Psoriasis

Roflumilast cream 0.3% is under review by the Food and Drug Administration for the treatment of plaque psoriasis in children as young as 2 years, according to a press release from the manufacturer.

The company, Arcutis Biotherapeutics, announced the submission of a supplemental new drug application for approval of roflumilast cream (Zoryve), a topical phosphodiesterase-4 (PDE-4) inhibitor, to treat psoriasis in children aged 2-11 years. If approved, this would be the first such product for young children with plaque psoriasis, according to the press release. In July 2022, the FDA approved roflumilast cream 0.3% for the treatment of plaque psoriasis in people 12 years of age and older, including in intertriginous areas, based on data from the phase 3 DERMIS-1 and DERMIS-2 trials.

The new submission is supported by data from two 4-week Maximal Usage Systemic Exposure (MUSE) studies in children ages 2-11 years with plaque psoriasis. In these phase 2, open-label studies, one study of children aged 2-5 years and another study of children aged 6-11 years, participants were treated with roflumilast cream 0.3% once daily for 4 weeks. The MUSE studies are also intended to fulfill postmarketing requirements for roflumilast, according to the company. The MUSE results were consistent with those from DERMIS-1 and DERMIS-2, according to the company press release. In DERMIS-1 and DERMIS-2, significantly more patients randomized to roflumilast met criteria for Investigators Global Success (IGA) scores after 8 weeks of daily treatment compared with placebo patients, and significantly more achieved a 75% reduction in Psoriasis Area and Severity Index (PASI) scores compared with those on placebo.

Common adverse events associated with roflumilast include diarrhea, headache, insomnia, nausea, application site pain, upper respiratory tract infection, and urinary tract infection. None of these have been reported in more than 3% of patients, the press release noted.

Roflumilast cream 0.3% is under review by the Food and Drug Administration for the treatment of plaque psoriasis in children as young as 2 years, according to a press release from the manufacturer.

The company, Arcutis Biotherapeutics, announced the submission of a supplemental new drug application for approval of roflumilast cream (Zoryve), a topical phosphodiesterase-4 (PDE-4) inhibitor, to treat psoriasis in children aged 2-11 years. If approved, this would be the first such product for young children with plaque psoriasis, according to the press release. In July 2022, the FDA approved roflumilast cream 0.3% for the treatment of plaque psoriasis in people 12 years of age and older, including in intertriginous areas, based on data from the phase 3 DERMIS-1 and DERMIS-2 trials.

The new submission is supported by data from two 4-week Maximal Usage Systemic Exposure (MUSE) studies in children ages 2-11 years with plaque psoriasis. In these phase 2, open-label studies, one study of children aged 2-5 years and another study of children aged 6-11 years, participants were treated with roflumilast cream 0.3% once daily for 4 weeks. The MUSE studies are also intended to fulfill postmarketing requirements for roflumilast, according to the company. The MUSE results were consistent with those from DERMIS-1 and DERMIS-2, according to the company press release. In DERMIS-1 and DERMIS-2, significantly more patients randomized to roflumilast met criteria for Investigators Global Success (IGA) scores after 8 weeks of daily treatment compared with placebo patients, and significantly more achieved a 75% reduction in Psoriasis Area and Severity Index (PASI) scores compared with those on placebo.

Common adverse events associated with roflumilast include diarrhea, headache, insomnia, nausea, application site pain, upper respiratory tract infection, and urinary tract infection. None of these have been reported in more than 3% of patients, the press release noted.

Roflumilast cream 0.3% is under review by the Food and Drug Administration for the treatment of plaque psoriasis in children as young as 2 years, according to a press release from the manufacturer.

The company, Arcutis Biotherapeutics, announced the submission of a supplemental new drug application for approval of roflumilast cream (Zoryve), a topical phosphodiesterase-4 (PDE-4) inhibitor, to treat psoriasis in children aged 2-11 years. If approved, this would be the first such product for young children with plaque psoriasis, according to the press release. In July 2022, the FDA approved roflumilast cream 0.3% for the treatment of plaque psoriasis in people 12 years of age and older, including in intertriginous areas, based on data from the phase 3 DERMIS-1 and DERMIS-2 trials.

The new submission is supported by data from two 4-week Maximal Usage Systemic Exposure (MUSE) studies in children ages 2-11 years with plaque psoriasis. In these phase 2, open-label studies, one study of children aged 2-5 years and another study of children aged 6-11 years, participants were treated with roflumilast cream 0.3% once daily for 4 weeks. The MUSE studies are also intended to fulfill postmarketing requirements for roflumilast, according to the company. The MUSE results were consistent with those from DERMIS-1 and DERMIS-2, according to the company press release. In DERMIS-1 and DERMIS-2, significantly more patients randomized to roflumilast met criteria for Investigators Global Success (IGA) scores after 8 weeks of daily treatment compared with placebo patients, and significantly more achieved a 75% reduction in Psoriasis Area and Severity Index (PASI) scores compared with those on placebo.

Common adverse events associated with roflumilast include diarrhea, headache, insomnia, nausea, application site pain, upper respiratory tract infection, and urinary tract infection. None of these have been reported in more than 3% of patients, the press release noted.

A biosimilar drug to the tumor necrosis factor inhibitor adalimumab, marketed as Idacio (adalimumab-aacf), has been approved by the Food and Drug Administration for use in the United States, according to a press release from manufacturer Fresenius Kabi.

Idacio is a citrate-free, low-concentration formulation of adalimumab and is now approved for use for all but three of the indications that currently apply to the reference adalimumab product (Humira): rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis in adults, ankylosing spondylitis, Crohn’s disease in adults and children aged 6 years or older, ulcerative colitis in adults, and plaque psoriasis in adults. It does not apply to Humira’s indications for hidradenitis suppurativa, uveitis, or ulcerative colitis in pediatric patients aged 5 years and older.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Idacio is the eighth adalimumab biosimilar to be approved in the United States. Its approval was based on evidence of a similar profile of pharmacokinetics, safety, efficacy, and immunogenicity to Humira.

Idacio was first launched in 2019 and has been marketed in more than 37 countries worldwide, according to Fresenius Kabi. The U.S. launch is scheduled for July, and Idacio will be available as a self-administered prefilled syringe or prefilled pen.

A version of this article first appeared on Medscape.com.

A biosimilar drug to the tumor necrosis factor inhibitor adalimumab, marketed as Idacio (adalimumab-aacf), has been approved by the Food and Drug Administration for use in the United States, according to a press release from manufacturer Fresenius Kabi.

Idacio is a citrate-free, low-concentration formulation of adalimumab and is now approved for use for all but three of the indications that currently apply to the reference adalimumab product (Humira): rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis in adults, ankylosing spondylitis, Crohn’s disease in adults and children aged 6 years or older, ulcerative colitis in adults, and plaque psoriasis in adults. It does not apply to Humira’s indications for hidradenitis suppurativa, uveitis, or ulcerative colitis in pediatric patients aged 5 years and older.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Idacio is the eighth adalimumab biosimilar to be approved in the United States. Its approval was based on evidence of a similar profile of pharmacokinetics, safety, efficacy, and immunogenicity to Humira.

Idacio was first launched in 2019 and has been marketed in more than 37 countries worldwide, according to Fresenius Kabi. The U.S. launch is scheduled for July, and Idacio will be available as a self-administered prefilled syringe or prefilled pen.

A version of this article first appeared on Medscape.com.

A biosimilar drug to the tumor necrosis factor inhibitor adalimumab, marketed as Idacio (adalimumab-aacf), has been approved by the Food and Drug Administration for use in the United States, according to a press release from manufacturer Fresenius Kabi.

Idacio is a citrate-free, low-concentration formulation of adalimumab and is now approved for use for all but three of the indications that currently apply to the reference adalimumab product (Humira): rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis in adults, ankylosing spondylitis, Crohn’s disease in adults and children aged 6 years or older, ulcerative colitis in adults, and plaque psoriasis in adults. It does not apply to Humira’s indications for hidradenitis suppurativa, uveitis, or ulcerative colitis in pediatric patients aged 5 years and older.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Idacio is the eighth adalimumab biosimilar to be approved in the United States. Its approval was based on evidence of a similar profile of pharmacokinetics, safety, efficacy, and immunogenicity to Humira.

Idacio was first launched in 2019 and has been marketed in more than 37 countries worldwide, according to Fresenius Kabi. The U.S. launch is scheduled for July, and Idacio will be available as a self-administered prefilled syringe or prefilled pen.

A version of this article first appeared on Medscape.com.

LAS VEGAS – Disparities in the diagnosis and treatment of skin of color can stem from incorrect diagnoses and lack of knowledge on the part of clinicians, and also from knowledge gaps on the part of other health care providers and patients, Susan C. Taylor, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

Additionally, some disparities occur because of gaps in access to health care, said Dr. Taylor, vice chair, diversity, equity and inclusion, in the department of dermatology at the University of Pennsylvania, Philadelphia, who moderated an expert panel discussion of treatment tips for several common dermatologic conditions in skin of color patients.

Atopic dermatitis angles

Atopic dermatitis (AD) is the fourth most common dermatologic complaint in Black patients, based on data from the United States National Ambulatory Medical Care Survey. Also, data from the National Health and Nutrition Examination Survey show that Black children are nearly twice as likely as White children to develop AD after controlling for socioeconomic factors, Dr. Taylor said.

When Black patients present with AD, “you may not see the erythema,” said Valerie D. Callender, MD, of Howard University, Washington, who presented on AD. Instead, “you may see more follicular and papular presentations.” Erythema and erythroderma can present as shades of violet, gray, or dark brown in patients with rich skin tones, added Dr. Callender, who practices in Glenn Dale, Md.

Consequently, disease severity can be misinterpreted, she said, noting that data suggest that scoring systems such as the Eczema Area and Severity Index and Scoring Atopic Dermatitis underestimate AD severity in dark skin.

As for treatment, skin of color patients with AD are often as bothered by postinflammatory hyperpigmentation (PIH) as by active lesions, so treatment should take these concerns into account, Dr. Callender said. Studies evaluating the effectiveness of AD treatments in diverse populations are limited by lack of representation of racial groups in clinical trials and lack of subset analyses by race.
 

Acne awareness

An important consideration of acne in skin of color patients is that the acne “might not be red, it might just be darker,” said Andrew F. Alexis, MD, vice-chair for diversity and inclusion in the department of dermatology, and professor of clinical dermatology at Weill Cornell Medicine, New York. A study published in JAMA Dermatology of nearly 30,000 patients with acne from 2007 to 2017 found that non-Hispanic Black patients were more likely than non-Hispanic White patients to see a dermatologist for acne, but Black patients received fewer prescriptions for acne medications than White patients.

The study also showed that Black patients who received prescriptions for acne were more likely to receive topical retinoids and topical antibiotics, and less likely to receive oral antibiotics, spironolactone, or isotretinoin, compared with White patients. Similarly, Asian patients were more likely to receive topical antibiotics and less likely to receive oral antibiotics, compared with White patients.

Other panelists shared some of their best practices for acne in patients with skin of color, including treatment with topical retinoids (for inflammation) and spironolactone, and therapies that address both inflammation and pigmentation, such as salicylic acid and azelaic acid. Dr. Callender also advised asking patients about makeup, as they may not know that many types of makeup used to cover acne are in fact comedogenic.
 

Melanoma misconceptions

One of the most common misperceptions about melanoma among skin of color patients is that they don’t think they can get it, Dr. Taylor said. Many health care providers don’t think about melanoma in skin of color patients because of the dramatically lower incidence in this population, but as a result, cases may go undiagnosed, and as studies have shown, the mortality rate from melanoma is higher in Black patients.

Consider the palms, soles, nails, and web spaces as possible melanoma sites, Dr. Taylor added.

Educating skin of color patients about melanoma is important, although the incidence is 20 to 30 times lower than in non-Hispanic Whites, said Nada Elbuluk, MD, the founder and director of the University of Southern California Skin of Color Center and Pigmentary Disorders Clinic, Los Angeles. A 2020 editorial published in Cancer Cytopathology pointed out that 1 in 3 Black men or women with a melanoma diagnosis in the United States dies of the disease, compared with 1 in 7 non-Hispanic White men and 1 in 11 non-Hispanic White women with melanoma.

Don’t skip the total body skin exam in these patients, Dr. Elbuluk emphasized. Many patients will only partially undress, and areas such as toes can be missed.
 

Rosacea review

For patients with skin of color, clinicians need to look for different signs of rosacea than those typically seen in White patients, Dr. Elbuluk said. “The most common presentation of rosacea in skin of color is papulopustular,” and the granulomatous variant.

“These patients will often give you a history of sensitivity to products,” Dr. Elbuluk noted. They may not always have the flushing, but they may report warmth or itching, in addition to product sensitivity.

When considering rosacea in skin of color patients, be sure to have good lighting for close examination, as skin thickening is another subtle sign of rosacea in these patients, she said. Skin thickening “is a very early sign that will present in skin of color with no erythema, so keep that in mind.”

Stinging and burning sensations may be reported by skin of color patients with rosacea. Use patient history to confirm the diagnosis of rosacea, which is often delayed in skin of color patients because of a low index of suspicion, she said.

Psoriasis pointers

Psoriasis in skin of color patients used to be considered rare, “but that is far from true,” Dr. Alexis said. In fact, many cases of psoriasis are undiagnosed or the diagnosis is delayed in these patients.

The panelists noted that current guidelines for psoriasis treatment are based on clinical trials composed mainly of White patients, and do not contain specific recommendations for skin of color patients.

Notably, the morphology, location, and color of psoriasis lesions may be different for patients with darker skin, such as thicker plaques and more scaling over larger areas, they said. Also, skin of color patients may experience long-lasting dyspigmentation from psoriasis lesions that have resolved.

When developing a strategy for psoriasis in skin of color patients, consider not only disease severity, but also comorbidities and medications, response (if any) to prior therapies, patient preferences, and quality of life, the panelists said.

Dr. Callender, Dr. Elbuluk, Dr. Taylor, and Dr. Alexis reported conflicts of interest from numerous sources in industry. MedscapeLive and this news organization are owned by the same parent company.

LAS VEGAS – Disparities in the diagnosis and treatment of skin of color can stem from incorrect diagnoses and lack of knowledge on the part of clinicians, and also from knowledge gaps on the part of other health care providers and patients, Susan C. Taylor, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

Additionally, some disparities occur because of gaps in access to health care, said Dr. Taylor, vice chair, diversity, equity and inclusion, in the department of dermatology at the University of Pennsylvania, Philadelphia, who moderated an expert panel discussion of treatment tips for several common dermatologic conditions in skin of color patients.

Atopic dermatitis angles

Atopic dermatitis (AD) is the fourth most common dermatologic complaint in Black patients, based on data from the United States National Ambulatory Medical Care Survey. Also, data from the National Health and Nutrition Examination Survey show that Black children are nearly twice as likely as White children to develop AD after controlling for socioeconomic factors, Dr. Taylor said.

When Black patients present with AD, “you may not see the erythema,” said Valerie D. Callender, MD, of Howard University, Washington, who presented on AD. Instead, “you may see more follicular and papular presentations.” Erythema and erythroderma can present as shades of violet, gray, or dark brown in patients with rich skin tones, added Dr. Callender, who practices in Glenn Dale, Md.

Consequently, disease severity can be misinterpreted, she said, noting that data suggest that scoring systems such as the Eczema Area and Severity Index and Scoring Atopic Dermatitis underestimate AD severity in dark skin.

As for treatment, skin of color patients with AD are often as bothered by postinflammatory hyperpigmentation (PIH) as by active lesions, so treatment should take these concerns into account, Dr. Callender said. Studies evaluating the effectiveness of AD treatments in diverse populations are limited by lack of representation of racial groups in clinical trials and lack of subset analyses by race.
 

Acne awareness

An important consideration of acne in skin of color patients is that the acne “might not be red, it might just be darker,” said Andrew F. Alexis, MD, vice-chair for diversity and inclusion in the department of dermatology, and professor of clinical dermatology at Weill Cornell Medicine, New York. A study published in JAMA Dermatology of nearly 30,000 patients with acne from 2007 to 2017 found that non-Hispanic Black patients were more likely than non-Hispanic White patients to see a dermatologist for acne, but Black patients received fewer prescriptions for acne medications than White patients.

The study also showed that Black patients who received prescriptions for acne were more likely to receive topical retinoids and topical antibiotics, and less likely to receive oral antibiotics, spironolactone, or isotretinoin, compared with White patients. Similarly, Asian patients were more likely to receive topical antibiotics and less likely to receive oral antibiotics, compared with White patients.

Other panelists shared some of their best practices for acne in patients with skin of color, including treatment with topical retinoids (for inflammation) and spironolactone, and therapies that address both inflammation and pigmentation, such as salicylic acid and azelaic acid. Dr. Callender also advised asking patients about makeup, as they may not know that many types of makeup used to cover acne are in fact comedogenic.
 

Melanoma misconceptions

One of the most common misperceptions about melanoma among skin of color patients is that they don’t think they can get it, Dr. Taylor said. Many health care providers don’t think about melanoma in skin of color patients because of the dramatically lower incidence in this population, but as a result, cases may go undiagnosed, and as studies have shown, the mortality rate from melanoma is higher in Black patients.

Consider the palms, soles, nails, and web spaces as possible melanoma sites, Dr. Taylor added.

Educating skin of color patients about melanoma is important, although the incidence is 20 to 30 times lower than in non-Hispanic Whites, said Nada Elbuluk, MD, the founder and director of the University of Southern California Skin of Color Center and Pigmentary Disorders Clinic, Los Angeles. A 2020 editorial published in Cancer Cytopathology pointed out that 1 in 3 Black men or women with a melanoma diagnosis in the United States dies of the disease, compared with 1 in 7 non-Hispanic White men and 1 in 11 non-Hispanic White women with melanoma.

Don’t skip the total body skin exam in these patients, Dr. Elbuluk emphasized. Many patients will only partially undress, and areas such as toes can be missed.
 

Rosacea review

For patients with skin of color, clinicians need to look for different signs of rosacea than those typically seen in White patients, Dr. Elbuluk said. “The most common presentation of rosacea in skin of color is papulopustular,” and the granulomatous variant.

“These patients will often give you a history of sensitivity to products,” Dr. Elbuluk noted. They may not always have the flushing, but they may report warmth or itching, in addition to product sensitivity.

When considering rosacea in skin of color patients, be sure to have good lighting for close examination, as skin thickening is another subtle sign of rosacea in these patients, she said. Skin thickening “is a very early sign that will present in skin of color with no erythema, so keep that in mind.”

Stinging and burning sensations may be reported by skin of color patients with rosacea. Use patient history to confirm the diagnosis of rosacea, which is often delayed in skin of color patients because of a low index of suspicion, she said.

Psoriasis pointers

Psoriasis in skin of color patients used to be considered rare, “but that is far from true,” Dr. Alexis said. In fact, many cases of psoriasis are undiagnosed or the diagnosis is delayed in these patients.

The panelists noted that current guidelines for psoriasis treatment are based on clinical trials composed mainly of White patients, and do not contain specific recommendations for skin of color patients.

