Dermatology

MADRID – Adding the oral Janus kinase (JAK) inhibitor baricitinib to standard atopic dermatitis therapy with low- and midpotency topical corticosteroids markedly improved disease severity and key patient-reported outcomes, compared with topical corticosteroids alone, in the phase 3, randomized, double-blind BREEZE-AD7 trial, Kristian Reich, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Baricitinib, a JAK 1/2 inhibitor, had already proved superior to placebo as monotherapy for adults with moderate to severe atopic dermatitis in the phase 3 BREEZE-AD1 and -AD2 trials. But BREEZE-AD7 further advances the field because it’s the first phase 3 study testing the efficacy of a JAK inhibitor in combination with low- and midpotency topical steroids.

“I think this study is important because it looks into the situation that’s more like what happens in the real world, which is, as with dupilumab and other drugs, we use the systemic agent in combination with topical therapies and, in particular, with topical corticosteroids,” commented Dr. Reich, professor of dermatology at University Medical Center, Hamburg, and medical director at SCIderm, a scientific research company.

“This is what I think we can expect from existing and upcoming systemic therapies in atopic dermatitis: We will use them in combination with topical corticosteroids, and hopefully this will allow patients to dramatically reduce the concomitant use of topical corticosteroids, as shown here in BREEZE-AD7,” he added.

BREEZE-AD7 was a 16-week study that included 329 adults with moderate or severe atopic dermatitis who were randomized to low- and midpotency topical corticosteroids plus either baricitinib at 2 mg once daily, baricitinib at 4 mg once daily, or placebo. The group’s mean baseline Eczema Area and Severity Index (EASI) score was 29. Overall, 45% of participants had a baseline Investigator’s Global Assessment (IGA) of disease severity of 4 on a 0-4 scale.

The primary endpoint was achievement of an IGA of 0 or 1, meaning clear or almost clear, along with at least a 2-point IGA improvement from baseline at week 16. This was accomplished in 30.6% of those on 4 mg/day of baricitinib, 23.9% of patients in the 2-mg group, and 14.7% of controls.

The 4-mg dose of baricitinib was statistically superior to placebo; the 2-mg dose was not. However, Dr. Reich indicated he was untroubled by this because the primary endpoint was set at a high bar, and both doses of baricitinib proved to be significantly better than topical steroids plus placebo in terms of EASI 75 response rates, as well as reductions in itch, skin pain, and sleep problems, which aren’t captured in EASI scores (see graphic).

“One of my big learnings from this year’s EADV is that we have to rethink the dimensions of atopic dermatitis. I think we have underestimated the relevance of important symptoms such as itch, the impact atopic dermatitis has on pain, and the effect it has on sleeping problems,” the dermatologist said. “My feeling is that baricitinib is strongest in reducing itch, improving sleep, and reducing pain, but it also has good effects on the clinical signs of atopic dermatitis.”

The baricitinib-treated patients’ rapidity of improvement in the various endpoints was particularly impressive. Both doses of the JAK 1/2 inhibitor showed significant separation from the control group in the first week, and the majority of improvement occurred by week 4.

A key finding was that patients on baricitinib at 2 mg/day and 4 mg/day used a mean total of 162 g and 137 g of midpotency topical steroids, respectively, during the 16 weeks, compared with 225 g in the control group. The higher-dose baricitinib group was topical corticosteroid-free on 33% of study days, compared with 25% of days for the baricitinib 2 mg patients and 17% of days for controls.

In terms of safety, there was a case of pulmonary embolism in the higher-dose baricitinib group and an opportunistic toxoplasmosis eye infection in the control population. The frequency of oral herpes and herpes simplex virus infections was 2.8% in controls, 4.6% in the baricitinib 2-mg group, and 6.3% in the 4-mg group. There was also a signal of a dose-dependent increased risk of new-onset acne, with rates of 0.9% in controls and patients on baricitinib 2 mg, climbing to 3.6% with baricitinib 4 mg.

“In phase 2 results with upadacitinib [another oral JAK inhibitor], we saw that more than 10% of patients in the highest-dose group developed what was classified as acne. I cannot explain this, but it’s something we will monitor in the future,” Dr. Reich promised.

A fuller picture of baricitinib’s safety profile in the setting of atopic dermatitis clearly requires larger and longer-term studies, he added.

Baricitinib at the 2 mg daily dose is already marketed as Olumiant for the treatment of rheumatoid arthritis, with labeling that includes a boxed warning about serious infections, malignancy, and thrombosis. The Food and Drug Administration did not approve the 4-mg dose after determining that its higher safety hazard outweighed the efficacy advantage over the lower dose.

The BREEZE-AD7 study was sponsored by Eli Lilly. Dr. Reich reported serving as an adviser to, paid speaker for, and recipient of research grants from that pharmaceutical company and more than two dozen others.
 

[email protected]

MADRID – Adding the oral Janus kinase (JAK) inhibitor baricitinib to standard atopic dermatitis therapy with low- and midpotency topical corticosteroids markedly improved disease severity and key patient-reported outcomes, compared with topical corticosteroids alone, in the phase 3, randomized, double-blind BREEZE-AD7 trial, Kristian Reich, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Baricitinib, a JAK 1/2 inhibitor, had already proved superior to placebo as monotherapy for adults with moderate to severe atopic dermatitis in the phase 3 BREEZE-AD1 and -AD2 trials. But BREEZE-AD7 further advances the field because it’s the first phase 3 study testing the efficacy of a JAK inhibitor in combination with low- and midpotency topical steroids.

“I think this study is important because it looks into the situation that’s more like what happens in the real world, which is, as with dupilumab and other drugs, we use the systemic agent in combination with topical therapies and, in particular, with topical corticosteroids,” commented Dr. Reich, professor of dermatology at University Medical Center, Hamburg, and medical director at SCIderm, a scientific research company.

“This is what I think we can expect from existing and upcoming systemic therapies in atopic dermatitis: We will use them in combination with topical corticosteroids, and hopefully this will allow patients to dramatically reduce the concomitant use of topical corticosteroids, as shown here in BREEZE-AD7,” he added.

BREEZE-AD7 was a 16-week study that included 329 adults with moderate or severe atopic dermatitis who were randomized to low- and midpotency topical corticosteroids plus either baricitinib at 2 mg once daily, baricitinib at 4 mg once daily, or placebo. The group’s mean baseline Eczema Area and Severity Index (EASI) score was 29. Overall, 45% of participants had a baseline Investigator’s Global Assessment (IGA) of disease severity of 4 on a 0-4 scale.

The primary endpoint was achievement of an IGA of 0 or 1, meaning clear or almost clear, along with at least a 2-point IGA improvement from baseline at week 16. This was accomplished in 30.6% of those on 4 mg/day of baricitinib, 23.9% of patients in the 2-mg group, and 14.7% of controls.

The 4-mg dose of baricitinib was statistically superior to placebo; the 2-mg dose was not. However, Dr. Reich indicated he was untroubled by this because the primary endpoint was set at a high bar, and both doses of baricitinib proved to be significantly better than topical steroids plus placebo in terms of EASI 75 response rates, as well as reductions in itch, skin pain, and sleep problems, which aren’t captured in EASI scores (see graphic).

“One of my big learnings from this year’s EADV is that we have to rethink the dimensions of atopic dermatitis. I think we have underestimated the relevance of important symptoms such as itch, the impact atopic dermatitis has on pain, and the effect it has on sleeping problems,” the dermatologist said. “My feeling is that baricitinib is strongest in reducing itch, improving sleep, and reducing pain, but it also has good effects on the clinical signs of atopic dermatitis.”

The baricitinib-treated patients’ rapidity of improvement in the various endpoints was particularly impressive. Both doses of the JAK 1/2 inhibitor showed significant separation from the control group in the first week, and the majority of improvement occurred by week 4.

A key finding was that patients on baricitinib at 2 mg/day and 4 mg/day used a mean total of 162 g and 137 g of midpotency topical steroids, respectively, during the 16 weeks, compared with 225 g in the control group. The higher-dose baricitinib group was topical corticosteroid-free on 33% of study days, compared with 25% of days for the baricitinib 2 mg patients and 17% of days for controls.

In terms of safety, there was a case of pulmonary embolism in the higher-dose baricitinib group and an opportunistic toxoplasmosis eye infection in the control population. The frequency of oral herpes and herpes simplex virus infections was 2.8% in controls, 4.6% in the baricitinib 2-mg group, and 6.3% in the 4-mg group. There was also a signal of a dose-dependent increased risk of new-onset acne, with rates of 0.9% in controls and patients on baricitinib 2 mg, climbing to 3.6% with baricitinib 4 mg.

“In phase 2 results with upadacitinib [another oral JAK inhibitor], we saw that more than 10% of patients in the highest-dose group developed what was classified as acne. I cannot explain this, but it’s something we will monitor in the future,” Dr. Reich promised.

A fuller picture of baricitinib’s safety profile in the setting of atopic dermatitis clearly requires larger and longer-term studies, he added.

Baricitinib at the 2 mg daily dose is already marketed as Olumiant for the treatment of rheumatoid arthritis, with labeling that includes a boxed warning about serious infections, malignancy, and thrombosis. The Food and Drug Administration did not approve the 4-mg dose after determining that its higher safety hazard outweighed the efficacy advantage over the lower dose.

The BREEZE-AD7 study was sponsored by Eli Lilly. Dr. Reich reported serving as an adviser to, paid speaker for, and recipient of research grants from that pharmaceutical company and more than two dozen others.
 

