Article

In a new attempt to replenish the constantly draining pool of mental health professionals, the US Department of Veterans Affairs (VA) is establishing a scholarship program for students pursuing graduate degrees in psychology, social work, marriage and family therapy, or mental health counseling. 

Staffing shortages in mental health have reached crisis proportions across the country, driven in part by 3 years of the pandemic. The VA is not immune. VA shortages go back a long way and have never really been resolved. In 2012, for instance, the VA announced that it planned to expand its mental health staff by nearly 10%, hiring about 1600 additional psychiatrists, psychologists, social workers, and other mental health clinicians to reduce long wait times at many VA medical centers. And indeed, between 2018 and 2021, the number of severe shortages reported declined from 3,068 to 2,152.

However, in 2021, the VA Office of the Inspector General (OIG) released its eighth report in a series on occupational staffing shortages for the 139 facilities. According to the OIG report, 136 facilities reported at least 1 severe occupational staffing shortage, an increase from 132 in fiscal year 2020. Psychiatry was the most frequently reported clinical occupation with severe staffing shortages.

In July 2022, the OIG released its ninth report and the fifth to identify “severe occupational staffing shortages” for VA facilities. The OIG found severe shortages were widespread: Facilities identified 2,622 severe occupational staffing shortages across 285 occupations, which ended a downward trend. Of the 139 facilities, 73 identified severe shortage in psychology, 71 listed psychiatry, 44 listed social work, and 30 listed registered nurse staff for inpatient mental health sections. 

In fact, although the Veterans Health Administration has been increasing the number of staff since 2017, psychology and psychiatry have remained in the top 10 most frequently reported severe shortages annually. 

The scholarship program, expected to start in summer 2023, will fund up to 2 years of graduate studies. After completing their degrees, the mental health professionals will serve full time for 6 years at one of the VA’s Vet Centers, specifically in underserved areas and in states with a per capita population of more than 5% veterans. Vet Centers are community-based outpatient counseling centers that provide a wide range of social and psychological services. 

“In 300 communities across the country, Vet Centers provide veterans, service members, and their families with quick and easy access to the mental health care they need and deserve,” said VA Secretary Denis McDonough. “These scholarships will help VA ensure all veterans and service members—including those in historically underserved areas—have access to Vet Centers with highly qualified, trained and compassionate staff.” 

The VA has posted a final rule for public inspection in the Federal Register 86 FR 81094 to create the scholarship program. 

In a new attempt to replenish the constantly draining pool of mental health professionals, the US Department of Veterans Affairs (VA) is establishing a scholarship program for students pursuing graduate degrees in psychology, social work, marriage and family therapy, or mental health counseling. 

Staffing shortages in mental health have reached crisis proportions across the country, driven in part by 3 years of the pandemic. The VA is not immune. VA shortages go back a long way and have never really been resolved. In 2012, for instance, the VA announced that it planned to expand its mental health staff by nearly 10%, hiring about 1600 additional psychiatrists, psychologists, social workers, and other mental health clinicians to reduce long wait times at many VA medical centers. And indeed, between 2018 and 2021, the number of severe shortages reported declined from 3,068 to 2,152.

However, in 2021, the VA Office of the Inspector General (OIG) released its eighth report in a series on occupational staffing shortages for the 139 facilities. According to the OIG report, 136 facilities reported at least 1 severe occupational staffing shortage, an increase from 132 in fiscal year 2020. Psychiatry was the most frequently reported clinical occupation with severe staffing shortages.

In July 2022, the OIG released its ninth report and the fifth to identify “severe occupational staffing shortages” for VA facilities. The OIG found severe shortages were widespread: Facilities identified 2,622 severe occupational staffing shortages across 285 occupations, which ended a downward trend. Of the 139 facilities, 73 identified severe shortage in psychology, 71 listed psychiatry, 44 listed social work, and 30 listed registered nurse staff for inpatient mental health sections. 

In fact, although the Veterans Health Administration has been increasing the number of staff since 2017, psychology and psychiatry have remained in the top 10 most frequently reported severe shortages annually. 

The scholarship program, expected to start in summer 2023, will fund up to 2 years of graduate studies. After completing their degrees, the mental health professionals will serve full time for 6 years at one of the VA’s Vet Centers, specifically in underserved areas and in states with a per capita population of more than 5% veterans. Vet Centers are community-based outpatient counseling centers that provide a wide range of social and psychological services. 

“In 300 communities across the country, Vet Centers provide veterans, service members, and their families with quick and easy access to the mental health care they need and deserve,” said VA Secretary Denis McDonough. “These scholarships will help VA ensure all veterans and service members—including those in historically underserved areas—have access to Vet Centers with highly qualified, trained and compassionate staff.” 

The VA has posted a final rule for public inspection in the Federal Register 86 FR 81094 to create the scholarship program. 

In a new attempt to replenish the constantly draining pool of mental health professionals, the US Department of Veterans Affairs (VA) is establishing a scholarship program for students pursuing graduate degrees in psychology, social work, marriage and family therapy, or mental health counseling. 

Staffing shortages in mental health have reached crisis proportions across the country, driven in part by 3 years of the pandemic. The VA is not immune. VA shortages go back a long way and have never really been resolved. In 2012, for instance, the VA announced that it planned to expand its mental health staff by nearly 10%, hiring about 1600 additional psychiatrists, psychologists, social workers, and other mental health clinicians to reduce long wait times at many VA medical centers. And indeed, between 2018 and 2021, the number of severe shortages reported declined from 3,068 to 2,152.

However, in 2021, the VA Office of the Inspector General (OIG) released its eighth report in a series on occupational staffing shortages for the 139 facilities. According to the OIG report, 136 facilities reported at least 1 severe occupational staffing shortage, an increase from 132 in fiscal year 2020. Psychiatry was the most frequently reported clinical occupation with severe staffing shortages.

In July 2022, the OIG released its ninth report and the fifth to identify “severe occupational staffing shortages” for VA facilities. The OIG found severe shortages were widespread: Facilities identified 2,622 severe occupational staffing shortages across 285 occupations, which ended a downward trend. Of the 139 facilities, 73 identified severe shortage in psychology, 71 listed psychiatry, 44 listed social work, and 30 listed registered nurse staff for inpatient mental health sections. 

In fact, although the Veterans Health Administration has been increasing the number of staff since 2017, psychology and psychiatry have remained in the top 10 most frequently reported severe shortages annually. 

The scholarship program, expected to start in summer 2023, will fund up to 2 years of graduate studies. After completing their degrees, the mental health professionals will serve full time for 6 years at one of the VA’s Vet Centers, specifically in underserved areas and in states with a per capita population of more than 5% veterans. Vet Centers are community-based outpatient counseling centers that provide a wide range of social and psychological services. 

“In 300 communities across the country, Vet Centers provide veterans, service members, and their families with quick and easy access to the mental health care they need and deserve,” said VA Secretary Denis McDonough. “These scholarships will help VA ensure all veterans and service members—including those in historically underserved areas—have access to Vet Centers with highly qualified, trained and compassionate staff.” 

The VA has posted a final rule for public inspection in the Federal Register 86 FR 81094 to create the scholarship program. 

These hyperpigmented lesions with fine scale on the outer edges are characteristic of pityriasis versicolor, also known as tinea versicolor. These macules (or patches) are commonly found on the trunk, proximal extremities, or neck. The lesions can be hypopigmented (pityriasis versicolor alba), hyperpigmented (pityriasis versicolor nigra), or erythematous (pityriasis versicolor rubra).¹ It is common to see hyperpigmentation in people with darker skin tones, as was the case with this patient. Pityriasis versicolor is often asymptomatic, but patients may describe mild to moderate pruritis.

Pityriasis versicolor is a common fungal infection of the superficial layers of the dermis caused by Malassezia furfur.² Impaired immunity and excessive sweating are risk factors for pityriasis versicolor; other risk factors include having a family member with tinea versicolor and living in a hot, humid region.¹ Adolescents and young adults are most often affected.¹

An evoked scale sign is a helpful tool to confirm the diagnosis clinically.³ Scale will appear when you stretch the affected skin with your thumb and index finger (or you scrape the area with a scalpel blade).³ If there is doubt about the diagnosis, use a potassium hydroxide (KOH) preparation; a positive test will reveal the classic “spaghetti and meatballs” pattern.¹

Selenium sulfide 2.5%, zinc pyrithione 1%, and ketoconazole 2% shampoo are effective topical treatments. The shampoo is applied full strength to the affected skin daily for 5 to 10 minutes before it’s washed off. This can be done for 1 to 4 weeks, with longer treatment courses resulting in higher cure rates. Systemic therapy is reserved for patients with widespread infection or those who do not respond to topical treatment.⁴ It’s important to advise patients that the restoration of normal skin pigmentation can takes months.

This patient was treated with ketoconazole 2% shampoo for 3 weeks. A complete return of skin color was achieved 6 months after completion of therapy.

‌

Image courtesy of Judy Jasser, MD. Text courtesy of Judy Jasser, MD, Department of Pediatrics, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

These hyperpigmented lesions with fine scale on the outer edges are characteristic of pityriasis versicolor, also known as tinea versicolor. These macules (or patches) are commonly found on the trunk, proximal extremities, or neck. The lesions can be hypopigmented (pityriasis versicolor alba), hyperpigmented (pityriasis versicolor nigra), or erythematous (pityriasis versicolor rubra).¹ It is common to see hyperpigmentation in people with darker skin tones, as was the case with this patient. Pityriasis versicolor is often asymptomatic, but patients may describe mild to moderate pruritis.

Pityriasis versicolor is a common fungal infection of the superficial layers of the dermis caused by Malassezia furfur.² Impaired immunity and excessive sweating are risk factors for pityriasis versicolor; other risk factors include having a family member with tinea versicolor and living in a hot, humid region.¹ Adolescents and young adults are most often affected.¹

An evoked scale sign is a helpful tool to confirm the diagnosis clinically.³ Scale will appear when you stretch the affected skin with your thumb and index finger (or you scrape the area with a scalpel blade).³ If there is doubt about the diagnosis, use a potassium hydroxide (KOH) preparation; a positive test will reveal the classic “spaghetti and meatballs” pattern.¹

Selenium sulfide 2.5%, zinc pyrithione 1%, and ketoconazole 2% shampoo are effective topical treatments. The shampoo is applied full strength to the affected skin daily for 5 to 10 minutes before it’s washed off. This can be done for 1 to 4 weeks, with longer treatment courses resulting in higher cure rates. Systemic therapy is reserved for patients with widespread infection or those who do not respond to topical treatment.⁴ It’s important to advise patients that the restoration of normal skin pigmentation can takes months.

This patient was treated with ketoconazole 2% shampoo for 3 weeks. A complete return of skin color was achieved 6 months after completion of therapy.

‌

Image courtesy of Judy Jasser, MD. Text courtesy of Judy Jasser, MD, Department of Pediatrics, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

These hyperpigmented lesions with fine scale on the outer edges are characteristic of pityriasis versicolor, also known as tinea versicolor. These macules (or patches) are commonly found on the trunk, proximal extremities, or neck. The lesions can be hypopigmented (pityriasis versicolor alba), hyperpigmented (pityriasis versicolor nigra), or erythematous (pityriasis versicolor rubra).¹ It is common to see hyperpigmentation in people with darker skin tones, as was the case with this patient. Pityriasis versicolor is often asymptomatic, but patients may describe mild to moderate pruritis.

Pityriasis versicolor is a common fungal infection of the superficial layers of the dermis caused by Malassezia furfur.² Impaired immunity and excessive sweating are risk factors for pityriasis versicolor; other risk factors include having a family member with tinea versicolor and living in a hot, humid region.¹ Adolescents and young adults are most often affected.¹

An evoked scale sign is a helpful tool to confirm the diagnosis clinically.³ Scale will appear when you stretch the affected skin with your thumb and index finger (or you scrape the area with a scalpel blade).³ If there is doubt about the diagnosis, use a potassium hydroxide (KOH) preparation; a positive test will reveal the classic “spaghetti and meatballs” pattern.¹

Selenium sulfide 2.5%, zinc pyrithione 1%, and ketoconazole 2% shampoo are effective topical treatments. The shampoo is applied full strength to the affected skin daily for 5 to 10 minutes before it’s washed off. This can be done for 1 to 4 weeks, with longer treatment courses resulting in higher cure rates. Systemic therapy is reserved for patients with widespread infection or those who do not respond to topical treatment.⁴ It’s important to advise patients that the restoration of normal skin pigmentation can takes months.

This patient was treated with ketoconazole 2% shampoo for 3 weeks. A complete return of skin color was achieved 6 months after completion of therapy.

‌

Image courtesy of Judy Jasser, MD. Text courtesy of Judy Jasser, MD, Department of Pediatrics, and Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

Evidence summary

GAHT may improve depression and quality of life, but not anxiety

A well-done systematic review of transgender men and transgender women demonstrated that GAHT of more than a year’s duration was associated with modestly improved standardized scores for QOL, depression, and possibly anxiety.¹ It was also associated with improved scores for depression in transgender adolescents.

The authors identified 15 prospective cohort studies (n = 626 transgender adults [mean age, 25-34 years]; 198 transgender adolescent girls and boys [mean age, 15-16 years]), 2 retrospective cohort studies (n = 1756 adults; mean age, 25-32 years), and 4 cross-sectional studies (n = 336 adults; mean age, 30-37 years).

Researchers recruited participants using strict eligibility criteria (psychiatric evaluation and formal diagnosis of gender dysphoria), with no prior history of GAHT, largely from gender-affirming specialty clinics at university hospitals. Most studies were conducted after the year 2000, predominantly in Europe (8 studies in Italy; 2 each in Belgium, the Netherlands, the United States, and Spain).

GAHT comprised testosterone for transgender men (14 studies used injectable testosterone cypionate, enanthate, undecanoate, or transdermal gels), estrogens (usually with an anti-androgen such as cyproterone acetate or spironolactone) for transgender women (10 studies used transdermal, oral, or injectable estradiol valerate or conjugated estrogens), and gonadotropin-releasing hormone (GnRH) therapy for transgender adolescents (3 studies).

Researchers evaluated the outcomes of QOL, depression, and anxiety with standardized scores on validated screening tools and suicide (2 studies) by medical records. GAHT in adult transgender men and transgender women was associated with modest improvements in QOL (3 of 5 studies) and depression (8 of 12 studies), and some improvement in anxiety scores (2 of 8 studies; see TABLE¹). There was insufficient evidence to determine whether GAHT had any effect on suicide. In adolescent transgender girls and boys, GAHT was associated with modest improvements in depression but not QOL or anxiety scores.

The authors rated the strength of evidence from the included studies as low, based on study quality (small study sizes, uncontrolled confounding factors, and risk of bias in study designs).

Additional research supports GAHT’s association with improved outcomes

Three studies, published after the systematic review, evaluated outcomes before and after GAHT and found similar results. All studies recruited treatment-seeking participants from specialty clinics.

Continue to: An Australian propsective longitudinal..

An Australian prospective longitudinal controlled study (n = 77 transgender adults; 103 cisgender controls) evaluated GAHT outcomes after 6 months and found a significant reduction in gender dysphoria scores in both transgender males (adjusted mean difference [aMD] = –6.8; 95% CI, –8.7 to –4.9; P < .001) and transgender females (aMD = –4.2; 95% CI, –6.2 to –2.2; P < .001) vs controls. QOL scores (emotional well-being, social functioning) improved only for transgender males (well-being: aMD = +7.5; 95% CI, 1.3 to 13.6; P < .018; social functioning: aMD = +12.5; 95% CI, 2.8 to 22.2; P = .011).²

A US prospective cohort study (n = 104 adolescents; mean age, 16 years) examined the effect of GnRH and/or GAHT over a 12-month period and found significant decreases in standardized scores for depression (adjusted odds ratio [aOR] = 0.4; 95% CI, 0.17-0.95) and suicidality (aOR = 0.27; 95% CI, 0.11-0.65) but not for anxiety. Participants who did not receive hormonal interventions had increased scores for depression and suicidality at 3 and 6 months’ follow-up.³

Gender-affirming hormone therapy in adult transgender men and transgender women was associated with modest improvements in QOL and depression, and some improvement in anxiety scores.

A prospective cohort study from the UK (n = 178 transgender adults) examined outcomes before and after GAHT treatment over 18 months and found significant decreases in standardized scores for depression (transgender males: –2.1; 95% CI, –3.2 to –1.2; P < .001; transgender females: –1.9; 95% CI, –2.8 to –1.0; P < .001) but not for anxiety.⁴

A large US study shows GAHT may reduce depression scores

A recent large cross-sectional study from the United States (n = 11,914 transgender or nonbinary youth, ages 13-24 years) found that receiving GAHT was associated with significantly lower odds of recent depression (aOR = 0.73; P < .001) and suicidality (aOR = 0.74; P < .001) compared to those who wanted GAHT but did not receive it. The authors were unable to differentiate the effects of receiving GAHT from the effects of parental support for their child’s gender identity, which may be a confounding factor.⁵

Recommendations from others

The World Professional Association for Transgender Health Standards of Care state that “gender incongruence that causes clinically significant distress and impairment often requires medically necessary clinical interventions” and recommends “health care professionals initiate and continue gender-affirming hormone therapy … due to demonstrated improvement in psychosocial functioning and quality of life.”⁶ The Endocrine Society Position Statement on Transgender Health states that “medical intervention for transgender youth and adults (including … hormone therapy) is effective, relatively safe (when appropriately monitored), and has been established as the standard of care.”⁷ The American Academy of Family Physicians “supports gender-­affirming care as an evidence-informed intervention that can promote health equity for gender-diverse individuals.”⁸

Editor’s takeaway

Family physicians commonly address many factors that can impact the QOL for our patients with gender dysphoria: lack of fixed residence, underemployment, food insecurity, and trauma. GAHT, especially in male-to-female transgender patients, may further improve QOL without evidence of harm.

Evidence summary

GAHT may improve depression and quality of life, but not anxiety

A well-done systematic review of transgender men and transgender women demonstrated that GAHT of more than a year’s duration was associated with modestly improved standardized scores for QOL, depression, and possibly anxiety.¹ It was also associated with improved scores for depression in transgender adolescents.

The authors identified 15 prospective cohort studies (n = 626 transgender adults [mean age, 25-34 years]; 198 transgender adolescent girls and boys [mean age, 15-16 years]), 2 retrospective cohort studies (n = 1756 adults; mean age, 25-32 years), and 4 cross-sectional studies (n = 336 adults; mean age, 30-37 years).

Researchers recruited participants using strict eligibility criteria (psychiatric evaluation and formal diagnosis of gender dysphoria), with no prior history of GAHT, largely from gender-affirming specialty clinics at university hospitals. Most studies were conducted after the year 2000, predominantly in Europe (8 studies in Italy; 2 each in Belgium, the Netherlands, the United States, and Spain).

GAHT comprised testosterone for transgender men (14 studies used injectable testosterone cypionate, enanthate, undecanoate, or transdermal gels), estrogens (usually with an anti-androgen such as cyproterone acetate or spironolactone) for transgender women (10 studies used transdermal, oral, or injectable estradiol valerate or conjugated estrogens), and gonadotropin-releasing hormone (GnRH) therapy for transgender adolescents (3 studies).

Researchers evaluated the outcomes of QOL, depression, and anxiety with standardized scores on validated screening tools and suicide (2 studies) by medical records. GAHT in adult transgender men and transgender women was associated with modest improvements in QOL (3 of 5 studies) and depression (8 of 12 studies), and some improvement in anxiety scores (2 of 8 studies; see TABLE¹). There was insufficient evidence to determine whether GAHT had any effect on suicide. In adolescent transgender girls and boys, GAHT was associated with modest improvements in depression but not QOL or anxiety scores.

The authors rated the strength of evidence from the included studies as low, based on study quality (small study sizes, uncontrolled confounding factors, and risk of bias in study designs).

Additional research supports GAHT’s association with improved outcomes

Three studies, published after the systematic review, evaluated outcomes before and after GAHT and found similar results. All studies recruited treatment-seeking participants from specialty clinics.

Continue to: An Australian propsective longitudinal..

An Australian prospective longitudinal controlled study (n = 77 transgender adults; 103 cisgender controls) evaluated GAHT outcomes after 6 months and found a significant reduction in gender dysphoria scores in both transgender males (adjusted mean difference [aMD] = –6.8; 95% CI, –8.7 to –4.9; P < .001) and transgender females (aMD = –4.2; 95% CI, –6.2 to –2.2; P < .001) vs controls. QOL scores (emotional well-being, social functioning) improved only for transgender males (well-being: aMD = +7.5; 95% CI, 1.3 to 13.6; P < .018; social functioning: aMD = +12.5; 95% CI, 2.8 to 22.2; P = .011).²

A US prospective cohort study (n = 104 adolescents; mean age, 16 years) examined the effect of GnRH and/or GAHT over a 12-month period and found significant decreases in standardized scores for depression (adjusted odds ratio [aOR] = 0.4; 95% CI, 0.17-0.95) and suicidality (aOR = 0.27; 95% CI, 0.11-0.65) but not for anxiety. Participants who did not receive hormonal interventions had increased scores for depression and suicidality at 3 and 6 months’ follow-up.³

Gender-affirming hormone therapy in adult transgender men and transgender women was associated with modest improvements in QOL and depression, and some improvement in anxiety scores.

A prospective cohort study from the UK (n = 178 transgender adults) examined outcomes before and after GAHT treatment over 18 months and found significant decreases in standardized scores for depression (transgender males: –2.1; 95% CI, –3.2 to –1.2; P < .001; transgender females: –1.9; 95% CI, –2.8 to –1.0; P < .001) but not for anxiety.⁴

A large US study shows GAHT may reduce depression scores

A recent large cross-sectional study from the United States (n = 11,914 transgender or nonbinary youth, ages 13-24 years) found that receiving GAHT was associated with significantly lower odds of recent depression (aOR = 0.73; P < .001) and suicidality (aOR = 0.74; P < .001) compared to those who wanted GAHT but did not receive it. The authors were unable to differentiate the effects of receiving GAHT from the effects of parental support for their child’s gender identity, which may be a confounding factor.⁵

Recommendations from others

The World Professional Association for Transgender Health Standards of Care state that “gender incongruence that causes clinically significant distress and impairment often requires medically necessary clinical interventions” and recommends “health care professionals initiate and continue gender-affirming hormone therapy … due to demonstrated improvement in psychosocial functioning and quality of life.”⁶ The Endocrine Society Position Statement on Transgender Health states that “medical intervention for transgender youth and adults (including … hormone therapy) is effective, relatively safe (when appropriately monitored), and has been established as the standard of care.”⁷ The American Academy of Family Physicians “supports gender-­affirming care as an evidence-informed intervention that can promote health equity for gender-diverse individuals.”⁸

Editor’s takeaway

Family physicians commonly address many factors that can impact the QOL for our patients with gender dysphoria: lack of fixed residence, underemployment, food insecurity, and trauma. GAHT, especially in male-to-female transgender patients, may further improve QOL without evidence of harm.

Evidence summary

GAHT may improve depression and quality of life, but not anxiety

A well-done systematic review of transgender men and transgender women demonstrated that GAHT of more than a year’s duration was associated with modestly improved standardized scores for QOL, depression, and possibly anxiety.¹ It was also associated with improved scores for depression in transgender adolescents.

The authors identified 15 prospective cohort studies (n = 626 transgender adults [mean age, 25-34 years]; 198 transgender adolescent girls and boys [mean age, 15-16 years]), 2 retrospective cohort studies (n = 1756 adults; mean age, 25-32 years), and 4 cross-sectional studies (n = 336 adults; mean age, 30-37 years).

Researchers recruited participants using strict eligibility criteria (psychiatric evaluation and formal diagnosis of gender dysphoria), with no prior history of GAHT, largely from gender-affirming specialty clinics at university hospitals. Most studies were conducted after the year 2000, predominantly in Europe (8 studies in Italy; 2 each in Belgium, the Netherlands, the United States, and Spain).

GAHT comprised testosterone for transgender men (14 studies used injectable testosterone cypionate, enanthate, undecanoate, or transdermal gels), estrogens (usually with an anti-androgen such as cyproterone acetate or spironolactone) for transgender women (10 studies used transdermal, oral, or injectable estradiol valerate or conjugated estrogens), and gonadotropin-releasing hormone (GnRH) therapy for transgender adolescents (3 studies).

Researchers evaluated the outcomes of QOL, depression, and anxiety with standardized scores on validated screening tools and suicide (2 studies) by medical records. GAHT in adult transgender men and transgender women was associated with modest improvements in QOL (3 of 5 studies) and depression (8 of 12 studies), and some improvement in anxiety scores (2 of 8 studies; see TABLE¹). There was insufficient evidence to determine whether GAHT had any effect on suicide. In adolescent transgender girls and boys, GAHT was associated with modest improvements in depression but not QOL or anxiety scores.

The authors rated the strength of evidence from the included studies as low, based on study quality (small study sizes, uncontrolled confounding factors, and risk of bias in study designs).

Additional research supports GAHT’s association with improved outcomes

Three studies, published after the systematic review, evaluated outcomes before and after GAHT and found similar results. All studies recruited treatment-seeking participants from specialty clinics.

Continue to: An Australian propsective longitudinal..

An Australian prospective longitudinal controlled study (n = 77 transgender adults; 103 cisgender controls) evaluated GAHT outcomes after 6 months and found a significant reduction in gender dysphoria scores in both transgender males (adjusted mean difference [aMD] = –6.8; 95% CI, –8.7 to –4.9; P < .001) and transgender females (aMD = –4.2; 95% CI, –6.2 to –2.2; P < .001) vs controls. QOL scores (emotional well-being, social functioning) improved only for transgender males (well-being: aMD = +7.5; 95% CI, 1.3 to 13.6; P < .018; social functioning: aMD = +12.5; 95% CI, 2.8 to 22.2; P = .011).²

A US prospective cohort study (n = 104 adolescents; mean age, 16 years) examined the effect of GnRH and/or GAHT over a 12-month period and found significant decreases in standardized scores for depression (adjusted odds ratio [aOR] = 0.4; 95% CI, 0.17-0.95) and suicidality (aOR = 0.27; 95% CI, 0.11-0.65) but not for anxiety. Participants who did not receive hormonal interventions had increased scores for depression and suicidality at 3 and 6 months’ follow-up.³

Gender-affirming hormone therapy in adult transgender men and transgender women was associated with modest improvements in QOL and depression, and some improvement in anxiety scores.

A prospective cohort study from the UK (n = 178 transgender adults) examined outcomes before and after GAHT treatment over 18 months and found significant decreases in standardized scores for depression (transgender males: –2.1; 95% CI, –3.2 to –1.2; P < .001; transgender females: –1.9; 95% CI, –2.8 to –1.0; P < .001) but not for anxiety.⁴

A large US study shows GAHT may reduce depression scores

A recent large cross-sectional study from the United States (n = 11,914 transgender or nonbinary youth, ages 13-24 years) found that receiving GAHT was associated with significantly lower odds of recent depression (aOR = 0.73; P < .001) and suicidality (aOR = 0.74; P < .001) compared to those who wanted GAHT but did not receive it. The authors were unable to differentiate the effects of receiving GAHT from the effects of parental support for their child’s gender identity, which may be a confounding factor.⁵

Recommendations from others

The World Professional Association for Transgender Health Standards of Care state that “gender incongruence that causes clinically significant distress and impairment often requires medically necessary clinical interventions” and recommends “health care professionals initiate and continue gender-affirming hormone therapy … due to demonstrated improvement in psychosocial functioning and quality of life.”⁶ The Endocrine Society Position Statement on Transgender Health states that “medical intervention for transgender youth and adults (including … hormone therapy) is effective, relatively safe (when appropriately monitored), and has been established as the standard of care.”⁷ The American Academy of Family Physicians “supports gender-­affirming care as an evidence-informed intervention that can promote health equity for gender-diverse individuals.”⁸

Editor’s takeaway

Family physicians commonly address many factors that can impact the QOL for our patients with gender dysphoria: lack of fixed residence, underemployment, food insecurity, and trauma. GAHT, especially in male-to-female transgender patients, may further improve QOL without evidence of harm.

THE COMPARISON

A and B Axilla of a 65-year-old White man with erythrasma showing a well-demarcated erythematous plaque with fine scale (A). Wood-lamp examination of the area showed characteristic bright coral red fluorescence (B).

C and D A well-demarcated, red-brown plaque with fine scale in the antecubital fossa of an obese Hispanic woman (C). Wood-lamp examination revealed bright coral red fluorescence (D).

E Hypopigmented patches (with pruritus) in the groin of a Black man. He also had erythrasma between the toes.

Erythrasma is a skin condition caused by acute or chronic infection of the outermost layer of the epidermis (stratum corneum) with Corynebacterium minutissimum. It has a predilection for intertriginous regions such as the axillae, groin, and interdigital spaces of the toes. It can be associated with pruritus or can be asymptomatic.

Epidemiology

Erythrasma typically affects adults, with greater prevalence among those residing in shared living facilities, such as dormitories or nursing homes, or in humid climates.¹ It is a common disorder with an estimated prevalence of 17.6% of bacterial skin infections in elderly patients and 44% of diabetic interdigital toe space infections.^2,3

Key clinical features

Erythrasma can manifest as red-brown hyperpigmented plaques with fine scale and little central clearing (FIGURES A and C) or as a hypopigmented patch (FIGURE E) with a sharply marginated, hyperpigmented border in patients with skin of color. In the interdigital toe spaces, the skin often is white and macerated. These findings may appear in patients of all skin tones.

Worth noting

• C minutissimum produces coproporphyrin III, which glows fluorescent red under Wood-lamp examination (FIGURES B and D). A recent shower or bath may remove the fluorescent coproporphyrins and cause a false-negative result. The interdigital space between the fourth and fifth toes is a common location for C minutissimum; thus clinicians should consider examining these areas with a Wood lamp.
• Associated risk factors include obesity, immunosuppression, diabetes mellitus, and excessive sweating.¹
• The differential diagnosis includes intertrigo, inverse psoriasis, confluent and reticulated papillomatosis (Gougerot-Carteaud syndrome), acanthosis nigricans, seborrheic dermatitis, and tinea pedis when present in the interdigital toe spaces. Plaques occurring in circular patterns may be mistaken for tinea corporis or pityriasis rotunda.
• There is a high prevalence of erythrasma in patients with inverse psoriasis, and it may exacerbate psoriatic plaques.⁴
• Treatment options include application of topical clindamycin or erythromycin to the affected area.1 Some patients have responded to topical mupiricin.2 For larger areas, a 1-g dose of clarithromycin⁵ or a 14-day course of erythromycin may be appropriate.¹ Avoid prescribing clarithromycin to patients with preexisting heart disease due to its increased risk for cardiac events or death; consider other agents.

Health disparity highlight

Obesity, most prevalent in non-Hispanic Black adults (49.9%) and Hispanic adults (45.6%) followed by non-Hispanic White adults (41.4%),⁶ may cause velvety dark plaques on the neck called acanthosis nigricans. However, acute or chronic erythrasma also may cause hyperpigmentation of the body folds. Although the pathology of erythrasma is due to bacterial infection of the superficial layer of the stratum corneum, acanthosis nigricans is due to fibroblast proliferation and stimulation of epidermal keratinocytes, likely from increased growth factors and insulinlike growth factor.⁷ If erythrasma is mistaken for acanthosis nigricans, the patient may be counseled inappropriately that the hyperpigmentation is something not easily resolved and subsequently left with an active treatable condition that adversely affects their quality of life.

THE COMPARISON

A and B Axilla of a 65-year-old White man with erythrasma showing a well-demarcated erythematous plaque with fine scale (A). Wood-lamp examination of the area showed characteristic bright coral red fluorescence (B).

C and D A well-demarcated, red-brown plaque with fine scale in the antecubital fossa of an obese Hispanic woman (C). Wood-lamp examination revealed bright coral red fluorescence (D).

E Hypopigmented patches (with pruritus) in the groin of a Black man. He also had erythrasma between the toes.

Erythrasma is a skin condition caused by acute or chronic infection of the outermost layer of the epidermis (stratum corneum) with Corynebacterium minutissimum. It has a predilection for intertriginous regions such as the axillae, groin, and interdigital spaces of the toes. It can be associated with pruritus or can be asymptomatic.

Epidemiology

Erythrasma typically affects adults, with greater prevalence among those residing in shared living facilities, such as dormitories or nursing homes, or in humid climates.¹ It is a common disorder with an estimated prevalence of 17.6% of bacterial skin infections in elderly patients and 44% of diabetic interdigital toe space infections.^2,3

Key clinical features

Erythrasma can manifest as red-brown hyperpigmented plaques with fine scale and little central clearing (FIGURES A and C) or as a hypopigmented patch (FIGURE E) with a sharply marginated, hyperpigmented border in patients with skin of color. In the interdigital toe spaces, the skin often is white and macerated. These findings may appear in patients of all skin tones.

Worth noting

• C minutissimum produces coproporphyrin III, which glows fluorescent red under Wood-lamp examination (FIGURES B and D). A recent shower or bath may remove the fluorescent coproporphyrins and cause a false-negative result. The interdigital space between the fourth and fifth toes is a common location for C minutissimum; thus clinicians should consider examining these areas with a Wood lamp.
• Associated risk factors include obesity, immunosuppression, diabetes mellitus, and excessive sweating.¹
• The differential diagnosis includes intertrigo, inverse psoriasis, confluent and reticulated papillomatosis (Gougerot-Carteaud syndrome), acanthosis nigricans, seborrheic dermatitis, and tinea pedis when present in the interdigital toe spaces. Plaques occurring in circular patterns may be mistaken for tinea corporis or pityriasis rotunda.
• There is a high prevalence of erythrasma in patients with inverse psoriasis, and it may exacerbate psoriatic plaques.⁴
• Treatment options include application of topical clindamycin or erythromycin to the affected area.1 Some patients have responded to topical mupiricin.2 For larger areas, a 1-g dose of clarithromycin⁵ or a 14-day course of erythromycin may be appropriate.¹ Avoid prescribing clarithromycin to patients with preexisting heart disease due to its increased risk for cardiac events or death; consider other agents.

Health disparity highlight

Obesity, most prevalent in non-Hispanic Black adults (49.9%) and Hispanic adults (45.6%) followed by non-Hispanic White adults (41.4%),⁶ may cause velvety dark plaques on the neck called acanthosis nigricans. However, acute or chronic erythrasma also may cause hyperpigmentation of the body folds. Although the pathology of erythrasma is due to bacterial infection of the superficial layer of the stratum corneum, acanthosis nigricans is due to fibroblast proliferation and stimulation of epidermal keratinocytes, likely from increased growth factors and insulinlike growth factor.⁷ If erythrasma is mistaken for acanthosis nigricans, the patient may be counseled inappropriately that the hyperpigmentation is something not easily resolved and subsequently left with an active treatable condition that adversely affects their quality of life.

THE COMPARISON

A and B Axilla of a 65-year-old White man with erythrasma showing a well-demarcated erythematous plaque with fine scale (A). Wood-lamp examination of the area showed characteristic bright coral red fluorescence (B).

C and D A well-demarcated, red-brown plaque with fine scale in the antecubital fossa of an obese Hispanic woman (C). Wood-lamp examination revealed bright coral red fluorescence (D).

E Hypopigmented patches (with pruritus) in the groin of a Black man. He also had erythrasma between the toes.

Erythrasma is a skin condition caused by acute or chronic infection of the outermost layer of the epidermis (stratum corneum) with Corynebacterium minutissimum. It has a predilection for intertriginous regions such as the axillae, groin, and interdigital spaces of the toes. It can be associated with pruritus or can be asymptomatic.

Epidemiology

Erythrasma typically affects adults, with greater prevalence among those residing in shared living facilities, such as dormitories or nursing homes, or in humid climates.¹ It is a common disorder with an estimated prevalence of 17.6% of bacterial skin infections in elderly patients and 44% of diabetic interdigital toe space infections.^2,3

Key clinical features

Erythrasma can manifest as red-brown hyperpigmented plaques with fine scale and little central clearing (FIGURES A and C) or as a hypopigmented patch (FIGURE E) with a sharply marginated, hyperpigmented border in patients with skin of color. In the interdigital toe spaces, the skin often is white and macerated. These findings may appear in patients of all skin tones.

Worth noting

• C minutissimum produces coproporphyrin III, which glows fluorescent red under Wood-lamp examination (FIGURES B and D). A recent shower or bath may remove the fluorescent coproporphyrins and cause a false-negative result. The interdigital space between the fourth and fifth toes is a common location for C minutissimum; thus clinicians should consider examining these areas with a Wood lamp.
• Associated risk factors include obesity, immunosuppression, diabetes mellitus, and excessive sweating.¹
• The differential diagnosis includes intertrigo, inverse psoriasis, confluent and reticulated papillomatosis (Gougerot-Carteaud syndrome), acanthosis nigricans, seborrheic dermatitis, and tinea pedis when present in the interdigital toe spaces. Plaques occurring in circular patterns may be mistaken for tinea corporis or pityriasis rotunda.
• There is a high prevalence of erythrasma in patients with inverse psoriasis, and it may exacerbate psoriatic plaques.⁴
• Treatment options include application of topical clindamycin or erythromycin to the affected area.1 Some patients have responded to topical mupiricin.2 For larger areas, a 1-g dose of clarithromycin⁵ or a 14-day course of erythromycin may be appropriate.¹ Avoid prescribing clarithromycin to patients with preexisting heart disease due to its increased risk for cardiac events or death; consider other agents.

Health disparity highlight

Obesity, most prevalent in non-Hispanic Black adults (49.9%) and Hispanic adults (45.6%) followed by non-Hispanic White adults (41.4%),⁶ may cause velvety dark plaques on the neck called acanthosis nigricans. However, acute or chronic erythrasma also may cause hyperpigmentation of the body folds. Although the pathology of erythrasma is due to bacterial infection of the superficial layer of the stratum corneum, acanthosis nigricans is due to fibroblast proliferation and stimulation of epidermal keratinocytes, likely from increased growth factors and insulinlike growth factor.⁷ If erythrasma is mistaken for acanthosis nigricans, the patient may be counseled inappropriately that the hyperpigmentation is something not easily resolved and subsequently left with an active treatable condition that adversely affects their quality of life.

Hidradenitis suppurativa (HS), also known as acne inversa or Verneuil disease, is a chronic, recurrent, inflammatory occlusive disease affecting the terminal follicular epithelium in apocrine gland–bearing skin areas.¹ HS manifests as painful nodules, abscesses, fistulas, and scarring and often has a severe psychological impact on the affected patient.²

When HS was first identified in the 1800s, it was believed to result from a dysfunction of the sweat glands.³ In 1939, scientists identified the true cause: follicular occlusion.³

Due to its chronic nature, heterogeneity in presentation, and apparent low prevalence,⁴ HS is considered an orphan disease.⁵ Over the past 10 years, there has been a surge in HS research—particularly in medical management—which has provided a better understanding of this condition.^6,7

In this review, we discuss the most updated evidence regarding the diagnosis and treatment of HS to guide the family physician (FP)’s approach to managing this debilitating disease. But first, we offer a word about the etiology and pathophysiology of the condition.

3 events set the stage for hidradenitis suppurativa

Although the exact cause of HS is still unknown, some researchers have hypothesized that HS results from a combination of genetic predisposition and environmental and lifestyle factors.^8-12 The primary mechanism of HS is the obstruction of the terminal follicular epithelium by a keratin plug.^1,13,14 A systematic review of molecular inflammatory pathways involved in HS divides the pathogenesis of HS into 3 events: follicular occlusion followed by dilation, follicular rupture and inflammatory response, and chronic inflammatory state with sinus tracts.⁸

An underreported condition

HS is often underreported and misdiagnosed.^4,15 Globally, the prevalence of HS varies from < 1% to 4%.^15,16 A systematic review with meta-analysis showed a higher prevalence of HS in females compared to males in American and European populations.¹⁷ In the United States, the overall frequency of HS is 0.1%, or 98 per 100,000 persons.¹⁶ The prevalence of HS is highest among patients ages 30 to 39 years; there is decreased prevalence in patients ages 55 years and older.^16,18

Who is at heightened risk?

Recent research has shown a relationship between ethnicity and HS.^16,19,20 African American and biracial groups (defined as African American and White) have a 3-fold and 2-fold greater prevalence of HS, respectively, compared to White patients.¹⁶ However, the prevalence of HS in non-White ethnic groups may be underestimated in clinical trials due to a lack of representation and subgroup analyses based on ethnicity, which may affect generalizability in HS recommendations.²¹

Continue to: Genetic predisposition

Genetic predisposition. As many as 40% of patients with HS report having at least 1 affected family member. A positive family history of HS is associated with earlier onset, longer disease duration, and severe disease.²² HS is genetically heterogeneous, and several mutations (eg, gamma secretase, PSTPIP1, PSEN1 genes) have been identified in patients and in vitro as the cause of dysregulation of epidermal proliferation and differentiation, immune dysregulation, and promotion of amyloid formation.^8,23-25

Obesity and metabolic risk factors. There is a strong relationship between HS and obesity. As many as 70% of patients with HS are obese, and 9% to 40% have metabolic syndrome.^12,18,26-28 Obesity is associated with maceration and mechanical stress, increased fragility of the dermo-epidermal junction, changes in cutaneous blood flow, and subdermal fat inflammation—all of which favor the pathophysiology of HS.^29,30

Smoking. Tobacco smoking is associated with severe HS and a lower chance of remission.¹² Population-based studies have shown that as many as 90% of patients with HS have a history of smoking ≥ 20 packs of cigarettes per year.^{1,12,18,31,32} The nicotine and thousands of other chemicals present in cigarettes trigger keratinocytes and fibroblasts, resulting in epidermal hyperplasia, infundibular hyperkeratosis, excessive cornification, and dysbiosis.^8,23,24

Hormones. The exact role sex hormones play in the pathogenesis of HS remains unclear.^8,32 Most information is based primarily on small studies looking at antiandrogen treatments, HS activity during the menstrual cycle and pregnancy, HS exacerbation related to androgenic effects of hormonal contraception, and the association of HS with metabolic-endocrine disorders (eg, polycystic ovary syndrome [PCOS]).^8,33

A family history of hidradenitis suppurativa is associated with earlier onset, longer disease duration, and severe disease.

Androgens induce hyperkeratosis that may lead to follicular occlusion—the hallmark of HS pathology.³⁴ A systematic review looking at the role of androgen and estrogen in HS found that while some patients with HS have elevated androgen levels, most have androgen and estrogen levels within normal range.³⁵ Therefore, increased peripheral androgen receptor sensitivity has been hypothesized as the mechanism of action contributing to HS manifestation.³⁴

Continue to: Host-defense defects

Host-defense defects. HS shares a similar cytokine profile with other well-­established immune-mediated inflammatory diseases, including pyoderma gangrenosum (PG)^36,37 and Crohn disease.^38-40 HS is characterized by the expression of several immune mediators, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1 ­alpha (IL-1 alpha), IL-1 beta, IL-8, IL-17, and the IL-23/T helper 17 pathway, all of which are upregulated in other inflammatory diseases and also result in an abnormal innate immune response.^8,24 The recently described clinical triad of PG, acne, and HS (PASH) and the tetrad of pyogenic arthritis, PG, acne, and HS (PAPASH) further support the role of immune dysregulation in the pathogenesis of HS.⁴⁰ Nonetheless, further studies are needed to determine the exact pathways of cytokine effect in HS.⁴¹

Use these criteria to make the diagnosis

The US and Canadian Hidradenitis Suppurativa Foundations (HSF) guidelines base the clinical diagnosis of HS on the following criteria²:

• Typical HS lesions: Erythematous skin lesions; inflamed, deep-seated painful nodules; “tombstone” double-ended comedones; sinus tracts; scarring; deformity. FIGURES 1A-1E show typical lesions seen in patients with HS.
• Typical locations: Intertriginous regions—apocrine gland–containing areas in axilla, groin, perineal region, buttocks, gluteal cleft, and mammary folds; beltline and waistband areas; areas of skin compression and friction.
• Recurrence and chronicity: Recurrent painful or suppurating lesions that appear more than twice in a 6-month period.^2,41-43

Patients with HS usually present with painful recurrent abscesses and scarring and often report multiple visits to the emergency department for drainage or failed antibiotic treatment for abscesses.^15,44

Ask patients these 2 questions. Vinding et al⁴⁵ developed a survey for the diagnosis of HS using 2 simple questions based on the 3 criteria established by the HSF:

1. “Have you had an outbreak of boils during the last 6 months?” and
2. “Where and how many boils have you had?” (This question includes a list of the typical HS locations—eg, axilla, groin, genitals, area under breast.)

In their questionnaire, Vinding et al⁴⁵ found that an affirmative answer to Question 1 and reports of > 2 boils in response to Question 2 correlated to a sensitivity of 90%, specificity of 97%, positive predictive value of 96%, and negative predictive value of 92% for the diagnosis of HS. The differential diagnosis of HS is summarized in TABLE 1.^42,45-52

Continue to: These tools can help you to stage hidradenitis suppurativa

Multiple tools are available to assess the severity of HS.⁵³ We will describe the Hurley staging system and the International Hidradenitis Suppurativa Severity Score System (IHS4). Other diagnostic tools, such as the Sartorius score and the Hidradenitis Suppurativa Physician’s Global Assessment Scale (HS-PGA), can be time-consuming and challenging to interpret, limiting their use in the clinical setting.^2,54

Hurley staging system (available at www.hsdiseasesource.com/hs-disease-­staging) considers the presence of nodules, abscesses, sinus tracts, and scarring affecting an entire anatomical area.^13,55 This system is most useful as a rapid classification tool for patients with HS in the clinical setting but should not be used to assess clinical response.^2,13,56

The IHS4 (available at https://online­ library.wiley.com/doi/10.1111/bjd.15748) is a validated and easy-to-use tool for assessing HS and guiding the therapeutic strategy in clinical practice.⁵⁴ With IHS4, the clinician must calculate the following:

• total number of nodules > 10 mm in diameter
• total number of abscesses multiplied by 2, and
• total number of draining tunnels (fistulae/sinuses) multiplied by 4.

Mild HS is defined as a score ≤ 3 points; moderate HS, 4 to 10 points; and severe HS, ≥ 11 points.⁵⁴

No diagnostic tests, but ultrasound may be helpful

There are currently no established biological markers or specific tests for diagnosing HS.¹⁵ Ultrasound is emerging as a tool to assess dermal thickness, hair follicle morphology, and number and extent of fluid collections. Two recent studies showed that pairing clinical assessment with ultrasound findings improves accuracy of scoring in 84% of cases.^57,58 For patients with severe HS, skin biopsy can be considered to rule out squamous cell carcinoma. Cultures, however, have limited utility except for suspected superimposed bacterial infection.²

Continue to: Screening for comorbidities

Screening for comorbidities

HSF recommends clinicians screen patients for comorbidities associated with HS (TABLE 2).² Overall, screening patients for active and past history of smoking is strongly recommended, as is screening for metabolic syndrome, hyperlipidemia, type 2 diabetes (1.5- to 3-fold greater risk of type 2 diabetes in HS patients), and PCOS (3-fold greater risk).^2,26,27,59 Screening patients for depression and anxiety is also routinely recommended.² However, the authors of this article strongly recommend screening all patients with HS for psychiatric comorbidities, as research has shown a 2-fold greater risk of depression and anxiety, social isolation, and low self-esteem that severely limits quality of life (QOL) in this patient population.^60,61

Management

Treat existing lesions, reduce formation of new ones

The main goals of treatment for patients with HS are to treat existing lesions and reduce associated symptoms, reduce the formation of new lesions, and minimize associated psychological morbidity.¹⁵ FPs play an important role in the early diagnosis, treatment, and comprehensive care of patients with HS. This includes monitoring patients, managing comorbidities, making appropriate referrals to dermatologists, and coordinating the multidisciplinary care that patients with HS require.

As many as 90% of patients with hidradenitis suppurativa have a history of smoking ≥ 20 packs of cigarettes per year.

A systematic review identified more than 50 interventions used to treat HS, most based on small observational studies and randomized controlled trials (RCTs) with a high risk of bias.⁶² FIGURE 2^2,62-69 provides an evidence-based treatment algorithm for HS, and TABLE 3^{2,63,64,70-75} summarizes the most commonly used treatments.

Biologic agents

Adalimumab (ADA) is a fully human immunoglobulin G1 monoclonal antibody that binds to TNF-alpha, neutralizes its bioactivity, and induces apoptosis of TNF-expressing mononuclear cells. It is the only medication approved by the US Food and Drug Administration for active refractory moderate and severe HS.^62,65 Several double-blinded RCTs, including PIONEER I and PIONEER II, studied the effectiveness of ADA for HS and found significant clinical responses at Week 12, 50% reduction in abscess and nodule counts, no increase in abscesses or draining fistulas at Week 12, and sustained improvement in lesion counts, pain, and QOL.^66,67,76

IL-1 and IL-23 inhibitors. The efficacy of etanercept and golimumab (anti-TNF), as well as anakinra (IL-1 inhibitor) and ustekinumab (IL-1/IL-23 inhibitor), continue to be investigated with variable results; they are considered second-line treatment for active refractory moderate and severe HS after ADA.^65,77-80 In­fliximab (IL-1 beta inhibitor) has shown no effect on reducing disease severity.⁷⁰Compared to other treatments, biologic therapy is associated with higher costs (TABLE 3),^{2,63,64,70-75} an increased risk for reactivation of latent infections (eg, tuberculosis, herpes simplex, and hepatitis C virus [HCV], and B [HBV]), and an attenuated response to vaccines.⁸¹ Prior to starting biologic therapy, FPs should screen patients with HS for tuberculosis and HBV, consider HIV and HCV screening in at-risk patients, and optimize the immunization status of the patient.^82,83 While inactivated vaccines can be administered without discontinuing biologic treatment, patients should avoid live-attenuated vaccines while taking biologics.⁸³

Continue to: Antibiotic therapy

Topical antibiotics are considered first-line treatment for mild and moderate uncomplicated HS.^63,64 Clindamycin 1%, the only topical antibiotic studied in a small double-blind RCT of patients with Hurley stage I and stage II HS, demonstrated significant clinical improvement after 12 weeks of treatment (twice- daily application), compared to placebo.⁸⁴ Topical clindamycin is also recommended to treat flares in patients with mild disease.^2,64

Oral antibiotics. Tetracycline (500 mg twice daily for 4 months) is considered a second-line treatment for patients with mild HS.^64,68 Doxycycline (200 mg/d for 3 months) may also be considered as a second-line treatment in patients with mild disease.⁸⁵

All patients with hidradenitis suppurativa should be screened for depression, anxiety, social isolation, and low self-esteem.

Combination oral clindamycin (300 mg) and rifampicin (300 mg) twice daily for 10 weeks is recommended as first-line treatment for patients with moderate HS.^2,64,69 Combination rifampin (300 mg twice daily), moxifloxacin (400 mg/d), and metronidazole (500 mg three times a day) is not routinely recommended due to increased risk of ­toxicity.²

Ertapenem (1 g intravenously daily for 6 weeks) is supported by lower-level evidence as a third-line rescue therapy option and as a bridge to surgery; however, limitations for home infusions, costs, and concerns for antibiotic resistance limit its use.^2,86

Corticosteroids and systemic immunomodulators

Intralesional triamcinolone (2-20 mg) may be beneficial in the early stages of HS, although its use is based on a small prospective open study of 33 patients.⁸⁷ A recent double-blind placebo-controlled RCT comparing varying concentrations of intralesional triamcinolone (10 mg/mL and 40 mg/mL) vs normal saline showed no statistically significant difference in inflammatory clearance, pain reduction, or patient satisfaction.⁸⁸

Continue to: Short-term systemic corticosteroid tapers...

Short-term systemic corticosteroid tapers (eg, prednisone, starting at 0.5-1 mg/kg) are recommended to treat flares. Long-term corticosteroids and cyclosporine are reserved for patients with severe refractory disease; however, due to safety concerns, their regular use is strongly discouraged.^63,64,85 There is limited evidence to support the use of methotrexate for severe refractory disease, and its use is not recommended.⁶³

Hormonal therapy

The use of hormonal therapy for HS is limited by the low-quality evidence (eg, anecdotal evidence, small retrospective analyses, uncontrolled trials).^33,63 The only exception is a small double-blind controlled crossover trial from 1986 showing that the antiandrogen effects of combination oral contraceptives (ethinyloestradiol 50 mcg/cyproterone acetate in a reverse sequential regimen and ethinyloestradiol 50 mcg/norgestrel 500 mcg) improved HS lesions.⁸⁹

Spironolactone, an antiandrogen diuretic, has been studied in small case report series with a high risk for bias. It is used mainly in female patients with mild or moderate disease, or in combination with other agents in patients with severe HS. Further research is needed to determine its utility in the treatment of HS.^63,90,91

Metformin, alone or in combination with other therapies (dapsone, finasteride, liraglutide), has been analyzed in small prospective studies of primarily female patients with different severities of HS, obesity, and PCOS. These studies have shown improvement in lesions, QOL, and reduction of workdays lost.^92,93

Finasteride. Studies have shown finasteride (1.25-5 mg/d) alone or in combination with other treatments (metformin, liraglutide, levonorgestrel-ethinyl estradiol, and dapsone) provided varying degrees of resolution or improvement in patients with severe and advanced HS. Finasteride has been used for 4 to 16 weeks with a good safety profile.^92,94-96

Continue to: Retinoids

Acitretin, alitretinoin, and isotretinoin have been studied in small retrospective studies to manage HS, with variable results.^97-99 Robust prospective studies are needed. Retinoids, in general, should be considered as a second- or third-line treatment for moderate to severe HS.⁶³

Surgical intervention

Surgical interventions, which should be considered in patients with widespread mild, moderate, or severe disease, are associated with improved daily activity and work productivity.¹⁰⁰ Incision and drainage should be avoided in patients with HS, as this technique does not remove the affected follicles and is associated with 100% recurrence.¹⁰¹

Wide excision is the preferred surgical technique for patients with Hurley stage II and stage III HS; it is associated with lower recurrence rates (13%) compared to local excision (22%) and deroofing (27%).¹⁰² Secondary intention healing is the most commonly chosen method, based on lower recurrence rates than primary closure.¹⁰²

STEEP and laser techniques. The skin-tissue-sparing excision with electrosurgical peeling (STEEP) procedure involves successive tangential excision of affected tissue until the epithelized bottom of the sinus tracts has been reached. This allows for the removal of fibrotic tissue and the sparing of the deep subcutaneous fat. STEEP is associated with 30% of relapses after 43 months.⁷¹

When considering biologic therapy, screen all patients with hidradenitis suppurativa for tuberculosis and hepatitis B, and confirm they are current with age-appropriate immunizations.

Laser surgery has also been studied in patients with Hurley stage II and stage III HS. The most commonly used lasers for HS are the 1064-nm neodymium-doped yttrium aluminum garnet (Nd: YAG) and the carbon dioxide laser; they have been shown to reduce disease severity in inguinal, axillary, and inflammatory sites.^72-74

Pain management: Start with lidocaine, NSAIDs

There are few studies about HS-associated pain management.¹⁰³ For acute episodes, short-acting nonopioid local treatment with lidocaine, topical or oral nonsteroidal anti-inflammatory drugs, and acetaminophen are preferred. Opioids should be reserved for moderate-to-severe pain that has not responded to other analgesics. Adjuvant therapy with pregabalin, gabapentin, selective serotonin reuptake inhibitors, or serotonin-norepinephrine reuptake inhibitors can also be considered for the comanagement of pain and depression.^62,104

Consider this tool to measure treatment response

The HS clinical response (HiSCR) tool is an outcome measure used to evaluate treatment outcomes. The tool uses an HS-specific binary score with the following criteria:

1. ≥ 50% reduction in the number of inflammatory nodules;
2. no increase in the number of abscesses; and
3. no increase in the number of draining fistulas.¹⁰⁵

The HiSCR was developed for the ­PIONEER studies^105,106 to assess the response to ADA treatment. It is the only HS scoring system to undergo an extensive validation process with a meaningful clinical endpoint for HS treatment evaluation that is easy to use. Compared to the HS-PGA score (clear, minimal, mild), HiSCR was more responsive to change in patients with HS.^105,106 

CORRESPONDENCE
Cristina Marti-Amarista, MD, 101 Nicolls Road, Stony Brook, NY, 11794-8228; [email protected]

Hidradenitis suppurativa (HS), also known as acne inversa or Verneuil disease, is a chronic, recurrent, inflammatory occlusive disease affecting the terminal follicular epithelium in apocrine gland–bearing skin areas.¹ HS manifests as painful nodules, abscesses, fistulas, and scarring and often has a severe psychological impact on the affected patient.²

When HS was first identified in the 1800s, it was believed to result from a dysfunction of the sweat glands.³ In 1939, scientists identified the true cause: follicular occlusion.³

Due to its chronic nature, heterogeneity in presentation, and apparent low prevalence,⁴ HS is considered an orphan disease.⁵ Over the past 10 years, there has been a surge in HS research—particularly in medical management—which has provided a better understanding of this condition.^6,7

In this review, we discuss the most updated evidence regarding the diagnosis and treatment of HS to guide the family physician (FP)’s approach to managing this debilitating disease. But first, we offer a word about the etiology and pathophysiology of the condition.

3 events set the stage for hidradenitis suppurativa

Although the exact cause of HS is still unknown, some researchers have hypothesized that HS results from a combination of genetic predisposition and environmental and lifestyle factors.^8-12 The primary mechanism of HS is the obstruction of the terminal follicular epithelium by a keratin plug.^1,13,14 A systematic review of molecular inflammatory pathways involved in HS divides the pathogenesis of HS into 3 events: follicular occlusion followed by dilation, follicular rupture and inflammatory response, and chronic inflammatory state with sinus tracts.⁸

An underreported condition

HS is often underreported and misdiagnosed.^4,15 Globally, the prevalence of HS varies from < 1% to 4%.^15,16 A systematic review with meta-analysis showed a higher prevalence of HS in females compared to males in American and European populations.¹⁷ In the United States, the overall frequency of HS is 0.1%, or 98 per 100,000 persons.¹⁶ The prevalence of HS is highest among patients ages 30 to 39 years; there is decreased prevalence in patients ages 55 years and older.^16,18

Who is at heightened risk?

Recent research has shown a relationship between ethnicity and HS.^16,19,20 African American and biracial groups (defined as African American and White) have a 3-fold and 2-fold greater prevalence of HS, respectively, compared to White patients.¹⁶ However, the prevalence of HS in non-White ethnic groups may be underestimated in clinical trials due to a lack of representation and subgroup analyses based on ethnicity, which may affect generalizability in HS recommendations.²¹

Continue to: Genetic predisposition

Genetic predisposition. As many as 40% of patients with HS report having at least 1 affected family member. A positive family history of HS is associated with earlier onset, longer disease duration, and severe disease.²² HS is genetically heterogeneous, and several mutations (eg, gamma secretase, PSTPIP1, PSEN1 genes) have been identified in patients and in vitro as the cause of dysregulation of epidermal proliferation and differentiation, immune dysregulation, and promotion of amyloid formation.^8,23-25

Obesity and metabolic risk factors. There is a strong relationship between HS and obesity. As many as 70% of patients with HS are obese, and 9% to 40% have metabolic syndrome.^12,18,26-28 Obesity is associated with maceration and mechanical stress, increased fragility of the dermo-epidermal junction, changes in cutaneous blood flow, and subdermal fat inflammation—all of which favor the pathophysiology of HS.^29,30

Smoking. Tobacco smoking is associated with severe HS and a lower chance of remission.¹² Population-based studies have shown that as many as 90% of patients with HS have a history of smoking ≥ 20 packs of cigarettes per year.^{1,12,18,31,32} The nicotine and thousands of other chemicals present in cigarettes trigger keratinocytes and fibroblasts, resulting in epidermal hyperplasia, infundibular hyperkeratosis, excessive cornification, and dysbiosis.^8,23,24

Hormones. The exact role sex hormones play in the pathogenesis of HS remains unclear.^8,32 Most information is based primarily on small studies looking at antiandrogen treatments, HS activity during the menstrual cycle and pregnancy, HS exacerbation related to androgenic effects of hormonal contraception, and the association of HS with metabolic-endocrine disorders (eg, polycystic ovary syndrome [PCOS]).^8,33

A family history of hidradenitis suppurativa is associated with earlier onset, longer disease duration, and severe disease.

Androgens induce hyperkeratosis that may lead to follicular occlusion—the hallmark of HS pathology.³⁴ A systematic review looking at the role of androgen and estrogen in HS found that while some patients with HS have elevated androgen levels, most have androgen and estrogen levels within normal range.³⁵ Therefore, increased peripheral androgen receptor sensitivity has been hypothesized as the mechanism of action contributing to HS manifestation.³⁴

Continue to: Host-defense defects

Host-defense defects. HS shares a similar cytokine profile with other well-­established immune-mediated inflammatory diseases, including pyoderma gangrenosum (PG)^36,37 and Crohn disease.^38-40 HS is characterized by the expression of several immune mediators, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1 ­alpha (IL-1 alpha), IL-1 beta, IL-8, IL-17, and the IL-23/T helper 17 pathway, all of which are upregulated in other inflammatory diseases and also result in an abnormal innate immune response.^8,24 The recently described clinical triad of PG, acne, and HS (PASH) and the tetrad of pyogenic arthritis, PG, acne, and HS (PAPASH) further support the role of immune dysregulation in the pathogenesis of HS.⁴⁰ Nonetheless, further studies are needed to determine the exact pathways of cytokine effect in HS.⁴¹

Use these criteria to make the diagnosis

The US and Canadian Hidradenitis Suppurativa Foundations (HSF) guidelines base the clinical diagnosis of HS on the following criteria²:

• Typical HS lesions: Erythematous skin lesions; inflamed, deep-seated painful nodules; “tombstone” double-ended comedones; sinus tracts; scarring; deformity. FIGURES 1A-1E show typical lesions seen in patients with HS.
• Typical locations: Intertriginous regions—apocrine gland–containing areas in axilla, groin, perineal region, buttocks, gluteal cleft, and mammary folds; beltline and waistband areas; areas of skin compression and friction.
• Recurrence and chronicity: Recurrent painful or suppurating lesions that appear more than twice in a 6-month period.^2,41-43

Patients with HS usually present with painful recurrent abscesses and scarring and often report multiple visits to the emergency department for drainage or failed antibiotic treatment for abscesses.^15,44

Ask patients these 2 questions. Vinding et al⁴⁵ developed a survey for the diagnosis of HS using 2 simple questions based on the 3 criteria established by the HSF:

1. “Have you had an outbreak of boils during the last 6 months?” and
2. “Where and how many boils have you had?” (This question includes a list of the typical HS locations—eg, axilla, groin, genitals, area under breast.)

In their questionnaire, Vinding et al⁴⁵ found that an affirmative answer to Question 1 and reports of > 2 boils in response to Question 2 correlated to a sensitivity of 90%, specificity of 97%, positive predictive value of 96%, and negative predictive value of 92% for the diagnosis of HS. The differential diagnosis of HS is summarized in TABLE 1.^42,45-52

Continue to: These tools can help you to stage hidradenitis suppurativa

Multiple tools are available to assess the severity of HS.⁵³ We will describe the Hurley staging system and the International Hidradenitis Suppurativa Severity Score System (IHS4). Other diagnostic tools, such as the Sartorius score and the Hidradenitis Suppurativa Physician’s Global Assessment Scale (HS-PGA), can be time-consuming and challenging to interpret, limiting their use in the clinical setting.^2,54

Hurley staging system (available at www.hsdiseasesource.com/hs-disease-­staging) considers the presence of nodules, abscesses, sinus tracts, and scarring affecting an entire anatomical area.^13,55 This system is most useful as a rapid classification tool for patients with HS in the clinical setting but should not be used to assess clinical response.^2,13,56

The IHS4 (available at https://online­ library.wiley.com/doi/10.1111/bjd.15748) is a validated and easy-to-use tool for assessing HS and guiding the therapeutic strategy in clinical practice.⁵⁴ With IHS4, the clinician must calculate the following:

• total number of nodules > 10 mm in diameter
• total number of abscesses multiplied by 2, and
• total number of draining tunnels (fistulae/sinuses) multiplied by 4.

Mild HS is defined as a score ≤ 3 points; moderate HS, 4 to 10 points; and severe HS, ≥ 11 points.⁵⁴

No diagnostic tests, but ultrasound may be helpful

There are currently no established biological markers or specific tests for diagnosing HS.¹⁵ Ultrasound is emerging as a tool to assess dermal thickness, hair follicle morphology, and number and extent of fluid collections. Two recent studies showed that pairing clinical assessment with ultrasound findings improves accuracy of scoring in 84% of cases.^57,58 For patients with severe HS, skin biopsy can be considered to rule out squamous cell carcinoma. Cultures, however, have limited utility except for suspected superimposed bacterial infection.²

Continue to: Screening for comorbidities

Screening for comorbidities

HSF recommends clinicians screen patients for comorbidities associated with HS (TABLE 2).² Overall, screening patients for active and past history of smoking is strongly recommended, as is screening for metabolic syndrome, hyperlipidemia, type 2 diabetes (1.5- to 3-fold greater risk of type 2 diabetes in HS patients), and PCOS (3-fold greater risk).^2,26,27,59 Screening patients for depression and anxiety is also routinely recommended.² However, the authors of this article strongly recommend screening all patients with HS for psychiatric comorbidities, as research has shown a 2-fold greater risk of depression and anxiety, social isolation, and low self-esteem that severely limits quality of life (QOL) in this patient population.^60,61

Management

Treat existing lesions, reduce formation of new ones

The main goals of treatment for patients with HS are to treat existing lesions and reduce associated symptoms, reduce the formation of new lesions, and minimize associated psychological morbidity.¹⁵ FPs play an important role in the early diagnosis, treatment, and comprehensive care of patients with HS. This includes monitoring patients, managing comorbidities, making appropriate referrals to dermatologists, and coordinating the multidisciplinary care that patients with HS require.

As many as 90% of patients with hidradenitis suppurativa have a history of smoking ≥ 20 packs of cigarettes per year.

A systematic review identified more than 50 interventions used to treat HS, most based on small observational studies and randomized controlled trials (RCTs) with a high risk of bias.⁶² FIGURE 2^2,62-69 provides an evidence-based treatment algorithm for HS, and TABLE 3^{2,63,64,70-75} summarizes the most commonly used treatments.

Biologic agents

Adalimumab (ADA) is a fully human immunoglobulin G1 monoclonal antibody that binds to TNF-alpha, neutralizes its bioactivity, and induces apoptosis of TNF-expressing mononuclear cells. It is the only medication approved by the US Food and Drug Administration for active refractory moderate and severe HS.^62,65 Several double-blinded RCTs, including PIONEER I and PIONEER II, studied the effectiveness of ADA for HS and found significant clinical responses at Week 12, 50% reduction in abscess and nodule counts, no increase in abscesses or draining fistulas at Week 12, and sustained improvement in lesion counts, pain, and QOL.^66,67,76

IL-1 and IL-23 inhibitors. The efficacy of etanercept and golimumab (anti-TNF), as well as anakinra (IL-1 inhibitor) and ustekinumab (IL-1/IL-23 inhibitor), continue to be investigated with variable results; they are considered second-line treatment for active refractory moderate and severe HS after ADA.^65,77-80 In­fliximab (IL-1 beta inhibitor) has shown no effect on reducing disease severity.⁷⁰Compared to other treatments, biologic therapy is associated with higher costs (TABLE 3),^{2,63,64,70-75} an increased risk for reactivation of latent infections (eg, tuberculosis, herpes simplex, and hepatitis C virus [HCV], and B [HBV]), and an attenuated response to vaccines.⁸¹ Prior to starting biologic therapy, FPs should screen patients with HS for tuberculosis and HBV, consider HIV and HCV screening in at-risk patients, and optimize the immunization status of the patient.^82,83 While inactivated vaccines can be administered without discontinuing biologic treatment, patients should avoid live-attenuated vaccines while taking biologics.⁸³

Continue to: Antibiotic therapy

Topical antibiotics are considered first-line treatment for mild and moderate uncomplicated HS.^63,64 Clindamycin 1%, the only topical antibiotic studied in a small double-blind RCT of patients with Hurley stage I and stage II HS, demonstrated significant clinical improvement after 12 weeks of treatment (twice- daily application), compared to placebo.⁸⁴ Topical clindamycin is also recommended to treat flares in patients with mild disease.^2,64

Oral antibiotics. Tetracycline (500 mg twice daily for 4 months) is considered a second-line treatment for patients with mild HS.^64,68 Doxycycline (200 mg/d for 3 months) may also be considered as a second-line treatment in patients with mild disease.⁸⁵

All patients with hidradenitis suppurativa should be screened for depression, anxiety, social isolation, and low self-esteem.

Combination oral clindamycin (300 mg) and rifampicin (300 mg) twice daily for 10 weeks is recommended as first-line treatment for patients with moderate HS.^2,64,69 Combination rifampin (300 mg twice daily), moxifloxacin (400 mg/d), and metronidazole (500 mg three times a day) is not routinely recommended due to increased risk of ­toxicity.²

Ertapenem (1 g intravenously daily for 6 weeks) is supported by lower-level evidence as a third-line rescue therapy option and as a bridge to surgery; however, limitations for home infusions, costs, and concerns for antibiotic resistance limit its use.^2,86

Corticosteroids and systemic immunomodulators

Intralesional triamcinolone (2-20 mg) may be beneficial in the early stages of HS, although its use is based on a small prospective open study of 33 patients.⁸⁷ A recent double-blind placebo-controlled RCT comparing varying concentrations of intralesional triamcinolone (10 mg/mL and 40 mg/mL) vs normal saline showed no statistically significant difference in inflammatory clearance, pain reduction, or patient satisfaction.⁸⁸

Continue to: Short-term systemic corticosteroid tapers...

Short-term systemic corticosteroid tapers (eg, prednisone, starting at 0.5-1 mg/kg) are recommended to treat flares. Long-term corticosteroids and cyclosporine are reserved for patients with severe refractory disease; however, due to safety concerns, their regular use is strongly discouraged.^63,64,85 There is limited evidence to support the use of methotrexate for severe refractory disease, and its use is not recommended.⁶³

Hormonal therapy

The use of hormonal therapy for HS is limited by the low-quality evidence (eg, anecdotal evidence, small retrospective analyses, uncontrolled trials).^33,63 The only exception is a small double-blind controlled crossover trial from 1986 showing that the antiandrogen effects of combination oral contraceptives (ethinyloestradiol 50 mcg/cyproterone acetate in a reverse sequential regimen and ethinyloestradiol 50 mcg/norgestrel 500 mcg) improved HS lesions.⁸⁹

Spironolactone, an antiandrogen diuretic, has been studied in small case report series with a high risk for bias. It is used mainly in female patients with mild or moderate disease, or in combination with other agents in patients with severe HS. Further research is needed to determine its utility in the treatment of HS.^63,90,91

Metformin, alone or in combination with other therapies (dapsone, finasteride, liraglutide), has been analyzed in small prospective studies of primarily female patients with different severities of HS, obesity, and PCOS. These studies have shown improvement in lesions, QOL, and reduction of workdays lost.^92,93

Finasteride. Studies have shown finasteride (1.25-5 mg/d) alone or in combination with other treatments (metformin, liraglutide, levonorgestrel-ethinyl estradiol, and dapsone) provided varying degrees of resolution or improvement in patients with severe and advanced HS. Finasteride has been used for 4 to 16 weeks with a good safety profile.^92,94-96

Continue to: Retinoids

Acitretin, alitretinoin, and isotretinoin have been studied in small retrospective studies to manage HS, with variable results.^97-99 Robust prospective studies are needed. Retinoids, in general, should be considered as a second- or third-line treatment for moderate to severe HS.⁶³

Surgical intervention

Surgical interventions, which should be considered in patients with widespread mild, moderate, or severe disease, are associated with improved daily activity and work productivity.¹⁰⁰ Incision and drainage should be avoided in patients with HS, as this technique does not remove the affected follicles and is associated with 100% recurrence.¹⁰¹

Wide excision is the preferred surgical technique for patients with Hurley stage II and stage III HS; it is associated with lower recurrence rates (13%) compared to local excision (22%) and deroofing (27%).¹⁰² Secondary intention healing is the most commonly chosen method, based on lower recurrence rates than primary closure.¹⁰²

STEEP and laser techniques. The skin-tissue-sparing excision with electrosurgical peeling (STEEP) procedure involves successive tangential excision of affected tissue until the epithelized bottom of the sinus tracts has been reached. This allows for the removal of fibrotic tissue and the sparing of the deep subcutaneous fat. STEEP is associated with 30% of relapses after 43 months.⁷¹

When considering biologic therapy, screen all patients with hidradenitis suppurativa for tuberculosis and hepatitis B, and confirm they are current with age-appropriate immunizations.

Laser surgery has also been studied in patients with Hurley stage II and stage III HS. The most commonly used lasers for HS are the 1064-nm neodymium-doped yttrium aluminum garnet (Nd: YAG) and the carbon dioxide laser; they have been shown to reduce disease severity in inguinal, axillary, and inflammatory sites.^72-74

Pain management: Start with lidocaine, NSAIDs

There are few studies about HS-associated pain management.¹⁰³ For acute episodes, short-acting nonopioid local treatment with lidocaine, topical or oral nonsteroidal anti-inflammatory drugs, and acetaminophen are preferred. Opioids should be reserved for moderate-to-severe pain that has not responded to other analgesics. Adjuvant therapy with pregabalin, gabapentin, selective serotonin reuptake inhibitors, or serotonin-norepinephrine reuptake inhibitors can also be considered for the comanagement of pain and depression.^62,104

Consider this tool to measure treatment response

The HS clinical response (HiSCR) tool is an outcome measure used to evaluate treatment outcomes. The tool uses an HS-specific binary score with the following criteria:

1. ≥ 50% reduction in the number of inflammatory nodules;
2. no increase in the number of abscesses; and
3. no increase in the number of draining fistulas.¹⁰⁵

The HiSCR was developed for the ­PIONEER studies^105,106 to assess the response to ADA treatment. It is the only HS scoring system to undergo an extensive validation process with a meaningful clinical endpoint for HS treatment evaluation that is easy to use. Compared to the HS-PGA score (clear, minimal, mild), HiSCR was more responsive to change in patients with HS.^105,106 

CORRESPONDENCE
Cristina Marti-Amarista, MD, 101 Nicolls Road, Stony Brook, NY, 11794-8228; [email protected]

Hidradenitis suppurativa (HS), also known as acne inversa or Verneuil disease, is a chronic, recurrent, inflammatory occlusive disease affecting the terminal follicular epithelium in apocrine gland–bearing skin areas.¹ HS manifests as painful nodules, abscesses, fistulas, and scarring and often has a severe psychological impact on the affected patient.²

When HS was first identified in the 1800s, it was believed to result from a dysfunction of the sweat glands.³ In 1939, scientists identified the true cause: follicular occlusion.³

Due to its chronic nature, heterogeneity in presentation, and apparent low prevalence,⁴ HS is considered an orphan disease.⁵ Over the past 10 years, there has been a surge in HS research—particularly in medical management—which has provided a better understanding of this condition.^6,7

In this review, we discuss the most updated evidence regarding the diagnosis and treatment of HS to guide the family physician (FP)’s approach to managing this debilitating disease. But first, we offer a word about the etiology and pathophysiology of the condition.

3 events set the stage for hidradenitis suppurativa

Although the exact cause of HS is still unknown, some researchers have hypothesized that HS results from a combination of genetic predisposition and environmental and lifestyle factors.^8-12 The primary mechanism of HS is the obstruction of the terminal follicular epithelium by a keratin plug.^1,13,14 A systematic review of molecular inflammatory pathways involved in HS divides the pathogenesis of HS into 3 events: follicular occlusion followed by dilation, follicular rupture and inflammatory response, and chronic inflammatory state with sinus tracts.⁸

An underreported condition

HS is often underreported and misdiagnosed.^4,15 Globally, the prevalence of HS varies from < 1% to 4%.^15,16 A systematic review with meta-analysis showed a higher prevalence of HS in females compared to males in American and European populations.¹⁷ In the United States, the overall frequency of HS is 0.1%, or 98 per 100,000 persons.¹⁶ The prevalence of HS is highest among patients ages 30 to 39 years; there is decreased prevalence in patients ages 55 years and older.^16,18

Who is at heightened risk?

Recent research has shown a relationship between ethnicity and HS.^16,19,20 African American and biracial groups (defined as African American and White) have a 3-fold and 2-fold greater prevalence of HS, respectively, compared to White patients.¹⁶ However, the prevalence of HS in non-White ethnic groups may be underestimated in clinical trials due to a lack of representation and subgroup analyses based on ethnicity, which may affect generalizability in HS recommendations.²¹

Continue to: Genetic predisposition

Genetic predisposition. As many as 40% of patients with HS report having at least 1 affected family member. A positive family history of HS is associated with earlier onset, longer disease duration, and severe disease.²² HS is genetically heterogeneous, and several mutations (eg, gamma secretase, PSTPIP1, PSEN1 genes) have been identified in patients and in vitro as the cause of dysregulation of epidermal proliferation and differentiation, immune dysregulation, and promotion of amyloid formation.^8,23-25

Obesity and metabolic risk factors. There is a strong relationship between HS and obesity. As many as 70% of patients with HS are obese, and 9% to 40% have metabolic syndrome.^12,18,26-28 Obesity is associated with maceration and mechanical stress, increased fragility of the dermo-epidermal junction, changes in cutaneous blood flow, and subdermal fat inflammation—all of which favor the pathophysiology of HS.^29,30

Smoking. Tobacco smoking is associated with severe HS and a lower chance of remission.¹² Population-based studies have shown that as many as 90% of patients with HS have a history of smoking ≥ 20 packs of cigarettes per year.^{1,12,18,31,32} The nicotine and thousands of other chemicals present in cigarettes trigger keratinocytes and fibroblasts, resulting in epidermal hyperplasia, infundibular hyperkeratosis, excessive cornification, and dysbiosis.^8,23,24

Hormones. The exact role sex hormones play in the pathogenesis of HS remains unclear.^8,32 Most information is based primarily on small studies looking at antiandrogen treatments, HS activity during the menstrual cycle and pregnancy, HS exacerbation related to androgenic effects of hormonal contraception, and the association of HS with metabolic-endocrine disorders (eg, polycystic ovary syndrome [PCOS]).^8,33

A family history of hidradenitis suppurativa is associated with earlier onset, longer disease duration, and severe disease.

Androgens induce hyperkeratosis that may lead to follicular occlusion—the hallmark of HS pathology.³⁴ A systematic review looking at the role of androgen and estrogen in HS found that while some patients with HS have elevated androgen levels, most have androgen and estrogen levels within normal range.³⁵ Therefore, increased peripheral androgen receptor sensitivity has been hypothesized as the mechanism of action contributing to HS manifestation.³⁴

Continue to: Host-defense defects

Host-defense defects. HS shares a similar cytokine profile with other well-­established immune-mediated inflammatory diseases, including pyoderma gangrenosum (PG)^36,37 and Crohn disease.^38-40 HS is characterized by the expression of several immune mediators, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1 ­alpha (IL-1 alpha), IL-1 beta, IL-8, IL-17, and the IL-23/T helper 17 pathway, all of which are upregulated in other inflammatory diseases and also result in an abnormal innate immune response.^8,24 The recently described clinical triad of PG, acne, and HS (PASH) and the tetrad of pyogenic arthritis, PG, acne, and HS (PAPASH) further support the role of immune dysregulation in the pathogenesis of HS.⁴⁰ Nonetheless, further studies are needed to determine the exact pathways of cytokine effect in HS.⁴¹

Use these criteria to make the diagnosis

The US and Canadian Hidradenitis Suppurativa Foundations (HSF) guidelines base the clinical diagnosis of HS on the following criteria²:

• Typical HS lesions: Erythematous skin lesions; inflamed, deep-seated painful nodules; “tombstone” double-ended comedones; sinus tracts; scarring; deformity. FIGURES 1A-1E show typical lesions seen in patients with HS.
• Typical locations: Intertriginous regions—apocrine gland–containing areas in axilla, groin, perineal region, buttocks, gluteal cleft, and mammary folds; beltline and waistband areas; areas of skin compression and friction.
• Recurrence and chronicity: Recurrent painful or suppurating lesions that appear more than twice in a 6-month period.^2,41-43

Patients with HS usually present with painful recurrent abscesses and scarring and often report multiple visits to the emergency department for drainage or failed antibiotic treatment for abscesses.^15,44

Ask patients these 2 questions. Vinding et al⁴⁵ developed a survey for the diagnosis of HS using 2 simple questions based on the 3 criteria established by the HSF:

1. “Have you had an outbreak of boils during the last 6 months?” and
2. “Where and how many boils have you had?” (This question includes a list of the typical HS locations—eg, axilla, groin, genitals, area under breast.)

In their questionnaire, Vinding et al⁴⁵ found that an affirmative answer to Question 1 and reports of > 2 boils in response to Question 2 correlated to a sensitivity of 90%, specificity of 97%, positive predictive value of 96%, and negative predictive value of 92% for the diagnosis of HS. The differential diagnosis of HS is summarized in TABLE 1.^42,45-52

Continue to: These tools can help you to stage hidradenitis suppurativa

Multiple tools are available to assess the severity of HS.⁵³ We will describe the Hurley staging system and the International Hidradenitis Suppurativa Severity Score System (IHS4). Other diagnostic tools, such as the Sartorius score and the Hidradenitis Suppurativa Physician’s Global Assessment Scale (HS-PGA), can be time-consuming and challenging to interpret, limiting their use in the clinical setting.^2,54

Hurley staging system (available at www.hsdiseasesource.com/hs-disease-­staging) considers the presence of nodules, abscesses, sinus tracts, and scarring affecting an entire anatomical area.^13,55 This system is most useful as a rapid classification tool for patients with HS in the clinical setting but should not be used to assess clinical response.^2,13,56

The IHS4 (available at https://online­ library.wiley.com/doi/10.1111/bjd.15748) is a validated and easy-to-use tool for assessing HS and guiding the therapeutic strategy in clinical practice.⁵⁴ With IHS4, the clinician must calculate the following:

• total number of nodules > 10 mm in diameter
• total number of abscesses multiplied by 2, and
• total number of draining tunnels (fistulae/sinuses) multiplied by 4.

Mild HS is defined as a score ≤ 3 points; moderate HS, 4 to 10 points; and severe HS, ≥ 11 points.⁵⁴

No diagnostic tests, but ultrasound may be helpful

There are currently no established biological markers or specific tests for diagnosing HS.¹⁵ Ultrasound is emerging as a tool to assess dermal thickness, hair follicle morphology, and number and extent of fluid collections. Two recent studies showed that pairing clinical assessment with ultrasound findings improves accuracy of scoring in 84% of cases.^57,58 For patients with severe HS, skin biopsy can be considered to rule out squamous cell carcinoma. Cultures, however, have limited utility except for suspected superimposed bacterial infection.²

Continue to: Screening for comorbidities

Screening for comorbidities

HSF recommends clinicians screen patients for comorbidities associated with HS (TABLE 2).² Overall, screening patients for active and past history of smoking is strongly recommended, as is screening for metabolic syndrome, hyperlipidemia, type 2 diabetes (1.5- to 3-fold greater risk of type 2 diabetes in HS patients), and PCOS (3-fold greater risk).^2,26,27,59 Screening patients for depression and anxiety is also routinely recommended.² However, the authors of this article strongly recommend screening all patients with HS for psychiatric comorbidities, as research has shown a 2-fold greater risk of depression and anxiety, social isolation, and low self-esteem that severely limits quality of life (QOL) in this patient population.^60,61

Management

Treat existing lesions, reduce formation of new ones

The main goals of treatment for patients with HS are to treat existing lesions and reduce associated symptoms, reduce the formation of new lesions, and minimize associated psychological morbidity.¹⁵ FPs play an important role in the early diagnosis, treatment, and comprehensive care of patients with HS. This includes monitoring patients, managing comorbidities, making appropriate referrals to dermatologists, and coordinating the multidisciplinary care that patients with HS require.

As many as 90% of patients with hidradenitis suppurativa have a history of smoking ≥ 20 packs of cigarettes per year.

A systematic review identified more than 50 interventions used to treat HS, most based on small observational studies and randomized controlled trials (RCTs) with a high risk of bias.⁶² FIGURE 2^2,62-69 provides an evidence-based treatment algorithm for HS, and TABLE 3^{2,63,64,70-75} summarizes the most commonly used treatments.

Biologic agents

Adalimumab (ADA) is a fully human immunoglobulin G1 monoclonal antibody that binds to TNF-alpha, neutralizes its bioactivity, and induces apoptosis of TNF-expressing mononuclear cells. It is the only medication approved by the US Food and Drug Administration for active refractory moderate and severe HS.^62,65 Several double-blinded RCTs, including PIONEER I and PIONEER II, studied the effectiveness of ADA for HS and found significant clinical responses at Week 12, 50% reduction in abscess and nodule counts, no increase in abscesses or draining fistulas at Week 12, and sustained improvement in lesion counts, pain, and QOL.^66,67,76

IL-1 and IL-23 inhibitors. The efficacy of etanercept and golimumab (anti-TNF), as well as anakinra (IL-1 inhibitor) and ustekinumab (IL-1/IL-23 inhibitor), continue to be investigated with variable results; they are considered second-line treatment for active refractory moderate and severe HS after ADA.^65,77-80 In­fliximab (IL-1 beta inhibitor) has shown no effect on reducing disease severity.⁷⁰Compared to other treatments, biologic therapy is associated with higher costs (TABLE 3),^{2,63,64,70-75} an increased risk for reactivation of latent infections (eg, tuberculosis, herpes simplex, and hepatitis C virus [HCV], and B [HBV]), and an attenuated response to vaccines.⁸¹ Prior to starting biologic therapy, FPs should screen patients with HS for tuberculosis and HBV, consider HIV and HCV screening in at-risk patients, and optimize the immunization status of the patient.^82,83 While inactivated vaccines can be administered without discontinuing biologic treatment, patients should avoid live-attenuated vaccines while taking biologics.⁸³

Continue to: Antibiotic therapy

Topical antibiotics are considered first-line treatment for mild and moderate uncomplicated HS.^63,64 Clindamycin 1%, the only topical antibiotic studied in a small double-blind RCT of patients with Hurley stage I and stage II HS, demonstrated significant clinical improvement after 12 weeks of treatment (twice- daily application), compared to placebo.⁸⁴ Topical clindamycin is also recommended to treat flares in patients with mild disease.^2,64

Oral antibiotics. Tetracycline (500 mg twice daily for 4 months) is considered a second-line treatment for patients with mild HS.^64,68 Doxycycline (200 mg/d for 3 months) may also be considered as a second-line treatment in patients with mild disease.⁸⁵

All patients with hidradenitis suppurativa should be screened for depression, anxiety, social isolation, and low self-esteem.

Combination oral clindamycin (300 mg) and rifampicin (300 mg) twice daily for 10 weeks is recommended as first-line treatment for patients with moderate HS.^2,64,69 Combination rifampin (300 mg twice daily), moxifloxacin (400 mg/d), and metronidazole (500 mg three times a day) is not routinely recommended due to increased risk of ­toxicity.²

Ertapenem (1 g intravenously daily for 6 weeks) is supported by lower-level evidence as a third-line rescue therapy option and as a bridge to surgery; however, limitations for home infusions, costs, and concerns for antibiotic resistance limit its use.^2,86

Corticosteroids and systemic immunomodulators

Intralesional triamcinolone (2-20 mg) may be beneficial in the early stages of HS, although its use is based on a small prospective open study of 33 patients.⁸⁷ A recent double-blind placebo-controlled RCT comparing varying concentrations of intralesional triamcinolone (10 mg/mL and 40 mg/mL) vs normal saline showed no statistically significant difference in inflammatory clearance, pain reduction, or patient satisfaction.⁸⁸

Continue to: Short-term systemic corticosteroid tapers...

Short-term systemic corticosteroid tapers (eg, prednisone, starting at 0.5-1 mg/kg) are recommended to treat flares. Long-term corticosteroids and cyclosporine are reserved for patients with severe refractory disease; however, due to safety concerns, their regular use is strongly discouraged.^63,64,85 There is limited evidence to support the use of methotrexate for severe refractory disease, and its use is not recommended.⁶³

Hormonal therapy

The use of hormonal therapy for HS is limited by the low-quality evidence (eg, anecdotal evidence, small retrospective analyses, uncontrolled trials).^33,63 The only exception is a small double-blind controlled crossover trial from 1986 showing that the antiandrogen effects of combination oral contraceptives (ethinyloestradiol 50 mcg/cyproterone acetate in a reverse sequential regimen and ethinyloestradiol 50 mcg/norgestrel 500 mcg) improved HS lesions.⁸⁹

Spironolactone, an antiandrogen diuretic, has been studied in small case report series with a high risk for bias. It is used mainly in female patients with mild or moderate disease, or in combination with other agents in patients with severe HS. Further research is needed to determine its utility in the treatment of HS.^63,90,91

Metformin, alone or in combination with other therapies (dapsone, finasteride, liraglutide), has been analyzed in small prospective studies of primarily female patients with different severities of HS, obesity, and PCOS. These studies have shown improvement in lesions, QOL, and reduction of workdays lost.^92,93

Finasteride. Studies have shown finasteride (1.25-5 mg/d) alone or in combination with other treatments (metformin, liraglutide, levonorgestrel-ethinyl estradiol, and dapsone) provided varying degrees of resolution or improvement in patients with severe and advanced HS. Finasteride has been used for 4 to 16 weeks with a good safety profile.^92,94-96

Continue to: Retinoids

Acitretin, alitretinoin, and isotretinoin have been studied in small retrospective studies to manage HS, with variable results.^97-99 Robust prospective studies are needed. Retinoids, in general, should be considered as a second- or third-line treatment for moderate to severe HS.⁶³

Surgical intervention

Surgical interventions, which should be considered in patients with widespread mild, moderate, or severe disease, are associated with improved daily activity and work productivity.¹⁰⁰ Incision and drainage should be avoided in patients with HS, as this technique does not remove the affected follicles and is associated with 100% recurrence.¹⁰¹

Wide excision is the preferred surgical technique for patients with Hurley stage II and stage III HS; it is associated with lower recurrence rates (13%) compared to local excision (22%) and deroofing (27%).¹⁰² Secondary intention healing is the most commonly chosen method, based on lower recurrence rates than primary closure.¹⁰²

STEEP and laser techniques. The skin-tissue-sparing excision with electrosurgical peeling (STEEP) procedure involves successive tangential excision of affected tissue until the epithelized bottom of the sinus tracts has been reached. This allows for the removal of fibrotic tissue and the sparing of the deep subcutaneous fat. STEEP is associated with 30% of relapses after 43 months.⁷¹

When considering biologic therapy, screen all patients with hidradenitis suppurativa for tuberculosis and hepatitis B, and confirm they are current with age-appropriate immunizations.

Laser surgery has also been studied in patients with Hurley stage II and stage III HS. The most commonly used lasers for HS are the 1064-nm neodymium-doped yttrium aluminum garnet (Nd: YAG) and the carbon dioxide laser; they have been shown to reduce disease severity in inguinal, axillary, and inflammatory sites.^72-74

Pain management: Start with lidocaine, NSAIDs

There are few studies about HS-associated pain management.¹⁰³ For acute episodes, short-acting nonopioid local treatment with lidocaine, topical or oral nonsteroidal anti-inflammatory drugs, and acetaminophen are preferred. Opioids should be reserved for moderate-to-severe pain that has not responded to other analgesics. Adjuvant therapy with pregabalin, gabapentin, selective serotonin reuptake inhibitors, or serotonin-norepinephrine reuptake inhibitors can also be considered for the comanagement of pain and depression.^62,104

Consider this tool to measure treatment response

The HS clinical response (HiSCR) tool is an outcome measure used to evaluate treatment outcomes. The tool uses an HS-specific binary score with the following criteria:

1. ≥ 50% reduction in the number of inflammatory nodules;
2. no increase in the number of abscesses; and
3. no increase in the number of draining fistulas.¹⁰⁵

The HiSCR was developed for the ­PIONEER studies^105,106 to assess the response to ADA treatment. It is the only HS scoring system to undergo an extensive validation process with a meaningful clinical endpoint for HS treatment evaluation that is easy to use. Compared to the HS-PGA score (clear, minimal, mild), HiSCR was more responsive to change in patients with HS.^105,106 

CORRESPONDENCE
Cristina Marti-Amarista, MD, 101 Nicolls Road, Stony Brook, NY, 11794-8228; [email protected]

A 48-YEAR-OLD WOMAN presented to Dermatology for evaluation of a 6-cm abdominal lesion that had been present for 5 weeks ­(FIGURE 1). The lesion was originally about the size of a quarter, but it started to enlarge after treatment of an asthma exacerbation with a 4-day course of prednisone. It continued to grow after another physician, likely presuming the lesion was a corticosteroid-responsive dermatosis (eg, nummular eczema, granuloma annulare, or erythema annulare centrifugum), prescribed a 2-week trial of clobetasol ointment. Physical examination revealed a mildly pruritic, 6-cm erythematous plaque with scaly, annular, concentric rings on the left lower abdomen. The patient had no travel history.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient was given a diagnosis of tinea incognito, a form of tinea corporis that is exacerbated by the inappropriate use of corticosteroids in the management of a cutaneous fungal infection.¹ Furthermore, this patient’s case was consistent with tinea pseudoimbricata, a variant of tinea incognito. Tinea pseudoimbricata is characterized by striking concentric scaly rings that mimic tinea imbricata, a fungal infection caused by the dermatophyte Trichophyton concentricum, which is commonly found in tropical areas.²

A common infection is alteredby steroid use

Tinea corporis has a relatively high prevalence. Approximately 10% to 20% of the world population is affected by fungal skin infections.³ 

T rubrum is the most common cause of tinea corporis. Other causes include T tonsurans, T interdigitale, T ­violaceum, Microsporum canis, M gypseum, and M audouinii.

These steroid treatments caused the abdominal lesion to morph from the typical appearance of tinea corporis to an erythematous plaque with striking concentric scaly rings.

Tinea corporis can be acquired through direct contact with an infected person, animal, or fomite. It may also be acquired through autoinoculation from another area of the body containing a dermatophyte fungal infection. Tinea corporis lesions are usually pruritic, erythematous, annular plaques with overlying scale and central clearing.

How steroid use can change the picture. Treatment with corticosteroids is ineffective for fungal skin infections and causes immunosuppression, allowing the fungus to thrive. This patient had been treated with a topical steroid (clobetasol) for the abdominal lesion caused by tinea corporis, as well as an oral steroid (prednisone) for an asthma exacerbation. These steroid treatments caused the abdominal lesion to morph from the typical appearance of tinea corporis—classically an annular erythematous plaque with overlying scale and central clearing—to an erythematous plaque with striking concentric scaly rings.

Continue to: Clinical exam can provide clues; KOH examination can reveal the Dx

The differential diagnosis for an annular skin lesion includes not only tinea corporis, but also superficial erythema annulare centrifugum, pityriasis rosea, granuloma annulare, subacute cutaneous lupus erythematosus (SCLE), and nummular eczema.

Superficial erythema annulare centrifugum, like tinea corporis, has scale. But the location of the scale sets the 2 apart. Superficial erythema annulare centrifugum lesions have a central trailing scale, whereas tinea corporis lesions have a peripheral leading scale.⁴

Pityriasis rosea forms multiple lesions in a “Christmas tree” pattern on the trunk, sometimes beginning with a single herald patch. Our patient’s single lesion with concentric scaly rings was inconsistent with the distribution and quality of the lesions in pityriasis rosea.⁴

Granuloma annulare lesions are smooth, nonscaly plaques that are most often seen on the dorsal hands and feet. The scaly manifestation of our patient’s lesion was not consistent with this diagnosis.⁴

SCLE lesions are typically photodistributed on sun-exposed skin (eg, the neck, upper trunk, or arms), whereas our patient’s lesion involved a sun-protected site.⁴

Continue to: Nummular eczema

Nummular eczema can be differentiated from tinea corporis by potassium hydroxide (KOH) examination. Nummular eczema is characterized by a negative KOH exam and response to topical corticosteroids.⁴

Performing a KOH examination, using the skin scrapings from the active border of a plaque, is useful on any lesion with potential fungal etiology. If the cause is indeed a dermatophyte infection, segmented fungal hyphae will be seen under light microscopy (FIGURE 2).¹ If a KOH examination is not feasible, a skin scraping can be performed with a surgical scalpel blade and collected in a sterile urine cup for stain and culture at a qualified laboratory.

Topical and oral antifungal medications combat dermatophyte fungi

Treatments for cutaneous infections caused by dermatophyte fungi, such as tinea corporis, include topical and oral antifungals. The choice of agent depends on the extent of the disease.

Limited, localized disease can be treated topically with allylamines (terbinafine, naftifine) or imidazoles (clotrimazole). Other topical agents, such as butenafine, ciclopirox, and tolnaftate, also may be used.

Extensive disease, or tinea infection of vellus hairs, may require treatment with oral antifungal medications, such as the azoles (itraconazole, fluconazole), allylamines (terbinafine), or griseofulvin. Systemic therapy with oral antifungals has been associated with liver damage; therefore, oral therapy should not be used in patients with liver disease and liver enzymes should be monitored when appropriate.⁵ Nystatin is not effective in treating dermatophyte fungal infections.¹

One complication of the inappropriate use of steroids on a dermatophyte infection is an increased risk of the fungus extending from the superficial skin into the hair follicles in the dermis, resulting in a condition known as Majocchi granuloma. Follicular infection is more severe and requires oral antifungal medication, such as terbinafine, itraconazole, fluconazole, or griseofulvin.¹

Our patient was treated with terbinafine 250 mg/d for 4 weeks, due to the possibility of follicular infection. After the completion of 4 weeks of therapy, the patient’s cutaneous symptoms had resolved.

A 48-YEAR-OLD WOMAN presented to Dermatology for evaluation of a 6-cm abdominal lesion that had been present for 5 weeks ­(FIGURE 1). The lesion was originally about the size of a quarter, but it started to enlarge after treatment of an asthma exacerbation with a 4-day course of prednisone. It continued to grow after another physician, likely presuming the lesion was a corticosteroid-responsive dermatosis (eg, nummular eczema, granuloma annulare, or erythema annulare centrifugum), prescribed a 2-week trial of clobetasol ointment. Physical examination revealed a mildly pruritic, 6-cm erythematous plaque with scaly, annular, concentric rings on the left lower abdomen. The patient had no travel history.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient was given a diagnosis of tinea incognito, a form of tinea corporis that is exacerbated by the inappropriate use of corticosteroids in the management of a cutaneous fungal infection.¹ Furthermore, this patient’s case was consistent with tinea pseudoimbricata, a variant of tinea incognito. Tinea pseudoimbricata is characterized by striking concentric scaly rings that mimic tinea imbricata, a fungal infection caused by the dermatophyte Trichophyton concentricum, which is commonly found in tropical areas.²

A common infection is alteredby steroid use

Tinea corporis has a relatively high prevalence. Approximately 10% to 20% of the world population is affected by fungal skin infections.³ 

T rubrum is the most common cause of tinea corporis. Other causes include T tonsurans, T interdigitale, T ­violaceum, Microsporum canis, M gypseum, and M audouinii.

These steroid treatments caused the abdominal lesion to morph from the typical appearance of tinea corporis to an erythematous plaque with striking concentric scaly rings.

Tinea corporis can be acquired through direct contact with an infected person, animal, or fomite. It may also be acquired through autoinoculation from another area of the body containing a dermatophyte fungal infection. Tinea corporis lesions are usually pruritic, erythematous, annular plaques with overlying scale and central clearing.

How steroid use can change the picture. Treatment with corticosteroids is ineffective for fungal skin infections and causes immunosuppression, allowing the fungus to thrive. This patient had been treated with a topical steroid (clobetasol) for the abdominal lesion caused by tinea corporis, as well as an oral steroid (prednisone) for an asthma exacerbation. These steroid treatments caused the abdominal lesion to morph from the typical appearance of tinea corporis—classically an annular erythematous plaque with overlying scale and central clearing—to an erythematous plaque with striking concentric scaly rings.

Continue to: Clinical exam can provide clues; KOH examination can reveal the Dx

The differential diagnosis for an annular skin lesion includes not only tinea corporis, but also superficial erythema annulare centrifugum, pityriasis rosea, granuloma annulare, subacute cutaneous lupus erythematosus (SCLE), and nummular eczema.

Superficial erythema annulare centrifugum, like tinea corporis, has scale. But the location of the scale sets the 2 apart. Superficial erythema annulare centrifugum lesions have a central trailing scale, whereas tinea corporis lesions have a peripheral leading scale.⁴

Pityriasis rosea forms multiple lesions in a “Christmas tree” pattern on the trunk, sometimes beginning with a single herald patch. Our patient’s single lesion with concentric scaly rings was inconsistent with the distribution and quality of the lesions in pityriasis rosea.⁴

Granuloma annulare lesions are smooth, nonscaly plaques that are most often seen on the dorsal hands and feet. The scaly manifestation of our patient’s lesion was not consistent with this diagnosis.⁴

SCLE lesions are typically photodistributed on sun-exposed skin (eg, the neck, upper trunk, or arms), whereas our patient’s lesion involved a sun-protected site.⁴

Continue to: Nummular eczema

Nummular eczema can be differentiated from tinea corporis by potassium hydroxide (KOH) examination. Nummular eczema is characterized by a negative KOH exam and response to topical corticosteroids.⁴

Performing a KOH examination, using the skin scrapings from the active border of a plaque, is useful on any lesion with potential fungal etiology. If the cause is indeed a dermatophyte infection, segmented fungal hyphae will be seen under light microscopy (FIGURE 2).¹ If a KOH examination is not feasible, a skin scraping can be performed with a surgical scalpel blade and collected in a sterile urine cup for stain and culture at a qualified laboratory.

Topical and oral antifungal medications combat dermatophyte fungi

Treatments for cutaneous infections caused by dermatophyte fungi, such as tinea corporis, include topical and oral antifungals. The choice of agent depends on the extent of the disease.

Limited, localized disease can be treated topically with allylamines (terbinafine, naftifine) or imidazoles (clotrimazole). Other topical agents, such as butenafine, ciclopirox, and tolnaftate, also may be used.

Extensive disease, or tinea infection of vellus hairs, may require treatment with oral antifungal medications, such as the azoles (itraconazole, fluconazole), allylamines (terbinafine), or griseofulvin. Systemic therapy with oral antifungals has been associated with liver damage; therefore, oral therapy should not be used in patients with liver disease and liver enzymes should be monitored when appropriate.⁵ Nystatin is not effective in treating dermatophyte fungal infections.¹

One complication of the inappropriate use of steroids on a dermatophyte infection is an increased risk of the fungus extending from the superficial skin into the hair follicles in the dermis, resulting in a condition known as Majocchi granuloma. Follicular infection is more severe and requires oral antifungal medication, such as terbinafine, itraconazole, fluconazole, or griseofulvin.¹

Our patient was treated with terbinafine 250 mg/d for 4 weeks, due to the possibility of follicular infection. After the completion of 4 weeks of therapy, the patient’s cutaneous symptoms had resolved.

A 48-YEAR-OLD WOMAN presented to Dermatology for evaluation of a 6-cm abdominal lesion that had been present for 5 weeks ­(FIGURE 1). The lesion was originally about the size of a quarter, but it started to enlarge after treatment of an asthma exacerbation with a 4-day course of prednisone. It continued to grow after another physician, likely presuming the lesion was a corticosteroid-responsive dermatosis (eg, nummular eczema, granuloma annulare, or erythema annulare centrifugum), prescribed a 2-week trial of clobetasol ointment. Physical examination revealed a mildly pruritic, 6-cm erythematous plaque with scaly, annular, concentric rings on the left lower abdomen. The patient had no travel history.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient was given a diagnosis of tinea incognito, a form of tinea corporis that is exacerbated by the inappropriate use of corticosteroids in the management of a cutaneous fungal infection.¹ Furthermore, this patient’s case was consistent with tinea pseudoimbricata, a variant of tinea incognito. Tinea pseudoimbricata is characterized by striking concentric scaly rings that mimic tinea imbricata, a fungal infection caused by the dermatophyte Trichophyton concentricum, which is commonly found in tropical areas.²

A common infection is alteredby steroid use

Tinea corporis has a relatively high prevalence. Approximately 10% to 20% of the world population is affected by fungal skin infections.³ 

T rubrum is the most common cause of tinea corporis. Other causes include T tonsurans, T interdigitale, T ­violaceum, Microsporum canis, M gypseum, and M audouinii.

These steroid treatments caused the abdominal lesion to morph from the typical appearance of tinea corporis to an erythematous plaque with striking concentric scaly rings.

Tinea corporis can be acquired through direct contact with an infected person, animal, or fomite. It may also be acquired through autoinoculation from another area of the body containing a dermatophyte fungal infection. Tinea corporis lesions are usually pruritic, erythematous, annular plaques with overlying scale and central clearing.

How steroid use can change the picture. Treatment with corticosteroids is ineffective for fungal skin infections and causes immunosuppression, allowing the fungus to thrive. This patient had been treated with a topical steroid (clobetasol) for the abdominal lesion caused by tinea corporis, as well as an oral steroid (prednisone) for an asthma exacerbation. These steroid treatments caused the abdominal lesion to morph from the typical appearance of tinea corporis—classically an annular erythematous plaque with overlying scale and central clearing—to an erythematous plaque with striking concentric scaly rings.

Continue to: Clinical exam can provide clues; KOH examination can reveal the Dx

The differential diagnosis for an annular skin lesion includes not only tinea corporis, but also superficial erythema annulare centrifugum, pityriasis rosea, granuloma annulare, subacute cutaneous lupus erythematosus (SCLE), and nummular eczema.

Superficial erythema annulare centrifugum, like tinea corporis, has scale. But the location of the scale sets the 2 apart. Superficial erythema annulare centrifugum lesions have a central trailing scale, whereas tinea corporis lesions have a peripheral leading scale.⁴

Pityriasis rosea forms multiple lesions in a “Christmas tree” pattern on the trunk, sometimes beginning with a single herald patch. Our patient’s single lesion with concentric scaly rings was inconsistent with the distribution and quality of the lesions in pityriasis rosea.⁴

Granuloma annulare lesions are smooth, nonscaly plaques that are most often seen on the dorsal hands and feet. The scaly manifestation of our patient’s lesion was not consistent with this diagnosis.⁴

SCLE lesions are typically photodistributed on sun-exposed skin (eg, the neck, upper trunk, or arms), whereas our patient’s lesion involved a sun-protected site.⁴

Continue to: Nummular eczema

Nummular eczema can be differentiated from tinea corporis by potassium hydroxide (KOH) examination. Nummular eczema is characterized by a negative KOH exam and response to topical corticosteroids.⁴

Performing a KOH examination, using the skin scrapings from the active border of a plaque, is useful on any lesion with potential fungal etiology. If the cause is indeed a dermatophyte infection, segmented fungal hyphae will be seen under light microscopy (FIGURE 2).¹ If a KOH examination is not feasible, a skin scraping can be performed with a surgical scalpel blade and collected in a sterile urine cup for stain and culture at a qualified laboratory.

Topical and oral antifungal medications combat dermatophyte fungi

Treatments for cutaneous infections caused by dermatophyte fungi, such as tinea corporis, include topical and oral antifungals. The choice of agent depends on the extent of the disease.

Limited, localized disease can be treated topically with allylamines (terbinafine, naftifine) or imidazoles (clotrimazole). Other topical agents, such as butenafine, ciclopirox, and tolnaftate, also may be used.

Extensive disease, or tinea infection of vellus hairs, may require treatment with oral antifungal medications, such as the azoles (itraconazole, fluconazole), allylamines (terbinafine), or griseofulvin. Systemic therapy with oral antifungals has been associated with liver damage; therefore, oral therapy should not be used in patients with liver disease and liver enzymes should be monitored when appropriate.⁵ Nystatin is not effective in treating dermatophyte fungal infections.¹

One complication of the inappropriate use of steroids on a dermatophyte infection is an increased risk of the fungus extending from the superficial skin into the hair follicles in the dermis, resulting in a condition known as Majocchi granuloma. Follicular infection is more severe and requires oral antifungal medication, such as terbinafine, itraconazole, fluconazole, or griseofulvin.¹

Our patient was treated with terbinafine 250 mg/d for 4 weeks, due to the possibility of follicular infection. After the completion of 4 weeks of therapy, the patient’s cutaneous symptoms had resolved.

Several years into the pandemic, COVID-19 continues to deeply impact our society; at the time of publication of this review, 98.8 million cases in the United States have been reported to the Centers for Disease Control and Prevention (CDC).¹ Although many people recover well from infection, there is mounting concern regarding long-term sequelae of COVID-19. These long-term symptoms have been termed long COVID, among other names.

What exactly is long COVID?

The CDC and National Institutes of Health define long COVID as new or ongoing health problems experienced ≥ 4 weeks after initial infection.² Evidence suggests that even people who have mild initial COVID-19 symptoms are at risk for long COVID.

Available data about long COVID are imperfect, however; much about the condition remains poorly understood. For example, there is little evidence regarding the effect of vaccination and viral variants on the prevalence of long ­COVID. A recent study of more than 13 million people from the US Department of Veterans Affairs database did demonstrate that vaccination against SARS-CoV-2 lowered the risk for long ­COVID by only about 15%.³

Persistent symptoms associated with long COVID often lead to disability and decreased quality of life. Furthermore, long COVID is a challenge to treat because there is a paucity of evidence to guide COVID-19 treatment beyond initial infection.

The prevalence of long COVID symptoms appears to increase with age.

Because many patients who have ongoing COVID-19 symptoms will be seen in primary care, it is important to understand how to manage and support them. In this article, we discuss current understanding of long COVID epidemiology, symptoms that can persist 4 weeks after initial infection, and potential treatment options.

Prevalence and diagnosis

The prevalence of long COVID is not well defined because many epidemiologic studies rely on self-reporting. The CDC reports that 20% to 25% of COVID-19 survivors experience a new condition that might be attributable to their initial infection.⁴ Other studies variously cite 5% to 85% of people who have had a diagnosis of COVID-19 as experiencing long COVID, although that rate more consistently appears to be 10% to 30%.⁵

Copyright Brian Stauffer

A study of adult patients in France found that self-reported symptoms of long COVID, 10 to 12 months after the first wave of the pandemic (May through November 2020), were associated with the belief of having had COVID-19 but not necessarily with having tested positive for anti-SARS-CoV-2 antibodies,⁶ which indicates prior COVID-19. This complicates research on long COVID because, first, there is no specific test to confirm a diagnosis of long COVID and, second, studies often rely on self-reporting of earlier COVID-19.

Continue to: As such, long COVID...

As such, long COVID is diagnosed primarily through a medical history and physical examination. The medical history provides a guide as to whether additional testing is warranted to evaluate for known complications of COVID-19, such as deep vein thrombosis, pulmonary embolism, myocarditis, and pulmonary fibrosis. As of October 1, 2021, a new International Classification of Disease (10th Revision) code went into effect for post ­COVID condition, unspecified (U09.9).⁷

The prevalence of long COVID symptoms appears to increase with age. Among patients whose disease was diagnosed using code U09.9, most were 36 to 64 years of age; children and adults ages 22 years or younger constituted only 10.5% of diagnoses.⁷ Long COVID symptoms might also be more prevalent among women and in people with a preexisting chronic comorbidity.^2,7

Symptoms can be numerous, severe or mild, and lasting

Initially, there was no widely accepted definition of long COVID; follow-up in early studies ranged from 21 days to 2 years after initial infection (or from discharge, for hospitalized patients).⁸ Differences in descriptions that have been used on surveys to self-report symptoms make it a challenge to clearly summarize the frequency of each aspect of long COVID.

Long COVID can be mild or debilitating; severity can fluctuate. Common symptoms include fatigue, dyspnea or other breathing difficulties, headache, and cognitive dysfunction, but as many as 203 lasting symptoms have been reported.^2,8-12 From October 1, 2021, through January 31, 2022, the most common accompanying manifestations of long COVID were difficulty breathing, cough, and fatigue.⁷ Long COVID can affect multiple organ systems,^13,14 with symptoms varying by organ system affected. Regardless of the need for hospitalization initially, having had COVID-19 significantly increases the risk for subsequent death at 30 days and at 6 months after initial infection.¹⁵

The CDC reports that 20% to 25% of COVID-19 survivors experience a new condition that might be attributable to their initial infection.

Symptoms of long COVID have been reported as long as 2 years after initial infection.⁸ When Davis and colleagues studied the onset and progression of reported symptoms of long COVID,⁹ they determined that, among patients who reported recovery from COVID-19 in < 90 days, symptoms peaked at approximately Week 2 of infection. In comparison, patients who reported not having recovered in < 90 days had (1) symptoms that peaked later (2 months) and (2) on average, more symptoms (mean, 17 reported symptoms, compared to 11 in recovered ­patients).⁹

Continue to: Fatigue

Fatigue, including postexertion malaise and impaired daily function and mobility, is the most common symptom of long COVID,^8-10,14 reported in 28% to 98%¹⁴ of patients after initial COVID-19. This fatigue is more than simply being tired: Patients describe profound exhaustion, in which fatigue is out of proportion to exertion. Fatigue and myalgia are commonly reported among patients with impaired hepatic and pulmonary function as a consequence of long COVID.¹³ Patients often report that even minor activities result in decreased attention, focus, and energy, for many hours or days afterward. Fatigue has been reported to persist from 2.5 months to as long as 6 months after initial infection or hospitalization.^9,16

Postviral fatigue has been seen in other viral outbreaks and seems to share characteristics with myalgic encephalomyelitis/­chronic fatigue syndrome, or ME/CFS, which itself has historically been stigmatized and poorly understood.¹⁷ Long COVID fatigue might be more common among women and patients who have an existing diagnosis of depression and antidepressant use,^10,11,16,18 although the mechanism of this relationship is unclear. Potential mechanisms include damage from systemic inflammation to metabolism in the frontal lobe and cerebellum¹⁹ and direct infection by SARS-CoV-2 in skeletal muscle.²⁰ Townsend and colleagues¹⁶ found no relationship between long COVID fatigue and markers of inflammation (leukocyte, neutrophil, and lymphocyte counts; the neutrophil-to-lymphocyte ratio; lactate dehydrogenase; C-reactive protein; serum interleukin-6; and soluble CD25).

Neuropsychiatric symptoms are also common in long COVID and can have a significant impact on patients’ quality of life. Studies have reported poor sleep quality or insomnia (38% to 90%), headache (17% to 91.2%), speech and language problems (48% to 50%), confusion (20%), dementia (28.6%), difficulty concentrating (1.9% to 27%), and memory loss or cognitive impairment (5.4% to 73%).^9,10,14,15 For some patients, these symptoms persisted for ≥ 6 months, making it difficult for those affected to return to work.⁹

Isolation and loneliness, a common situation for patients with COVID-19, can have long-term effects on mental health.²¹ The COVID-19 pandemic itself has had a negative effect on behavioral health, including depression (4.3% to 25% of patients), anxiety (1.9% to 46%), obsessive compulsive disorder (4.9% to 20%), and posttraumatic stress disorder (29%).²² The persistence of symptoms of long COVID has resulted in a great deal of frustration, fear, and confusion for those affected—some of whom report a loss of trust in their community health care providers to address their ongoing struggles.²³ Such loss can be accompanied by a reported increase in feelings of anxiety and changes to perceptions of self (ie, “how I used to be” in contrast to “how I am now”).²³ These neuropsychiatric symptoms, including mental health conditions, appear to be more common among older adults.⁴

Other neurologic deficits found in long COVID include olfactory disorders (9% to 27% of patients), altered taste (5% to 18%), numbness or tingling sensations (6%), blurred vision (17.1%), and tinnitus (16.%).¹⁴ Dizziness (2.6% to 6%) and lightheadedness or presyncope (7%) have also been reported, although these symptoms appear to be less common than other neurocognitive effects.¹⁴

Continue to: The mechanism of action...

The mechanism of action of damage to the nervous system in long COVID is likely multifactorial. COVID-19 can directly infect the central nervous system through a hematogenous route, which can result in direct cytolytic damage to neurons. Infection can also affect the blood–brain barrier.²⁴ Additionally, COVID-19 can invade the central nervous system through peripheral nerves, including the olfactory and vagus nerves.²⁵ Many human respiratory viruses, including SARS-CoV-2, result in an increase in pro-inflammatory and anti-inflammatory cytokines; this so-called cytokine storm is an exaggerated response to infection and can trigger neurodegenerative and psychiatric syndromes.²⁶ It is unclear whether the cytokine storm is different for people with COVID-19, compared to other respiratory viruses.

Respiratory symptoms are very common after COVID-19¹⁵: In studies, as many as 87.1% of patients continued to have shortness of breath ≥ 140 days after initial symptom onset, including breathlessness (48% to 60%), wheezing (5.3%), cough (10.5% to 46%), and congestion (32%),^14,18 any of which can persist for as long as 6 months.⁹ Among a sample of previously hospitalized COVID-19 patients in Wuhan, China, 22% to 56% displayed a pulmonary diffusion abnormality 6 months later, with those who required supplemental oxygen during initial COVID-19 having a greater risk for these abnormalities at follow-up, compared to those who did not require supplemental oxygen (odds ratio = 2.42; 95% CI, 1.15-5.08).¹¹

Cardiovascular symptoms. New-onset autonomic dysfunction has been described in multiple case reports and in some larger cohort studies of patients post COVID-19.²⁷ Many common long COVID symptoms, including fatigue and orthostatic intolerance, are commonly seen in postural orthostatic tachycardia syndrome. Emerging evidence indicates that there are likely similar underlying mechanisms and a significant amount of overlap between long COVID and postural orthostatic tachycardia syndrome.²⁷

The high rate of cardiac complications post COVID-19 highlights the importance of a thorough evaluation and work-up of chest pain in patients who have had COVID-19.

A study of patients within the US Department of Veterans Affairs population found that, regardless of disease severity, patients who had a positive COVID-19 test had a higher rate of cardiac disease 30 days after diagnosis,²⁸ including stroke, transient ischemic attack, dysrhythmia, inflammatory heart disease, acute coronary disease, myocardial infarction, ischemic cardiopathy, angina, heart failure, nonischemic cardiomyopathy, and cardiac arrest. Patients with COVID-19 were at increased risk for major adverse cardiovascular events (myocardial infarction, stroke, and all-cause mortality).²⁸ Demographics of the VA population (ie, most are White men) might limit the generalizability of these data, but similar findings have been found elsewhere.^5,10,15Given that, in general, chest pain is common after the acute phase of an infection and the causes of chest pain are broad, the high rate of cardiac complications post COVID-19 nevertheless highlights the importance of a thorough evaluation and work-up of chest pain in patients who have had COVID-19.

Other symptoms. Body aches and generalized joint pain are another common symptom group of long COVID.⁹ These include body aches (20%), joint pain (78%), and muscle aches (87.7%).^14,18

Continue to: Commonly reported...

Commonly reported gastrointestinal symptoms include diarrhea, loss of appetite, nausea, and abdominal pain.^9,15

Other symptoms reported less commonly include dermatologic conditions, such as pruritus and rash; reproductive and endocrine symptoms, including extreme thirst, irregular menstruation, and sexual dysfunction; and new or exacerbated allergic response.⁹

Does severity of initial disease play a role?

Keep in mind that long COVID is not specific to patients who were hospitalized or had severe initial infection. In fact, 75% of patients who have a diagnosis of a post–COVID-19 condition were not hospitalized for their initial infection.⁷ However, the severity of initial COVID-19 infection might contribute to the presence or severity of long COVID symptoms²—although findings in current literature are mixed. For example:

• In reporting from Wuhan, China, higher position on a disease severity scale during a hospital stay for COVID-19 was associated with:
  • greater likelihood of reporting ≥ 1 symptoms at a 6-month ­follow-up
  • increased risk for pulmonary diffusion abnormalities, fatigue, and mood disorders.¹¹
• After 2 years’ follow-up of the same cohort, 55% of patients continued to report ≥ 1 symptoms of long COVID, and those who had been hospitalized with COVID-19 continued to report reduced health-related quality of life, compared to the control group.⁸
• Similarly, patients initially hospitalized with COVID-19 were more likely to experience impairment of ≥ 2 organs—in particular, the liver and pancreas—compared to nonhospitalized patients after a median 5 months post initial infection, among a sample in the United Kingdom.¹³
• In an international cohort, patients who reported a greater number of symptoms during initial COVID-19 were more likely to experience long COVID.¹²
• Last, long COVID fatigue did not vary by severity of initial COVID-19 infection among a sample of hospitalized and nonhospitalized participants in Dublin, Ireland.¹⁶

No specific treatments yet available

There are no specific treatments for long ­COVID; overall, the emphasis is on providing supportive care and managing preexisting chronic conditions.⁵ This is where expertise in primary care, relationships with patients and the community, and psychosocial knowledge can help patients recover from ongoing ­COVID-19 symptoms.

Long COVID–associated fatigue is more than simply being tired. Patients describe profound exhaustion, in which fatigue is out of proportion to exertion.

Clinicians should continue to perform a thorough physical assessment of patients with previous or ongoing COVID-19 to identify and monitor new or recurring symptoms after hospital discharge or initial resolution of symptoms.²⁹ This approach includes developing an individualized plan for care and rehabilitation that is specific to presenting symptoms, including psychological support. We encourage family physicians to familiarize themselves with the work of Vance and colleagues,³⁰ who have created a comprehensive table^a to guide treatment and referral for the gamut of long COVID symptoms, including cardiovascular issues (eg, palpitations, edema), chronic cough, headache, pain, and insomnia.

Continue to: This new clinical entity is a formidable challenge

Long COVID is a new condition that requires comprehensive evaluation to understand the full, often long-term, effects of COVID-19. Our review of this condition substantiated that symptoms of long COVID often affect a variety of organs^13,14 and have been observed to persist for ≥ 2 years.⁸

Some studies that have examined the long-term effects of COVID-19 included only participants who were not hospitalized; others include hospitalized patients exclusively. The literature is mixed in regard to including severity of initial infection as it relates to long COVID. Available research demonstrates that it is common for people with COVID-19 to experience persistent symptoms that can significantly impact daily life and well-being.

Likely, it will be several years before we even begin to understand the full extent of COVID-19. Until research elucidates the relationship between the disease and short- and long-term health outcomes, clinicians should:

• acknowledge and address the reality of long COVID when meeting with persistently symptomatic patients,
• provide support, therapeutic listening, and referral to rehabilitation as appropriate, and
• offer information on the potential for long-term effects of COVID-19 to vaccine-hesitant patients.

^a “Systems, symptoms, and treatments for post-COVID patients,” pages 1231-1234 in the source article (www.jabfm.org/content/jabfp/34/6/1229.full.pdf).³⁰

CORRESPONDENCE
Nicole Mayo, PhD, 46 Prince Street, Rochester, NY 14607; [email protected]

Several years into the pandemic, COVID-19 continues to deeply impact our society; at the time of publication of this review, 98.8 million cases in the United States have been reported to the Centers for Disease Control and Prevention (CDC).¹ Although many people recover well from infection, there is mounting concern regarding long-term sequelae of COVID-19. These long-term symptoms have been termed long COVID, among other names.

What exactly is long COVID?

The CDC and National Institutes of Health define long COVID as new or ongoing health problems experienced ≥ 4 weeks after initial infection.² Evidence suggests that even people who have mild initial COVID-19 symptoms are at risk for long COVID.

Available data about long COVID are imperfect, however; much about the condition remains poorly understood. For example, there is little evidence regarding the effect of vaccination and viral variants on the prevalence of long ­COVID. A recent study of more than 13 million people from the US Department of Veterans Affairs database did demonstrate that vaccination against SARS-CoV-2 lowered the risk for long ­COVID by only about 15%.³

Persistent symptoms associated with long COVID often lead to disability and decreased quality of life. Furthermore, long COVID is a challenge to treat because there is a paucity of evidence to guide COVID-19 treatment beyond initial infection.

The prevalence of long COVID symptoms appears to increase with age.

Because many patients who have ongoing COVID-19 symptoms will be seen in primary care, it is important to understand how to manage and support them. In this article, we discuss current understanding of long COVID epidemiology, symptoms that can persist 4 weeks after initial infection, and potential treatment options.

Prevalence and diagnosis

The prevalence of long COVID is not well defined because many epidemiologic studies rely on self-reporting. The CDC reports that 20% to 25% of COVID-19 survivors experience a new condition that might be attributable to their initial infection.⁴ Other studies variously cite 5% to 85% of people who have had a diagnosis of COVID-19 as experiencing long COVID, although that rate more consistently appears to be 10% to 30%.⁵

Copyright Brian Stauffer

A study of adult patients in France found that self-reported symptoms of long COVID, 10 to 12 months after the first wave of the pandemic (May through November 2020), were associated with the belief of having had COVID-19 but not necessarily with having tested positive for anti-SARS-CoV-2 antibodies,⁶ which indicates prior COVID-19. This complicates research on long COVID because, first, there is no specific test to confirm a diagnosis of long COVID and, second, studies often rely on self-reporting of earlier COVID-19.

Continue to: As such, long COVID...

As such, long COVID is diagnosed primarily through a medical history and physical examination. The medical history provides a guide as to whether additional testing is warranted to evaluate for known complications of COVID-19, such as deep vein thrombosis, pulmonary embolism, myocarditis, and pulmonary fibrosis. As of October 1, 2021, a new International Classification of Disease (10th Revision) code went into effect for post ­COVID condition, unspecified (U09.9).⁷

The prevalence of long COVID symptoms appears to increase with age. Among patients whose disease was diagnosed using code U09.9, most were 36 to 64 years of age; children and adults ages 22 years or younger constituted only 10.5% of diagnoses.⁷ Long COVID symptoms might also be more prevalent among women and in people with a preexisting chronic comorbidity.^2,7

Symptoms can be numerous, severe or mild, and lasting

Initially, there was no widely accepted definition of long COVID; follow-up in early studies ranged from 21 days to 2 years after initial infection (or from discharge, for hospitalized patients).⁸ Differences in descriptions that have been used on surveys to self-report symptoms make it a challenge to clearly summarize the frequency of each aspect of long COVID.

Long COVID can be mild or debilitating; severity can fluctuate. Common symptoms include fatigue, dyspnea or other breathing difficulties, headache, and cognitive dysfunction, but as many as 203 lasting symptoms have been reported.^2,8-12 From October 1, 2021, through January 31, 2022, the most common accompanying manifestations of long COVID were difficulty breathing, cough, and fatigue.⁷ Long COVID can affect multiple organ systems,^13,14 with symptoms varying by organ system affected. Regardless of the need for hospitalization initially, having had COVID-19 significantly increases the risk for subsequent death at 30 days and at 6 months after initial infection.¹⁵

The CDC reports that 20% to 25% of COVID-19 survivors experience a new condition that might be attributable to their initial infection.

Symptoms of long COVID have been reported as long as 2 years after initial infection.⁸ When Davis and colleagues studied the onset and progression of reported symptoms of long COVID,⁹ they determined that, among patients who reported recovery from COVID-19 in < 90 days, symptoms peaked at approximately Week 2 of infection. In comparison, patients who reported not having recovered in < 90 days had (1) symptoms that peaked later (2 months) and (2) on average, more symptoms (mean, 17 reported symptoms, compared to 11 in recovered ­patients).⁹

Continue to: Fatigue

Fatigue, including postexertion malaise and impaired daily function and mobility, is the most common symptom of long COVID,^8-10,14 reported in 28% to 98%¹⁴ of patients after initial COVID-19. This fatigue is more than simply being tired: Patients describe profound exhaustion, in which fatigue is out of proportion to exertion. Fatigue and myalgia are commonly reported among patients with impaired hepatic and pulmonary function as a consequence of long COVID.¹³ Patients often report that even minor activities result in decreased attention, focus, and energy, for many hours or days afterward. Fatigue has been reported to persist from 2.5 months to as long as 6 months after initial infection or hospitalization.^9,16

Postviral fatigue has been seen in other viral outbreaks and seems to share characteristics with myalgic encephalomyelitis/­chronic fatigue syndrome, or ME/CFS, which itself has historically been stigmatized and poorly understood.¹⁷ Long COVID fatigue might be more common among women and patients who have an existing diagnosis of depression and antidepressant use,^10,11,16,18 although the mechanism of this relationship is unclear. Potential mechanisms include damage from systemic inflammation to metabolism in the frontal lobe and cerebellum¹⁹ and direct infection by SARS-CoV-2 in skeletal muscle.²⁰ Townsend and colleagues¹⁶ found no relationship between long COVID fatigue and markers of inflammation (leukocyte, neutrophil, and lymphocyte counts; the neutrophil-to-lymphocyte ratio; lactate dehydrogenase; C-reactive protein; serum interleukin-6; and soluble CD25).

Neuropsychiatric symptoms are also common in long COVID and can have a significant impact on patients’ quality of life. Studies have reported poor sleep quality or insomnia (38% to 90%), headache (17% to 91.2%), speech and language problems (48% to 50%), confusion (20%), dementia (28.6%), difficulty concentrating (1.9% to 27%), and memory loss or cognitive impairment (5.4% to 73%).^9,10,14,15 For some patients, these symptoms persisted for ≥ 6 months, making it difficult for those affected to return to work.⁹

Isolation and loneliness, a common situation for patients with COVID-19, can have long-term effects on mental health.²¹ The COVID-19 pandemic itself has had a negative effect on behavioral health, including depression (4.3% to 25% of patients), anxiety (1.9% to 46%), obsessive compulsive disorder (4.9% to 20%), and posttraumatic stress disorder (29%).²² The persistence of symptoms of long COVID has resulted in a great deal of frustration, fear, and confusion for those affected—some of whom report a loss of trust in their community health care providers to address their ongoing struggles.²³ Such loss can be accompanied by a reported increase in feelings of anxiety and changes to perceptions of self (ie, “how I used to be” in contrast to “how I am now”).²³ These neuropsychiatric symptoms, including mental health conditions, appear to be more common among older adults.⁴

Other neurologic deficits found in long COVID include olfactory disorders (9% to 27% of patients), altered taste (5% to 18%), numbness or tingling sensations (6%), blurred vision (17.1%), and tinnitus (16.%).¹⁴ Dizziness (2.6% to 6%) and lightheadedness or presyncope (7%) have also been reported, although these symptoms appear to be less common than other neurocognitive effects.¹⁴

Continue to: The mechanism of action...

The mechanism of action of damage to the nervous system in long COVID is likely multifactorial. COVID-19 can directly infect the central nervous system through a hematogenous route, which can result in direct cytolytic damage to neurons. Infection can also affect the blood–brain barrier.²⁴ Additionally, COVID-19 can invade the central nervous system through peripheral nerves, including the olfactory and vagus nerves.²⁵ Many human respiratory viruses, including SARS-CoV-2, result in an increase in pro-inflammatory and anti-inflammatory cytokines; this so-called cytokine storm is an exaggerated response to infection and can trigger neurodegenerative and psychiatric syndromes.²⁶ It is unclear whether the cytokine storm is different for people with COVID-19, compared to other respiratory viruses.

Respiratory symptoms are very common after COVID-19¹⁵: In studies, as many as 87.1% of patients continued to have shortness of breath ≥ 140 days after initial symptom onset, including breathlessness (48% to 60%), wheezing (5.3%), cough (10.5% to 46%), and congestion (32%),^14,18 any of which can persist for as long as 6 months.⁹ Among a sample of previously hospitalized COVID-19 patients in Wuhan, China, 22% to 56% displayed a pulmonary diffusion abnormality 6 months later, with those who required supplemental oxygen during initial COVID-19 having a greater risk for these abnormalities at follow-up, compared to those who did not require supplemental oxygen (odds ratio = 2.42; 95% CI, 1.15-5.08).¹¹

Cardiovascular symptoms. New-onset autonomic dysfunction has been described in multiple case reports and in some larger cohort studies of patients post COVID-19.²⁷ Many common long COVID symptoms, including fatigue and orthostatic intolerance, are commonly seen in postural orthostatic tachycardia syndrome. Emerging evidence indicates that there are likely similar underlying mechanisms and a significant amount of overlap between long COVID and postural orthostatic tachycardia syndrome.²⁷

The high rate of cardiac complications post COVID-19 highlights the importance of a thorough evaluation and work-up of chest pain in patients who have had COVID-19.

A study of patients within the US Department of Veterans Affairs population found that, regardless of disease severity, patients who had a positive COVID-19 test had a higher rate of cardiac disease 30 days after diagnosis,²⁸ including stroke, transient ischemic attack, dysrhythmia, inflammatory heart disease, acute coronary disease, myocardial infarction, ischemic cardiopathy, angina, heart failure, nonischemic cardiomyopathy, and cardiac arrest. Patients with COVID-19 were at increased risk for major adverse cardiovascular events (myocardial infarction, stroke, and all-cause mortality).²⁸ Demographics of the VA population (ie, most are White men) might limit the generalizability of these data, but similar findings have been found elsewhere.^5,10,15Given that, in general, chest pain is common after the acute phase of an infection and the causes of chest pain are broad, the high rate of cardiac complications post COVID-19 nevertheless highlights the importance of a thorough evaluation and work-up of chest pain in patients who have had COVID-19.

Other symptoms. Body aches and generalized joint pain are another common symptom group of long COVID.⁹ These include body aches (20%), joint pain (78%), and muscle aches (87.7%).^14,18

Continue to: Commonly reported...

Commonly reported gastrointestinal symptoms include diarrhea, loss of appetite, nausea, and abdominal pain.^9,15

Other symptoms reported less commonly include dermatologic conditions, such as pruritus and rash; reproductive and endocrine symptoms, including extreme thirst, irregular menstruation, and sexual dysfunction; and new or exacerbated allergic response.⁹

Does severity of initial disease play a role?

Keep in mind that long COVID is not specific to patients who were hospitalized or had severe initial infection. In fact, 75% of patients who have a diagnosis of a post–COVID-19 condition were not hospitalized for their initial infection.⁷ However, the severity of initial COVID-19 infection might contribute to the presence or severity of long COVID symptoms²—although findings in current literature are mixed. For example:

• In reporting from Wuhan, China, higher position on a disease severity scale during a hospital stay for COVID-19 was associated with:
  • greater likelihood of reporting ≥ 1 symptoms at a 6-month ­follow-up
  • increased risk for pulmonary diffusion abnormalities, fatigue, and mood disorders.¹¹
• After 2 years’ follow-up of the same cohort, 55% of patients continued to report ≥ 1 symptoms of long COVID, and those who had been hospitalized with COVID-19 continued to report reduced health-related quality of life, compared to the control group.⁸
• Similarly, patients initially hospitalized with COVID-19 were more likely to experience impairment of ≥ 2 organs—in particular, the liver and pancreas—compared to nonhospitalized patients after a median 5 months post initial infection, among a sample in the United Kingdom.¹³
• In an international cohort, patients who reported a greater number of symptoms during initial COVID-19 were more likely to experience long COVID.¹²
• Last, long COVID fatigue did not vary by severity of initial COVID-19 infection among a sample of hospitalized and nonhospitalized participants in Dublin, Ireland.¹⁶

No specific treatments yet available

There are no specific treatments for long ­COVID; overall, the emphasis is on providing supportive care and managing preexisting chronic conditions.⁵ This is where expertise in primary care, relationships with patients and the community, and psychosocial knowledge can help patients recover from ongoing ­COVID-19 symptoms.

Long COVID–associated fatigue is more than simply being tired. Patients describe profound exhaustion, in which fatigue is out of proportion to exertion.

Clinicians should continue to perform a thorough physical assessment of patients with previous or ongoing COVID-19 to identify and monitor new or recurring symptoms after hospital discharge or initial resolution of symptoms.²⁹ This approach includes developing an individualized plan for care and rehabilitation that is specific to presenting symptoms, including psychological support. We encourage family physicians to familiarize themselves with the work of Vance and colleagues,³⁰ who have created a comprehensive table^a to guide treatment and referral for the gamut of long COVID symptoms, including cardiovascular issues (eg, palpitations, edema), chronic cough, headache, pain, and insomnia.

Continue to: This new clinical entity is a formidable challenge

Long COVID is a new condition that requires comprehensive evaluation to understand the full, often long-term, effects of COVID-19. Our review of this condition substantiated that symptoms of long COVID often affect a variety of organs^13,14 and have been observed to persist for ≥ 2 years.⁸

Some studies that have examined the long-term effects of COVID-19 included only participants who were not hospitalized; others include hospitalized patients exclusively. The literature is mixed in regard to including severity of initial infection as it relates to long COVID. Available research demonstrates that it is common for people with COVID-19 to experience persistent symptoms that can significantly impact daily life and well-being.

Likely, it will be several years before we even begin to understand the full extent of COVID-19. Until research elucidates the relationship between the disease and short- and long-term health outcomes, clinicians should:

• acknowledge and address the reality of long COVID when meeting with persistently symptomatic patients,
• provide support, therapeutic listening, and referral to rehabilitation as appropriate, and
• offer information on the potential for long-term effects of COVID-19 to vaccine-hesitant patients.

^a “Systems, symptoms, and treatments for post-COVID patients,” pages 1231-1234 in the source article (www.jabfm.org/content/jabfp/34/6/1229.full.pdf).³⁰

CORRESPONDENCE
Nicole Mayo, PhD, 46 Prince Street, Rochester, NY 14607; [email protected]

Several years into the pandemic, COVID-19 continues to deeply impact our society; at the time of publication of this review, 98.8 million cases in the United States have been reported to the Centers for Disease Control and Prevention (CDC).¹ Although many people recover well from infection, there is mounting concern regarding long-term sequelae of COVID-19. These long-term symptoms have been termed long COVID, among other names.

What exactly is long COVID?

The CDC and National Institutes of Health define long COVID as new or ongoing health problems experienced ≥ 4 weeks after initial infection.² Evidence suggests that even people who have mild initial COVID-19 symptoms are at risk for long COVID.

Available data about long COVID are imperfect, however; much about the condition remains poorly understood. For example, there is little evidence regarding the effect of vaccination and viral variants on the prevalence of long ­COVID. A recent study of more than 13 million people from the US Department of Veterans Affairs database did demonstrate that vaccination against SARS-CoV-2 lowered the risk for long ­COVID by only about 15%.³

Persistent symptoms associated with long COVID often lead to disability and decreased quality of life. Furthermore, long COVID is a challenge to treat because there is a paucity of evidence to guide COVID-19 treatment beyond initial infection.

The prevalence of long COVID symptoms appears to increase with age.

Because many patients who have ongoing COVID-19 symptoms will be seen in primary care, it is important to understand how to manage and support them. In this article, we discuss current understanding of long COVID epidemiology, symptoms that can persist 4 weeks after initial infection, and potential treatment options.

Prevalence and diagnosis

The prevalence of long COVID is not well defined because many epidemiologic studies rely on self-reporting. The CDC reports that 20% to 25% of COVID-19 survivors experience a new condition that might be attributable to their initial infection.⁴ Other studies variously cite 5% to 85% of people who have had a diagnosis of COVID-19 as experiencing long COVID, although that rate more consistently appears to be 10% to 30%.⁵

Copyright Brian Stauffer

A study of adult patients in France found that self-reported symptoms of long COVID, 10 to 12 months after the first wave of the pandemic (May through November 2020), were associated with the belief of having had COVID-19 but not necessarily with having tested positive for anti-SARS-CoV-2 antibodies,⁶ which indicates prior COVID-19. This complicates research on long COVID because, first, there is no specific test to confirm a diagnosis of long COVID and, second, studies often rely on self-reporting of earlier COVID-19.

Continue to: As such, long COVID...

As such, long COVID is diagnosed primarily through a medical history and physical examination. The medical history provides a guide as to whether additional testing is warranted to evaluate for known complications of COVID-19, such as deep vein thrombosis, pulmonary embolism, myocarditis, and pulmonary fibrosis. As of October 1, 2021, a new International Classification of Disease (10th Revision) code went into effect for post ­COVID condition, unspecified (U09.9).⁷

The prevalence of long COVID symptoms appears to increase with age. Among patients whose disease was diagnosed using code U09.9, most were 36 to 64 years of age; children and adults ages 22 years or younger constituted only 10.5% of diagnoses.⁷ Long COVID symptoms might also be more prevalent among women and in people with a preexisting chronic comorbidity.^2,7

Symptoms can be numerous, severe or mild, and lasting

Initially, there was no widely accepted definition of long COVID; follow-up in early studies ranged from 21 days to 2 years after initial infection (or from discharge, for hospitalized patients).⁸ Differences in descriptions that have been used on surveys to self-report symptoms make it a challenge to clearly summarize the frequency of each aspect of long COVID.

Long COVID can be mild or debilitating; severity can fluctuate. Common symptoms include fatigue, dyspnea or other breathing difficulties, headache, and cognitive dysfunction, but as many as 203 lasting symptoms have been reported.^2,8-12 From October 1, 2021, through January 31, 2022, the most common accompanying manifestations of long COVID were difficulty breathing, cough, and fatigue.⁷ Long COVID can affect multiple organ systems,^13,14 with symptoms varying by organ system affected. Regardless of the need for hospitalization initially, having had COVID-19 significantly increases the risk for subsequent death at 30 days and at 6 months after initial infection.¹⁵

The CDC reports that 20% to 25% of COVID-19 survivors experience a new condition that might be attributable to their initial infection.

Symptoms of long COVID have been reported as long as 2 years after initial infection.⁸ When Davis and colleagues studied the onset and progression of reported symptoms of long COVID,⁹ they determined that, among patients who reported recovery from COVID-19 in < 90 days, symptoms peaked at approximately Week 2 of infection. In comparison, patients who reported not having recovered in < 90 days had (1) symptoms that peaked later (2 months) and (2) on average, more symptoms (mean, 17 reported symptoms, compared to 11 in recovered ­patients).⁹

Continue to: Fatigue

Fatigue, including postexertion malaise and impaired daily function and mobility, is the most common symptom of long COVID,^8-10,14 reported in 28% to 98%¹⁴ of patients after initial COVID-19. This fatigue is more than simply being tired: Patients describe profound exhaustion, in which fatigue is out of proportion to exertion. Fatigue and myalgia are commonly reported among patients with impaired hepatic and pulmonary function as a consequence of long COVID.¹³ Patients often report that even minor activities result in decreased attention, focus, and energy, for many hours or days afterward. Fatigue has been reported to persist from 2.5 months to as long as 6 months after initial infection or hospitalization.^9,16

Postviral fatigue has been seen in other viral outbreaks and seems to share characteristics with myalgic encephalomyelitis/­chronic fatigue syndrome, or ME/CFS, which itself has historically been stigmatized and poorly understood.¹⁷ Long COVID fatigue might be more common among women and patients who have an existing diagnosis of depression and antidepressant use,^10,11,16,18 although the mechanism of this relationship is unclear. Potential mechanisms include damage from systemic inflammation to metabolism in the frontal lobe and cerebellum¹⁹ and direct infection by SARS-CoV-2 in skeletal muscle.²⁰ Townsend and colleagues¹⁶ found no relationship between long COVID fatigue and markers of inflammation (leukocyte, neutrophil, and lymphocyte counts; the neutrophil-to-lymphocyte ratio; lactate dehydrogenase; C-reactive protein; serum interleukin-6; and soluble CD25).

Neuropsychiatric symptoms are also common in long COVID and can have a significant impact on patients’ quality of life. Studies have reported poor sleep quality or insomnia (38% to 90%), headache (17% to 91.2%), speech and language problems (48% to 50%), confusion (20%), dementia (28.6%), difficulty concentrating (1.9% to 27%), and memory loss or cognitive impairment (5.4% to 73%).^9,10,14,15 For some patients, these symptoms persisted for ≥ 6 months, making it difficult for those affected to return to work.⁹

Isolation and loneliness, a common situation for patients with COVID-19, can have long-term effects on mental health.²¹ The COVID-19 pandemic itself has had a negative effect on behavioral health, including depression (4.3% to 25% of patients), anxiety (1.9% to 46%), obsessive compulsive disorder (4.9% to 20%), and posttraumatic stress disorder (29%).²² The persistence of symptoms of long COVID has resulted in a great deal of frustration, fear, and confusion for those affected—some of whom report a loss of trust in their community health care providers to address their ongoing struggles.²³ Such loss can be accompanied by a reported increase in feelings of anxiety and changes to perceptions of self (ie, “how I used to be” in contrast to “how I am now”).²³ These neuropsychiatric symptoms, including mental health conditions, appear to be more common among older adults.⁴

Other neurologic deficits found in long COVID include olfactory disorders (9% to 27% of patients), altered taste (5% to 18%), numbness or tingling sensations (6%), blurred vision (17.1%), and tinnitus (16.%).¹⁴ Dizziness (2.6% to 6%) and lightheadedness or presyncope (7%) have also been reported, although these symptoms appear to be less common than other neurocognitive effects.¹⁴

Continue to: The mechanism of action...

The mechanism of action of damage to the nervous system in long COVID is likely multifactorial. COVID-19 can directly infect the central nervous system through a hematogenous route, which can result in direct cytolytic damage to neurons. Infection can also affect the blood–brain barrier.²⁴ Additionally, COVID-19 can invade the central nervous system through peripheral nerves, including the olfactory and vagus nerves.²⁵ Many human respiratory viruses, including SARS-CoV-2, result in an increase in pro-inflammatory and anti-inflammatory cytokines; this so-called cytokine storm is an exaggerated response to infection and can trigger neurodegenerative and psychiatric syndromes.²⁶ It is unclear whether the cytokine storm is different for people with COVID-19, compared to other respiratory viruses.

Respiratory symptoms are very common after COVID-19¹⁵: In studies, as many as 87.1% of patients continued to have shortness of breath ≥ 140 days after initial symptom onset, including breathlessness (48% to 60%), wheezing (5.3%), cough (10.5% to 46%), and congestion (32%),^14,18 any of which can persist for as long as 6 months.⁹ Among a sample of previously hospitalized COVID-19 patients in Wuhan, China, 22% to 56% displayed a pulmonary diffusion abnormality 6 months later, with those who required supplemental oxygen during initial COVID-19 having a greater risk for these abnormalities at follow-up, compared to those who did not require supplemental oxygen (odds ratio = 2.42; 95% CI, 1.15-5.08).¹¹

Cardiovascular symptoms. New-onset autonomic dysfunction has been described in multiple case reports and in some larger cohort studies of patients post COVID-19.²⁷ Many common long COVID symptoms, including fatigue and orthostatic intolerance, are commonly seen in postural orthostatic tachycardia syndrome. Emerging evidence indicates that there are likely similar underlying mechanisms and a significant amount of overlap between long COVID and postural orthostatic tachycardia syndrome.²⁷

The high rate of cardiac complications post COVID-19 highlights the importance of a thorough evaluation and work-up of chest pain in patients who have had COVID-19.

A study of patients within the US Department of Veterans Affairs population found that, regardless of disease severity, patients who had a positive COVID-19 test had a higher rate of cardiac disease 30 days after diagnosis,²⁸ including stroke, transient ischemic attack, dysrhythmia, inflammatory heart disease, acute coronary disease, myocardial infarction, ischemic cardiopathy, angina, heart failure, nonischemic cardiomyopathy, and cardiac arrest. Patients with COVID-19 were at increased risk for major adverse cardiovascular events (myocardial infarction, stroke, and all-cause mortality).²⁸ Demographics of the VA population (ie, most are White men) might limit the generalizability of these data, but similar findings have been found elsewhere.^5,10,15Given that, in general, chest pain is common after the acute phase of an infection and the causes of chest pain are broad, the high rate of cardiac complications post COVID-19 nevertheless highlights the importance of a thorough evaluation and work-up of chest pain in patients who have had COVID-19.

Other symptoms. Body aches and generalized joint pain are another common symptom group of long COVID.⁹ These include body aches (20%), joint pain (78%), and muscle aches (87.7%).^14,18

Continue to: Commonly reported...

Commonly reported gastrointestinal symptoms include diarrhea, loss of appetite, nausea, and abdominal pain.^9,15

Other symptoms reported less commonly include dermatologic conditions, such as pruritus and rash; reproductive and endocrine symptoms, including extreme thirst, irregular menstruation, and sexual dysfunction; and new or exacerbated allergic response.⁹

Does severity of initial disease play a role?

Keep in mind that long COVID is not specific to patients who were hospitalized or had severe initial infection. In fact, 75% of patients who have a diagnosis of a post–COVID-19 condition were not hospitalized for their initial infection.⁷ However, the severity of initial COVID-19 infection might contribute to the presence or severity of long COVID symptoms²—although findings in current literature are mixed. For example:

• In reporting from Wuhan, China, higher position on a disease severity scale during a hospital stay for COVID-19 was associated with:
  • greater likelihood of reporting ≥ 1 symptoms at a 6-month ­follow-up
  • increased risk for pulmonary diffusion abnormalities, fatigue, and mood disorders.¹¹
• After 2 years’ follow-up of the same cohort, 55% of patients continued to report ≥ 1 symptoms of long COVID, and those who had been hospitalized with COVID-19 continued to report reduced health-related quality of life, compared to the control group.⁸
• Similarly, patients initially hospitalized with COVID-19 were more likely to experience impairment of ≥ 2 organs—in particular, the liver and pancreas—compared to nonhospitalized patients after a median 5 months post initial infection, among a sample in the United Kingdom.¹³
• In an international cohort, patients who reported a greater number of symptoms during initial COVID-19 were more likely to experience long COVID.¹²
• Last, long COVID fatigue did not vary by severity of initial COVID-19 infection among a sample of hospitalized and nonhospitalized participants in Dublin, Ireland.¹⁶

No specific treatments yet available

There are no specific treatments for long ­COVID; overall, the emphasis is on providing supportive care and managing preexisting chronic conditions.⁵ This is where expertise in primary care, relationships with patients and the community, and psychosocial knowledge can help patients recover from ongoing ­COVID-19 symptoms.

Long COVID–associated fatigue is more than simply being tired. Patients describe profound exhaustion, in which fatigue is out of proportion to exertion.

Clinicians should continue to perform a thorough physical assessment of patients with previous or ongoing COVID-19 to identify and monitor new or recurring symptoms after hospital discharge or initial resolution of symptoms.²⁹ This approach includes developing an individualized plan for care and rehabilitation that is specific to presenting symptoms, including psychological support. We encourage family physicians to familiarize themselves with the work of Vance and colleagues,³⁰ who have created a comprehensive table^a to guide treatment and referral for the gamut of long COVID symptoms, including cardiovascular issues (eg, palpitations, edema), chronic cough, headache, pain, and insomnia.

Continue to: This new clinical entity is a formidable challenge

Long COVID is a new condition that requires comprehensive evaluation to understand the full, often long-term, effects of COVID-19. Our review of this condition substantiated that symptoms of long COVID often affect a variety of organs^13,14 and have been observed to persist for ≥ 2 years.⁸

Some studies that have examined the long-term effects of COVID-19 included only participants who were not hospitalized; others include hospitalized patients exclusively. The literature is mixed in regard to including severity of initial infection as it relates to long COVID. Available research demonstrates that it is common for people with COVID-19 to experience persistent symptoms that can significantly impact daily life and well-being.

Likely, it will be several years before we even begin to understand the full extent of COVID-19. Until research elucidates the relationship between the disease and short- and long-term health outcomes, clinicians should:

• acknowledge and address the reality of long COVID when meeting with persistently symptomatic patients,
• provide support, therapeutic listening, and referral to rehabilitation as appropriate, and
• offer information on the potential for long-term effects of COVID-19 to vaccine-hesitant patients.

^a “Systems, symptoms, and treatments for post-COVID patients,” pages 1231-1234 in the source article (www.jabfm.org/content/jabfp/34/6/1229.full.pdf).³⁰

CORRESPONDENCE
Nicole Mayo, PhD, 46 Prince Street, Rochester, NY 14607; [email protected]

The Supreme Court’s Dobbs decision on June 24, 2022, which nullified the federal protections of Roe v Wade, resulted in the swift and devastating dissolution of access to abortion care for hundreds of thousands of patients in the United States.¹ Within days of the decision, 11 states in the South and Midwest implemented complete or 6-week abortion bans that, in part, led to the closure of over half the abortion clinics in these states.² Abortion bans, severe restrictions, and clinic closures affect all patients and magnify existing health care inequities. 

Medication abortion is becoming increasingly popular; as of 2020, approximately 50% of US abortions were performed using this method.³ Through a combination of mifepristone and misoprostol, medication abortion induces the physiologic process and symptoms similar to those of a miscarriage. Notably, this regimen is also the most effective medical management method for a missed abortion in the first trimester, and therefore, should already be incorporated into any general ObGyn practice.⁴

Although a recent study found that 97% of ObGyn physicians report encountering patients who seek an abortion, only 15% to 25% of them reported providing abortion services.^5,6 Given our expertise, ObGyns are well-positioned to incorporate medication abortion into our practices. For those ObGyn providers who practice in states without extreme abortion bans, this article provides guidance on how to incorporate medication abortion into your practice (FIGURE). Several states now have early gestational limits on abortion, and the abortion-dedicated clinics that remain open are over capacity. Therefore, by incorporating medication abortion into your practice you can contribute to timely abortion access for your patients. 

Medication abortion:  The process

Determine your ability and  patient’s eligibility

Abortion-specific laws for your state have now become the first determinant of your ability to provide medication abortion to your patients. The Guttmacher Institute is one reliable source of specific state laws that your practice can reference and is updated regularly.⁷

From a practice perspective, most ObGyn physicians already have the technical capabilities in place to provide medication abortion. First, you must be able to accurately determine the patient’s gestational age by their last menstrual period, which is often confirmed through ultrasonography.

Medication abortion is safe and routinely used in many practices up to 77 days, or 11 weeks, of gestation. Authors of a recent retrospective cohort study found that medication abortion also may be initiated for a pregnancy of unknown location in patients who are asymptomatic and determined to have low risk for an ectopic pregnancy. In this study, initiation of medication abortion on the day of presentation, with concurrent evaluation for ectopic pregnancy, was associated with a shorter time to a completed abortion, but a lower rate of successful medication abortion when compared with patients who delayed the initiation of medication abortion until a clear intrauterine pregnancy was diagnosed.⁸

Few medical contraindications exist for patients who seek a medication abortion. These contraindications include allergy to or medication interaction with mifepristone or misoprostol, chronic adrenal failure or long-term corticosteroid therapy, acute porphyria, anemia or the use of anticoagulation therapy, or current intrauterine device (IUD) use. 

Continue to: Gather consents and  administer treatment...

Historically, mifepristone has been dispensed directly at an ObGyn physician’s office. However, the US Food and Drug Administration (FDA) regulations requiring this were lifted during the COVID-19 pandemic, and as of December 2021, the inperson dispensing requirement was permanently removed.⁹ To provide mifepristone in a medical practice under current guidelines, a confidential prescriber agreement must be completed once by one person on behalf of the practice. Then each patient must read the manufacturer’s medication guide and sign the patient agreement form as part of the consent process (available on the FDA’s website).¹⁰ These agreement forms must be filled out by a physician and each patient if your practice uses mifepristone for any pregnancy indication, including induction of labor or medical management of miscarriage. Given the multiple evidence-based indications for mifepristone in pregnancy, it is hoped that these agreement forms will become a routine part of most ObGyn practices. Other consent requirements vary by state. 

After signing consent forms, patients receive and often immediately take mifepristone 200 mg orally. Mifepristone is a progesterone receptor antagonist that sensitizes the uterine myometrium to the effects of prostaglandin.¹¹ Rarely, patients may experience symptoms of bleeding or cramping after mifepristone administration alone. 

Patients are discharged home with ibuprofen and an antiemetic for symptom relief to be taken around the time of administration of misoprostol. Misoprostol is a synthetic prostaglandin that causes uterine cramping and expulsion of the pregnancy typically within 4 hours of administration. Patients leave with the pills of misoprostol  800 μg (4 tablets, 200 µg each), which they self-administer buccally 24-48 hours after mifepristone administration. A prescription for misoprostol can be given instead of the actual pills, but geographic distance to the pharmacy and other potential barriers should be considered when evaluating the feasibility and convenience of providing pharmacy-dispensed misoprostol. 

We instruct patients to place 2 tablets buccally between each gum and cheek, dosing all 4 tablets at the same time. Patients are instructed to let the tablets dissolve buccally and, after 30 minutes, to swallow the tablets with water. Administration of an automatic second dose of misoprostol 3-6 hours after the first dose for pregnancies between 9-11 weeks of gestation is recommended to increase success rate at these later gestational ages.^12,13 Several different routes of administration, including buccal, vaginal, and sublingual, have been used for first trimester medication abortion with misoprostol.

Follow up and confirm the results

Patients can safely follow up after their medication abortion in several ways. In our practice, patients are offered 3 possible options. 

1. The first is ultrasound follow-up, whereby the patient returns to the clinic 1 week after their medication abortion for a pelvic ultrasound to confirm the gestational sac has passed. 
2. The second method is to test beta-human chorionic gonadotropin (B-hCG) levels. Patients interested in this option have a baseline B-hCG drawn on the day of presentation and follow up 7-10 days later for a repeat B-hCG test. An 80% drop in B-hCG level is consistent with a successful medication abortion.
3. The third option, a phone checklist that is usually combined with a urine pregnancy test 4-6 weeks after a medication abortion, is an effective patient-centered approach. The COVID-19 pandemic and the subsequent compulsory shift to providing medical care via telemedicine highlighted the safety, acceptability, and patient preference for the provision of medication abortion using telehealth platforms.¹⁴ 

Outcomes and complications

Medication abortion using a combined regimen of mifepristone followed by misoprostol is approximately 95% effective at complete expulsion of the pregnancy.^15,16 Complications after a first trimester medication abortion are rare. In a retrospective cohort study of 54,911 abortions, the most common complication was incomplete abortion.¹⁷ Symptoms concerning for incomplete abortion included persistent heavy vaginal bleeding and pelvic cramping. An incomplete or failed abortion should be managed with an additional dose of misoprostol or dilation and evacuation. Other possible complications such as infection are also rare, and prophylactic antibiotics are not encouraged.¹⁸

Future fertility and  pregnancy implications

Patients should be counseled that a medication abortion is not associated with infertility or increased risk for adverse outcomes in future pregnancies.¹⁹ Contraceptive counseling should be provided to all interested patients at the time of a medication abortion and ideally provided to the patient on the day of their visit. Oral contraceptives, the patch, and the ring can be started on the day of misoprostol administration.²⁰ The optimal timing of IUD insertion has been examined in 2 randomized control trials. Results indicated a higher uptake in the group of patients who received their IUD approximately 1 week after medication abortion versus delaying placement for several weeks, with no difference in IUD expulsion rates.^21,22 Patients interested in depot-medroxyprogesterone acetate (DMPA) injection should be counseled on the theoretical decreased efficacy of medication abortion in the setting of concurrent DMPA administration. If possible, a follow-up plan should be made so that the patient can receive DMPA, if desired, at a later date.²³ The etonogestrel implant (Nexplanon), however, can be placed on the day of mifepristone administration and does not affect the efficacy of a medication abortion.^24,25

Summary

During this critical time for reproductive health care, it is essential that ObGyns  consider how their professional position and expertise can assist with the provision of medication abortions. Most ObGyn practices already have the resources in place to effectively care for patients before, during, and after a medication abortion. Integrating abortion health care into your practice promotes patient-centered care, continuity, and patient satisfaction. Furthermore, by improving abortion referrals or offering information on safe, self-procured abortion, you can contribute to destigmatizing abortion care, while playing an integral role in connecting your patients with the care they need and desire. ●

The Supreme Court’s Dobbs decision on June 24, 2022, which nullified the federal protections of Roe v Wade, resulted in the swift and devastating dissolution of access to abortion care for hundreds of thousands of patients in the United States.¹ Within days of the decision, 11 states in the South and Midwest implemented complete or 6-week abortion bans that, in part, led to the closure of over half the abortion clinics in these states.² Abortion bans, severe restrictions, and clinic closures affect all patients and magnify existing health care inequities. 

Medication abortion is becoming increasingly popular; as of 2020, approximately 50% of US abortions were performed using this method.³ Through a combination of mifepristone and misoprostol, medication abortion induces the physiologic process and symptoms similar to those of a miscarriage. Notably, this regimen is also the most effective medical management method for a missed abortion in the first trimester, and therefore, should already be incorporated into any general ObGyn practice.⁴

Although a recent study found that 97% of ObGyn physicians report encountering patients who seek an abortion, only 15% to 25% of them reported providing abortion services.^5,6 Given our expertise, ObGyns are well-positioned to incorporate medication abortion into our practices. For those ObGyn providers who practice in states without extreme abortion bans, this article provides guidance on how to incorporate medication abortion into your practice (FIGURE). Several states now have early gestational limits on abortion, and the abortion-dedicated clinics that remain open are over capacity. Therefore, by incorporating medication abortion into your practice you can contribute to timely abortion access for your patients. 

Medication abortion:  The process

Determine your ability and  patient’s eligibility

Abortion-specific laws for your state have now become the first determinant of your ability to provide medication abortion to your patients. The Guttmacher Institute is one reliable source of specific state laws that your practice can reference and is updated regularly.⁷

From a practice perspective, most ObGyn physicians already have the technical capabilities in place to provide medication abortion. First, you must be able to accurately determine the patient’s gestational age by their last menstrual period, which is often confirmed through ultrasonography.

Medication abortion is safe and routinely used in many practices up to 77 days, or 11 weeks, of gestation. Authors of a recent retrospective cohort study found that medication abortion also may be initiated for a pregnancy of unknown location in patients who are asymptomatic and determined to have low risk for an ectopic pregnancy. In this study, initiation of medication abortion on the day of presentation, with concurrent evaluation for ectopic pregnancy, was associated with a shorter time to a completed abortion, but a lower rate of successful medication abortion when compared with patients who delayed the initiation of medication abortion until a clear intrauterine pregnancy was diagnosed.⁸

Few medical contraindications exist for patients who seek a medication abortion. These contraindications include allergy to or medication interaction with mifepristone or misoprostol, chronic adrenal failure or long-term corticosteroid therapy, acute porphyria, anemia or the use of anticoagulation therapy, or current intrauterine device (IUD) use. 

Continue to: Gather consents and  administer treatment...

Historically, mifepristone has been dispensed directly at an ObGyn physician’s office. However, the US Food and Drug Administration (FDA) regulations requiring this were lifted during the COVID-19 pandemic, and as of December 2021, the inperson dispensing requirement was permanently removed.⁹ To provide mifepristone in a medical practice under current guidelines, a confidential prescriber agreement must be completed once by one person on behalf of the practice. Then each patient must read the manufacturer’s medication guide and sign the patient agreement form as part of the consent process (available on the FDA’s website).¹⁰ These agreement forms must be filled out by a physician and each patient if your practice uses mifepristone for any pregnancy indication, including induction of labor or medical management of miscarriage. Given the multiple evidence-based indications for mifepristone in pregnancy, it is hoped that these agreement forms will become a routine part of most ObGyn practices. Other consent requirements vary by state. 

After signing consent forms, patients receive and often immediately take mifepristone 200 mg orally. Mifepristone is a progesterone receptor antagonist that sensitizes the uterine myometrium to the effects of prostaglandin.¹¹ Rarely, patients may experience symptoms of bleeding or cramping after mifepristone administration alone. 

Patients are discharged home with ibuprofen and an antiemetic for symptom relief to be taken around the time of administration of misoprostol. Misoprostol is a synthetic prostaglandin that causes uterine cramping and expulsion of the pregnancy typically within 4 hours of administration. Patients leave with the pills of misoprostol  800 μg (4 tablets, 200 µg each), which they self-administer buccally 24-48 hours after mifepristone administration. A prescription for misoprostol can be given instead of the actual pills, but geographic distance to the pharmacy and other potential barriers should be considered when evaluating the feasibility and convenience of providing pharmacy-dispensed misoprostol. 

We instruct patients to place 2 tablets buccally between each gum and cheek, dosing all 4 tablets at the same time. Patients are instructed to let the tablets dissolve buccally and, after 30 minutes, to swallow the tablets with water. Administration of an automatic second dose of misoprostol 3-6 hours after the first dose for pregnancies between 9-11 weeks of gestation is recommended to increase success rate at these later gestational ages.^12,13 Several different routes of administration, including buccal, vaginal, and sublingual, have been used for first trimester medication abortion with misoprostol.

Follow up and confirm the results

Patients can safely follow up after their medication abortion in several ways. In our practice, patients are offered 3 possible options. 

1. The first is ultrasound follow-up, whereby the patient returns to the clinic 1 week after their medication abortion for a pelvic ultrasound to confirm the gestational sac has passed. 
2. The second method is to test beta-human chorionic gonadotropin (B-hCG) levels. Patients interested in this option have a baseline B-hCG drawn on the day of presentation and follow up 7-10 days later for a repeat B-hCG test. An 80% drop in B-hCG level is consistent with a successful medication abortion.
3. The third option, a phone checklist that is usually combined with a urine pregnancy test 4-6 weeks after a medication abortion, is an effective patient-centered approach. The COVID-19 pandemic and the subsequent compulsory shift to providing medical care via telemedicine highlighted the safety, acceptability, and patient preference for the provision of medication abortion using telehealth platforms.¹⁴ 

Outcomes and complications

Medication abortion using a combined regimen of mifepristone followed by misoprostol is approximately 95% effective at complete expulsion of the pregnancy.^15,16 Complications after a first trimester medication abortion are rare. In a retrospective cohort study of 54,911 abortions, the most common complication was incomplete abortion.¹⁷ Symptoms concerning for incomplete abortion included persistent heavy vaginal bleeding and pelvic cramping. An incomplete or failed abortion should be managed with an additional dose of misoprostol or dilation and evacuation. Other possible complications such as infection are also rare, and prophylactic antibiotics are not encouraged.¹⁸

Future fertility and  pregnancy implications

Patients should be counseled that a medication abortion is not associated with infertility or increased risk for adverse outcomes in future pregnancies.¹⁹ Contraceptive counseling should be provided to all interested patients at the time of a medication abortion and ideally provided to the patient on the day of their visit. Oral contraceptives, the patch, and the ring can be started on the day of misoprostol administration.²⁰ The optimal timing of IUD insertion has been examined in 2 randomized control trials. Results indicated a higher uptake in the group of patients who received their IUD approximately 1 week after medication abortion versus delaying placement for several weeks, with no difference in IUD expulsion rates.^21,22 Patients interested in depot-medroxyprogesterone acetate (DMPA) injection should be counseled on the theoretical decreased efficacy of medication abortion in the setting of concurrent DMPA administration. If possible, a follow-up plan should be made so that the patient can receive DMPA, if desired, at a later date.²³ The etonogestrel implant (Nexplanon), however, can be placed on the day of mifepristone administration and does not affect the efficacy of a medication abortion.^24,25

Summary

During this critical time for reproductive health care, it is essential that ObGyns  consider how their professional position and expertise can assist with the provision of medication abortions. Most ObGyn practices already have the resources in place to effectively care for patients before, during, and after a medication abortion. Integrating abortion health care into your practice promotes patient-centered care, continuity, and patient satisfaction. Furthermore, by improving abortion referrals or offering information on safe, self-procured abortion, you can contribute to destigmatizing abortion care, while playing an integral role in connecting your patients with the care they need and desire. ●

The Supreme Court’s Dobbs decision on June 24, 2022, which nullified the federal protections of Roe v Wade, resulted in the swift and devastating dissolution of access to abortion care for hundreds of thousands of patients in the United States.¹ Within days of the decision, 11 states in the South and Midwest implemented complete or 6-week abortion bans that, in part, led to the closure of over half the abortion clinics in these states.² Abortion bans, severe restrictions, and clinic closures affect all patients and magnify existing health care inequities. 

Medication abortion is becoming increasingly popular; as of 2020, approximately 50% of US abortions were performed using this method.³ Through a combination of mifepristone and misoprostol, medication abortion induces the physiologic process and symptoms similar to those of a miscarriage. Notably, this regimen is also the most effective medical management method for a missed abortion in the first trimester, and therefore, should already be incorporated into any general ObGyn practice.⁴

Although a recent study found that 97% of ObGyn physicians report encountering patients who seek an abortion, only 15% to 25% of them reported providing abortion services.^5,6 Given our expertise, ObGyns are well-positioned to incorporate medication abortion into our practices. For those ObGyn providers who practice in states without extreme abortion bans, this article provides guidance on how to incorporate medication abortion into your practice (FIGURE). Several states now have early gestational limits on abortion, and the abortion-dedicated clinics that remain open are over capacity. Therefore, by incorporating medication abortion into your practice you can contribute to timely abortion access for your patients. 

Medication abortion:  The process

Determine your ability and  patient’s eligibility

Abortion-specific laws for your state have now become the first determinant of your ability to provide medication abortion to your patients. The Guttmacher Institute is one reliable source of specific state laws that your practice can reference and is updated regularly.⁷

From a practice perspective, most ObGyn physicians already have the technical capabilities in place to provide medication abortion. First, you must be able to accurately determine the patient’s gestational age by their last menstrual period, which is often confirmed through ultrasonography.

Medication abortion is safe and routinely used in many practices up to 77 days, or 11 weeks, of gestation. Authors of a recent retrospective cohort study found that medication abortion also may be initiated for a pregnancy of unknown location in patients who are asymptomatic and determined to have low risk for an ectopic pregnancy. In this study, initiation of medication abortion on the day of presentation, with concurrent evaluation for ectopic pregnancy, was associated with a shorter time to a completed abortion, but a lower rate of successful medication abortion when compared with patients who delayed the initiation of medication abortion until a clear intrauterine pregnancy was diagnosed.⁸

Few medical contraindications exist for patients who seek a medication abortion. These contraindications include allergy to or medication interaction with mifepristone or misoprostol, chronic adrenal failure or long-term corticosteroid therapy, acute porphyria, anemia or the use of anticoagulation therapy, or current intrauterine device (IUD) use. 

Continue to: Gather consents and  administer treatment...

Historically, mifepristone has been dispensed directly at an ObGyn physician’s office. However, the US Food and Drug Administration (FDA) regulations requiring this were lifted during the COVID-19 pandemic, and as of December 2021, the inperson dispensing requirement was permanently removed.⁹ To provide mifepristone in a medical practice under current guidelines, a confidential prescriber agreement must be completed once by one person on behalf of the practice. Then each patient must read the manufacturer’s medication guide and sign the patient agreement form as part of the consent process (available on the FDA’s website).¹⁰ These agreement forms must be filled out by a physician and each patient if your practice uses mifepristone for any pregnancy indication, including induction of labor or medical management of miscarriage. Given the multiple evidence-based indications for mifepristone in pregnancy, it is hoped that these agreement forms will become a routine part of most ObGyn practices. Other consent requirements vary by state. 

After signing consent forms, patients receive and often immediately take mifepristone 200 mg orally. Mifepristone is a progesterone receptor antagonist that sensitizes the uterine myometrium to the effects of prostaglandin.¹¹ Rarely, patients may experience symptoms of bleeding or cramping after mifepristone administration alone. 

Patients are discharged home with ibuprofen and an antiemetic for symptom relief to be taken around the time of administration of misoprostol. Misoprostol is a synthetic prostaglandin that causes uterine cramping and expulsion of the pregnancy typically within 4 hours of administration. Patients leave with the pills of misoprostol  800 μg (4 tablets, 200 µg each), which they self-administer buccally 24-48 hours after mifepristone administration. A prescription for misoprostol can be given instead of the actual pills, but geographic distance to the pharmacy and other potential barriers should be considered when evaluating the feasibility and convenience of providing pharmacy-dispensed misoprostol. 

We instruct patients to place 2 tablets buccally between each gum and cheek, dosing all 4 tablets at the same time. Patients are instructed to let the tablets dissolve buccally and, after 30 minutes, to swallow the tablets with water. Administration of an automatic second dose of misoprostol 3-6 hours after the first dose for pregnancies between 9-11 weeks of gestation is recommended to increase success rate at these later gestational ages.^12,13 Several different routes of administration, including buccal, vaginal, and sublingual, have been used for first trimester medication abortion with misoprostol.

Follow up and confirm the results

Patients can safely follow up after their medication abortion in several ways. In our practice, patients are offered 3 possible options. 

1. The first is ultrasound follow-up, whereby the patient returns to the clinic 1 week after their medication abortion for a pelvic ultrasound to confirm the gestational sac has passed. 
2. The second method is to test beta-human chorionic gonadotropin (B-hCG) levels. Patients interested in this option have a baseline B-hCG drawn on the day of presentation and follow up 7-10 days later for a repeat B-hCG test. An 80% drop in B-hCG level is consistent with a successful medication abortion.
3. The third option, a phone checklist that is usually combined with a urine pregnancy test 4-6 weeks after a medication abortion, is an effective patient-centered approach. The COVID-19 pandemic and the subsequent compulsory shift to providing medical care via telemedicine highlighted the safety, acceptability, and patient preference for the provision of medication abortion using telehealth platforms.¹⁴ 

Outcomes and complications

Medication abortion using a combined regimen of mifepristone followed by misoprostol is approximately 95% effective at complete expulsion of the pregnancy.^15,16 Complications after a first trimester medication abortion are rare. In a retrospective cohort study of 54,911 abortions, the most common complication was incomplete abortion.¹⁷ Symptoms concerning for incomplete abortion included persistent heavy vaginal bleeding and pelvic cramping. An incomplete or failed abortion should be managed with an additional dose of misoprostol or dilation and evacuation. Other possible complications such as infection are also rare, and prophylactic antibiotics are not encouraged.¹⁸

Future fertility and  pregnancy implications

Patients should be counseled that a medication abortion is not associated with infertility or increased risk for adverse outcomes in future pregnancies.¹⁹ Contraceptive counseling should be provided to all interested patients at the time of a medication abortion and ideally provided to the patient on the day of their visit. Oral contraceptives, the patch, and the ring can be started on the day of misoprostol administration.²⁰ The optimal timing of IUD insertion has been examined in 2 randomized control trials. Results indicated a higher uptake in the group of patients who received their IUD approximately 1 week after medication abortion versus delaying placement for several weeks, with no difference in IUD expulsion rates.^21,22 Patients interested in depot-medroxyprogesterone acetate (DMPA) injection should be counseled on the theoretical decreased efficacy of medication abortion in the setting of concurrent DMPA administration. If possible, a follow-up plan should be made so that the patient can receive DMPA, if desired, at a later date.²³ The etonogestrel implant (Nexplanon), however, can be placed on the day of mifepristone administration and does not affect the efficacy of a medication abortion.^24,25

Summary

During this critical time for reproductive health care, it is essential that ObGyns  consider how their professional position and expertise can assist with the provision of medication abortions. Most ObGyn practices already have the resources in place to effectively care for patients before, during, and after a medication abortion. Integrating abortion health care into your practice promotes patient-centered care, continuity, and patient satisfaction. Furthermore, by improving abortion referrals or offering information on safe, self-procured abortion, you can contribute to destigmatizing abortion care, while playing an integral role in connecting your patients with the care they need and desire. ●

This combination of vascular features with excess keratin fit perfectly with the name of the diagnosis: angiokeratoma. The dark color of the lesion on magnification, or in this case with dermoscopy, showed the lacunar pattern of dilated vessels. The overlying keratin was likely accentuated because it was on an extensor surface; the rim of hyperpigmentation is common for these lesions.

Angiokeratomas result from dilation of the blood vessels underneath the epidermis. There are different inciting events that lead to the 5 different types of angiokeratomas. The overlying epidermal changes are secondary to the underlying process of capillary ectasia.¹ This lesion was not part of a cluster, so it was characterized as a solitary angiokeratoma. Smaller lesions are usually less keratinized and are commonly seen on the scrotum and vulva, where there are usually multiple lesions (referred to as angiokeratoma of Fordyce).

Zaballos² studied the dermoscopic characteristics of 32 solitary angiokeratomas and reported 6 findings in at least half of the solitary lesions. The most common features were dark lacunae in 94% of the lesions, white veil in 91%, and erythema in 69%. Peripheral erythema, red lacunae, and hemorrhagic crusts were all seen at a rate of 53%. The most common location was the lower extremities.

This patient’s previous pathology report from a shave biopsy was found, confirming that the original diagnosis was angiokeratoma. Since the patient’s lesion had not resolved and was symptomatic from minor trauma, he was scheduled to come back in for an elliptical excision to remove the lesion.

‌

Image and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

This combination of vascular features with excess keratin fit perfectly with the name of the diagnosis: angiokeratoma. The dark color of the lesion on magnification, or in this case with dermoscopy, showed the lacunar pattern of dilated vessels. The overlying keratin was likely accentuated because it was on an extensor surface; the rim of hyperpigmentation is common for these lesions.

Angiokeratomas result from dilation of the blood vessels underneath the epidermis. There are different inciting events that lead to the 5 different types of angiokeratomas. The overlying epidermal changes are secondary to the underlying process of capillary ectasia.¹ This lesion was not part of a cluster, so it was characterized as a solitary angiokeratoma. Smaller lesions are usually less keratinized and are commonly seen on the scrotum and vulva, where there are usually multiple lesions (referred to as angiokeratoma of Fordyce).

Zaballos² studied the dermoscopic characteristics of 32 solitary angiokeratomas and reported 6 findings in at least half of the solitary lesions. The most common features were dark lacunae in 94% of the lesions, white veil in 91%, and erythema in 69%. Peripheral erythema, red lacunae, and hemorrhagic crusts were all seen at a rate of 53%. The most common location was the lower extremities.

This patient’s previous pathology report from a shave biopsy was found, confirming that the original diagnosis was angiokeratoma. Since the patient’s lesion had not resolved and was symptomatic from minor trauma, he was scheduled to come back in for an elliptical excision to remove the lesion.

‌

Image and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

This combination of vascular features with excess keratin fit perfectly with the name of the diagnosis: angiokeratoma. The dark color of the lesion on magnification, or in this case with dermoscopy, showed the lacunar pattern of dilated vessels. The overlying keratin was likely accentuated because it was on an extensor surface; the rim of hyperpigmentation is common for these lesions.

Angiokeratomas result from dilation of the blood vessels underneath the epidermis. There are different inciting events that lead to the 5 different types of angiokeratomas. The overlying epidermal changes are secondary to the underlying process of capillary ectasia.¹ This lesion was not part of a cluster, so it was characterized as a solitary angiokeratoma. Smaller lesions are usually less keratinized and are commonly seen on the scrotum and vulva, where there are usually multiple lesions (referred to as angiokeratoma of Fordyce).

Zaballos² studied the dermoscopic characteristics of 32 solitary angiokeratomas and reported 6 findings in at least half of the solitary lesions. The most common features were dark lacunae in 94% of the lesions, white veil in 91%, and erythema in 69%. Peripheral erythema, red lacunae, and hemorrhagic crusts were all seen at a rate of 53%. The most common location was the lower extremities.

This patient’s previous pathology report from a shave biopsy was found, confirming that the original diagnosis was angiokeratoma. Since the patient’s lesion had not resolved and was symptomatic from minor trauma, he was scheduled to come back in for an elliptical excision to remove the lesion.

‌

Image and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.

THE COMPARISON

A and B Axilla of a 65-year-old White man with erythrasma showing a well-demarcated erythematous plaque with fine scale (A). Wood lamp examination of the area showed characteristic bright coral red fluorescence (B).

C and D A well-demarcated, red-brown plaque with fine scale in the antecubital fossa of an obese Hispanic woman (C). Wood lamp examination revealed bright coral red fluorescence (D).

E Hypopigmented patches in the groin with pruritus in a Black man. He also had erythrasma between the toes.

Erythrasma is a skin condition caused by acute or chronic infection of the outermost layer of the epidermis (stratum corneum) with Corynebacterium minutissimum. It has a predilection for intertriginous regions such as the axillae, groin, and interdigital spaces of the toes. It can be associated with pruritus or can be asymptomatic.

Photographs courtesy of Richard P. Usatine, MD.

Epidemiology

Erythrasma typically affects adults, with greater prevalence among those residing in shared living facilities, such as dormitories or nursing homes, or in humid climates.¹ It is a common disorder with an estimated prevalence of 17.6% of bacterial skin infections in elderly patients and 44% of diabetic interdigital toe space infections.^2,3

Key clinical features

Erythrasma can manifest as red-brown hyperpigmented plaques with fine scale and little central clearing (Figures A and C) or as a hypopigmented patch (Figure E) with a sharply marginated, hyperpigmented border in patients with skin of color. In the interdigital toe spaces, the skin often is white and macerated. These findings may appear in patients of all skin tones.

Worth noting

• Corynebacterium minutissimum produces coproporphyrin III, which glows fluorescent red under Wood lamp examination (Figures B and D). A recent shower or bath may remove the fluorescent coproporphyrins and cause a false-negative result. The interdigital space between the fourth and fifth toes is a common location for C minutissimum; thus clinicians should consider examining these areas with a Wood lamp.

• Associated risk factors include obesity, immunosuppression, diabetes mellitus, and excessive sweating.¹

• The differential diagnosis includes intertrigo, inverse psoriasis, confluent and reticulated papillomatosis (Gougerot-Carteaud syndrome), acanthosis nigricans, seborrheic dermatitis, and tinea pedis when present in the interdigital toe spaces. Plaques occurring in circular patterns may be mistaken for tinea corporis or pityriasis rotunda.

• There is a high prevalence of erythrasma in patients with inverse psoriasis, and it may exacerbate psoriatic plaques.⁴

• Treatment options include application of topical clindamycin or erythromycin to the affected area.1 Some patients have responded to topical mupiricin.² For larger areas, a 1-g dose of clarithromycin⁵ or a 14-day course of erythromycin may be appropriate.1 Avoid prescribing clarithromycin to patients with preexisting heart disease due to its increased risk for cardiac events or death; consider other agents.

Health disparity highlight

Obesity, most prevalent in non-Hispanic Black adults (49.9%) and Hispanic adults (45.6%) followed by non- Hispanic White adults (41.4%),⁶ may cause velvety dark plaques on the neck called acanthosis nigricans. However, acute or chronic erythrasma also may cause hyperpigmentation of the body folds. Although the pathology of erythrasma is due to bacterial infection of the superficial layer of the stratum corneum, acanthosis nigricans is due to fibroblast proliferation and stimulation of epidermal keratinocytes likely from increased growth factors and insulinlike growth factor.⁷ If erythrasma is mistaken for acanthosis nigricans, the patient may be counseled inappropriately that the hyperpigmentation is something not easily resolved and subsequently left with an active treatable condition that adversely affects their quality of life.

THE COMPARISON

A and B Axilla of a 65-year-old White man with erythrasma showing a well-demarcated erythematous plaque with fine scale (A). Wood lamp examination of the area showed characteristic bright coral red fluorescence (B).

C and D A well-demarcated, red-brown plaque with fine scale in the antecubital fossa of an obese Hispanic woman (C). Wood lamp examination revealed bright coral red fluorescence (D).

E Hypopigmented patches in the groin with pruritus in a Black man. He also had erythrasma between the toes.

Erythrasma is a skin condition caused by acute or chronic infection of the outermost layer of the epidermis (stratum corneum) with Corynebacterium minutissimum. It has a predilection for intertriginous regions such as the axillae, groin, and interdigital spaces of the toes. It can be associated with pruritus or can be asymptomatic.

Photographs courtesy of Richard P. Usatine, MD.

Epidemiology

Erythrasma typically affects adults, with greater prevalence among those residing in shared living facilities, such as dormitories or nursing homes, or in humid climates.¹ It is a common disorder with an estimated prevalence of 17.6% of bacterial skin infections in elderly patients and 44% of diabetic interdigital toe space infections.^2,3

Key clinical features

Erythrasma can manifest as red-brown hyperpigmented plaques with fine scale and little central clearing (Figures A and C) or as a hypopigmented patch (Figure E) with a sharply marginated, hyperpigmented border in patients with skin of color. In the interdigital toe spaces, the skin often is white and macerated. These findings may appear in patients of all skin tones.

Worth noting

• Corynebacterium minutissimum produces coproporphyrin III, which glows fluorescent red under Wood lamp examination (Figures B and D). A recent shower or bath may remove the fluorescent coproporphyrins and cause a false-negative result. The interdigital space between the fourth and fifth toes is a common location for C minutissimum; thus clinicians should consider examining these areas with a Wood lamp.

• Associated risk factors include obesity, immunosuppression, diabetes mellitus, and excessive sweating.¹

• The differential diagnosis includes intertrigo, inverse psoriasis, confluent and reticulated papillomatosis (Gougerot-Carteaud syndrome), acanthosis nigricans, seborrheic dermatitis, and tinea pedis when present in the interdigital toe spaces. Plaques occurring in circular patterns may be mistaken for tinea corporis or pityriasis rotunda.

• There is a high prevalence of erythrasma in patients with inverse psoriasis, and it may exacerbate psoriatic plaques.⁴

• Treatment options include application of topical clindamycin or erythromycin to the affected area.1 Some patients have responded to topical mupiricin.² For larger areas, a 1-g dose of clarithromycin⁵ or a 14-day course of erythromycin may be appropriate.1 Avoid prescribing clarithromycin to patients with preexisting heart disease due to its increased risk for cardiac events or death; consider other agents.

Health disparity highlight

Obesity, most prevalent in non-Hispanic Black adults (49.9%) and Hispanic adults (45.6%) followed by non- Hispanic White adults (41.4%),⁶ may cause velvety dark plaques on the neck called acanthosis nigricans. However, acute or chronic erythrasma also may cause hyperpigmentation of the body folds. Although the pathology of erythrasma is due to bacterial infection of the superficial layer of the stratum corneum, acanthosis nigricans is due to fibroblast proliferation and stimulation of epidermal keratinocytes likely from increased growth factors and insulinlike growth factor.⁷ If erythrasma is mistaken for acanthosis nigricans, the patient may be counseled inappropriately that the hyperpigmentation is something not easily resolved and subsequently left with an active treatable condition that adversely affects their quality of life.

THE COMPARISON

A and B Axilla of a 65-year-old White man with erythrasma showing a well-demarcated erythematous plaque with fine scale (A). Wood lamp examination of the area showed characteristic bright coral red fluorescence (B).

C and D A well-demarcated, red-brown plaque with fine scale in the antecubital fossa of an obese Hispanic woman (C). Wood lamp examination revealed bright coral red fluorescence (D).

E Hypopigmented patches in the groin with pruritus in a Black man. He also had erythrasma between the toes.

Erythrasma is a skin condition caused by acute or chronic infection of the outermost layer of the epidermis (stratum corneum) with Corynebacterium minutissimum. It has a predilection for intertriginous regions such as the axillae, groin, and interdigital spaces of the toes. It can be associated with pruritus or can be asymptomatic.

Photographs courtesy of Richard P. Usatine, MD.

Epidemiology

Erythrasma typically affects adults, with greater prevalence among those residing in shared living facilities, such as dormitories or nursing homes, or in humid climates.¹ It is a common disorder with an estimated prevalence of 17.6% of bacterial skin infections in elderly patients and 44% of diabetic interdigital toe space infections.^2,3

Key clinical features

Erythrasma can manifest as red-brown hyperpigmented plaques with fine scale and little central clearing (Figures A and C) or as a hypopigmented patch (Figure E) with a sharply marginated, hyperpigmented border in patients with skin of color. In the interdigital toe spaces, the skin often is white and macerated. These findings may appear in patients of all skin tones.

Worth noting

• Corynebacterium minutissimum produces coproporphyrin III, which glows fluorescent red under Wood lamp examination (Figures B and D). A recent shower or bath may remove the fluorescent coproporphyrins and cause a false-negative result. The interdigital space between the fourth and fifth toes is a common location for C minutissimum; thus clinicians should consider examining these areas with a Wood lamp.

• Associated risk factors include obesity, immunosuppression, diabetes mellitus, and excessive sweating.¹

• The differential diagnosis includes intertrigo, inverse psoriasis, confluent and reticulated papillomatosis (Gougerot-Carteaud syndrome), acanthosis nigricans, seborrheic dermatitis, and tinea pedis when present in the interdigital toe spaces. Plaques occurring in circular patterns may be mistaken for tinea corporis or pityriasis rotunda.

• There is a high prevalence of erythrasma in patients with inverse psoriasis, and it may exacerbate psoriatic plaques.⁴

• Treatment options include application of topical clindamycin or erythromycin to the affected area.1 Some patients have responded to topical mupiricin.² For larger areas, a 1-g dose of clarithromycin⁵ or a 14-day course of erythromycin may be appropriate.1 Avoid prescribing clarithromycin to patients with preexisting heart disease due to its increased risk for cardiac events or death; consider other agents.

Health disparity highlight

Obesity, most prevalent in non-Hispanic Black adults (49.9%) and Hispanic adults (45.6%) followed by non- Hispanic White adults (41.4%),⁶ may cause velvety dark plaques on the neck called acanthosis nigricans. However, acute or chronic erythrasma also may cause hyperpigmentation of the body folds. Although the pathology of erythrasma is due to bacterial infection of the superficial layer of the stratum corneum, acanthosis nigricans is due to fibroblast proliferation and stimulation of epidermal keratinocytes likely from increased growth factors and insulinlike growth factor.⁷ If erythrasma is mistaken for acanthosis nigricans, the patient may be counseled inappropriately that the hyperpigmentation is something not easily resolved and subsequently left with an active treatable condition that adversely affects their quality of life.