Notably, the morphology, location, and color of psoriasis lesions may be different for patients with darker skin, such as thicker plaques and more scaling over larger areas, they said. Also, skin of color patients may experience long-lasting dyspigmentation from psoriasis lesions that have resolved.

When developing a strategy for psoriasis in skin of color patients, consider not only disease severity, but also comorbidities and medications, response (if any) to prior therapies, patient preferences, and quality of life, the panelists said.

Dr. Callender, Dr. Elbuluk, Dr. Taylor, and Dr. Alexis reported conflicts of interest from numerous sources in industry. MedscapeLive and this news organization are owned by the same parent company.

LAS VEGAS – Disparities in the diagnosis and treatment of skin of color can stem from incorrect diagnoses and lack of knowledge on the part of clinicians, and also from knowledge gaps on the part of other health care providers and patients, Susan C. Taylor, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

Additionally, some disparities occur because of gaps in access to health care, said Dr. Taylor, vice chair, diversity, equity and inclusion, in the department of dermatology at the University of Pennsylvania, Philadelphia, who moderated an expert panel discussion of treatment tips for several common dermatologic conditions in skin of color patients.

Atopic dermatitis angles

Atopic dermatitis (AD) is the fourth most common dermatologic complaint in Black patients, based on data from the United States National Ambulatory Medical Care Survey. Also, data from the National Health and Nutrition Examination Survey show that Black children are nearly twice as likely as White children to develop AD after controlling for socioeconomic factors, Dr. Taylor said.

When Black patients present with AD, “you may not see the erythema,” said Valerie D. Callender, MD, of Howard University, Washington, who presented on AD. Instead, “you may see more follicular and papular presentations.” Erythema and erythroderma can present as shades of violet, gray, or dark brown in patients with rich skin tones, added Dr. Callender, who practices in Glenn Dale, Md.

Consequently, disease severity can be misinterpreted, she said, noting that data suggest that scoring systems such as the Eczema Area and Severity Index and Scoring Atopic Dermatitis underestimate AD severity in dark skin.

As for treatment, skin of color patients with AD are often as bothered by postinflammatory hyperpigmentation (PIH) as by active lesions, so treatment should take these concerns into account, Dr. Callender said. Studies evaluating the effectiveness of AD treatments in diverse populations are limited by lack of representation of racial groups in clinical trials and lack of subset analyses by race.
 

Acne awareness

An important consideration of acne in skin of color patients is that the acne “might not be red, it might just be darker,” said Andrew F. Alexis, MD, vice-chair for diversity and inclusion in the department of dermatology, and professor of clinical dermatology at Weill Cornell Medicine, New York. A study published in JAMA Dermatology of nearly 30,000 patients with acne from 2007 to 2017 found that non-Hispanic Black patients were more likely than non-Hispanic White patients to see a dermatologist for acne, but Black patients received fewer prescriptions for acne medications than White patients.

The study also showed that Black patients who received prescriptions for acne were more likely to receive topical retinoids and topical antibiotics, and less likely to receive oral antibiotics, spironolactone, or isotretinoin, compared with White patients. Similarly, Asian patients were more likely to receive topical antibiotics and less likely to receive oral antibiotics, compared with White patients.

Other panelists shared some of their best practices for acne in patients with skin of color, including treatment with topical retinoids (for inflammation) and spironolactone, and therapies that address both inflammation and pigmentation, such as salicylic acid and azelaic acid. Dr. Callender also advised asking patients about makeup, as they may not know that many types of makeup used to cover acne are in fact comedogenic.
 

Melanoma misconceptions

One of the most common misperceptions about melanoma among skin of color patients is that they don’t think they can get it, Dr. Taylor said. Many health care providers don’t think about melanoma in skin of color patients because of the dramatically lower incidence in this population, but as a result, cases may go undiagnosed, and as studies have shown, the mortality rate from melanoma is higher in Black patients.

Consider the palms, soles, nails, and web spaces as possible melanoma sites, Dr. Taylor added.

Educating skin of color patients about melanoma is important, although the incidence is 20 to 30 times lower than in non-Hispanic Whites, said Nada Elbuluk, MD, the founder and director of the University of Southern California Skin of Color Center and Pigmentary Disorders Clinic, Los Angeles. A 2020 editorial published in Cancer Cytopathology pointed out that 1 in 3 Black men or women with a melanoma diagnosis in the United States dies of the disease, compared with 1 in 7 non-Hispanic White men and 1 in 11 non-Hispanic White women with melanoma.

Don’t skip the total body skin exam in these patients, Dr. Elbuluk emphasized. Many patients will only partially undress, and areas such as toes can be missed.
 

Rosacea review

For patients with skin of color, clinicians need to look for different signs of rosacea than those typically seen in White patients, Dr. Elbuluk said. “The most common presentation of rosacea in skin of color is papulopustular,” and the granulomatous variant.

“These patients will often give you a history of sensitivity to products,” Dr. Elbuluk noted. They may not always have the flushing, but they may report warmth or itching, in addition to product sensitivity.

When considering rosacea in skin of color patients, be sure to have good lighting for close examination, as skin thickening is another subtle sign of rosacea in these patients, she said. Skin thickening “is a very early sign that will present in skin of color with no erythema, so keep that in mind.”

Stinging and burning sensations may be reported by skin of color patients with rosacea. Use patient history to confirm the diagnosis of rosacea, which is often delayed in skin of color patients because of a low index of suspicion, she said.

Psoriasis pointers

Psoriasis in skin of color patients used to be considered rare, “but that is far from true,” Dr. Alexis said. In fact, many cases of psoriasis are undiagnosed or the diagnosis is delayed in these patients.

The panelists noted that current guidelines for psoriasis treatment are based on clinical trials composed mainly of White patients, and do not contain specific recommendations for skin of color patients.

Notably, the morphology, location, and color of psoriasis lesions may be different for patients with darker skin, such as thicker plaques and more scaling over larger areas, they said. Also, skin of color patients may experience long-lasting dyspigmentation from psoriasis lesions that have resolved.

When developing a strategy for psoriasis in skin of color patients, consider not only disease severity, but also comorbidities and medications, response (if any) to prior therapies, patient preferences, and quality of life, the panelists said.

Dr. Callender, Dr. Elbuluk, Dr. Taylor, and Dr. Alexis reported conflicts of interest from numerous sources in industry. MedscapeLive and this news organization are owned by the same parent company.

Competition between five biologic drugs and their skinny-label biosimilars saved Medicare an estimated $1.5 billion during 2015-2020. But these savings accruing to Medicare and the availability of those and other biosimilars through skinny labeling is under threat from recent court rulings, according to a research letter published online in JAMA Internal Medicine.

The authors highlighted the need for such savings by noting that, while biologics comprise less than 5% of prescription drug use, their price tag amounts to about 40% of U.S. drug spending, Biologic manufacturers often delay the availability of biosimilars for additional years beyond the original patent expiration through further patents for supplemental indications. To provide a counterbalance, federal law allows the Food and Drug Administration to approve “skinny-label” generics and biosimilars that carve out patent-protected indications or regulatory exclusivities. But once a generic drug reaches the market through this process with a skinny label, it may often be substituted for indications that go beyond the ones listed on the skinny label. In fact, some state laws mandate that pharmacists substitute interchangeable generics for brand-name drugs, helping to decrease drug prices. In response to legal threats to the skinny-label pathway, Alexander C. Egilman and colleagues at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, assessed the frequency of approval and marketing of skinny-label biosimilars from 2015 to 2021 and the resultant savings to Medicare.

TheaDesign/Thinkstock

The authors estimated annual Part B (clinician-administered) savings from skinny-label biosimilars through 2020 by comparing actual biologic and skinny-label biosimilar spending with estimated biologic spending without competition using the Medicare Dashboard. They assumed that the unit price of the biologic would increase at its 5-year compound annual growth rate prior to competition.

In that period, the FDA approved 33 biosimilars linked to 11 biologics. Among them, 22 (66.7%) had a skinny label. Of 21 biosimilars marketed before 2022, 13 (61.9%) were launched with a skinny label. Of the 8 biologics linked to these 21 biosimilars, 5 of the first-to-market biosimilars had skinny labels (bevacizumab, filgrastim, infliximab, pegfilgrastim, and rituximab), leading to earlier competition through 2021.

The estimated $1.5 billion in savings to Medicare from these skinny-label biosimilars over the 2015-2020 span represents 4.9% of the $30.2 billion that Medicare spent on the five biologics during this period. The researchers pointed out that once adalimumab (Humira) faces skinny-label biosimilar competition in 2023, savings will likely grow substantially.

In response to the research letter, an editor’s note by JAMA Internal Medicine Editorial Fellow Eric Ward, MD, and JAMA Internal Medicine Editor at Large and Online Editor Robert Steinbrook, MD, stated that, between 2015 and 2019, 24 (43%) of 56 brand-name drugs had competition from skinny-labeled generic formulations after first becoming available as generics.

The editors also referenced a JAMA Viewpoints article from 2021 that reviewed the most recent case challenging the skinny-label pathway in which GlaxoSmithKline sued Teva for its marketing of a skinny-label generic of the brand-name beta-blocker carvedilol (Coreg) that the plaintive claimed “induced physicians to prescribe carvedilol for indications that had been carved out by Teva’s skinny label, thus infringing GlaxoSmithKline’s patents.” A $235 million judgment against Teva was overturned by a district court and then reversed again by a Federal Circuit court that, after receiving criticism, reconsidered the case, and a panel affirmed the judgment against Teva.

“The Federal Circuit panel’s decision has the potential to put generic drugs that fail to adequately carve out indications from the brand name labeling at risk for damages related to infringement,” the authors wrote. Similar claims of infringement are being heard in other courts, they wrote, and they urged careful targeting of skinny-label carveouts, and suggest also that challenges to the arguments used against Teva focus on preservation of First Amendment rights as protection for lawful and accurate speech in drug labels.

“The legal uncertainties are likely to continue, as manufacturers pursue novel and complex strategies to protect the patents and regulatory exclusivities of brand-name drugs and biologics,” Dr. Ward and Dr. Steinbrook wrote, adding that “the path forward is for Congress to enact additional legislation that reaffirms and strengthens the permissibility of skinny labeling.”

The research letter’s corresponding author, Ameet Sarpatwari, PhD, JD, assistant professor at Harvard Medical School, and assistant director for the Harvard Program On Regulation, Therapeutics, And Law, echoed concerns over the Teva case in an interview. “There has certainly been concern that should the appellate decision stand, there will be a chilling effect. As the lone dissenter in that case noted, ‘no skinny-label generic is safe.’ I think many generic and biosimilar manufacturers are awaiting to see whether the Supreme Court will take the case.”

He added: “I do not believe the likelihood of skinny-label-supportive legislation making it through Congress will be greatly diminished in a divided Congress. Democrats and Republicans alike should seek to promote competition in the marketplace, which is what the skinny-labeling pathway accomplishes.”

The authors reported no relevant conflicts of interest. The research was funded by a grant from Arnold Ventures.

Competition between five biologic drugs and their skinny-label biosimilars saved Medicare an estimated $1.5 billion during 2015-2020. But these savings accruing to Medicare and the availability of those and other biosimilars through skinny labeling is under threat from recent court rulings, according to a research letter published online in JAMA Internal Medicine.

The authors highlighted the need for such savings by noting that, while biologics comprise less than 5% of prescription drug use, their price tag amounts to about 40% of U.S. drug spending, Biologic manufacturers often delay the availability of biosimilars for additional years beyond the original patent expiration through further patents for supplemental indications. To provide a counterbalance, federal law allows the Food and Drug Administration to approve “skinny-label” generics and biosimilars that carve out patent-protected indications or regulatory exclusivities. But once a generic drug reaches the market through this process with a skinny label, it may often be substituted for indications that go beyond the ones listed on the skinny label. In fact, some state laws mandate that pharmacists substitute interchangeable generics for brand-name drugs, helping to decrease drug prices. In response to legal threats to the skinny-label pathway, Alexander C. Egilman and colleagues at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, assessed the frequency of approval and marketing of skinny-label biosimilars from 2015 to 2021 and the resultant savings to Medicare.

TheaDesign/Thinkstock

The authors estimated annual Part B (clinician-administered) savings from skinny-label biosimilars through 2020 by comparing actual biologic and skinny-label biosimilar spending with estimated biologic spending without competition using the Medicare Dashboard. They assumed that the unit price of the biologic would increase at its 5-year compound annual growth rate prior to competition.

In that period, the FDA approved 33 biosimilars linked to 11 biologics. Among them, 22 (66.7%) had a skinny label. Of 21 biosimilars marketed before 2022, 13 (61.9%) were launched with a skinny label. Of the 8 biologics linked to these 21 biosimilars, 5 of the first-to-market biosimilars had skinny labels (bevacizumab, filgrastim, infliximab, pegfilgrastim, and rituximab), leading to earlier competition through 2021.

The estimated $1.5 billion in savings to Medicare from these skinny-label biosimilars over the 2015-2020 span represents 4.9% of the $30.2 billion that Medicare spent on the five biologics during this period. The researchers pointed out that once adalimumab (Humira) faces skinny-label biosimilar competition in 2023, savings will likely grow substantially.

In response to the research letter, an editor’s note by JAMA Internal Medicine Editorial Fellow Eric Ward, MD, and JAMA Internal Medicine Editor at Large and Online Editor Robert Steinbrook, MD, stated that, between 2015 and 2019, 24 (43%) of 56 brand-name drugs had competition from skinny-labeled generic formulations after first becoming available as generics.

The editors also referenced a JAMA Viewpoints article from 2021 that reviewed the most recent case challenging the skinny-label pathway in which GlaxoSmithKline sued Teva for its marketing of a skinny-label generic of the brand-name beta-blocker carvedilol (Coreg) that the plaintive claimed “induced physicians to prescribe carvedilol for indications that had been carved out by Teva’s skinny label, thus infringing GlaxoSmithKline’s patents.” A $235 million judgment against Teva was overturned by a district court and then reversed again by a Federal Circuit court that, after receiving criticism, reconsidered the case, and a panel affirmed the judgment against Teva.

“The Federal Circuit panel’s decision has the potential to put generic drugs that fail to adequately carve out indications from the brand name labeling at risk for damages related to infringement,” the authors wrote. Similar claims of infringement are being heard in other courts, they wrote, and they urged careful targeting of skinny-label carveouts, and suggest also that challenges to the arguments used against Teva focus on preservation of First Amendment rights as protection for lawful and accurate speech in drug labels.

“The legal uncertainties are likely to continue, as manufacturers pursue novel and complex strategies to protect the patents and regulatory exclusivities of brand-name drugs and biologics,” Dr. Ward and Dr. Steinbrook wrote, adding that “the path forward is for Congress to enact additional legislation that reaffirms and strengthens the permissibility of skinny labeling.”

The research letter’s corresponding author, Ameet Sarpatwari, PhD, JD, assistant professor at Harvard Medical School, and assistant director for the Harvard Program On Regulation, Therapeutics, And Law, echoed concerns over the Teva case in an interview. “There has certainly been concern that should the appellate decision stand, there will be a chilling effect. As the lone dissenter in that case noted, ‘no skinny-label generic is safe.’ I think many generic and biosimilar manufacturers are awaiting to see whether the Supreme Court will take the case.”

He added: “I do not believe the likelihood of skinny-label-supportive legislation making it through Congress will be greatly diminished in a divided Congress. Democrats and Republicans alike should seek to promote competition in the marketplace, which is what the skinny-labeling pathway accomplishes.”

The authors reported no relevant conflicts of interest. The research was funded by a grant from Arnold Ventures.

Competition between five biologic drugs and their skinny-label biosimilars saved Medicare an estimated $1.5 billion during 2015-2020. But these savings accruing to Medicare and the availability of those and other biosimilars through skinny labeling is under threat from recent court rulings, according to a research letter published online in JAMA Internal Medicine.

The authors highlighted the need for such savings by noting that, while biologics comprise less than 5% of prescription drug use, their price tag amounts to about 40% of U.S. drug spending, Biologic manufacturers often delay the availability of biosimilars for additional years beyond the original patent expiration through further patents for supplemental indications. To provide a counterbalance, federal law allows the Food and Drug Administration to approve “skinny-label” generics and biosimilars that carve out patent-protected indications or regulatory exclusivities. But once a generic drug reaches the market through this process with a skinny label, it may often be substituted for indications that go beyond the ones listed on the skinny label. In fact, some state laws mandate that pharmacists substitute interchangeable generics for brand-name drugs, helping to decrease drug prices. In response to legal threats to the skinny-label pathway, Alexander C. Egilman and colleagues at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, assessed the frequency of approval and marketing of skinny-label biosimilars from 2015 to 2021 and the resultant savings to Medicare.

TheaDesign/Thinkstock

The authors estimated annual Part B (clinician-administered) savings from skinny-label biosimilars through 2020 by comparing actual biologic and skinny-label biosimilar spending with estimated biologic spending without competition using the Medicare Dashboard. They assumed that the unit price of the biologic would increase at its 5-year compound annual growth rate prior to competition.

In that period, the FDA approved 33 biosimilars linked to 11 biologics. Among them, 22 (66.7%) had a skinny label. Of 21 biosimilars marketed before 2022, 13 (61.9%) were launched with a skinny label. Of the 8 biologics linked to these 21 biosimilars, 5 of the first-to-market biosimilars had skinny labels (bevacizumab, filgrastim, infliximab, pegfilgrastim, and rituximab), leading to earlier competition through 2021.

The estimated $1.5 billion in savings to Medicare from these skinny-label biosimilars over the 2015-2020 span represents 4.9% of the $30.2 billion that Medicare spent on the five biologics during this period. The researchers pointed out that once adalimumab (Humira) faces skinny-label biosimilar competition in 2023, savings will likely grow substantially.

In response to the research letter, an editor’s note by JAMA Internal Medicine Editorial Fellow Eric Ward, MD, and JAMA Internal Medicine Editor at Large and Online Editor Robert Steinbrook, MD, stated that, between 2015 and 2019, 24 (43%) of 56 brand-name drugs had competition from skinny-labeled generic formulations after first becoming available as generics.

The editors also referenced a JAMA Viewpoints article from 2021 that reviewed the most recent case challenging the skinny-label pathway in which GlaxoSmithKline sued Teva for its marketing of a skinny-label generic of the brand-name beta-blocker carvedilol (Coreg) that the plaintive claimed “induced physicians to prescribe carvedilol for indications that had been carved out by Teva’s skinny label, thus infringing GlaxoSmithKline’s patents.” A $235 million judgment against Teva was overturned by a district court and then reversed again by a Federal Circuit court that, after receiving criticism, reconsidered the case, and a panel affirmed the judgment against Teva.

“The Federal Circuit panel’s decision has the potential to put generic drugs that fail to adequately carve out indications from the brand name labeling at risk for damages related to infringement,” the authors wrote. Similar claims of infringement are being heard in other courts, they wrote, and they urged careful targeting of skinny-label carveouts, and suggest also that challenges to the arguments used against Teva focus on preservation of First Amendment rights as protection for lawful and accurate speech in drug labels.

“The legal uncertainties are likely to continue, as manufacturers pursue novel and complex strategies to protect the patents and regulatory exclusivities of brand-name drugs and biologics,” Dr. Ward and Dr. Steinbrook wrote, adding that “the path forward is for Congress to enact additional legislation that reaffirms and strengthens the permissibility of skinny labeling.”

The research letter’s corresponding author, Ameet Sarpatwari, PhD, JD, assistant professor at Harvard Medical School, and assistant director for the Harvard Program On Regulation, Therapeutics, And Law, echoed concerns over the Teva case in an interview. “There has certainly been concern that should the appellate decision stand, there will be a chilling effect. As the lone dissenter in that case noted, ‘no skinny-label generic is safe.’ I think many generic and biosimilar manufacturers are awaiting to see whether the Supreme Court will take the case.”

He added: “I do not believe the likelihood of skinny-label-supportive legislation making it through Congress will be greatly diminished in a divided Congress. Democrats and Republicans alike should seek to promote competition in the marketplace, which is what the skinny-labeling pathway accomplishes.”

The authors reported no relevant conflicts of interest. The research was funded by a grant from Arnold Ventures.

To the Editor:

The Moderna COVID-19 messenger RNA (mRNA) vaccine was authorized for use on December 18, 2020, with the second dose beginning on January 15, 2021.^1-3 Some individuals who received the Moderna vaccine experienced an intense rash known as “COVID arm,” a harmless but bothersome adverse effect that typically appears within a week and is a localized and transient immunogenic response.⁴ COVID arm differs from most vaccine adverse effects. The rash emerges not immediately but 5 to 9 days after the initial dose—on average, 1 week later. Apart from being itchy, the rash does not appear to be harmful and is not a reason to hesitate getting vaccinated.

Dermatologists and allergists have been studying this adverse effect, which has been formally termed delayed cutaneous hypersensitivity. Of potential clinical consequence is that the efficacy of the mRNA COVID-19 vaccine may be harmed if postvaccination dermal reactions necessitate systemic corticosteroid therapy. Because this vaccine stimulates an immune response as viral RNA integrates in cells secondary to production of the spike protein of the virus, the skin may be affected secondarily and manifestations of any underlying disease may be aggravated.⁵ We report a patient who developed a psoriasiform dermatitis after the first dose of the Moderna vaccine.

A 65-year-old woman presented to her primary care physician because of the severity of psoriasiform dermatitis that developed 5 days after she received the first dose of the Moderna COVID-19 mRNA vaccine. The patient had a medical history of Sjögren syndrome. Her medication history was negative, and her family history was negative for autoimmune disease. Physical examination by primary care revealed an erythematous scaly rash with plaques and papules on the neck and back (Figure 1). The patient presented again to primary care 2 days later with swollen, painful, discolored digits (Figure 2) and a stiff, sore neck.

Laboratory results were positive for anti–Sjögren syndrome–related antigens A and B. A complete blood cell count; comprehensive metabolic panel; erythrocyte sedimentation rate; and assays of rheumatoid factor, C-reactive protein, and anti–cyclic citrullinated peptide were within reference range. A biopsy of a lesion on the back showed psoriasiform dermatitis with confluent parakeratosis and scattered necrotic keratinocytes. There was superficial perivascular inflammation with rare eosinophils (Figure 3).

The patient was treated with a course of systemic corticosteroids. The rash resolved in 1 week. She did not receive the second dose due to the rash.

Two mRNA COVID-19 vaccines—Pfizer BioNTech and Moderna—have been granted emergency use authorization by the US Food and Drug Administration.⁶ The safety profile of the mRNA-1273 vaccine for the median 2-month follow-up showed no safety concerns.³ Minor localized adverse effects (eg, pain, redness, swelling) have been observed more frequently with the vaccines than with placebo. Systemic symptoms, such as fever, fatigue, headache, and muscle and joint pain, also were seen somewhat more often with the vaccines than with placebo; most such effects occurred 24 to 48 hours after vaccination.^3,6,7 The frequency of unsolicited adverse events and serious adverse events reported during the 28-day period after vaccination generally was similar among participants in the vaccine and placebo groups.³

There are 2 types of reactions to COVID-19 vaccination: immediate and delayed. Immediate reactions usually are due to anaphylaxis, requiring prompt recognition and treatment with epinephrine to stop rapid progression of life-threatening symptoms. Delayed reactions include localized reactions, such as urticaria and benign exanthema; serum sickness and serum sickness–like reactions; fever; and rare skin, organ, and neurologic sequelae.^1,6-8

Cutaneous manifestations, present in 16% to 50% of patients with Sjögren syndrome, are considered one of the most common extraglandular presentations of the syndrome. They are classified as nonvascular (eg, xerosis, angular cheilitis, eyelid dermatitis, annular erythema) and vascular (eg, Raynaud phenomenon, vasculitis).^9-11 Our patient did not have any of those findings. She had not taken any medications before the rash appeared, thereby ruling out a drug reaction.

The differential for our patient included post–urinary tract infection immune-reactive arthritis and rash, which is not typical with Escherichia coli infection but is described with infection with Chlamydia species and Salmonella species. Moreover, post–urinary tract infection immune-reactive arthritis and rash appear mostly on the palms and soles. Systemic lupus erythematosus–like rashes have a different histology and appear on sun-exposed areas; our patient’s rash was found mainly on unexposed areas.¹²

Because our patient received the Moderna vaccine 5 days before the rash appeared and later developed swelling of the digits with morning stiffness, a delayed serum sickness–like reaction secondary to COVID-19 vaccination was possible.^3,6

COVID-19 mRNA vaccines developed by Pfizer-BioNTech and Moderna incorporate a lipid-based nanoparticle carrier system that prevents rapid enzymatic degradation of mRNA and facilitates in vivo delivery of mRNA. This lipid-based nanoparticle carrier system is further stabilized by a polyethylene glycol 2000 lipid conjugate that provides a hydrophilic layer, thus prolonging half-life. The presence of lipid polyethylene glycol 2000 in mRNA vaccines has led to concern that this component could be implicated in anaphylaxis.⁶

COVID-19 antigens can give rise to varying clinical manifestations that are directly related to viral tissue damage or are indirectly induced by the antiviral immune response.^13,14 Hyperactivation of the immune system to eradicate COVID-19 may trigger autoimmunity; several immune-mediated disorders have been described in individuals infected with SARS-CoV-2. Dermal manifestations include cutaneous rash and vasculitis.^13-16 Crucial immunologic steps occur during SARS-CoV-2 infection that may link autoimmunity to COVID-19.^13,14 In preliminary published data on the efficacy of the Moderna vaccine on 45 trial enrollees, 3 did not receive the second dose of vaccination, including 1 who developed urticaria on both legs 5 days after the first dose.¹

Introduction of viral RNA can induce autoimmunity that can be explained by various phenomena, including epitope spreading, molecular mimicry, cryptic antigen, and bystander activation. Remarkably, more than one-third of immunogenic proteins in SARS-CoV-2 have potentially problematic homology to proteins that are key to the human adaptive immune system.⁵

Moreover, SARS-CoV-2 seems to induce organ injury through alternative mechanisms beyond direct viral infection, including immunologic injury. In some situations, hyperactivation of the immune response to SARS-CoV-2 RNA can result in autoimmune disease. COVID-19 has been associated with immune-mediated systemic or organ-selective manifestations, some of which fulfill the diagnostic or classification criteria of specific autoimmune diseases. It is unclear whether those medical disorders are the result of transitory postinfectious epiphenomena.⁵

A few studies have shown that patients with rheumatic disease have an incidence and prevalence of COVID-19 that is similar to the general population. A similar pattern has been detected in COVID-19 morbidity and mortality rates, even among patients with an autoimmune disease, such as rheumatoid arthritis and Sjögren syndrome.^5,17 Furthermore, exacerbation of preexisting rheumatic symptoms may be due to hyperactivation of antiviral pathways in a person with an autoimmune disease.^17-19 The findings in our patient suggested a direct role for the vaccine in skin manifestations, rather than for reactivation or development of new systemic autoimmune processes, such as systemic lupus erythematosus.

Exacerbation of psoriasis following COVID-19 vaccination has been described²⁰; however, the case patient did not have a history of psoriasis. The mechanism(s) of such exacerbation remain unclear; COVID-19 vaccine–induced helper T cells (T_H17) may play a role.²¹ Other skin manifestations encountered following COVID-19 vaccination include lichen planus, leukocytoclastic vasculitic rash, erythema multiforme–like rash, and pityriasis rosea–like rash.^22-25 The immune mechanisms of these manifestations remain unclear.

The clinical presentation of delayed vaccination reactions can be attributed to the timing of symptoms and, in this case, the immune-mediated background of a psoriasiform reaction. Although adverse reactions to the SARS-CoV-2 mRNA vaccine are rare, more individuals should be studied after vaccination to confirm and better understand this phenomenon.

To the Editor:

The Moderna COVID-19 messenger RNA (mRNA) vaccine was authorized for use on December 18, 2020, with the second dose beginning on January 15, 2021.^1-3 Some individuals who received the Moderna vaccine experienced an intense rash known as “COVID arm,” a harmless but bothersome adverse effect that typically appears within a week and is a localized and transient immunogenic response.⁴ COVID arm differs from most vaccine adverse effects. The rash emerges not immediately but 5 to 9 days after the initial dose—on average, 1 week later. Apart from being itchy, the rash does not appear to be harmful and is not a reason to hesitate getting vaccinated.

Dermatologists and allergists have been studying this adverse effect, which has been formally termed delayed cutaneous hypersensitivity. Of potential clinical consequence is that the efficacy of the mRNA COVID-19 vaccine may be harmed if postvaccination dermal reactions necessitate systemic corticosteroid therapy. Because this vaccine stimulates an immune response as viral RNA integrates in cells secondary to production of the spike protein of the virus, the skin may be affected secondarily and manifestations of any underlying disease may be aggravated.⁵ We report a patient who developed a psoriasiform dermatitis after the first dose of the Moderna vaccine.

A 65-year-old woman presented to her primary care physician because of the severity of psoriasiform dermatitis that developed 5 days after she received the first dose of the Moderna COVID-19 mRNA vaccine. The patient had a medical history of Sjögren syndrome. Her medication history was negative, and her family history was negative for autoimmune disease. Physical examination by primary care revealed an erythematous scaly rash with plaques and papules on the neck and back (Figure 1). The patient presented again to primary care 2 days later with swollen, painful, discolored digits (Figure 2) and a stiff, sore neck.

Laboratory results were positive for anti–Sjögren syndrome–related antigens A and B. A complete blood cell count; comprehensive metabolic panel; erythrocyte sedimentation rate; and assays of rheumatoid factor, C-reactive protein, and anti–cyclic citrullinated peptide were within reference range. A biopsy of a lesion on the back showed psoriasiform dermatitis with confluent parakeratosis and scattered necrotic keratinocytes. There was superficial perivascular inflammation with rare eosinophils (Figure 3).

The patient was treated with a course of systemic corticosteroids. The rash resolved in 1 week. She did not receive the second dose due to the rash.

Two mRNA COVID-19 vaccines—Pfizer BioNTech and Moderna—have been granted emergency use authorization by the US Food and Drug Administration.⁶ The safety profile of the mRNA-1273 vaccine for the median 2-month follow-up showed no safety concerns.³ Minor localized adverse effects (eg, pain, redness, swelling) have been observed more frequently with the vaccines than with placebo. Systemic symptoms, such as fever, fatigue, headache, and muscle and joint pain, also were seen somewhat more often with the vaccines than with placebo; most such effects occurred 24 to 48 hours after vaccination.^3,6,7 The frequency of unsolicited adverse events and serious adverse events reported during the 28-day period after vaccination generally was similar among participants in the vaccine and placebo groups.³

There are 2 types of reactions to COVID-19 vaccination: immediate and delayed. Immediate reactions usually are due to anaphylaxis, requiring prompt recognition and treatment with epinephrine to stop rapid progression of life-threatening symptoms. Delayed reactions include localized reactions, such as urticaria and benign exanthema; serum sickness and serum sickness–like reactions; fever; and rare skin, organ, and neurologic sequelae.^1,6-8

Cutaneous manifestations, present in 16% to 50% of patients with Sjögren syndrome, are considered one of the most common extraglandular presentations of the syndrome. They are classified as nonvascular (eg, xerosis, angular cheilitis, eyelid dermatitis, annular erythema) and vascular (eg, Raynaud phenomenon, vasculitis).^9-11 Our patient did not have any of those findings. She had not taken any medications before the rash appeared, thereby ruling out a drug reaction.

The differential for our patient included post–urinary tract infection immune-reactive arthritis and rash, which is not typical with Escherichia coli infection but is described with infection with Chlamydia species and Salmonella species. Moreover, post–urinary tract infection immune-reactive arthritis and rash appear mostly on the palms and soles. Systemic lupus erythematosus–like rashes have a different histology and appear on sun-exposed areas; our patient’s rash was found mainly on unexposed areas.¹²

Because our patient received the Moderna vaccine 5 days before the rash appeared and later developed swelling of the digits with morning stiffness, a delayed serum sickness–like reaction secondary to COVID-19 vaccination was possible.^3,6

COVID-19 mRNA vaccines developed by Pfizer-BioNTech and Moderna incorporate a lipid-based nanoparticle carrier system that prevents rapid enzymatic degradation of mRNA and facilitates in vivo delivery of mRNA. This lipid-based nanoparticle carrier system is further stabilized by a polyethylene glycol 2000 lipid conjugate that provides a hydrophilic layer, thus prolonging half-life. The presence of lipid polyethylene glycol 2000 in mRNA vaccines has led to concern that this component could be implicated in anaphylaxis.⁶

COVID-19 antigens can give rise to varying clinical manifestations that are directly related to viral tissue damage or are indirectly induced by the antiviral immune response.^13,14 Hyperactivation of the immune system to eradicate COVID-19 may trigger autoimmunity; several immune-mediated disorders have been described in individuals infected with SARS-CoV-2. Dermal manifestations include cutaneous rash and vasculitis.^13-16 Crucial immunologic steps occur during SARS-CoV-2 infection that may link autoimmunity to COVID-19.^13,14 In preliminary published data on the efficacy of the Moderna vaccine on 45 trial enrollees, 3 did not receive the second dose of vaccination, including 1 who developed urticaria on both legs 5 days after the first dose.¹

Introduction of viral RNA can induce autoimmunity that can be explained by various phenomena, including epitope spreading, molecular mimicry, cryptic antigen, and bystander activation. Remarkably, more than one-third of immunogenic proteins in SARS-CoV-2 have potentially problematic homology to proteins that are key to the human adaptive immune system.⁵

Moreover, SARS-CoV-2 seems to induce organ injury through alternative mechanisms beyond direct viral infection, including immunologic injury. In some situations, hyperactivation of the immune response to SARS-CoV-2 RNA can result in autoimmune disease. COVID-19 has been associated with immune-mediated systemic or organ-selective manifestations, some of which fulfill the diagnostic or classification criteria of specific autoimmune diseases. It is unclear whether those medical disorders are the result of transitory postinfectious epiphenomena.⁵

A few studies have shown that patients with rheumatic disease have an incidence and prevalence of COVID-19 that is similar to the general population. A similar pattern has been detected in COVID-19 morbidity and mortality rates, even among patients with an autoimmune disease, such as rheumatoid arthritis and Sjögren syndrome.^5,17 Furthermore, exacerbation of preexisting rheumatic symptoms may be due to hyperactivation of antiviral pathways in a person with an autoimmune disease.^17-19 The findings in our patient suggested a direct role for the vaccine in skin manifestations, rather than for reactivation or development of new systemic autoimmune processes, such as systemic lupus erythematosus.

Exacerbation of psoriasis following COVID-19 vaccination has been described²⁰; however, the case patient did not have a history of psoriasis. The mechanism(s) of such exacerbation remain unclear; COVID-19 vaccine–induced helper T cells (T_H17) may play a role.²¹ Other skin manifestations encountered following COVID-19 vaccination include lichen planus, leukocytoclastic vasculitic rash, erythema multiforme–like rash, and pityriasis rosea–like rash.^22-25 The immune mechanisms of these manifestations remain unclear.

The clinical presentation of delayed vaccination reactions can be attributed to the timing of symptoms and, in this case, the immune-mediated background of a psoriasiform reaction. Although adverse reactions to the SARS-CoV-2 mRNA vaccine are rare, more individuals should be studied after vaccination to confirm and better understand this phenomenon.

To the Editor:

The Moderna COVID-19 messenger RNA (mRNA) vaccine was authorized for use on December 18, 2020, with the second dose beginning on January 15, 2021.^1-3 Some individuals who received the Moderna vaccine experienced an intense rash known as “COVID arm,” a harmless but bothersome adverse effect that typically appears within a week and is a localized and transient immunogenic response.⁴ COVID arm differs from most vaccine adverse effects. The rash emerges not immediately but 5 to 9 days after the initial dose—on average, 1 week later. Apart from being itchy, the rash does not appear to be harmful and is not a reason to hesitate getting vaccinated.

Dermatologists and allergists have been studying this adverse effect, which has been formally termed delayed cutaneous hypersensitivity. Of potential clinical consequence is that the efficacy of the mRNA COVID-19 vaccine may be harmed if postvaccination dermal reactions necessitate systemic corticosteroid therapy. Because this vaccine stimulates an immune response as viral RNA integrates in cells secondary to production of the spike protein of the virus, the skin may be affected secondarily and manifestations of any underlying disease may be aggravated.⁵ We report a patient who developed a psoriasiform dermatitis after the first dose of the Moderna vaccine.

A 65-year-old woman presented to her primary care physician because of the severity of psoriasiform dermatitis that developed 5 days after she received the first dose of the Moderna COVID-19 mRNA vaccine. The patient had a medical history of Sjögren syndrome. Her medication history was negative, and her family history was negative for autoimmune disease. Physical examination by primary care revealed an erythematous scaly rash with plaques and papules on the neck and back (Figure 1). The patient presented again to primary care 2 days later with swollen, painful, discolored digits (Figure 2) and a stiff, sore neck.

Laboratory results were positive for anti–Sjögren syndrome–related antigens A and B. A complete blood cell count; comprehensive metabolic panel; erythrocyte sedimentation rate; and assays of rheumatoid factor, C-reactive protein, and anti–cyclic citrullinated peptide were within reference range. A biopsy of a lesion on the back showed psoriasiform dermatitis with confluent parakeratosis and scattered necrotic keratinocytes. There was superficial perivascular inflammation with rare eosinophils (Figure 3).

The patient was treated with a course of systemic corticosteroids. The rash resolved in 1 week. She did not receive the second dose due to the rash.

Two mRNA COVID-19 vaccines—Pfizer BioNTech and Moderna—have been granted emergency use authorization by the US Food and Drug Administration.⁶ The safety profile of the mRNA-1273 vaccine for the median 2-month follow-up showed no safety concerns.³ Minor localized adverse effects (eg, pain, redness, swelling) have been observed more frequently with the vaccines than with placebo. Systemic symptoms, such as fever, fatigue, headache, and muscle and joint pain, also were seen somewhat more often with the vaccines than with placebo; most such effects occurred 24 to 48 hours after vaccination.^3,6,7 The frequency of unsolicited adverse events and serious adverse events reported during the 28-day period after vaccination generally was similar among participants in the vaccine and placebo groups.³

There are 2 types of reactions to COVID-19 vaccination: immediate and delayed. Immediate reactions usually are due to anaphylaxis, requiring prompt recognition and treatment with epinephrine to stop rapid progression of life-threatening symptoms. Delayed reactions include localized reactions, such as urticaria and benign exanthema; serum sickness and serum sickness–like reactions; fever; and rare skin, organ, and neurologic sequelae.^1,6-8

Cutaneous manifestations, present in 16% to 50% of patients with Sjögren syndrome, are considered one of the most common extraglandular presentations of the syndrome. They are classified as nonvascular (eg, xerosis, angular cheilitis, eyelid dermatitis, annular erythema) and vascular (eg, Raynaud phenomenon, vasculitis).^9-11 Our patient did not have any of those findings. She had not taken any medications before the rash appeared, thereby ruling out a drug reaction.

The differential for our patient included post–urinary tract infection immune-reactive arthritis and rash, which is not typical with Escherichia coli infection but is described with infection with Chlamydia species and Salmonella species. Moreover, post–urinary tract infection immune-reactive arthritis and rash appear mostly on the palms and soles. Systemic lupus erythematosus–like rashes have a different histology and appear on sun-exposed areas; our patient’s rash was found mainly on unexposed areas.¹²

Because our patient received the Moderna vaccine 5 days before the rash appeared and later developed swelling of the digits with morning stiffness, a delayed serum sickness–like reaction secondary to COVID-19 vaccination was possible.^3,6

COVID-19 mRNA vaccines developed by Pfizer-BioNTech and Moderna incorporate a lipid-based nanoparticle carrier system that prevents rapid enzymatic degradation of mRNA and facilitates in vivo delivery of mRNA. This lipid-based nanoparticle carrier system is further stabilized by a polyethylene glycol 2000 lipid conjugate that provides a hydrophilic layer, thus prolonging half-life. The presence of lipid polyethylene glycol 2000 in mRNA vaccines has led to concern that this component could be implicated in anaphylaxis.⁶

COVID-19 antigens can give rise to varying clinical manifestations that are directly related to viral tissue damage or are indirectly induced by the antiviral immune response.^13,14 Hyperactivation of the immune system to eradicate COVID-19 may trigger autoimmunity; several immune-mediated disorders have been described in individuals infected with SARS-CoV-2. Dermal manifestations include cutaneous rash and vasculitis.^13-16 Crucial immunologic steps occur during SARS-CoV-2 infection that may link autoimmunity to COVID-19.^13,14 In preliminary published data on the efficacy of the Moderna vaccine on 45 trial enrollees, 3 did not receive the second dose of vaccination, including 1 who developed urticaria on both legs 5 days after the first dose.¹

Introduction of viral RNA can induce autoimmunity that can be explained by various phenomena, including epitope spreading, molecular mimicry, cryptic antigen, and bystander activation. Remarkably, more than one-third of immunogenic proteins in SARS-CoV-2 have potentially problematic homology to proteins that are key to the human adaptive immune system.⁵

Moreover, SARS-CoV-2 seems to induce organ injury through alternative mechanisms beyond direct viral infection, including immunologic injury. In some situations, hyperactivation of the immune response to SARS-CoV-2 RNA can result in autoimmune disease. COVID-19 has been associated with immune-mediated systemic or organ-selective manifestations, some of which fulfill the diagnostic or classification criteria of specific autoimmune diseases. It is unclear whether those medical disorders are the result of transitory postinfectious epiphenomena.⁵

A few studies have shown that patients with rheumatic disease have an incidence and prevalence of COVID-19 that is similar to the general population. A similar pattern has been detected in COVID-19 morbidity and mortality rates, even among patients with an autoimmune disease, such as rheumatoid arthritis and Sjögren syndrome.^5,17 Furthermore, exacerbation of preexisting rheumatic symptoms may be due to hyperactivation of antiviral pathways in a person with an autoimmune disease.^17-19 The findings in our patient suggested a direct role for the vaccine in skin manifestations, rather than for reactivation or development of new systemic autoimmune processes, such as systemic lupus erythematosus.

Exacerbation of psoriasis following COVID-19 vaccination has been described²⁰; however, the case patient did not have a history of psoriasis. The mechanism(s) of such exacerbation remain unclear; COVID-19 vaccine–induced helper T cells (T_H17) may play a role.²¹ Other skin manifestations encountered following COVID-19 vaccination include lichen planus, leukocytoclastic vasculitic rash, erythema multiforme–like rash, and pityriasis rosea–like rash.^22-25 The immune mechanisms of these manifestations remain unclear.

The clinical presentation of delayed vaccination reactions can be attributed to the timing of symptoms and, in this case, the immune-mediated background of a psoriasiform reaction. Although adverse reactions to the SARS-CoV-2 mRNA vaccine are rare, more individuals should be studied after vaccination to confirm and better understand this phenomenon.

LAS VEGAS – With the right regimen, a majority of patients with psoriasis can achieve at least a Psoriasis Area and Severity Index (PASI) 75 score, Jennifer Soung, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

The array of treatment options includes mainstay topicals, new nonsteroidals, traditional oral systemics, new oral systemics, biologics, and light therapy, said Dr. Soung, director of clinical research at Harbor-UCLA Medical Center, Santa Ana, Calif. However, some areas of the body require unique considerations for successful psoriasis treatment, notably the scalp, face, intertriginous areas, palms and soles, and nails, she said.

For these areas, make sure the diagnosis of psoriasis is correct, to avoid wasting time on the wrong course of treatment, Dr. Soung emphasized.

Scalp strategies

The scalp is often the first area of the body affected by psoriasis, and patients with severe scalp psoriasis may have minimal plaques on the body, Dr. Soung said. However, a differential diagnosis should include seborrheic dermatitis, she noted.

For most cases of scalp psoriasis, “start with localized topical treatment,” such as vitamin D and corticosteroid combination therapy, or excimer laser, Dr. Soung advised.

Systemic treatments with demonstrated effectiveness on scalp psoriasis in post hoc analyses of patients with moderate to severe plaque psoriasis include adalimumab, etanercept, ixekizumab, and secukinumab. Studies specifically focused on treatment of scalp psoriasis have shown success with secukinumab and apremilast, she noted.

Roflumilast foam, 0.3%, is in development and is an emerging option for scalp psoriasis. (A cream formulation of roflumilast, a topical phosphodiesterase 4 inhibitor, was approved for treatment of plaque psoriasis in July 2022.) A phase 2b study of roflumilast foam showed that approximately one-third of patients with scalp psoriasis achieved a status of clear based on scalp-investigator global assessment, compared with approximately 3% of those on vehicle, and similar results were seen in a recently completed phase 3 trial for scalp and body psoriasis, she added.
 

Facial psoriasis

Patients with facial psoriasis tend to be younger, and they may have more severe disease overall, Dr. Soung said. Given the sensitivity of facial skin, “it is nice to have a nonsteroidal option,” she noted. Current novel nonsteroidal therapies include a cream formulation of tapinarof, an aryl hydrocarbon receptor agonist, which was approved earlier this year for plaque psoriasis in adults, and roflumilast cream. Vitamin D and topical calcineurin inhibitors are options as well, she said.

Intertriginous tricks

Intertriginous (inverse) psoriasis is distinct from other areas in that the plaques are usually smooth and well-demarcated, with little or no scaling, Dr. Soung said. Erosions or signs of maceration may be present. The prevalence of inverse psoriasis is approximately 30%, but the prevalence on external genitalia is 80%, she noted. For inverse psoriasis, topical corticosteroids can result in adverse events such as poor wound healing and skin fragility, and some patients resist the idea of a steroid and don’t adhere to the medication, she added. Dr. Soung recommended topical corticosteroids for the short term, and topical calcineurin inhibitors or calcipotriol for the long term.

New topical options for inverse psoriasis include tapinarof and roflumilast, Dr. Soung said. For tapinarof, the phase 3 PSOARING program included assessment of tolerability in sensitive skin areas and found little to no irritation. Similarly, treatment with roflumilast cream was effective and well tolerated by patients with intertriginous plaque psoriasis in the DERMIS-1 and DERMIS-2 studies, she said.
 

Genital psoriasis

Ask patients with psoriasis about genital psoriasis, because they often are too embarrassed to provide that information on their own, said Dr. Soung. In fact, 63% of patients with psoriasis report ever experiencing genital psoriasis, but it often goes undiagnosed and undertreated, which has a significant impact on patient quality of life and sexual health.

A differential diagnosis of genital psoriasis should include dermatitis, tinea or candidiasis, and even squamous cell carcinoma, she noted. Other considerations include fixed drug eruption, lichen nitidus, lichen sclerosus, and scabies.

Dr. Soung’s first line of treatment for genital psoriasis is low-potency topical corticosteroids for 2-4 weeks. If long-term topical therapy is needed, alternatives include calcineurin inhibitors and vitamin D analogs, she said. The new topicals roflumilast and tapinarof are options as well, she said.

For those patients with severe and extensive genital psoriasis, consider systemic therapy, possibly with ixekizumab or secukinumab, she added. Patients with moderate to severe genital psoriasis treated with apremilast have shown improvement at week 16, in an ongoing clinical trial, she noted.

Palmoplantar involvement

For patients with palmar plantar psoriasis, “don’t underestimate the impact on quality of life,” said Dr. Soung. Approximately 12%-16% of patients with psoriasis report palmoplantar involvement, she noted.

Palmoplantar psoriasis can be stubborn, and many patients will need combination therapy with topicals and systemics, she said. “I am very curious about how well our new topical nonsteroidals will work in these areas,” she added.

Dr. Soung starts patients with palmoplantar psoriasis with a “potent to super-potent” twice daily topical corticosteroid, with or without occlusion. Her first-line systemic therapy is acitretin, 10-50 mg daily. However, keep in mind that acitretin is contraindicated in pregnancy, and also may cause side effects including cheilitis, alopecia, and peeling skin, she cautioned.

During the question and answer session, Dr. Soung was asked whether she routinely biopsies patients with palmoplantar psoriasis. “Not always,” was her answer. Instead, she looks for clues elsewhere on the body to confirm the diagnosis.
 

Nail know-how

Approximately 23%-27% of patients with psoriasis experience nail involvement, said Dr. Soung. Nail psoriasis can appear on the nail plate as pitting, onycholysis, or subungual hyperkeratosis, or in the nail bed as splinter hemorrhages or oil spots, she said.

For patients with psoriasis of the nails only, Dr. Soung described the use of high-potency topical corticosteroids, with or without calcipotriol. In her experience, she said that intralesional steroids for nail psoriasis are torturous to patients. For patients who have failed topical therapy or have psoriasis in other areas, with or without psoriatic arthritis, she advised the use of either IL-17 antagonists (secukinumab, ixekizumab, brodalumab) or IL-23 antagonists (risankizumab, guselkumab).

Dr. Soung disclosed serving as a consultant or advisor for Arcutis, Bristol Myers Squibb Company, Dermavant, and Novartis. She also disclosed serving as a speaker or member of the speakers’ bureau for AbbVie, Amgen, Arcutis, Bristol Myers Squibb Company, Celgene, Leo Pharma, Eli Lilly, Novartis, Ortho Dermatologics, Pfizer, Regeneron, and Sanofi, as well as research funding from AbbVie, Amgen, Arcutis, Castle Biosciences, Dermavant, KoBio, Kyowa Kirin, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB.

MedscapeLive and this news organization are owned by the same parent company.
 

LAS VEGAS – With the right regimen, a majority of patients with psoriasis can achieve at least a Psoriasis Area and Severity Index (PASI) 75 score, Jennifer Soung, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

The array of treatment options includes mainstay topicals, new nonsteroidals, traditional oral systemics, new oral systemics, biologics, and light therapy, said Dr. Soung, director of clinical research at Harbor-UCLA Medical Center, Santa Ana, Calif. However, some areas of the body require unique considerations for successful psoriasis treatment, notably the scalp, face, intertriginous areas, palms and soles, and nails, she said.

For these areas, make sure the diagnosis of psoriasis is correct, to avoid wasting time on the wrong course of treatment, Dr. Soung emphasized.

Scalp strategies

The scalp is often the first area of the body affected by psoriasis, and patients with severe scalp psoriasis may have minimal plaques on the body, Dr. Soung said. However, a differential diagnosis should include seborrheic dermatitis, she noted.

For most cases of scalp psoriasis, “start with localized topical treatment,” such as vitamin D and corticosteroid combination therapy, or excimer laser, Dr. Soung advised.

Systemic treatments with demonstrated effectiveness on scalp psoriasis in post hoc analyses of patients with moderate to severe plaque psoriasis include adalimumab, etanercept, ixekizumab, and secukinumab. Studies specifically focused on treatment of scalp psoriasis have shown success with secukinumab and apremilast, she noted.

Roflumilast foam, 0.3%, is in development and is an emerging option for scalp psoriasis. (A cream formulation of roflumilast, a topical phosphodiesterase 4 inhibitor, was approved for treatment of plaque psoriasis in July 2022.) A phase 2b study of roflumilast foam showed that approximately one-third of patients with scalp psoriasis achieved a status of clear based on scalp-investigator global assessment, compared with approximately 3% of those on vehicle, and similar results were seen in a recently completed phase 3 trial for scalp and body psoriasis, she added.
 

Facial psoriasis

Patients with facial psoriasis tend to be younger, and they may have more severe disease overall, Dr. Soung said. Given the sensitivity of facial skin, “it is nice to have a nonsteroidal option,” she noted. Current novel nonsteroidal therapies include a cream formulation of tapinarof, an aryl hydrocarbon receptor agonist, which was approved earlier this year for plaque psoriasis in adults, and roflumilast cream. Vitamin D and topical calcineurin inhibitors are options as well, she said.

Intertriginous tricks

Intertriginous (inverse) psoriasis is distinct from other areas in that the plaques are usually smooth and well-demarcated, with little or no scaling, Dr. Soung said. Erosions or signs of maceration may be present. The prevalence of inverse psoriasis is approximately 30%, but the prevalence on external genitalia is 80%, she noted. For inverse psoriasis, topical corticosteroids can result in adverse events such as poor wound healing and skin fragility, and some patients resist the idea of a steroid and don’t adhere to the medication, she added. Dr. Soung recommended topical corticosteroids for the short term, and topical calcineurin inhibitors or calcipotriol for the long term.

New topical options for inverse psoriasis include tapinarof and roflumilast, Dr. Soung said. For tapinarof, the phase 3 PSOARING program included assessment of tolerability in sensitive skin areas and found little to no irritation. Similarly, treatment with roflumilast cream was effective and well tolerated by patients with intertriginous plaque psoriasis in the DERMIS-1 and DERMIS-2 studies, she said.
 

Genital psoriasis

Ask patients with psoriasis about genital psoriasis, because they often are too embarrassed to provide that information on their own, said Dr. Soung. In fact, 63% of patients with psoriasis report ever experiencing genital psoriasis, but it often goes undiagnosed and undertreated, which has a significant impact on patient quality of life and sexual health.

A differential diagnosis of genital psoriasis should include dermatitis, tinea or candidiasis, and even squamous cell carcinoma, she noted. Other considerations include fixed drug eruption, lichen nitidus, lichen sclerosus, and scabies.

Dr. Soung’s first line of treatment for genital psoriasis is low-potency topical corticosteroids for 2-4 weeks. If long-term topical therapy is needed, alternatives include calcineurin inhibitors and vitamin D analogs, she said. The new topicals roflumilast and tapinarof are options as well, she said.

For those patients with severe and extensive genital psoriasis, consider systemic therapy, possibly with ixekizumab or secukinumab, she added. Patients with moderate to severe genital psoriasis treated with apremilast have shown improvement at week 16, in an ongoing clinical trial, she noted.

Palmoplantar involvement

For patients with palmar plantar psoriasis, “don’t underestimate the impact on quality of life,” said Dr. Soung. Approximately 12%-16% of patients with psoriasis report palmoplantar involvement, she noted.

Palmoplantar psoriasis can be stubborn, and many patients will need combination therapy with topicals and systemics, she said. “I am very curious about how well our new topical nonsteroidals will work in these areas,” she added.

Dr. Soung starts patients with palmoplantar psoriasis with a “potent to super-potent” twice daily topical corticosteroid, with or without occlusion. Her first-line systemic therapy is acitretin, 10-50 mg daily. However, keep in mind that acitretin is contraindicated in pregnancy, and also may cause side effects including cheilitis, alopecia, and peeling skin, she cautioned.

During the question and answer session, Dr. Soung was asked whether she routinely biopsies patients with palmoplantar psoriasis. “Not always,” was her answer. Instead, she looks for clues elsewhere on the body to confirm the diagnosis.
 

Nail know-how

Approximately 23%-27% of patients with psoriasis experience nail involvement, said Dr. Soung. Nail psoriasis can appear on the nail plate as pitting, onycholysis, or subungual hyperkeratosis, or in the nail bed as splinter hemorrhages or oil spots, she said.

For patients with psoriasis of the nails only, Dr. Soung described the use of high-potency topical corticosteroids, with or without calcipotriol. In her experience, she said that intralesional steroids for nail psoriasis are torturous to patients. For patients who have failed topical therapy or have psoriasis in other areas, with or without psoriatic arthritis, she advised the use of either IL-17 antagonists (secukinumab, ixekizumab, brodalumab) or IL-23 antagonists (risankizumab, guselkumab).

Dr. Soung disclosed serving as a consultant or advisor for Arcutis, Bristol Myers Squibb Company, Dermavant, and Novartis. She also disclosed serving as a speaker or member of the speakers’ bureau for AbbVie, Amgen, Arcutis, Bristol Myers Squibb Company, Celgene, Leo Pharma, Eli Lilly, Novartis, Ortho Dermatologics, Pfizer, Regeneron, and Sanofi, as well as research funding from AbbVie, Amgen, Arcutis, Castle Biosciences, Dermavant, KoBio, Kyowa Kirin, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB.

MedscapeLive and this news organization are owned by the same parent company.
 

LAS VEGAS – With the right regimen, a majority of patients with psoriasis can achieve at least a Psoriasis Area and Severity Index (PASI) 75 score, Jennifer Soung, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.

The array of treatment options includes mainstay topicals, new nonsteroidals, traditional oral systemics, new oral systemics, biologics, and light therapy, said Dr. Soung, director of clinical research at Harbor-UCLA Medical Center, Santa Ana, Calif. However, some areas of the body require unique considerations for successful psoriasis treatment, notably the scalp, face, intertriginous areas, palms and soles, and nails, she said.

For these areas, make sure the diagnosis of psoriasis is correct, to avoid wasting time on the wrong course of treatment, Dr. Soung emphasized.

Scalp strategies

The scalp is often the first area of the body affected by psoriasis, and patients with severe scalp psoriasis may have minimal plaques on the body, Dr. Soung said. However, a differential diagnosis should include seborrheic dermatitis, she noted.

For most cases of scalp psoriasis, “start with localized topical treatment,” such as vitamin D and corticosteroid combination therapy, or excimer laser, