ duration. Erythematous eczematous papules and plaques were observed on the face, neck, chest, abdomen, back, and upper and lower extremities, affecting approximately 60% of the body surface area. His current list of medications was reviewed and included a multivitamin, fish oil, and vitamin C. A punch biopsy revealed spongiotic dermatitis with eosinophils. Patch testing using the North American Contact Dermatitis Group Standard Series with supplemental allergens found in toiletries revealed a positive reaction to SSO and SMO that was persistent at 48 and 96 hours. Notably, patch testing for sodium benzoate, nickel, potassium dichromate, and balsam of Peru were negative. Investigation into the personal care products the patient used identified the presence of sorbitol solution in Vanicream bar soap and Vanicream moisturizing cream (Pharmaceutical Specialties Inc). These products were started after the development of the rash and were discontinued after positive patch testing, but the patient continued to experience the eruption with no improvement.

Retrospectively, the patient was able to correlate exacerbations with drinking beer and eating sandwiches. He habitually ate a sandwich on the same type of bread every single day and enjoyed the same brand of beer 2 to 4 times per week without much variation. To limit allergens, the patient gave up the daily sandwich and avoided bread altogether, noting remarkable clinical improvement over a few weeks. Later, he described even more improvement while on a trip where he did not have access to his usual beer. The eruption recurred when he returned home and excessively indulged in his favorite beer. He also noted recurrence with exposure to certain breads. No new lesions developed with avoidance of beer and bread, and he had less than 1% body surface area involvement at 2-month follow-up and 0% involvement at 1 year. For educational purposes, follow-up patch testing was performed using Vanicream sorbitol solution and the specific beer and bread the patient consumed. The Vanicream solution was obtained from the manufacturer. The beer was placed directly onto a test disc. The bread was moistened with a drop of saline and then placed directly onto a test disc. All were negative at 48 and 96 hours.

Comment

Sorbitol Ingredients
We report a case of systemic ACD with a positive patch test to sorbitans that was exacerbated with consumption of beer and bread and resolved with avoidance of these products. Although it was determined that the patient used personal care products containing a sorbitol solution, discontinuation did not result in clinical improvement. Sorbitol, sorbitans, and sorbitol derivatives are not commonly reported in the ingredient lists of foods such as beer and bread. Both beer and bread are created with the addition of yeast cultures, for fermentation in beer and for leavening in bread. Sorbitol is used as an osmotic stabilizer in the preparation of yeast strains² and also is a by-product of fermentation by certain bacteria³ found in beer. Additionally, review of commercially available preparations of baker’s and brewer’s yeasts, such as Fleischmann’s and Red Star, list sorbitan monostearate in the ingredients.^4-7 We propose that trace amounts are present in the yeast preparations for brewing and baking.

In this case, the offending beer and bread were locally made products (Abita Beer, Covington, Louisiana; Leidenheimer Bread, New Orleans, Louisiana). Both companies were unable to share their yeast sources, limiting our ability to confirm the use of sorbitol in their preparation. We hypothesize that if sorbitol is commonly used in yeast culture preparation and can be a by-product of fermentation, then it is present in trace amounts in many beers and breads and is not specific to these two products.

Contact Allergy
There are few prior reports of ACD due to beer. A case series in 1969 described 4 patients with positive patch testing to ethanol and alcohol by-products and clinical resolution with avoidance of alcohol.⁸ Another case from 1985 described ACD to beer where patch testing was positive to the beer itself.⁹ Other published cases of cutaneous reactions to beer demonstrated immediate-type hypersensitivity resulting from both ingestion and skin contact, which is thought to be caused by IgE antibodies to malt and barley proteins.^10,11

It is important to distinguish between systemic ACD and oral allergy syndrome (OAS). Although the defining features and criteria for diagnosing OAS have not been officially established, OAS is an IgE-mediated immune reaction commonly described as itching, tingling, or swelling, usually confined to the oral cavity after recent consumption of foods such as raw fruits, vegetables, and nuts.¹² Oral allergy syndrome is treated with antihistamines and avoidance of known food allergens. In comparison, ACD is a type IV hypersensitivity, delayed cell-mediated reaction, commonly presenting with widespread rash.

Occupational contact dermatitis is common in bakers and food handlers and is more often irritant than allergic. Several relevant allergens have been identified in these groups^13,14 and do not include sorbitans; our patient tested positive to both SSO and SMO. Sorbitan sesquioleate and SMO have been increasingly recognized as contact allergens over the last several years, both as standalone allergens and as potential cross-reactors.¹ Sorbitan sesquioleate, SMO, and other sorbitol derivatives are found in cosmetics, topical and oral medications, topical emollients, produce, and other commercial products, including but not limited to topical clindamycin, topical metronidazole, topical ketoconazole, tazarotene cream 0.05% and 0.1%, toothpastes, acetaminophen maximum strength liquid, apples, berries, and sucrose-free cakes and cookies.^1,15,16

In 2014, a study evaluated 12 oral antihistamines as potential sources for systemic contact allergens; 55% of these 12 oral antihistamine preparations included at least 1 of 10 allergen groups specifically identified. The sorbitans and sorbitol derivatives group ranked highest among the group of allergens found listed in these oral medications.¹⁷

Most patients found to have a contact allergy to the products containing SSO, SMO, or sorbitol derivatives reported notable improvement with discontinuation and change to sorbitol-free product use.^1,18 It should be noted that SSO is added as an emulsifier to many of the fragrances used for patch testing. A positive patch test to fragrance mix without concomitant sorbitan testing may incorrectly diagnose the allergen.¹⁹

Patients with atopic dermatitis, particularly those with a filaggrin mutation, are at increased risk for ACD to sorbitans due to a compromised skin barrier and frequent use of topical steroids. In one study, 75% of patients (n=12) with a positive patch test to SSO were using a topical steroid emulsified with sorbitol or sorbitan derivatives.¹⁹

Conclusion

Sorbitan sesquioleate and SMO are increasingly relevant contact allergens. Sorbitol and related substances have been identified in numerous products and may be present in yeast-fermented and leavened goods. When patch testing is positive to SSO and SMO, the dermatologist should inquire about dietary habits with specific attention to beer and bread, in addition to inventorying other dietary preferences, prescription and over-the-counter medications, and personal care products. We suggest dietary considerations only if topical exposures have been eliminated and the rash has not improved.

Fleas of the order Siphonaptera are insects that feed on the blood of a mammalian host. They have no wings but jump to near 150 times their body lengths to reach potential hosts.¹ An epidemiologic survey performed in 2016 demonstrated that 96% of fleas in the United States are cat fleas (Ctenocephalides felis).² The bites often present as pruritic, nonfollicular-based, excoriated papules; papular urticaria; or vesiculobullous lesions distributed across the lower legs. Antihistamines and topical steroids may be helpful for symptomatic relief, but flea eradication is key.

Identification

Ctenocephalides fleas, including the common cat flea and the dog flea, have a characteristic pronotal comb that resembles a mane of hair (Figure 1) and genal comb that resembles a mustache. Compared to the dog flea (Ctenocephalides canis), cat fleas have a flatter head and fewer hair-bearing notches on the dorsal hind tibia (the dog flea has 8 notches and the cat flea has 6 notches)(Figure 2).

Flea Prevention and Eradication

Effective management of flea bites requires avoidance of infested areas and eradication of fleas from the home and pets. Home treatment should be performed by a qualified specialist and a veterinarian should treat the pet, but the dermatologist must be knowledgeable about treatment options. Flea pupae can lie dormant between floorboards for extended periods of time and hatch rapidly when new tenants enter a house or apartment. Insecticidal dusts and spray formulations frequently are used to treat infested homes. It also is important to reduce flea egg numbers by vacuuming carpets and areas where pets sleep.³ Rodents often introduce fleas to households and pets, so eliminating them from the area may play an important role in flea control. Consulting with a veterinarian is important, as treatment directed at pets is critical to control flea populations. Oral agents, including fluralaner, afoxolaner, sarolaner, and spinosad, can reduce flea populations on animals by as much as 99.3% after 7 days.^4,5 Fast-acting pulicidal agents, such as the combination of dinotefuran and fipronil, demonstrate curative activity as soon as 3 hours after treatment, which also may prevent reinfestation for as long as 6 weeks after treatment.⁶

Vector-Borne Disease

Fleas living on animals in close contact with humans, such as cats and dogs, can transmit zoonotic pathogens. Around 12,000 outpatients and 500 inpatients are diagnosed with cat scratch disease, a form of bartonellosis, annually. Ctenocephalides felis transmits Bartonella henselae from cat-to-cat and often cat-to-human through infected flea feces, causing a primary inoculation lesion and lymphadenitis. Of 3011 primary care providers surveyed from 2014 to 2015, 37.2% had treated at least 1 patient with cat scratch disease, yet knowledge gaps remain regarding the proper treatment and preventative measures for the disease.⁷ Current recommendations for the treatment of lymphadenitis caused by B henselae include a 5-day course of oral azithromycin.⁸ The preferred dosing regimen in adults is 500 mg on day 1 and 250 mg on days 2 through 5. Pediatric patients weighing less than 45.5 kg should receive 10 mg/kg on day 1 and 5 mg/kg on days 2 through 5.⁸ Additionally, less than one-third of the primary care providers surveyed from 2014 to 2015 said they would discuss the importance of pet flea control with immunocompromised patients who own cats, despite evidence implicating fleas in disease transmission.⁷ Pet-directed topical therapy with agents such as selamectin prescribed by a qualified veterinarian can prevent transmission of B henselae in cats exposed to fleas infected with the bacteria,⁹ which supports the importance of patient education and flea control, especially in pets owned by immunocompromised patients. Patients who are immunocompromised are at increased risk for persistent or disseminated bartonellosis, including endocarditis, in addition to cat scratch disease. Although arriving at a diagnosis may be difficult, one study found that bartonellosis in 13 renal transplant recipients was best diagnosed using both serology and polymerase chain reaction via DNA extraction of tissue specimens.¹⁰ These findings may enhance diagnostic yield for similar patients when bartonellosis is suspected.

Flea-borne typhus is endemic to Texas and Southern California.^11,12 Evidence suggests that the pathogenic bacteria, Rickettsia typhi and Rickettsia felis, also commonly infect fleas in the Great Plains area.¹³ Opossums carry R felis, and the fleas transmit murine or endemic typhus. A retrospective case series in Texas identified 11 cases of fatal flea-borne typhus from 1985 to 2015.¹¹ More than half of the patients reported contact with animals or fleas prior to the illness. Patients with typhus may present with fever, nausea, vomiting, rash (macular, maculopapular, papular, petechial, or morbilliform), respiratory or neurologic symptoms, thrombocytopenia, and elevated hepatic liver enzymes. Unfortunately, there often is a notable delay in initiation of treatment with the appropriate class of antibiotics—tetracyclines—and such delays can prove fatal.¹¹ The current recommendation for nonpregnant adults is oral doxycycline 100 mg twice daily continued 48 hours after the patient becomes afebrile or for 7 days, whichever therapy duration is longer.¹⁴ Because of the consequences of delayed treatment, it is important for clinicians to consider a diagnosis of vector-borne illness in a febrile patient with other associated gastrointestinal, cutaneous, respiratory, or neurologic symptoms, especially if they have animal or flea exposures. Flea control and exposure awareness remains paramount in preventing and treating this illness.

Yersinia pestis causes the plague, an important re-emerging disease that causes infection through flea bites, inhalation, or ingestion.¹⁵ From 2000 to 2009, 56 cases and 7 deaths in the United States—New Mexico, Arizona, Colorado, California, and Texas—and 21,725 cases and 1612 deaths worldwide were attributed to Y pestis. Most patients present with the bubonic form of the disease, with fever and an enlarging painful femoral or inguinal lymph node due to leg flea bites.¹⁶ Other forms of disease, including septicemic and pneumonic plague, are less common but relevant, as one-third of cases in the United States present with septicemia.^15,17,18 Although molecular diagnosis and immunohistochemistry play important roles, the diagnosis of Y pestis infection often is still accomplished with culture. A 2012 survey of 392 strains from 17 countries demonstrated that Y pestis remained susceptible to the antibiotics currently used to treat the disease, including doxycycline, streptomycin, gentamicin, tetracycline, trimethoprim-sulfamethoxazole, and ciprofloxacin.¹⁹

Human infection with Dipylidium caninum, a dog tapeworm, has been reported after suspected accidental ingestion of cat fleas carrying the parasite.²⁰ Children, who may present with diarrhea or white worms in their feces, are more susceptible to the infection, perhaps due to accidental flea consumption while being licked by the pet.^20,21

Conclusion

Cat fleas may act as a pruritic nuisance for pet owners and even deliver deadly pathogens to immunocompromised patients. Providers can minimize their impact by educating patients on flea prevention and eradication as well as astutely recognizing and treating flea-borne diseases.

Fleas of the order Siphonaptera are insects that feed on the blood of a mammalian host. They have no wings but jump to near 150 times their body lengths to reach potential hosts.¹ An epidemiologic survey performed in 2016 demonstrated that 96% of fleas in the United States are cat fleas (Ctenocephalides felis).² The bites often present as pruritic, nonfollicular-based, excoriated papules; papular urticaria; or vesiculobullous lesions distributed across the lower legs. Antihistamines and topical steroids may be helpful for symptomatic relief, but flea eradication is key.

Identification

Ctenocephalides fleas, including the common cat flea and the dog flea, have a characteristic pronotal comb that resembles a mane of hair (Figure 1) and genal comb that resembles a mustache. Compared to the dog flea (Ctenocephalides canis), cat fleas have a flatter head and fewer hair-bearing notches on the dorsal hind tibia (the dog flea has 8 notches and the cat flea has 6 notches)(Figure 2).

Flea Prevention and Eradication

Effective management of flea bites requires avoidance of infested areas and eradication of fleas from the home and pets. Home treatment should be performed by a qualified specialist and a veterinarian should treat the pet, but the dermatologist must be knowledgeable about treatment options. Flea pupae can lie dormant between floorboards for extended periods of time and hatch rapidly when new tenants enter a house or apartment. Insecticidal dusts and spray formulations frequently are used to treat infested homes. It also is important to reduce flea egg numbers by vacuuming carpets and areas where pets sleep.³ Rodents often introduce fleas to households and pets, so eliminating them from the area may play an important role in flea control. Consulting with a veterinarian is important, as treatment directed at pets is critical to control flea populations. Oral agents, including fluralaner, afoxolaner, sarolaner, and spinosad, can reduce flea populations on animals by as much as 99.3% after 7 days.^4,5 Fast-acting pulicidal agents, such as the combination of dinotefuran and fipronil, demonstrate curative activity as soon as 3 hours after treatment, which also may prevent reinfestation for as long as 6 weeks after treatment.⁶

Vector-Borne Disease

Fleas living on animals in close contact with humans, such as cats and dogs, can transmit zoonotic pathogens. Around 12,000 outpatients and 500 inpatients are diagnosed with cat scratch disease, a form of bartonellosis, annually. Ctenocephalides felis transmits Bartonella henselae from cat-to-cat and often cat-to-human through infected flea feces, causing a primary inoculation lesion and lymphadenitis. Of 3011 primary care providers surveyed from 2014 to 2015, 37.2% had treated at least 1 patient with cat scratch disease, yet knowledge gaps remain regarding the proper treatment and preventative measures for the disease.⁷ Current recommendations for the treatment of lymphadenitis caused by B henselae include a 5-day course of oral azithromycin.⁸ The preferred dosing regimen in adults is 500 mg on day 1 and 250 mg on days 2 through 5. Pediatric patients weighing less than 45.5 kg should receive 10 mg/kg on day 1 and 5 mg/kg on days 2 through 5.⁸ Additionally, less than one-third of the primary care providers surveyed from 2014 to 2015 said they would discuss the importance of pet flea control with immunocompromised patients who own cats, despite evidence implicating fleas in disease transmission.⁷ Pet-directed topical therapy with agents such as selamectin prescribed by a qualified veterinarian can prevent transmission of B henselae in cats exposed to fleas infected with the bacteria,⁹ which supports the importance of patient education and flea control, especially in pets owned by immunocompromised patients. Patients who are immunocompromised are at increased risk for persistent or disseminated bartonellosis, including endocarditis, in addition to cat scratch disease. Although arriving at a diagnosis may be difficult, one study found that bartonellosis in 13 renal transplant recipients was best diagnosed using both serology and polymerase chain reaction via DNA extraction of tissue specimens.¹⁰ These findings may enhance diagnostic yield for similar patients when bartonellosis is suspected.

Flea-borne typhus is endemic to Texas and Southern California.^11,12 Evidence suggests that the pathogenic bacteria, Rickettsia typhi and Rickettsia felis, also commonly infect fleas in the Great Plains area.¹³ Opossums carry R felis, and the fleas transmit murine or endemic typhus. A retrospective case series in Texas identified 11 cases of fatal flea-borne typhus from 1985 to 2015.¹¹ More than half of the patients reported contact with animals or fleas prior to the illness. Patients with typhus may present with fever, nausea, vomiting, rash (macular, maculopapular, papular, petechial, or morbilliform), respiratory or neurologic symptoms, thrombocytopenia, and elevated hepatic liver enzymes. Unfortunately, there often is a notable delay in initiation of treatment with the appropriate class of antibiotics—tetracyclines—and such delays can prove fatal.¹¹ The current recommendation for nonpregnant adults is oral doxycycline 100 mg twice daily continued 48 hours after the patient becomes afebrile or for 7 days, whichever therapy duration is longer.¹⁴ Because of the consequences of delayed treatment, it is important for clinicians to consider a diagnosis of vector-borne illness in a febrile patient with other associated gastrointestinal, cutaneous, respiratory, or neurologic symptoms, especially if they have animal or flea exposures. Flea control and exposure awareness remains paramount in preventing and treating this illness.

Yersinia pestis causes the plague, an important re-emerging disease that causes infection through flea bites, inhalation, or ingestion.¹⁵ From 2000 to 2009, 56 cases and 7 deaths in the United States—New Mexico, Arizona, Colorado, California, and Texas—and 21,725 cases and 1612 deaths worldwide were attributed to Y pestis. Most patients present with the bubonic form of the disease, with fever and an enlarging painful femoral or inguinal lymph node due to leg flea bites.¹⁶ Other forms of disease, including septicemic and pneumonic plague, are less common but relevant, as one-third of cases in the United States present with septicemia.^15,17,18 Although molecular diagnosis and immunohistochemistry play important roles, the diagnosis of Y pestis infection often is still accomplished with culture. A 2012 survey of 392 strains from 17 countries demonstrated that Y pestis remained susceptible to the antibiotics currently used to treat the disease, including doxycycline, streptomycin, gentamicin, tetracycline, trimethoprim-sulfamethoxazole, and ciprofloxacin.¹⁹

Human infection with Dipylidium caninum, a dog tapeworm, has been reported after suspected accidental ingestion of cat fleas carrying the parasite.²⁰ Children, who may present with diarrhea or white worms in their feces, are more susceptible to the infection, perhaps due to accidental flea consumption while being licked by the pet.^20,21

Conclusion

Cat fleas may act as a pruritic nuisance for pet owners and even deliver deadly pathogens to immunocompromised patients. Providers can minimize their impact by educating patients on flea prevention and eradication as well as astutely recognizing and treating flea-borne diseases.

Fleas of the order Siphonaptera are insects that feed on the blood of a mammalian host. They have no wings but jump to near 150 times their body lengths to reach potential hosts.¹ An epidemiologic survey performed in 2016 demonstrated that 96% of fleas in the United States are cat fleas (Ctenocephalides felis).² The bites often present as pruritic, nonfollicular-based, excoriated papules; papular urticaria; or vesiculobullous lesions distributed across the lower legs. Antihistamines and topical steroids may be helpful for symptomatic relief, but flea eradication is key.

Identification

Ctenocephalides fleas, including the common cat flea and the dog flea, have a characteristic pronotal comb that resembles a mane of hair (Figure 1) and genal comb that resembles a mustache. Compared to the dog flea (Ctenocephalides canis), cat fleas have a flatter head and fewer hair-bearing notches on the dorsal hind tibia (the dog flea has 8 notches and the cat flea has 6 notches)(Figure 2).

Flea Prevention and Eradication

Effective management of flea bites requires avoidance of infested areas and eradication of fleas from the home and pets. Home treatment should be performed by a qualified specialist and a veterinarian should treat the pet, but the dermatologist must be knowledgeable about treatment options. Flea pupae can lie dormant between floorboards for extended periods of time and hatch rapidly when new tenants enter a house or apartment. Insecticidal dusts and spray formulations frequently are used to treat infested homes. It also is important to reduce flea egg numbers by vacuuming carpets and areas where pets sleep.³ Rodents often introduce fleas to households and pets, so eliminating them from the area may play an important role in flea control. Consulting with a veterinarian is important, as treatment directed at pets is critical to control flea populations. Oral agents, including fluralaner, afoxolaner, sarolaner, and spinosad, can reduce flea populations on animals by as much as 99.3% after 7 days.^4,5 Fast-acting pulicidal agents, such as the combination of dinotefuran and fipronil, demonstrate curative activity as soon as 3 hours after treatment, which also may prevent reinfestation for as long as 6 weeks after treatment.⁶

Vector-Borne Disease

Fleas living on animals in close contact with humans, such as cats and dogs, can transmit zoonotic pathogens. Around 12,000 outpatients and 500 inpatients are diagnosed with cat scratch disease, a form of bartonellosis, annually. Ctenocephalides felis transmits Bartonella henselae from cat-to-cat and often cat-to-human through infected flea feces, causing a primary inoculation lesion and lymphadenitis. Of 3011 primary care providers surveyed from 2014 to 2015, 37.2% had treated at least 1 patient with cat scratch disease, yet knowledge gaps remain regarding the proper treatment and preventative measures for the disease.⁷ Current recommendations for the treatment of lymphadenitis caused by B henselae include a 5-day course of oral azithromycin.⁸ The preferred dosing regimen in adults is 500 mg on day 1 and 250 mg on days 2 through 5. Pediatric patients weighing less than 45.5 kg should receive 10 mg/kg on day 1 and 5 mg/kg on days 2 through 5.⁸ Additionally, less than one-third of the primary care providers surveyed from 2014 to 2015 said they would discuss the importance of pet flea control with immunocompromised patients who own cats, despite evidence implicating fleas in disease transmission.⁷ Pet-directed topical therapy with agents such as selamectin prescribed by a qualified veterinarian can prevent transmission of B henselae in cats exposed to fleas infected with the bacteria,⁹ which supports the importance of patient education and flea control, especially in pets owned by immunocompromised patients. Patients who are immunocompromised are at increased risk for persistent or disseminated bartonellosis, including endocarditis, in addition to cat scratch disease. Although arriving at a diagnosis may be difficult, one study found that bartonellosis in 13 renal transplant recipients was best diagnosed using both serology and polymerase chain reaction via DNA extraction of tissue specimens.¹⁰ These findings may enhance diagnostic yield for similar patients when bartonellosis is suspected.

Flea-borne typhus is endemic to Texas and Southern California.^11,12 Evidence suggests that the pathogenic bacteria, Rickettsia typhi and Rickettsia felis, also commonly infect fleas in the Great Plains area.¹³ Opossums carry R felis, and the fleas transmit murine or endemic typhus. A retrospective case series in Texas identified 11 cases of fatal flea-borne typhus from 1985 to 2015.¹¹ More than half of the patients reported contact with animals or fleas prior to the illness. Patients with typhus may present with fever, nausea, vomiting, rash (macular, maculopapular, papular, petechial, or morbilliform), respiratory or neurologic symptoms, thrombocytopenia, and elevated hepatic liver enzymes. Unfortunately, there often is a notable delay in initiation of treatment with the appropriate class of antibiotics—tetracyclines—and such delays can prove fatal.¹¹ The current recommendation for nonpregnant adults is oral doxycycline 100 mg twice daily continued 48 hours after the patient becomes afebrile or for 7 days, whichever therapy duration is longer.¹⁴ Because of the consequences of delayed treatment, it is important for clinicians to consider a diagnosis of vector-borne illness in a febrile patient with other associated gastrointestinal, cutaneous, respiratory, or neurologic symptoms, especially if they have animal or flea exposures. Flea control and exposure awareness remains paramount in preventing and treating this illness.

Yersinia pestis causes the plague, an important re-emerging disease that causes infection through flea bites, inhalation, or ingestion.¹⁵ From 2000 to 2009, 56 cases and 7 deaths in the United States—New Mexico, Arizona, Colorado, California, and Texas—and 21,725 cases and 1612 deaths worldwide were attributed to Y pestis. Most patients present with the bubonic form of the disease, with fever and an enlarging painful femoral or inguinal lymph node due to leg flea bites.¹⁶ Other forms of disease, including septicemic and pneumonic plague, are less common but relevant, as one-third of cases in the United States present with septicemia.^15,17,18 Although molecular diagnosis and immunohistochemistry play important roles, the diagnosis of Y pestis infection often is still accomplished with culture. A 2012 survey of 392 strains from 17 countries demonstrated that Y pestis remained susceptible to the antibiotics currently used to treat the disease, including doxycycline, streptomycin, gentamicin, tetracycline, trimethoprim-sulfamethoxazole, and ciprofloxacin.¹⁹

Human infection with Dipylidium caninum, a dog tapeworm, has been reported after suspected accidental ingestion of cat fleas carrying the parasite.²⁰ Children, who may present with diarrhea or white worms in their feces, are more susceptible to the infection, perhaps due to accidental flea consumption while being licked by the pet.^20,21

Conclusion

Cat fleas may act as a pruritic nuisance for pet owners and even deliver deadly pathogens to immunocompromised patients. Providers can minimize their impact by educating patients on flea prevention and eradication as well as astutely recognizing and treating flea-borne diseases.

Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease typically with childhood onset. In some cases, the condition persists, but AD usually resolves by the time a child reaches adulthood. Prevalence is difficult to estimate but, in developed countries, is approximately 15% to 30% among children and 2% to 10% among adults.¹

Atopic dermatitis is characterized by chronically itchy dry skin, weeping erythematous papules and plaques, and lichenification. Furthermore, AD often is associated with other atopic diseases, such as food allergy, allergic rhinitis, and bronchial asthma.

In this article, we review the literature on the quality of life (QOL) of patients with AD. Our goals are to discuss the most common methods for measuring QOL in AD and how to use them; highlight specific alterations of QOL in AD; and review data about QOL of children with AD, which is underrepresented in the medical literature, as studies tend to focus on adults. In addition, we address the importance of assessing QOL in patients with AD due to the psychological burden of the disease.

Quality of Life

The harmful effects of AD can include a range of areas, including emotional and mental health, physical activity, social functioning, sleep disturbance, decreased work productivity, financial expenditure, leisure activities, and family relationships. The impact varies by age of the patient, and there are specific instruments for measuring QOL in infants, children, adolescents, and adults.

Because QOL is an important instrument used in many AD studies, we call attention to the work of the Harmonising Outcome Measures for Eczema (HOME) initiative, which established a core outcome set for all AD clinical trials to enable comparison of results of individual studies.² Quality of life was identified in HOME as one of 4 basic outcome measures that should be included in every AD trial (the others are clinician-reported signs, patient-reported symptoms, and long-term control).³ According to the recent agreement, the following QOL instruments should be used: Dermatology Life Quality Index (DLQI) for adults, Children’s Dermatology Life Quality Index (CDLQI) for children, and Infants’ Dermatitis Quality of Life Index (IDQOL) for infants.⁴

In dermatology, these instruments can be divided into 3 basic categories: generic, dermatology specific, and disease specific.⁵ Generic QOL questionnaires are beneficial when comparing the QOL of an AD patient to patients with other conditions or to healthy individuals. On the other hand, dermatology-specific and AD-specific methods are more effective instruments for detecting impairments linked directly to the disease and, therefore, are more sensitive to changes in QOL.⁵ Some of the most frequently used QOL measures^5,6 for AD along with their key attributes are listed in the Table.

In contrast, several other methods that also are administered by a parent/guardian assess how the parent perceives the QOL of their child with AD; these methods are essential for small children and infants who cannot answer questions themselves. The IDQOL⁹ was designed to assess the QOL of patients younger than 4 years using a parent-completed questionnaire. For older children and adolescents aged 4 to 16 years, the CDLQI¹⁰ is a widely used instrument; the questionnaire is completed by the child and is available in a cartoon format.¹⁰

For patients older than 16 years, 2 important instruments are the DLQI, a generic dermatology instrument, and the Quality of Life Index for Atopic Dermatitis (QoLIAD).¹¹

Clearly it can be troublesome for researchers and clinicians to find the most suitable instrument to evaluate QOL in AD patients. To make this task easier, the European Academy of Dermatology and Venereology Task Force released a position paper with the following recommendations: (1) only validated instruments should be used, and (2) their use should be based on the age of the patients for which the instruments were designed. It is reommended that researchers use a combination of a generic and a dermatology-specific or AD-specific instrument, whereas clinicians should apply a dermatology-specific or AD-specific method, or both.⁵

Alterations of QOL in AD

Sleep Disturbance in AD
Sleep disorders observed in AD include difficulty falling asleep, frequent waking episodes, shorter sleep duration, and feelings of inadequate sleep, which often result in impairment of daily activity.^12,13 Correlation has been found between sleep quality and QOL in both children and adults.¹⁴ Approximately 60% of children affected by AD experience a sleep disturbance,¹⁵ which seems to correlate well with disease severity.¹⁶ A US study found that adults with AD are more likely to experience a sleep disturbance, which often affects daytime functioning and work productivity.¹³

Financial Aspects and Impact on Work
The financial burden of AD is extensive.¹⁷ There are direct medical costs, including medication, visits to the physician, alternative therapies, and nonprescription products. Patients tend to spend relevant money on such items as moisturizers, bath products, antihistamines, topical steroids, and topical antibiotics.^18,19 However, it seems that most of the cost of AD is due to indirect and nonmedical costs, including transportation to medical visits; loss of work days; extra childcare; and expenditures associated with lifestyle changes,^19,20 such as modifying diet, wearing special clothes, using special bed linens, and purchasing special household items (eg, anti–dust mite vacuum cleaner, humidifier, new carpeting).^17,19

Absenteeism from work often is a consequence of physician appointments; in addition, parents/guardians of a child with AD often miss work due to medical care. Even at work, patients (or parents/guardians) often experience decreased work productivity (so-called presenteeism) due to loss of sleep and anxiety.²¹ In addressing the effects of AD on work life, a systematic literature review found that AD strongly affects sick leave and might have an impact on job choice and change or loss of job.²²

Furthermore, according to Su et al,²³ the costs of AD are related to disease severity. Moreover, their data suggest that among chronic childhood diseases, the financial burden of AD is greater than the cost of asthma and similar to the cost of diabetes mellitus.²³

Association Between QOL and Disease Severity

A large observational study found that improvement in AD severity was followed by an increase in QOL.²⁴ A positive correlation between disease severity and QOL has been found in other studies,^25,26 though no correlation or only moderate correlation also has been reported.²⁷ Apparently, in addition to QOL, disease severity scores are substantial parameters in the evaluation of distress caused by AD; the HOME initiative has identified clinician-reported signs and patient-reported symptoms as 2 of 4 core outcomes domains to include in all future AD clinical trials.³ For measuring symptoms, the Patient-Oriented Eczema Measure (POEM) is the recommended instrument.²⁸ Regarding clinical signs, the HOME group named the Eczema Area and Severity Index (EASI) as the preferred instrument.²⁹

Psychological Burden

Stress is a triggering factor for AD, but the connection between skin and mind appears bidirectional. The biological reaction to stress probably lowers the itch threshold and disrupts the skin barrier.³⁰ The Global Burden of Disease Study showed that skin diseases are the fourth leading cause of nonfatal disease burden.³¹ There are several factors—pruritus, scratch, and pain—that can all lead to sleep deprivation and daytime fatigue. Based on our experience, if lesions develop on visible areas, patients can feel stigmatized, which restricts their social life.

The most common psychological comorbidities of AD are anxiety and depression. In a cross-sectional, multicenter study, there was a significantly higher prevalence of depression (P<.001) and anxiety disorder (P=.02) among patients with common skin diseases compared to a control group.³² In a study that assessed AD patients, researchers found a higher risk of depression and anxiety.³³ Suicidal ideation also is more common in the population with AD^32,34; a study showed that the risk of suicidal ideation in adolescents was nearly 4-fold in patients with itching skin lesions compared to those without itch.³⁴

According to Linnet and Jemec,³⁵ mental and psychological comorbidities of AD are associated with lower QOL, not with clinical severity. As a result, to improve QOL in AD, one should take care of both dermatological and psychological problems. It has been demonstrated that psychological interventions, such as autogenic training, cognitive-behavioral therapy, relaxation techniques, habit reversal training,³⁶ and hypnotherapy³⁷ might be helpful in individual cases; educational interventions also are recommended.³⁶ With these adjuvant therapies, psychological status, unpleasant clinical symptoms, and QOL could be improved, though further studies are needed to confirm these benefits.

Conclusion

Atopic dermatitis places a notable burden on patients and their families. The degree of burden is probably related to disease severity. For measuring QOL, researchers and clinicians should use validated methods suited to the age of the patients for which they were designed. More studies are needed to assess the effects of different treatments on QOL. Besides pharmacotherapy, psychotherapy and educational programs might be beneficial for improving QOL, another important area to be studied.

Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease typically with childhood onset. In some cases, the condition persists, but AD usually resolves by the time a child reaches adulthood. Prevalence is difficult to estimate but, in developed countries, is approximately 15% to 30% among children and 2% to 10% among adults.¹

Atopic dermatitis is characterized by chronically itchy dry skin, weeping erythematous papules and plaques, and lichenification. Furthermore, AD often is associated with other atopic diseases, such as food allergy, allergic rhinitis, and bronchial asthma.

In this article, we review the literature on the quality of life (QOL) of patients with AD. Our goals are to discuss the most common methods for measuring QOL in AD and how to use them; highlight specific alterations of QOL in AD; and review data about QOL of children with AD, which is underrepresented in the medical literature, as studies tend to focus on adults. In addition, we address the importance of assessing QOL in patients with AD due to the psychological burden of the disease.

Quality of Life

The harmful effects of AD can include a range of areas, including emotional and mental health, physical activity, social functioning, sleep disturbance, decreased work productivity, financial expenditure, leisure activities, and family relationships. The impact varies by age of the patient, and there are specific instruments for measuring QOL in infants, children, adolescents, and adults.

Because QOL is an important instrument used in many AD studies, we call attention to the work of the Harmonising Outcome Measures for Eczema (HOME) initiative, which established a core outcome set for all AD clinical trials to enable comparison of results of individual studies.² Quality of life was identified in HOME as one of 4 basic outcome measures that should be included in every AD trial (the others are clinician-reported signs, patient-reported symptoms, and long-term control).³ According to the recent agreement, the following QOL instruments should be used: Dermatology Life Quality Index (DLQI) for adults, Children’s Dermatology Life Quality Index (CDLQI) for children, and Infants’ Dermatitis Quality of Life Index (IDQOL) for infants.⁴

In dermatology, these instruments can be divided into 3 basic categories: generic, dermatology specific, and disease specific.⁵ Generic QOL questionnaires are beneficial when comparing the QOL of an AD patient to patients with other conditions or to healthy individuals. On the other hand, dermatology-specific and AD-specific methods are more effective instruments for detecting impairments linked directly to the disease and, therefore, are more sensitive to changes in QOL.⁵ Some of the most frequently used QOL measures^5,6 for AD along with their key attributes are listed in the Table.

In contrast, several other methods that also are administered by a parent/guardian assess how the parent perceives the QOL of their child with AD; these methods are essential for small children and infants who cannot answer questions themselves. The IDQOL⁹ was designed to assess the QOL of patients younger than 4 years using a parent-completed questionnaire. For older children and adolescents aged 4 to 16 years, the CDLQI¹⁰ is a widely used instrument; the questionnaire is completed by the child and is available in a cartoon format.¹⁰

For patients older than 16 years, 2 important instruments are the DLQI, a generic dermatology instrument, and the Quality of Life Index for Atopic Dermatitis (QoLIAD).¹¹

Clearly it can be troublesome for researchers and clinicians to find the most suitable instrument to evaluate QOL in AD patients. To make this task easier, the European Academy of Dermatology and Venereology Task Force released a position paper with the following recommendations: (1) only validated instruments should be used, and (2) their use should be based on the age of the patients for which the instruments were designed. It is reommended that researchers use a combination of a generic and a dermatology-specific or AD-specific instrument, whereas clinicians should apply a dermatology-specific or AD-specific method, or both.⁵

Alterations of QOL in AD

Sleep Disturbance in AD
Sleep disorders observed in AD include difficulty falling asleep, frequent waking episodes, shorter sleep duration, and feelings of inadequate sleep, which often result in impairment of daily activity.^12,13 Correlation has been found between sleep quality and QOL in both children and adults.¹⁴ Approximately 60% of children affected by AD experience a sleep disturbance,¹⁵ which seems to correlate well with disease severity.¹⁶ A US study found that adults with AD are more likely to experience a sleep disturbance, which often affects daytime functioning and work productivity.¹³

Financial Aspects and Impact on Work
The financial burden of AD is extensive.¹⁷ There are direct medical costs, including medication, visits to the physician, alternative therapies, and nonprescription products. Patients tend to spend relevant money on such items as moisturizers, bath products, antihistamines, topical steroids, and topical antibiotics.^18,19 However, it seems that most of the cost of AD is due to indirect and nonmedical costs, including transportation to medical visits; loss of work days; extra childcare; and expenditures associated with lifestyle changes,^19,20 such as modifying diet, wearing special clothes, using special bed linens, and purchasing special household items (eg, anti–dust mite vacuum cleaner, humidifier, new carpeting).^17,19

Absenteeism from work often is a consequence of physician appointments; in addition, parents/guardians of a child with AD often miss work due to medical care. Even at work, patients (or parents/guardians) often experience decreased work productivity (so-called presenteeism) due to loss of sleep and anxiety.²¹ In addressing the effects of AD on work life, a systematic literature review found that AD strongly affects sick leave and might have an impact on job choice and change or loss of job.²²

Furthermore, according to Su et al,²³ the costs of AD are related to disease severity. Moreover, their data suggest that among chronic childhood diseases, the financial burden of AD is greater than the cost of asthma and similar to the cost of diabetes mellitus.²³

Association Between QOL and Disease Severity

A large observational study found that improvement in AD severity was followed by an increase in QOL.²⁴ A positive correlation between disease severity and QOL has been found in other studies,^25,26 though no correlation or only moderate correlation also has been reported.²⁷ Apparently, in addition to QOL, disease severity scores are substantial parameters in the evaluation of distress caused by AD; the HOME initiative has identified clinician-reported signs and patient-reported symptoms as 2 of 4 core outcomes domains to include in all future AD clinical trials.³ For measuring symptoms, the Patient-Oriented Eczema Measure (POEM) is the recommended instrument.²⁸ Regarding clinical signs, the HOME group named the Eczema Area and Severity Index (EASI) as the preferred instrument.²⁹

Psychological Burden

Stress is a triggering factor for AD, but the connection between skin and mind appears bidirectional. The biological reaction to stress probably lowers the itch threshold and disrupts the skin barrier.³⁰ The Global Burden of Disease Study showed that skin diseases are the fourth leading cause of nonfatal disease burden.³¹ There are several factors—pruritus, scratch, and pain—that can all lead to sleep deprivation and daytime fatigue. Based on our experience, if lesions develop on visible areas, patients can feel stigmatized, which restricts their social life.

The most common psychological comorbidities of AD are anxiety and depression. In a cross-sectional, multicenter study, there was a significantly higher prevalence of depression (P<.001) and anxiety disorder (P=.02) among patients with common skin diseases compared to a control group.³² In a study that assessed AD patients, researchers found a higher risk of depression and anxiety.³³ Suicidal ideation also is more common in the population with AD^32,34; a study showed that the risk of suicidal ideation in adolescents was nearly 4-fold in patients with itching skin lesions compared to those without itch.³⁴

According to Linnet and Jemec,³⁵ mental and psychological comorbidities of AD are associated with lower QOL, not with clinical severity. As a result, to improve QOL in AD, one should take care of both dermatological and psychological problems. It has been demonstrated that psychological interventions, such as autogenic training, cognitive-behavioral therapy, relaxation techniques, habit reversal training,³⁶ and hypnotherapy³⁷ might be helpful in individual cases; educational interventions also are recommended.³⁶ With these adjuvant therapies, psychological status, unpleasant clinical symptoms, and QOL could be improved, though further studies are needed to confirm these benefits.

Conclusion

Atopic dermatitis places a notable burden on patients and their families. The degree of burden is probably related to disease severity. For measuring QOL, researchers and clinicians should use validated methods suited to the age of the patients for which they were designed. More studies are needed to assess the effects of different treatments on QOL. Besides pharmacotherapy, psychotherapy and educational programs might be beneficial for improving QOL, another important area to be studied.

Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease typically with childhood onset. In some cases, the condition persists, but AD usually resolves by the time a child reaches adulthood. Prevalence is difficult to estimate but, in developed countries, is approximately 15% to 30% among children and 2% to 10% among adults.¹

Atopic dermatitis is characterized by chronically itchy dry skin, weeping erythematous papules and plaques, and lichenification. Furthermore, AD often is associated with other atopic diseases, such as food allergy, allergic rhinitis, and bronchial asthma.

In this article, we review the literature on the quality of life (QOL) of patients with AD. Our goals are to discuss the most common methods for measuring QOL in AD and how to use them; highlight specific alterations of QOL in AD; and review data about QOL of children with AD, which is underrepresented in the medical literature, as studies tend to focus on adults. In addition, we address the importance of assessing QOL in patients with AD due to the psychological burden of the disease.

Quality of Life

The harmful effects of AD can include a range of areas, including emotional and mental health, physical activity, social functioning, sleep disturbance, decreased work productivity, financial expenditure, leisure activities, and family relationships. The impact varies by age of the patient, and there are specific instruments for measuring QOL in infants, children, adolescents, and adults.

Because QOL is an important instrument used in many AD studies, we call attention to the work of the Harmonising Outcome Measures for Eczema (HOME) initiative, which established a core outcome set for all AD clinical trials to enable comparison of results of individual studies.² Quality of life was identified in HOME as one of 4 basic outcome measures that should be included in every AD trial (the others are clinician-reported signs, patient-reported symptoms, and long-term control).³ According to the recent agreement, the following QOL instruments should be used: Dermatology Life Quality Index (DLQI) for adults, Children’s Dermatology Life Quality Index (CDLQI) for children, and Infants’ Dermatitis Quality of Life Index (IDQOL) for infants.⁴

In dermatology, these instruments can be divided into 3 basic categories: generic, dermatology specific, and disease specific.⁵ Generic QOL questionnaires are beneficial when comparing the QOL of an AD patient to patients with other conditions or to healthy individuals. On the other hand, dermatology-specific and AD-specific methods are more effective instruments for detecting impairments linked directly to the disease and, therefore, are more sensitive to changes in QOL.⁵ Some of the most frequently used QOL measures^5,6 for AD along with their key attributes are listed in the Table.

In contrast, several other methods that also are administered by a parent/guardian assess how the parent perceives the QOL of their child with AD; these methods are essential for small children and infants who cannot answer questions themselves. The IDQOL⁹ was designed to assess the QOL of patients younger than 4 years using a parent-completed questionnaire. For older children and adolescents aged 4 to 16 years, the CDLQI¹⁰ is a widely used instrument; the questionnaire is completed by the child and is available in a cartoon format.¹⁰

For patients older than 16 years, 2 important instruments are the DLQI, a generic dermatology instrument, and the Quality of Life Index for Atopic Dermatitis (QoLIAD).¹¹

Clearly it can be troublesome for researchers and clinicians to find the most suitable instrument to evaluate QOL in AD patients. To make this task easier, the European Academy of Dermatology and Venereology Task Force released a position paper with the following recommendations: (1) only validated instruments should be used, and (2) their use should be based on the age of the patients for which the instruments were designed. It is reommended that researchers use a combination of a generic and a dermatology-specific or AD-specific instrument, whereas clinicians should apply a dermatology-specific or AD-specific method, or both.⁵

Alterations of QOL in AD

Sleep Disturbance in AD
Sleep disorders observed in AD include difficulty falling asleep, frequent waking episodes, shorter sleep duration, and feelings of inadequate sleep, which often result in impairment of daily activity.^12,13 Correlation has been found between sleep quality and QOL in both children and adults.¹⁴ Approximately 60% of children affected by AD experience a sleep disturbance,¹⁵ which seems to correlate well with disease severity.¹⁶ A US study found that adults with AD are more likely to experience a sleep disturbance, which often affects daytime functioning and work productivity.¹³

Financial Aspects and Impact on Work
The financial burden of AD is extensive.¹⁷ There are direct medical costs, including medication, visits to the physician, alternative therapies, and nonprescription products. Patients tend to spend relevant money on such items as moisturizers, bath products, antihistamines, topical steroids, and topical antibiotics.^18,19 However, it seems that most of the cost of AD is due to indirect and nonmedical costs, including transportation to medical visits; loss of work days; extra childcare; and expenditures associated with lifestyle changes,^19,20 such as modifying diet, wearing special clothes, using special bed linens, and purchasing special household items (eg, anti–dust mite vacuum cleaner, humidifier, new carpeting).^17,19

Absenteeism from work often is a consequence of physician appointments; in addition, parents/guardians of a child with AD often miss work due to medical care. Even at work, patients (or parents/guardians) often experience decreased work productivity (so-called presenteeism) due to loss of sleep and anxiety.²¹ In addressing the effects of AD on work life, a systematic literature review found that AD strongly affects sick leave and might have an impact on job choice and change or loss of job.²²

Furthermore, according to Su et al,²³ the costs of AD are related to disease severity. Moreover, their data suggest that among chronic childhood diseases, the financial burden of AD is greater than the cost of asthma and similar to the cost of diabetes mellitus.²³

Association Between QOL and Disease Severity

A large observational study found that improvement in AD severity was followed by an increase in QOL.²⁴ A positive correlation between disease severity and QOL has been found in other studies,^25,26 though no correlation or only moderate correlation also has been reported.²⁷ Apparently, in addition to QOL, disease severity scores are substantial parameters in the evaluation of distress caused by AD; the HOME initiative has identified clinician-reported signs and patient-reported symptoms as 2 of 4 core outcomes domains to include in all future AD clinical trials.³ For measuring symptoms, the Patient-Oriented Eczema Measure (POEM) is the recommended instrument.²⁸ Regarding clinical signs, the HOME group named the Eczema Area and Severity Index (EASI) as the preferred instrument.²⁹

Psychological Burden

Stress is a triggering factor for AD, but the connection between skin and mind appears bidirectional. The biological reaction to stress probably lowers the itch threshold and disrupts the skin barrier.³⁰ The Global Burden of Disease Study showed that skin diseases are the fourth leading cause of nonfatal disease burden.³¹ There are several factors—pruritus, scratch, and pain—that can all lead to sleep deprivation and daytime fatigue. Based on our experience, if lesions develop on visible areas, patients can feel stigmatized, which restricts their social life.

The most common psychological comorbidities of AD are anxiety and depression. In a cross-sectional, multicenter study, there was a significantly higher prevalence of depression (P<.001) and anxiety disorder (P=.02) among patients with common skin diseases compared to a control group.³² In a study that assessed AD patients, researchers found a higher risk of depression and anxiety.³³ Suicidal ideation also is more common in the population with AD^32,34; a study showed that the risk of suicidal ideation in adolescents was nearly 4-fold in patients with itching skin lesions compared to those without itch.³⁴

According to Linnet and Jemec,³⁵ mental and psychological comorbidities of AD are associated with lower QOL, not with clinical severity. As a result, to improve QOL in AD, one should take care of both dermatological and psychological problems. It has been demonstrated that psychological interventions, such as autogenic training, cognitive-behavioral therapy, relaxation techniques, habit reversal training,³⁶ and hypnotherapy³⁷ might be helpful in individual cases; educational interventions also are recommended.³⁶ With these adjuvant therapies, psychological status, unpleasant clinical symptoms, and QOL could be improved, though further studies are needed to confirm these benefits.

Conclusion

Atopic dermatitis places a notable burden on patients and their families. The degree of burden is probably related to disease severity. For measuring QOL, researchers and clinicians should use validated methods suited to the age of the patients for which they were designed. More studies are needed to assess the effects of different treatments on QOL. Besides pharmacotherapy, psychotherapy and educational programs might be beneficial for improving QOL, another important area to be studied.

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.