[email protected]

MADRID – Adding the oral Janus kinase (JAK) inhibitor baricitinib to standard atopic dermatitis therapy with low- and midpotency topical corticosteroids markedly improved disease severity and key patient-reported outcomes, compared with topical corticosteroids alone, in the phase 3, randomized, double-blind BREEZE-AD7 trial, Kristian Reich, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Baricitinib, a JAK 1/2 inhibitor, had already proved superior to placebo as monotherapy for adults with moderate to severe atopic dermatitis in the phase 3 BREEZE-AD1 and -AD2 trials. But BREEZE-AD7 further advances the field because it’s the first phase 3 study testing the efficacy of a JAK inhibitor in combination with low- and midpotency topical steroids.

“I think this study is important because it looks into the situation that’s more like what happens in the real world, which is, as with dupilumab and other drugs, we use the systemic agent in combination with topical therapies and, in particular, with topical corticosteroids,” commented Dr. Reich, professor of dermatology at University Medical Center, Hamburg, and medical director at SCIderm, a scientific research company.

“This is what I think we can expect from existing and upcoming systemic therapies in atopic dermatitis: We will use them in combination with topical corticosteroids, and hopefully this will allow patients to dramatically reduce the concomitant use of topical corticosteroids, as shown here in BREEZE-AD7,” he added.

BREEZE-AD7 was a 16-week study that included 329 adults with moderate or severe atopic dermatitis who were randomized to low- and midpotency topical corticosteroids plus either baricitinib at 2 mg once daily, baricitinib at 4 mg once daily, or placebo. The group’s mean baseline Eczema Area and Severity Index (EASI) score was 29. Overall, 45% of participants had a baseline Investigator’s Global Assessment (IGA) of disease severity of 4 on a 0-4 scale.

The primary endpoint was achievement of an IGA of 0 or 1, meaning clear or almost clear, along with at least a 2-point IGA improvement from baseline at week 16. This was accomplished in 30.6% of those on 4 mg/day of baricitinib, 23.9% of patients in the 2-mg group, and 14.7% of controls.

The 4-mg dose of baricitinib was statistically superior to placebo; the 2-mg dose was not. However, Dr. Reich indicated he was untroubled by this because the primary endpoint was set at a high bar, and both doses of baricitinib proved to be significantly better than topical steroids plus placebo in terms of EASI 75 response rates, as well as reductions in itch, skin pain, and sleep problems, which aren’t captured in EASI scores (see graphic).

“One of my big learnings from this year’s EADV is that we have to rethink the dimensions of atopic dermatitis. I think we have underestimated the relevance of important symptoms such as itch, the impact atopic dermatitis has on pain, and the effect it has on sleeping problems,” the dermatologist said. “My feeling is that baricitinib is strongest in reducing itch, improving sleep, and reducing pain, but it also has good effects on the clinical signs of atopic dermatitis.”

The baricitinib-treated patients’ rapidity of improvement in the various endpoints was particularly impressive. Both doses of the JAK 1/2 inhibitor showed significant separation from the control group in the first week, and the majority of improvement occurred by week 4.

A key finding was that patients on baricitinib at 2 mg/day and 4 mg/day used a mean total of 162 g and 137 g of midpotency topical steroids, respectively, during the 16 weeks, compared with 225 g in the control group. The higher-dose baricitinib group was topical corticosteroid-free on 33% of study days, compared with 25% of days for the baricitinib 2 mg patients and 17% of days for controls.

In terms of safety, there was a case of pulmonary embolism in the higher-dose baricitinib group and an opportunistic toxoplasmosis eye infection in the control population. The frequency of oral herpes and herpes simplex virus infections was 2.8% in controls, 4.6% in the baricitinib 2-mg group, and 6.3% in the 4-mg group. There was also a signal of a dose-dependent increased risk of new-onset acne, with rates of 0.9% in controls and patients on baricitinib 2 mg, climbing to 3.6% with baricitinib 4 mg.

“In phase 2 results with upadacitinib [another oral JAK inhibitor], we saw that more than 10% of patients in the highest-dose group developed what was classified as acne. I cannot explain this, but it’s something we will monitor in the future,” Dr. Reich promised.

A fuller picture of baricitinib’s safety profile in the setting of atopic dermatitis clearly requires larger and longer-term studies, he added.

Baricitinib at the 2 mg daily dose is already marketed as Olumiant for the treatment of rheumatoid arthritis, with labeling that includes a boxed warning about serious infections, malignancy, and thrombosis. The Food and Drug Administration did not approve the 4-mg dose after determining that its higher safety hazard outweighed the efficacy advantage over the lower dose.

The BREEZE-AD7 study was sponsored by Eli Lilly. Dr. Reich reported serving as an adviser to, paid speaker for, and recipient of research grants from that pharmaceutical company and more than two dozen others.
 

[email protected]

Earlier onset of atopic dermatitis in children could signify more difficult to control and persistent disease, according to a study published in the Journal of the American Academy of Dermatology.

LucaLorenzelli/Thinkstock

Atopic dermatitis most commonly arises in infancy but also can emerge in later childhood and even adolescence, leading to a distinction between early- and late-onset disease, wrote Joy Wan, MD, of the University of Pennsylvania, Philadelphia, and coauthors.

“Early-onset, mid-onset, and late-onset AD appear to differ in the presence of active disease over time; however, whether these groups also differ in terms of the severity of AD is unknown,” they wrote.

In this observational cohort study, 8,015 individuals with childhood-onset atopic dermatitis – 53% of whom were female – were assessed twice-yearly for up to 10 years. Nearly three-quarters (72%) of the group had early-onset atopic dermatitis – defined as onset before 2 years of age – while 19% had mid-onset disease (3-7 years) and 9% had late-onset disease (8-17 years).

The study found that older age of onset was associated with better control, such that for each additional year of age at the onset of disease, there was a 7% reduction in the odds of poorer control of disease. Those who had mid-onset disease had a 29% lower odds of poorer control compared with those with early-onset, while those with late-onset disease had a 49% lower odds of poorer control.

The likelihood of atopic dermatitis persisting beyond childhood also appeared to be linked to the age of onset. Those with mid-onset disease had a 55% lower odds of persistent atopic dermatitis, compared with those with early-onset disease, while those with late-onset disease had an 81% lower odds.

“In all 3 groups, the proportion of subjects reporting persistent AD generally declined with older age, and the differences among the 3 onset age groups were most pronounced from early adolescence onward,” the authors wrote.

They noted that there was considerable research currently focused on identifying distinct atopic dermatitis phenotypes and endotypes, and their evidence on the different disease course for early-, mid-, and late-onset disease supported this idea of disease subtypes.

“However, additional research is needed to understand whether and how early-, mid-, and late-onset AD differ molecularly or immunologically, and whether they respond differentially to treatment,” they wrote. They also suggested that the timing of onset could help identify patients who were at greater risk of persistent or poorly controlled disease, and who benefits from more intensive monitoring or treatment.

The study was partly supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Dermatology Foundation. Three authors declared funding, consultancies, or advisory board positions with the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Wan J et al. J Am Acad Dermatol. 2019 Dec;81(6):1292-9.

Earlier onset of atopic dermatitis in children could signify more difficult to control and persistent disease, according to a study published in the Journal of the American Academy of Dermatology.

LucaLorenzelli/Thinkstock

Atopic dermatitis most commonly arises in infancy but also can emerge in later childhood and even adolescence, leading to a distinction between early- and late-onset disease, wrote Joy Wan, MD, of the University of Pennsylvania, Philadelphia, and coauthors.

“Early-onset, mid-onset, and late-onset AD appear to differ in the presence of active disease over time; however, whether these groups also differ in terms of the severity of AD is unknown,” they wrote.

In this observational cohort study, 8,015 individuals with childhood-onset atopic dermatitis – 53% of whom were female – were assessed twice-yearly for up to 10 years. Nearly three-quarters (72%) of the group had early-onset atopic dermatitis – defined as onset before 2 years of age – while 19% had mid-onset disease (3-7 years) and 9% had late-onset disease (8-17 years).

The study found that older age of onset was associated with better control, such that for each additional year of age at the onset of disease, there was a 7% reduction in the odds of poorer control of disease. Those who had mid-onset disease had a 29% lower odds of poorer control compared with those with early-onset, while those with late-onset disease had a 49% lower odds of poorer control.

The likelihood of atopic dermatitis persisting beyond childhood also appeared to be linked to the age of onset. Those with mid-onset disease had a 55% lower odds of persistent atopic dermatitis, compared with those with early-onset disease, while those with late-onset disease had an 81% lower odds.

“In all 3 groups, the proportion of subjects reporting persistent AD generally declined with older age, and the differences among the 3 onset age groups were most pronounced from early adolescence onward,” the authors wrote.

They noted that there was considerable research currently focused on identifying distinct atopic dermatitis phenotypes and endotypes, and their evidence on the different disease course for early-, mid-, and late-onset disease supported this idea of disease subtypes.

“However, additional research is needed to understand whether and how early-, mid-, and late-onset AD differ molecularly or immunologically, and whether they respond differentially to treatment,” they wrote. They also suggested that the timing of onset could help identify patients who were at greater risk of persistent or poorly controlled disease, and who benefits from more intensive monitoring or treatment.

The study was partly supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Dermatology Foundation. Three authors declared funding, consultancies, or advisory board positions with the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Wan J et al. J Am Acad Dermatol. 2019 Dec;81(6):1292-9.

Earlier onset of atopic dermatitis in children could signify more difficult to control and persistent disease, according to a study published in the Journal of the American Academy of Dermatology.

LucaLorenzelli/Thinkstock

Atopic dermatitis most commonly arises in infancy but also can emerge in later childhood and even adolescence, leading to a distinction between early- and late-onset disease, wrote Joy Wan, MD, of the University of Pennsylvania, Philadelphia, and coauthors.

“Early-onset, mid-onset, and late-onset AD appear to differ in the presence of active disease over time; however, whether these groups also differ in terms of the severity of AD is unknown,” they wrote.

In this observational cohort study, 8,015 individuals with childhood-onset atopic dermatitis – 53% of whom were female – were assessed twice-yearly for up to 10 years. Nearly three-quarters (72%) of the group had early-onset atopic dermatitis – defined as onset before 2 years of age – while 19% had mid-onset disease (3-7 years) and 9% had late-onset disease (8-17 years).

The study found that older age of onset was associated with better control, such that for each additional year of age at the onset of disease, there was a 7% reduction in the odds of poorer control of disease. Those who had mid-onset disease had a 29% lower odds of poorer control compared with those with early-onset, while those with late-onset disease had a 49% lower odds of poorer control.

The likelihood of atopic dermatitis persisting beyond childhood also appeared to be linked to the age of onset. Those with mid-onset disease had a 55% lower odds of persistent atopic dermatitis, compared with those with early-onset disease, while those with late-onset disease had an 81% lower odds.

“In all 3 groups, the proportion of subjects reporting persistent AD generally declined with older age, and the differences among the 3 onset age groups were most pronounced from early adolescence onward,” the authors wrote.

They noted that there was considerable research currently focused on identifying distinct atopic dermatitis phenotypes and endotypes, and their evidence on the different disease course for early-, mid-, and late-onset disease supported this idea of disease subtypes.

“However, additional research is needed to understand whether and how early-, mid-, and late-onset AD differ molecularly or immunologically, and whether they respond differentially to treatment,” they wrote. They also suggested that the timing of onset could help identify patients who were at greater risk of persistent or poorly controlled disease, and who benefits from more intensive monitoring or treatment.

The study was partly supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Dermatology Foundation. Three authors declared funding, consultancies, or advisory board positions with the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Wan J et al. J Am Acad Dermatol. 2019 Dec;81(6):1292-9.

Among children with atopic dermatitis, genetic variants associated with skin barrier dysfunction vary significantly by race and by their influence on disease persistence, according to authors of a cohort study.

In the study, which was based on data from a pediatric eczema registry, white children with atopic dermatitis (AD) were more than twice as likely as black children to have a filaggrin gene (FLG) loss-of-function (LoF) variant. The investigators remarked on “profound” differences by race in the study, which used a high-throughput sequencing method to identify FLG LoF variants, some of which were common in white children but not so frequently seen in black children.

Conversely, some variants common in black children were completely absent in the white children, according to the investigators, led by David J. Margolis, MD, PhD, professor of dermatology at the University of Pennsylvania, Philadelphia. The study was published in JAMA Dermatology.

These findings imply that any genetic tests developed for AD should be “inclusive,” they wrote, and shouldn’t simply rely on the most common variants associated with patients of European ancestry, namely p.R501*, c.2282del4[p.S761fs], p.S3247*, and p.R2447*.

“Relying on the classic 4 FLG LoF variants would result in approximately 8% of white children and 64% of black children with an FLG LoF variant being improperly classified,” Dr. Margolis and coinvestigators wrote.

Their comprehensive analysis of FLG LoF variants was based on a U.S. cohort of 741 children with mild to moderate AD in the Pediatric Eczema Elective Registry (PEER), enrolled from 2005 to 2017. The mean age of onset of AD among the children was almost 2 years. Using massively parallel sequencing, the investigators identified a total of 23 FLG LoF variants in 177 children, or 23.9% of the overall cohort.

White children had a higher frequency of FLG LoF variants, according to the investigators. The prevalence of variants was 31.5% in white and 15.3% in black participants, translating into an odds ratio of 2.44 for carrying any variant in a white versus black child (95% confidence interval, 1.76-3.39).

In previous studies, FLG LoF variants are seen in 25%-30% of people with AD who have European and Asian ancestry; by contrast, they are “uncommonly” exhibited in individuals of African ancestry, the investigators wrote.

Persistent AD was more likely among children with FLG LoF variants, with an odds ratio of 0.67 (95% CI, 0.56-0.80), according to Dr. Margolis and coauthors. However, the black children in this cohort had more persistent disease, compared with white children, regardless of whether they had FLG LoF variants or not.

Exon 3 FLG LoF are known to be the most common variants linked to skin barrier dysfunction, the investigators noted.

“However, all FLG LoF variants might not confer an increased risk of AD, and further, they may not all have the same effect on the persistence of AD over time,” they added in a discussion of their results.

The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The PEER cohort is funded by Valeant Pharmaceuticals. Dr. Margolis reported receiving research funding as the principal investigator via the trustees of the University of Pennsylvania, and receiving funding from the National Institutes of Health and Valeant; disclosures not related to the study included consulting activities primarily as a member of a data monitoring or scientific advisory boards for several pharmaceutical companies.

SOURCE: Margolis DJ et al. JAMA Dermatol. 2019 Jul 31. doi: 10.1011/jamadermatol.2019.1946.

Among children with atopic dermatitis, genetic variants associated with skin barrier dysfunction vary significantly by race and by their influence on disease persistence, according to authors of a cohort study.

In the study, which was based on data from a pediatric eczema registry, white children with atopic dermatitis (AD) were more than twice as likely as black children to have a filaggrin gene (FLG) loss-of-function (LoF) variant. The investigators remarked on “profound” differences by race in the study, which used a high-throughput sequencing method to identify FLG LoF variants, some of which were common in white children but not so frequently seen in black children.

Conversely, some variants common in black children were completely absent in the white children, according to the investigators, led by David J. Margolis, MD, PhD, professor of dermatology at the University of Pennsylvania, Philadelphia. The study was published in JAMA Dermatology.

These findings imply that any genetic tests developed for AD should be “inclusive,” they wrote, and shouldn’t simply rely on the most common variants associated with patients of European ancestry, namely p.R501*, c.2282del4[p.S761fs], p.S3247*, and p.R2447*.

“Relying on the classic 4 FLG LoF variants would result in approximately 8% of white children and 64% of black children with an FLG LoF variant being improperly classified,” Dr. Margolis and coinvestigators wrote.

Their comprehensive analysis of FLG LoF variants was based on a U.S. cohort of 741 children with mild to moderate AD in the Pediatric Eczema Elective Registry (PEER), enrolled from 2005 to 2017. The mean age of onset of AD among the children was almost 2 years. Using massively parallel sequencing, the investigators identified a total of 23 FLG LoF variants in 177 children, or 23.9% of the overall cohort.

White children had a higher frequency of FLG LoF variants, according to the investigators. The prevalence of variants was 31.5% in white and 15.3% in black participants, translating into an odds ratio of 2.44 for carrying any variant in a white versus black child (95% confidence interval, 1.76-3.39).

In previous studies, FLG LoF variants are seen in 25%-30% of people with AD who have European and Asian ancestry; by contrast, they are “uncommonly” exhibited in individuals of African ancestry, the investigators wrote.

Persistent AD was more likely among children with FLG LoF variants, with an odds ratio of 0.67 (95% CI, 0.56-0.80), according to Dr. Margolis and coauthors. However, the black children in this cohort had more persistent disease, compared with white children, regardless of whether they had FLG LoF variants or not.

Exon 3 FLG LoF are known to be the most common variants linked to skin barrier dysfunction, the investigators noted.

“However, all FLG LoF variants might not confer an increased risk of AD, and further, they may not all have the same effect on the persistence of AD over time,” they added in a discussion of their results.

The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The PEER cohort is funded by Valeant Pharmaceuticals. Dr. Margolis reported receiving research funding as the principal investigator via the trustees of the University of Pennsylvania, and receiving funding from the National Institutes of Health and Valeant; disclosures not related to the study included consulting activities primarily as a member of a data monitoring or scientific advisory boards for several pharmaceutical companies.

SOURCE: Margolis DJ et al. JAMA Dermatol. 2019 Jul 31. doi: 10.1011/jamadermatol.2019.1946.

Among children with atopic dermatitis, genetic variants associated with skin barrier dysfunction vary significantly by race and by their influence on disease persistence, according to authors of a cohort study.

In the study, which was based on data from a pediatric eczema registry, white children with atopic dermatitis (AD) were more than twice as likely as black children to have a filaggrin gene (FLG) loss-of-function (LoF) variant. The investigators remarked on “profound” differences by race in the study, which used a high-throughput sequencing method to identify FLG LoF variants, some of which were common in white children but not so frequently seen in black children.

Conversely, some variants common in black children were completely absent in the white children, according to the investigators, led by David J. Margolis, MD, PhD, professor of dermatology at the University of Pennsylvania, Philadelphia. The study was published in JAMA Dermatology.

These findings imply that any genetic tests developed for AD should be “inclusive,” they wrote, and shouldn’t simply rely on the most common variants associated with patients of European ancestry, namely p.R501*, c.2282del4[p.S761fs], p.S3247*, and p.R2447*.

“Relying on the classic 4 FLG LoF variants would result in approximately 8% of white children and 64% of black children with an FLG LoF variant being improperly classified,” Dr. Margolis and coinvestigators wrote.

Their comprehensive analysis of FLG LoF variants was based on a U.S. cohort of 741 children with mild to moderate AD in the Pediatric Eczema Elective Registry (PEER), enrolled from 2005 to 2017. The mean age of onset of AD among the children was almost 2 years. Using massively parallel sequencing, the investigators identified a total of 23 FLG LoF variants in 177 children, or 23.9% of the overall cohort.

White children had a higher frequency of FLG LoF variants, according to the investigators. The prevalence of variants was 31.5% in white and 15.3% in black participants, translating into an odds ratio of 2.44 for carrying any variant in a white versus black child (95% confidence interval, 1.76-3.39).

In previous studies, FLG LoF variants are seen in 25%-30% of people with AD who have European and Asian ancestry; by contrast, they are “uncommonly” exhibited in individuals of African ancestry, the investigators wrote.

Persistent AD was more likely among children with FLG LoF variants, with an odds ratio of 0.67 (95% CI, 0.56-0.80), according to Dr. Margolis and coauthors. However, the black children in this cohort had more persistent disease, compared with white children, regardless of whether they had FLG LoF variants or not.

Exon 3 FLG LoF are known to be the most common variants linked to skin barrier dysfunction, the investigators noted.

“However, all FLG LoF variants might not confer an increased risk of AD, and further, they may not all have the same effect on the persistence of AD over time,” they added in a discussion of their results.

The study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The PEER cohort is funded by Valeant Pharmaceuticals. Dr. Margolis reported receiving research funding as the principal investigator via the trustees of the University of Pennsylvania, and receiving funding from the National Institutes of Health and Valeant; disclosures not related to the study included consulting activities primarily as a member of a data monitoring or scientific advisory boards for several pharmaceutical companies.

SOURCE: Margolis DJ et al. JAMA Dermatol. 2019 Jul 31. doi: 10.1011/jamadermatol.2019.1946.

The FP referred the patient to a dermatology clinic that specialized in hair loss. Based on the clinical findings, physicians at the clinic suspected that this was a case of frontal fibrosing alopecia (FFA), a primary lymphocytic cicatricial (scarring) alopecia. A dermatopathologist confirmed the diagnosis via histologic review.

FFA is characterized by symmetric band-like hair loss with evidence of scarring in the frontal and temporal regions of the scalp. (The extent of hair loss can be assessed by retracting the patient’s hair and having the patient raise his or her eyebrows and wrinkle the forehead in a surprised look.) FFA is accompanied by eyebrow loss in 73% to 95% of patients. Mild to severe perifollicular (and possibly more generalized) erythema and scale are usually present. In addition, erythematous or skin-colored papules may appear on the face, and marked exaggeration of the temporal veins is a common finding.

Most patients with FFA (83%) are postmenopausal women and nearly all (98.6%) have Fitzpatrick skin type 1 or 2 (white skin that burns easily and doesn’t readily tan). Other pertinent findings include the absence of oral lesions, nail changes, or other skin diseases.

A punch biopsy taken from the leading edge of the hair loss confirms the diagnosis of FFA and, ideally, should be reviewed by a dermatopathologist. Histologic examination will reveal a lichenoid lymphocytic infiltrate (predominantly around the hair follicle where the follicular stem cells reside), resulting in fibrosis and scarring. In addition to confirming the diagnosis with histologic examination, the following conditions must be ruled out in the differential: alopecia areata, female pattern hair loss, discoid lupus erythematosus, central centrifugal cicatricial alopecia, and traction alopecia.

Early detection is key. In general, physicians should initiate treatment as soon as possible to prevent disease progression and reduce permanent scarring and hair loss. Intralesional steroids such as triamcinolone acetonide (5-10 mg/cc), as well as high-potency topical steroids, are generally helpful to stabilize the disease. There is also some evidence of benefit from oral dutasteride or finasteride at variable doses. Immunosuppressants such as hydroxychloroquine also may be used as second-line treatments, although the benefit-to-risk ratio needs to be taken into consideration.

This patient was started on a regimen of topical high-potency steroids (clobetasol foam, 0.05%), with targeted, intralesional injection of steroids (10 mg/cc of triamcinolone acetonide) to areas with the most inflammation. She also was advised to use ketoconazole 2% shampoo while showering. These interventions decreased the patient’s symptoms dramatically. Her scalp erythema and scale improved, but the hair did not regrow. One year later, her hairline was clinically stable with no evidence of disease progression. She continued to see a dermatologist annually.

‌

This case was adapted from: Power DV, Disse M, Hordinsky M. Progressive hair loss. J Fam Pract. 2017;66:521-523.

The FP referred the patient to a dermatology clinic that specialized in hair loss. Based on the clinical findings, physicians at the clinic suspected that this was a case of frontal fibrosing alopecia (FFA), a primary lymphocytic cicatricial (scarring) alopecia. A dermatopathologist confirmed the diagnosis via histologic review.

FFA is characterized by symmetric band-like hair loss with evidence of scarring in the frontal and temporal regions of the scalp. (The extent of hair loss can be assessed by retracting the patient’s hair and having the patient raise his or her eyebrows and wrinkle the forehead in a surprised look.) FFA is accompanied by eyebrow loss in 73% to 95% of patients. Mild to severe perifollicular (and possibly more generalized) erythema and scale are usually present. In addition, erythematous or skin-colored papules may appear on the face, and marked exaggeration of the temporal veins is a common finding.

Most patients with FFA (83%) are postmenopausal women and nearly all (98.6%) have Fitzpatrick skin type 1 or 2 (white skin that burns easily and doesn’t readily tan). Other pertinent findings include the absence of oral lesions, nail changes, or other skin diseases.

A punch biopsy taken from the leading edge of the hair loss confirms the diagnosis of FFA and, ideally, should be reviewed by a dermatopathologist. Histologic examination will reveal a lichenoid lymphocytic infiltrate (predominantly around the hair follicle where the follicular stem cells reside), resulting in fibrosis and scarring. In addition to confirming the diagnosis with histologic examination, the following conditions must be ruled out in the differential: alopecia areata, female pattern hair loss, discoid lupus erythematosus, central centrifugal cicatricial alopecia, and traction alopecia.

Early detection is key. In general, physicians should initiate treatment as soon as possible to prevent disease progression and reduce permanent scarring and hair loss. Intralesional steroids such as triamcinolone acetonide (5-10 mg/cc), as well as high-potency topical steroids, are generally helpful to stabilize the disease. There is also some evidence of benefit from oral dutasteride or finasteride at variable doses. Immunosuppressants such as hydroxychloroquine also may be used as second-line treatments, although the benefit-to-risk ratio needs to be taken into consideration.

This patient was started on a regimen of topical high-potency steroids (clobetasol foam, 0.05%), with targeted, intralesional injection of steroids (10 mg/cc of triamcinolone acetonide) to areas with the most inflammation. She also was advised to use ketoconazole 2% shampoo while showering. These interventions decreased the patient’s symptoms dramatically. Her scalp erythema and scale improved, but the hair did not regrow. One year later, her hairline was clinically stable with no evidence of disease progression. She continued to see a dermatologist annually.

‌

This case was adapted from: Power DV, Disse M, Hordinsky M. Progressive hair loss. J Fam Pract. 2017;66:521-523.

The FP referred the patient to a dermatology clinic that specialized in hair loss. Based on the clinical findings, physicians at the clinic suspected that this was a case of frontal fibrosing alopecia (FFA), a primary lymphocytic cicatricial (scarring) alopecia. A dermatopathologist confirmed the diagnosis via histologic review.

FFA is characterized by symmetric band-like hair loss with evidence of scarring in the frontal and temporal regions of the scalp. (The extent of hair loss can be assessed by retracting the patient’s hair and having the patient raise his or her eyebrows and wrinkle the forehead in a surprised look.) FFA is accompanied by eyebrow loss in 73% to 95% of patients. Mild to severe perifollicular (and possibly more generalized) erythema and scale are usually present. In addition, erythematous or skin-colored papules may appear on the face, and marked exaggeration of the temporal veins is a common finding.

Most patients with FFA (83%) are postmenopausal women and nearly all (98.6%) have Fitzpatrick skin type 1 or 2 (white skin that burns easily and doesn’t readily tan). Other pertinent findings include the absence of oral lesions, nail changes, or other skin diseases.

A punch biopsy taken from the leading edge of the hair loss confirms the diagnosis of FFA and, ideally, should be reviewed by a dermatopathologist. Histologic examination will reveal a lichenoid lymphocytic infiltrate (predominantly around the hair follicle where the follicular stem cells reside), resulting in fibrosis and scarring. In addition to confirming the diagnosis with histologic examination, the following conditions must be ruled out in the differential: alopecia areata, female pattern hair loss, discoid lupus erythematosus, central centrifugal cicatricial alopecia, and traction alopecia.

Early detection is key. In general, physicians should initiate treatment as soon as possible to prevent disease progression and reduce permanent scarring and hair loss. Intralesional steroids such as triamcinolone acetonide (5-10 mg/cc), as well as high-potency topical steroids, are generally helpful to stabilize the disease. There is also some evidence of benefit from oral dutasteride or finasteride at variable doses. Immunosuppressants such as hydroxychloroquine also may be used as second-line treatments, although the benefit-to-risk ratio needs to be taken into consideration.

This patient was started on a regimen of topical high-potency steroids (clobetasol foam, 0.05%), with targeted, intralesional injection of steroids (10 mg/cc of triamcinolone acetonide) to areas with the most inflammation. She also was advised to use ketoconazole 2% shampoo while showering. These interventions decreased the patient’s symptoms dramatically. Her scalp erythema and scale improved, but the hair did not regrow. One year later, her hairline was clinically stable with no evidence of disease progression. She continued to see a dermatologist annually.

‌

This case was adapted from: Power DV, Disse M, Hordinsky M. Progressive hair loss. J Fam Pract. 2017;66:521-523.

A 14-year-old boy presents to dermatology for evaluation of an asymptomatic “rash” present on his arms since age 6. The condition has caught the attention of family members and teachers over the years, particularly in regard to possible contagion.

The patient is otherwise reasonably healthy, although he has asthma and seasonal allergies.

EXAMINATION
The "rash" consists of uniformly distributed and sized planar papules. Although they are tiny, averaging only 1 mm wide, they are prominent enough to be noticeable and palpable. They appear slightly lighter than the surrounding skin. Distribution is from the lower deltoid to mid-dorsal forearm, affecting both arms identically. The volar aspects and triceps of both arms are totally spared.

The patient has type IV skin.

What’s the diagnosis?

DISCUSSION
This case is an almost perfect representation of lichen nitidus (LN), in terms of morphology, distribution, and configuration. Close examination of individual lesions revealed that the papules were somewhat planar (ie, flat-topped), giving their surfaces a reflective appearance that the eye interprets as white (particularly contrasted with darker skin).

LN can occur in anyone, but it is most often seen in those with darker skin. It is also frequently seen in children, many of whom are atopic, with dry, sensitive skin that is prone to eczema.

In terms of distribution, LN typically affects the extensor triceps, elbow, and forearms bilaterally. With its flat-topped and shiny appearance, LN is sometimes called "mini-lichen planus"—a condition that can demonstrate similar features. Fortunately, LN is seldom itchy and shares none of the distinct histologic characteristics of lichen planus.

LN is quite unusual, if not rare. It is also idiopathic and nearly always resolves on its own—although this can take months to years.

Emollients help to make the affected skin smoother and less visible. Class 4 steroid creams (eg, triamcinolone 0.05%) can help with itching.

TAKE-HOME LEARNING POINTS

• Lichen nitidus (LN) is a rare idiopathic skin condition manifesting with patches of tiny planar papules; it typically affects the elbow and dorsal forearm.
• LN has no pathologic implications and is asymptomatic and self-limited.
• The lesions of LN have a “lichenoid” appearance—ie, a shiny, flat-topped look similar to that seen with lichen planus.
• Fortunately, LN rarely requires treatment, aside from relief of mild itching.

A 14-year-old boy presents to dermatology for evaluation of an asymptomatic “rash” present on his arms since age 6. The condition has caught the attention of family members and teachers over the years, particularly in regard to possible contagion.

The patient is otherwise reasonably healthy, although he has asthma and seasonal allergies.

EXAMINATION
The "rash" consists of uniformly distributed and sized planar papules. Although they are tiny, averaging only 1 mm wide, they are prominent enough to be noticeable and palpable. They appear slightly lighter than the surrounding skin. Distribution is from the lower deltoid to mid-dorsal forearm, affecting both arms identically. The volar aspects and triceps of both arms are totally spared.

The patient has type IV skin.

What’s the diagnosis?

DISCUSSION
This case is an almost perfect representation of lichen nitidus (LN), in terms of morphology, distribution, and configuration. Close examination of individual lesions revealed that the papules were somewhat planar (ie, flat-topped), giving their surfaces a reflective appearance that the eye interprets as white (particularly contrasted with darker skin).

LN can occur in anyone, but it is most often seen in those with darker skin. It is also frequently seen in children, many of whom are atopic, with dry, sensitive skin that is prone to eczema.

In terms of distribution, LN typically affects the extensor triceps, elbow, and forearms bilaterally. With its flat-topped and shiny appearance, LN is sometimes called "mini-lichen planus"—a condition that can demonstrate similar features. Fortunately, LN is seldom itchy and shares none of the distinct histologic characteristics of lichen planus.

LN is quite unusual, if not rare. It is also idiopathic and nearly always resolves on its own—although this can take months to years.

Emollients help to make the affected skin smoother and less visible. Class 4 steroid creams (eg, triamcinolone 0.05%) can help with itching.

TAKE-HOME LEARNING POINTS

• Lichen nitidus (LN) is a rare idiopathic skin condition manifesting with patches of tiny planar papules; it typically affects the elbow and dorsal forearm.
• LN has no pathologic implications and is asymptomatic and self-limited.
• The lesions of LN have a “lichenoid” appearance—ie, a shiny, flat-topped look similar to that seen with lichen planus.
• Fortunately, LN rarely requires treatment, aside from relief of mild itching.

A 14-year-old boy presents to dermatology for evaluation of an asymptomatic “rash” present on his arms since age 6. The condition has caught the attention of family members and teachers over the years, particularly in regard to possible contagion.

The patient is otherwise reasonably healthy, although he has asthma and seasonal allergies.

EXAMINATION
The "rash" consists of uniformly distributed and sized planar papules. Although they are tiny, averaging only 1 mm wide, they are prominent enough to be noticeable and palpable. They appear slightly lighter than the surrounding skin. Distribution is from the lower deltoid to mid-dorsal forearm, affecting both arms identically. The volar aspects and triceps of both arms are totally spared.

The patient has type IV skin.

What’s the diagnosis?

DISCUSSION
This case is an almost perfect representation of lichen nitidus (LN), in terms of morphology, distribution, and configuration. Close examination of individual lesions revealed that the papules were somewhat planar (ie, flat-topped), giving their surfaces a reflective appearance that the eye interprets as white (particularly contrasted with darker skin).

LN can occur in anyone, but it is most often seen in those with darker skin. It is also frequently seen in children, many of whom are atopic, with dry, sensitive skin that is prone to eczema.

In terms of distribution, LN typically affects the extensor triceps, elbow, and forearms bilaterally. With its flat-topped and shiny appearance, LN is sometimes called "mini-lichen planus"—a condition that can demonstrate similar features. Fortunately, LN is seldom itchy and shares none of the distinct histologic characteristics of lichen planus.

LN is quite unusual, if not rare. It is also idiopathic and nearly always resolves on its own—although this can take months to years.

Emollients help to make the affected skin smoother and less visible. Class 4 steroid creams (eg, triamcinolone 0.05%) can help with itching.

TAKE-HOME LEARNING POINTS

• Lichen nitidus (LN) is a rare idiopathic skin condition manifesting with patches of tiny planar papules; it typically affects the elbow and dorsal forearm.
• LN has no pathologic implications and is asymptomatic and self-limited.
• The lesions of LN have a “lichenoid” appearance—ie, a shiny, flat-topped look similar to that seen with lichen planus.
• Fortunately, LN rarely requires treatment, aside from relief of mild itching.

The clinical features were consistent with a filiform wart, which is caused by human papillomavirus and common on the face. Filiform warts may occur on mucosal surfaces, including the nasal mucosa, lips, or eyelids. Most are benign and resolve within 2 years without treatment, but others can be symptomatic. Larger filiform warts may develop the clinical features of a cutaneous horn and mimic a squamous cell carcinoma.

Patients often want the wart removed for functional or cosmetic reasons. Although, there are many treatments available for warts, none have success rates that exceed about 70%. The most common options for treatment include topical salicylic acid in a liquid or plaster, cryotherapy, intralesional immunotherapy with candida antigen, excision, and topical acid.

The location of this patient’s wart limited the treatment options to cryotherapy or snip excision and cautery. The patient opted for cryotherapy. In this process, a hemostat or heavy gauge tweezer is dipped in liquid nitrogen and allowed to cool. Then, without anesthesia, the clinician pinches the lesion gently with the instrument and holds it until the freeze horizon extends to the base. This is then repeated. Each cycle may take 10 and 15 seconds. A benefit of this technique (which is also useful for skin tags and lesions close to the eye) is the ability to avoid overspray of liquid nitrogen and thus, minimize collateral tissue damage. It is also quick and bloodless.

The FP performed cryotherapy on the wart and advised the patient to expect the lesion to become more inflamed over the next 2 to 3 days and then peel off within 1 to 2 weeks. The FP also instructed the patient to return in a week or 2 so that the FP could evaluate whether additional treatment would be necessary. In general, non-genital warts require 2 to 3 individual treatments to clear, but a smaller and pedunculated wart like the one seen in this case tend to clear more easily.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained).

The clinical features were consistent with a filiform wart, which is caused by human papillomavirus and common on the face. Filiform warts may occur on mucosal surfaces, including the nasal mucosa, lips, or eyelids. Most are benign and resolve within 2 years without treatment, but others can be symptomatic. Larger filiform warts may develop the clinical features of a cutaneous horn and mimic a squamous cell carcinoma.

Patients often want the wart removed for functional or cosmetic reasons. Although, there are many treatments available for warts, none have success rates that exceed about 70%. The most common options for treatment include topical salicylic acid in a liquid or plaster, cryotherapy, intralesional immunotherapy with candida antigen, excision, and topical acid.

The location of this patient’s wart limited the treatment options to cryotherapy or snip excision and cautery. The patient opted for cryotherapy. In this process, a hemostat or heavy gauge tweezer is dipped in liquid nitrogen and allowed to cool. Then, without anesthesia, the clinician pinches the lesion gently with the instrument and holds it until the freeze horizon extends to the base. This is then repeated. Each cycle may take 10 and 15 seconds. A benefit of this technique (which is also useful for skin tags and lesions close to the eye) is the ability to avoid overspray of liquid nitrogen and thus, minimize collateral tissue damage. It is also quick and bloodless.

The FP performed cryotherapy on the wart and advised the patient to expect the lesion to become more inflamed over the next 2 to 3 days and then peel off within 1 to 2 weeks. The FP also instructed the patient to return in a week or 2 so that the FP could evaluate whether additional treatment would be necessary. In general, non-genital warts require 2 to 3 individual treatments to clear, but a smaller and pedunculated wart like the one seen in this case tend to clear more easily.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained).

The clinical features were consistent with a filiform wart, which is caused by human papillomavirus and common on the face. Filiform warts may occur on mucosal surfaces, including the nasal mucosa, lips, or eyelids. Most are benign and resolve within 2 years without treatment, but others can be symptomatic. Larger filiform warts may develop the clinical features of a cutaneous horn and mimic a squamous cell carcinoma.

Patients often want the wart removed for functional or cosmetic reasons. Although, there are many treatments available for warts, none have success rates that exceed about 70%. The most common options for treatment include topical salicylic acid in a liquid or plaster, cryotherapy, intralesional immunotherapy with candida antigen, excision, and topical acid.

The location of this patient’s wart limited the treatment options to cryotherapy or snip excision and cautery. The patient opted for cryotherapy. In this process, a hemostat or heavy gauge tweezer is dipped in liquid nitrogen and allowed to cool. Then, without anesthesia, the clinician pinches the lesion gently with the instrument and holds it until the freeze horizon extends to the base. This is then repeated. Each cycle may take 10 and 15 seconds. A benefit of this technique (which is also useful for skin tags and lesions close to the eye) is the ability to avoid overspray of liquid nitrogen and thus, minimize collateral tissue damage. It is also quick and bloodless.

The FP performed cryotherapy on the wart and advised the patient to expect the lesion to become more inflamed over the next 2 to 3 days and then peel off within 1 to 2 weeks. The FP also instructed the patient to return in a week or 2 so that the FP could evaluate whether additional treatment would be necessary. In general, non-genital warts require 2 to 3 individual treatments to clear, but a smaller and pedunculated wart like the one seen in this case tend to clear more easily.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained).

The incidence of melanoma in the United States dropped significantly among adolescents and young adults aged 10 to 29 years between 2006 and 2015, according to results of a population-based registry study of 988,103 cases of invasive melanoma.

These data are observational, “and thus cannot conclusively determine the cause of this statistically and clinically significant decrease,” wrote Kelly G. Paulson, MD, PhD, of the Fred Hutchinson Cancer Research Center, Seattle, and colleagues. However, they added, “a likely explanation for the reduced melanoma incidence in adolescents and young adults is success at increased UV exposure protection. These data provide an impetus to further improve multimodal efforts aimed at reducing the burden of melanoma and encourage ongoing UV exposure protection efforts throughout the lifetime of individuals.”

Public health measures to promote sun-protective behaviors including sunscreen use, protective clothing, and seeking shade were initiated in the United States in the late 1990s and early 2000s, but the public health impact remains unknown, they noted in the study, published in JAMA Dermatology.

For the study, they reviewed data from the National Program of Cancer Registries – Surveillance Epidemiology and End Results combined database for the years 2001-2015. Overall, the incidence of invasive melanoma among people of all ages in the United States increased from 50,272 cases in 2001 to 83,362 in 2015. However, in 2015 only 67 cases were reported in children younger than 10 years, 251 in adolescents aged 10-19 years, and 1,973 in young adults (aged 20-29 years).

Between 2006 and 2015, the annual percentage change in melanoma incidence decreased by 4.4% for male adolescents, 5.4% for female adolescents, 3.7% for male young adults, and 3.6% for female young adults; these changes were statistically significant. The trends in incidence was similar when the population was limited to non-Hispanic whites, considered a high-risk group for melanoma.

By contrast, melanoma incidence increased by an annual percentage change of 1.8% for both men and women aged 40 years and older during the same period of time. Young adult women had a greater incidence of melanoma compared with young adult men (about twofold greater), but older men had a greater incidence of melanoma compared with older women, the researchers said.

The findings were limited by a lack of data about potential confounders, such as skin pigmentation, UV light exposure, sunburn history, sunscreen use, sun avoidance, protective clothing, and tanning bed use; and the absence of information kept the researchers from estimating an association between increased sun-protective behaviors and decreased incidence of melanoma.

“However, this change in behavior remains a plausible explanation for decreased melanoma rates in adolescent and young adult populations,” and the data support continued strategies to promote UV protection throughout life, they said.

The study was supported in part by the National Institutes of Health, the Fred Hutchinson Cancer Research Center Integrated Immunotherapy Research Core, and a Society for Immunotherapy of Cancer–Merck fellowship. Dr. Paulson disclosed grants from the Society for Immunotherapy of Cancer–Merck, bluebird biosciences, EMD Serono; she also disclosed an issued and licensed patent for a Merkel cell carcinoma T cell receptor.

SOURCE: Paulson KG et al. JAMA Dermatol. 2019. Nov 13. doi: 10.1001/jamadermatol.2019.3353.

The incidence of melanoma in the United States dropped significantly among adolescents and young adults aged 10 to 29 years between 2006 and 2015, according to results of a population-based registry study of 988,103 cases of invasive melanoma.

These data are observational, “and thus cannot conclusively determine the cause of this statistically and clinically significant decrease,” wrote Kelly G. Paulson, MD, PhD, of the Fred Hutchinson Cancer Research Center, Seattle, and colleagues. However, they added, “a likely explanation for the reduced melanoma incidence in adolescents and young adults is success at increased UV exposure protection. These data provide an impetus to further improve multimodal efforts aimed at reducing the burden of melanoma and encourage ongoing UV exposure protection efforts throughout the lifetime of individuals.”

Public health measures to promote sun-protective behaviors including sunscreen use, protective clothing, and seeking shade were initiated in the United States in the late 1990s and early 2000s, but the public health impact remains unknown, they noted in the study, published in JAMA Dermatology.

For the study, they reviewed data from the National Program of Cancer Registries – Surveillance Epidemiology and End Results combined database for the years 2001-2015. Overall, the incidence of invasive melanoma among people of all ages in the United States increased from 50,272 cases in 2001 to 83,362 in 2015. However, in 2015 only 67 cases were reported in children younger than 10 years, 251 in adolescents aged 10-19 years, and 1,973 in young adults (aged 20-29 years).

Between 2006 and 2015, the annual percentage change in melanoma incidence decreased by 4.4% for male adolescents, 5.4% for female adolescents, 3.7% for male young adults, and 3.6% for female young adults; these changes were statistically significant. The trends in incidence was similar when the population was limited to non-Hispanic whites, considered a high-risk group for melanoma.

By contrast, melanoma incidence increased by an annual percentage change of 1.8% for both men and women aged 40 years and older during the same period of time. Young adult women had a greater incidence of melanoma compared with young adult men (about twofold greater), but older men had a greater incidence of melanoma compared with older women, the researchers said.

The findings were limited by a lack of data about potential confounders, such as skin pigmentation, UV light exposure, sunburn history, sunscreen use, sun avoidance, protective clothing, and tanning bed use; and the absence of information kept the researchers from estimating an association between increased sun-protective behaviors and decreased incidence of melanoma.

“However, this change in behavior remains a plausible explanation for decreased melanoma rates in adolescent and young adult populations,” and the data support continued strategies to promote UV protection throughout life, they said.

The study was supported in part by the National Institutes of Health, the Fred Hutchinson Cancer Research Center Integrated Immunotherapy Research Core, and a Society for Immunotherapy of Cancer–Merck fellowship. Dr. Paulson disclosed grants from the Society for Immunotherapy of Cancer–Merck, bluebird biosciences, EMD Serono; she also disclosed an issued and licensed patent for a Merkel cell carcinoma T cell receptor.

SOURCE: Paulson KG et al. JAMA Dermatol. 2019. Nov 13. doi: 10.1001/jamadermatol.2019.3353.

The incidence of melanoma in the United States dropped significantly among adolescents and young adults aged 10 to 29 years between 2006 and 2015, according to results of a population-based registry study of 988,103 cases of invasive melanoma.

These data are observational, “and thus cannot conclusively determine the cause of this statistically and clinically significant decrease,” wrote Kelly G. Paulson, MD, PhD, of the Fred Hutchinson Cancer Research Center, Seattle, and colleagues. However, they added, “a likely explanation for the reduced melanoma incidence in adolescents and young adults is success at increased UV exposure protection. These data provide an impetus to further improve multimodal efforts aimed at reducing the burden of melanoma and encourage ongoing UV exposure protection efforts throughout the lifetime of individuals.”

Public health measures to promote sun-protective behaviors including sunscreen use, protective clothing, and seeking shade were initiated in the United States in the late 1990s and early 2000s, but the public health impact remains unknown, they noted in the study, published in JAMA Dermatology.

For the study, they reviewed data from the National Program of Cancer Registries – Surveillance Epidemiology and End Results combined database for the years 2001-2015. Overall, the incidence of invasive melanoma among people of all ages in the United States increased from 50,272 cases in 2001 to 83,362 in 2015. However, in 2015 only 67 cases were reported in children younger than 10 years, 251 in adolescents aged 10-19 years, and 1,973 in young adults (aged 20-29 years).

Between 2006 and 2015, the annual percentage change in melanoma incidence decreased by 4.4% for male adolescents, 5.4% for female adolescents, 3.7% for male young adults, and 3.6% for female young adults; these changes were statistically significant. The trends in incidence was similar when the population was limited to non-Hispanic whites, considered a high-risk group for melanoma.

By contrast, melanoma incidence increased by an annual percentage change of 1.8% for both men and women aged 40 years and older during the same period of time. Young adult women had a greater incidence of melanoma compared with young adult men (about twofold greater), but older men had a greater incidence of melanoma compared with older women, the researchers said.

The findings were limited by a lack of data about potential confounders, such as skin pigmentation, UV light exposure, sunburn history, sunscreen use, sun avoidance, protective clothing, and tanning bed use; and the absence of information kept the researchers from estimating an association between increased sun-protective behaviors and decreased incidence of melanoma.

“However, this change in behavior remains a plausible explanation for decreased melanoma rates in adolescent and young adult populations,” and the data support continued strategies to promote UV protection throughout life, they said.

The study was supported in part by the National Institutes of Health, the Fred Hutchinson Cancer Research Center Integrated Immunotherapy Research Core, and a Society for Immunotherapy of Cancer–Merck fellowship. Dr. Paulson disclosed grants from the Society for Immunotherapy of Cancer–Merck, bluebird biosciences, EMD Serono; she also disclosed an issued and licensed patent for a Merkel cell carcinoma T cell receptor.

SOURCE: Paulson KG et al. JAMA Dermatol. 2019. Nov 13. doi: 10.1001/jamadermatol.2019.3353.

MADRID – Oral apremilast’s beneficial effects on Behçet’s disease oral ulcer disease severity and patient quality of life were sustained through week 64 of the long-term extension phase of the pivotal RELIEF trial, Alfred Mahr, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“We now have strong evidence that apremilast is an effective and safe therapy to treat oral ulcers in patients with Behçet’s syndrome. I think this is a major advance in the field,” declared Dr. Mahr, a rheumatologist at St. Gallen (Switzerland) Cantonal Hospital.

Based largely upon the results of the 12-week, double-blind portion of the phase 3 RELIEF trial, the Food and Drug Administration approved apremilast (Otezla) for the treatment of oral ulcers in patients with Behçet’s disease in the summer of 2019.

The safety profile of the oral phosphodiesterase-4 inhibitor was as seen in other studies, including in patients with psoriatic arthritis, an FDA-approved indication for the drug since 2014. The main side effects in the long-term extension of RELIEF were diarrhea and nausea, typically mild or moderate in nature and roughly twice as frequent as in placebo-treated controls in the double-blind study phase.

“At the end of the day, at week 64, only 12% of patients treated with apremilast during the entire 64 weeks discontinued the drug due to a treatment-emergent adverse event, which I believe is a good indicator of the safety of this medication,” the rheumatologist said. “The overall feeling is that the benefit-to-risk ratio is very good and it’s a safe drug to prescribe.”

At the close of the initial 12-week, double-blind phase of RELIEF, 178 of the original 207 participants elected to enter the long-term extension, either staying on apremilast at 30 mg twice a day for an additional 52 weeks or switching to that regimen from placebo.

The focus of the long-term extension was on disease activity and quality of life outcomes. The results in patients who had switched from placebo to apremilast after 12 weeks proved to be reassuringly similar to outcomes in patients on the drug for the full duration. For example, the mean improvement on the patient-reported Behçet’s Syndrome Activity Scale was 18.6 points after 12 weeks of double-blind apremilast, 16.9 points after 64 weeks of continuous apremilast, and 16.8 points with 12 weeks of placebo followed by 52 weeks of active therapy.

After 12 weeks of double-blind apremilast, patients averaged a 3.4-point improvement on the Behçet’s Disease Quality of Life measure. After 64 weeks on the drug, the improvement over baseline was 3.6 points, while in the switch group it was 3.4 points. Similarly, on all three components of the SF-36 quality of life metric, the continuous apremilast group showed maintenance of effect from week 12 to week 64, while the placebo-to-apremilast group caught up. The same was true with regards to the Behçet’s Disease Current Activity Index, which encompasses measures of both the patient’s and clinician’s perception of disease activity.

At the outset of the RELIEF trial, participants averaged four oral ulcers. At week 64, the continuous apremilast group averaged 1.4 and the switch group 0.8, a nonsignificant difference.

Asked if apremilast had a favorable impact upon other manifestations of Behçet’s disease besides the oral ulcers, Dr. Mahr replied, “This is a very good question. People often wonder about it. We do, too. But this trial was not designed to capture less common manifestations of Behçet’s syndrome, such as genital ulcers. There have been some analyses done, but the number of patients who had genital ulcers at 12 weeks were very few. The same was true for eye manifestations. There was sort of a signal that it works, but we can’t prove it in a placebo-controlled trial.”

Dr. Mahr reported receiving research funding from and serving as a consultant to Celgene, the study sponsor.

[email protected]

MADRID – Oral apremilast’s beneficial effects on Behçet’s disease oral ulcer disease severity and patient quality of life were sustained through week 64 of the long-term extension phase of the pivotal RELIEF trial, Alfred Mahr, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“We now have strong evidence that apremilast is an effective and safe therapy to treat oral ulcers in patients with Behçet’s syndrome. I think this is a major advance in the field,” declared Dr. Mahr, a rheumatologist at St. Gallen (Switzerland) Cantonal Hospital.

Based largely upon the results of the 12-week, double-blind portion of the phase 3 RELIEF trial, the Food and Drug Administration approved apremilast (Otezla) for the treatment of oral ulcers in patients with Behçet’s disease in the summer of 2019.

The safety profile of the oral phosphodiesterase-4 inhibitor was as seen in other studies, including in patients with psoriatic arthritis, an FDA-approved indication for the drug since 2014. The main side effects in the long-term extension of RELIEF were diarrhea and nausea, typically mild or moderate in nature and roughly twice as frequent as in placebo-treated controls in the double-blind study phase.

“At the end of the day, at week 64, only 12% of patients treated with apremilast during the entire 64 weeks discontinued the drug due to a treatment-emergent adverse event, which I believe is a good indicator of the safety of this medication,” the rheumatologist said. “The overall feeling is that the benefit-to-risk ratio is very good and it’s a safe drug to prescribe.”

At the close of the initial 12-week, double-blind phase of RELIEF, 178 of the original 207 participants elected to enter the long-term extension, either staying on apremilast at 30 mg twice a day for an additional 52 weeks or switching to that regimen from placebo.

The focus of the long-term extension was on disease activity and quality of life outcomes. The results in patients who had switched from placebo to apremilast after 12 weeks proved to be reassuringly similar to outcomes in patients on the drug for the full duration. For example, the mean improvement on the patient-reported Behçet’s Syndrome Activity Scale was 18.6 points after 12 weeks of double-blind apremilast, 16.9 points after 64 weeks of continuous apremilast, and 16.8 points with 12 weeks of placebo followed by 52 weeks of active therapy.

After 12 weeks of double-blind apremilast, patients averaged a 3.4-point improvement on the Behçet’s Disease Quality of Life measure. After 64 weeks on the drug, the improvement over baseline was 3.6 points, while in the switch group it was 3.4 points. Similarly, on all three components of the SF-36 quality of life metric, the continuous apremilast group showed maintenance of effect from week 12 to week 64, while the placebo-to-apremilast group caught up. The same was true with regards to the Behçet’s Disease Current Activity Index, which encompasses measures of both the patient’s and clinician’s perception of disease activity.

At the outset of the RELIEF trial, participants averaged four oral ulcers. At week 64, the continuous apremilast group averaged 1.4 and the switch group 0.8, a nonsignificant difference.

Asked if apremilast had a favorable impact upon other manifestations of Behçet’s disease besides the oral ulcers, Dr. Mahr replied, “This is a very good question. People often wonder about it. We do, too. But this trial was not designed to capture less common manifestations of Behçet’s syndrome, such as genital ulcers. There have been some analyses done, but the number of patients who had genital ulcers at 12 weeks were very few. The same was true for eye manifestations. There was sort of a signal that it works, but we can’t prove it in a placebo-controlled trial.”

Dr. Mahr reported receiving research funding from and serving as a consultant to Celgene, the study sponsor.

[email protected]

MADRID – Oral apremilast’s beneficial effects on Behçet’s disease oral ulcer disease severity and patient quality of life were sustained through week 64 of the long-term extension phase of the pivotal RELIEF trial, Alfred Mahr, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“We now have strong evidence that apremilast is an effective and safe therapy to treat oral ulcers in patients with Behçet’s syndrome. I think this is a major advance in the field,” declared Dr. Mahr, a rheumatologist at St. Gallen (Switzerland) Cantonal Hospital.

Based largely upon the results of the 12-week, double-blind portion of the phase 3 RELIEF trial, the Food and Drug Administration approved apremilast (Otezla) for the treatment of oral ulcers in patients with Behçet’s disease in the summer of 2019.

The safety profile of the oral phosphodiesterase-4 inhibitor was as seen in other studies, including in patients with psoriatic arthritis, an FDA-approved indication for the drug since 2014. The main side effects in the long-term extension of RELIEF were diarrhea and nausea, typically mild or moderate in nature and roughly twice as frequent as in placebo-treated controls in the double-blind study phase.

“At the end of the day, at week 64, only 12% of patients treated with apremilast during the entire 64 weeks discontinued the drug due to a treatment-emergent adverse event, which I believe is a good indicator of the safety of this medication,” the rheumatologist said. “The overall feeling is that the benefit-to-risk ratio is very good and it’s a safe drug to prescribe.”

At the close of the initial 12-week, double-blind phase of RELIEF, 178 of the original 207 participants elected to enter the long-term extension, either staying on apremilast at 30 mg twice a day for an additional 52 weeks or switching to that regimen from placebo.

The focus of the long-term extension was on disease activity and quality of life outcomes. The results in patients who had switched from placebo to apremilast after 12 weeks proved to be reassuringly similar to outcomes in patients on the drug for the full duration. For example, the mean improvement on the patient-reported Behçet’s Syndrome Activity Scale was 18.6 points after 12 weeks of double-blind apremilast, 16.9 points after 64 weeks of continuous apremilast, and 16.8 points with 12 weeks of placebo followed by 52 weeks of active therapy.

After 12 weeks of double-blind apremilast, patients averaged a 3.4-point improvement on the Behçet’s Disease Quality of Life measure. After 64 weeks on the drug, the improvement over baseline was 3.6 points, while in the switch group it was 3.4 points. Similarly, on all three components of the SF-36 quality of life metric, the continuous apremilast group showed maintenance of effect from week 12 to week 64, while the placebo-to-apremilast group caught up. The same was true with regards to the Behçet’s Disease Current Activity Index, which encompasses measures of both the patient’s and clinician’s perception of disease activity.

At the outset of the RELIEF trial, participants averaged four oral ulcers. At week 64, the continuous apremilast group averaged 1.4 and the switch group 0.8, a nonsignificant difference.

Asked if apremilast had a favorable impact upon other manifestations of Behçet’s disease besides the oral ulcers, Dr. Mahr replied, “This is a very good question. People often wonder about it. We do, too. But this trial was not designed to capture less common manifestations of Behçet’s syndrome, such as genital ulcers. There have been some analyses done, but the number of patients who had genital ulcers at 12 weeks were very few. The same was true for eye manifestations. There was sort of a signal that it works, but we can’t prove it in a placebo-controlled trial.”

Dr. Mahr reported receiving research funding from and serving as a consultant to Celgene, the study sponsor.

[email protected]

The Food and Drug Administration has cleared adalimumab-afzb (Abrilada) as the fifth approved Humira biosimilar and the 25th approved biosimilar drug overall, the agency said in a Nov. 15 announcement.

Olivier Le Moal/Getty Images

According to a press release from Pfizer, approval for Abrilada was based on review of a comprehensive data package demonstrating biosimilarity of the drug to the reference product. This included data from a clinical comparative study, which found no clinically meaningful difference between Abrilada and the reference in terms of efficacy, safety, and immunogenicity in patients with moderate to severe rheumatoid arthritis (RA). In addition to RA, Abrilada is indicated for juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis.

Common adverse events in adalimumab clinical trials included infection, injection-site reactions, headache, and rash.

Pfizer said that it “is working to make Abrilada available to U.S. patients as soon as feasible based on the terms of our agreement with AbbVie [the manufacturer of Humira]. Our current plans are to launch in 2023.”

[email protected]

The Food and Drug Administration has cleared adalimumab-afzb (Abrilada) as the fifth approved Humira biosimilar and the 25th approved biosimilar drug overall, the agency said in a Nov. 15 announcement.

Olivier Le Moal/Getty Images

According to a press release from Pfizer, approval for Abrilada was based on review of a comprehensive data package demonstrating biosimilarity of the drug to the reference product. This included data from a clinical comparative study, which found no clinically meaningful difference between Abrilada and the reference in terms of efficacy, safety, and immunogenicity in patients with moderate to severe rheumatoid arthritis (RA). In addition to RA, Abrilada is indicated for juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis.

Common adverse events in adalimumab clinical trials included infection, injection-site reactions, headache, and rash.

Pfizer said that it “is working to make Abrilada available to U.S. patients as soon as feasible based on the terms of our agreement with AbbVie [the manufacturer of Humira]. Our current plans are to launch in 2023.”

[email protected]

The Food and Drug Administration has cleared adalimumab-afzb (Abrilada) as the fifth approved Humira biosimilar and the 25th approved biosimilar drug overall, the agency said in a Nov. 15 announcement.

Olivier Le Moal/Getty Images

According to a press release from Pfizer, approval for Abrilada was based on review of a comprehensive data package demonstrating biosimilarity of the drug to the reference product. This included data from a clinical comparative study, which found no clinically meaningful difference between Abrilada and the reference in terms of efficacy, safety, and immunogenicity in patients with moderate to severe rheumatoid arthritis (RA). In addition to RA, Abrilada is indicated for juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis.

Common adverse events in adalimumab clinical trials included infection, injection-site reactions, headache, and rash.

Pfizer said that it “is working to make Abrilada available to U.S. patients as soon as feasible based on the terms of our agreement with AbbVie [the manufacturer of Humira]. Our current plans are to launch in 2023.”

[email protected]

The FP initially treated the area with topical ketoconazole cream, which stung, but partially improved the patient’s symptoms. Because the rash persisted, the FP performed a punch biopsy, which showed widespread epidermal acantholysis or separation of epidermal cells. This is a hallmark of pemphigus vulgaris and benign familial pemphigus (Hailey-Hailey disease).

Hailey-Hailey disease is an uncommon autosomal dominant inherited blistering disorder that affects connecting proteins in the epidermis, which is why histology overlaps with pemphigus. Symptoms may not present until the second or third decade of life and often occur in flexural or high friction areas, including the axilla and inguinal folds. Any skin injury may trigger a flare, including sunburn, infections, heavy sweating, or friction from clothes. Bacterial overgrowth or colonization can cause a bad odor and social isolation in severe cases.

The differential diagnosis of axillary skin disorders is broad and includes irritant contact dermatitis, contact dermatitis, seborrheic dermatitis, hidradenitis suppurativa, candida intertrigo, and psoriasis. Clinical clues that favor Hailey-Hailey disease include fragile vesicles or pustules at the periphery and small focal erosions. The family history is helpful but not always known.

Some patients require topical therapy sequentially, in combination, or personalized through trial and error that addresses the inflammation, bacterial overgrowth, and fungal disease. Patients also may require long-term doxycycline therapy to suppress flares. Most patients will benefit from at least prn use of topical steroids for inflammation. Addressing sweating with topical aluminum chloride or botulinum injections can be beneficial. Low dose naltrexone, as well as afamelanotide, has shown promise in a few small case series.

The patient in this case improved with topical triamcinolone 0.1% ointment bid and systemic doxycycline 100 mg bid for 2 weeks. However, he continued to require occasional rounds of oral doxycycline with flares.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained).

The FP initially treated the area with topical ketoconazole cream, which stung, but partially improved the patient’s symptoms. Because the rash persisted, the FP performed a punch biopsy, which showed widespread epidermal acantholysis or separation of epidermal cells. This is a hallmark of pemphigus vulgaris and benign familial pemphigus (Hailey-Hailey disease).

Hailey-Hailey disease is an uncommon autosomal dominant inherited blistering disorder that affects connecting proteins in the epidermis, which is why histology overlaps with pemphigus. Symptoms may not present until the second or third decade of life and often occur in flexural or high friction areas, including the axilla and inguinal folds. Any skin injury may trigger a flare, including sunburn, infections, heavy sweating, or friction from clothes. Bacterial overgrowth or colonization can cause a bad odor and social isolation in severe cases.

The differential diagnosis of axillary skin disorders is broad and includes irritant contact dermatitis, contact dermatitis, seborrheic dermatitis, hidradenitis suppurativa, candida intertrigo, and psoriasis. Clinical clues that favor Hailey-Hailey disease include fragile vesicles or pustules at the periphery and small focal erosions. The family history is helpful but not always known.

Some patients require topical therapy sequentially, in combination, or personalized through trial and error that addresses the inflammation, bacterial overgrowth, and fungal disease. Patients also may require long-term doxycycline therapy to suppress flares. Most patients will benefit from at least prn use of topical steroids for inflammation. Addressing sweating with topical aluminum chloride or botulinum injections can be beneficial. Low dose naltrexone, as well as afamelanotide, has shown promise in a few small case series.

The patient in this case improved with topical triamcinolone 0.1% ointment bid and systemic doxycycline 100 mg bid for 2 weeks. However, he continued to require occasional rounds of oral doxycycline with flares.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained).

The FP initially treated the area with topical ketoconazole cream, which stung, but partially improved the patient’s symptoms. Because the rash persisted, the FP performed a punch biopsy, which showed widespread epidermal acantholysis or separation of epidermal cells. This is a hallmark of pemphigus vulgaris and benign familial pemphigus (Hailey-Hailey disease).

Hailey-Hailey disease is an uncommon autosomal dominant inherited blistering disorder that affects connecting proteins in the epidermis, which is why histology overlaps with pemphigus. Symptoms may not present until the second or third decade of life and often occur in flexural or high friction areas, including the axilla and inguinal folds. Any skin injury may trigger a flare, including sunburn, infections, heavy sweating, or friction from clothes. Bacterial overgrowth or colonization can cause a bad odor and social isolation in severe cases.

The differential diagnosis of axillary skin disorders is broad and includes irritant contact dermatitis, contact dermatitis, seborrheic dermatitis, hidradenitis suppurativa, candida intertrigo, and psoriasis. Clinical clues that favor Hailey-Hailey disease include fragile vesicles or pustules at the periphery and small focal erosions. The family history is helpful but not always known.

Some patients require topical therapy sequentially, in combination, or personalized through trial and error that addresses the inflammation, bacterial overgrowth, and fungal disease. Patients also may require long-term doxycycline therapy to suppress flares. Most patients will benefit from at least prn use of topical steroids for inflammation. Addressing sweating with topical aluminum chloride or botulinum injections can be beneficial. Low dose naltrexone, as well as afamelanotide, has shown promise in a few small case series.

The patient in this case improved with topical triamcinolone 0.1% ointment bid and systemic doxycycline 100 mg bid for 2 weeks. However, he continued to require occasional rounds of oral doxycycline with flares.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained).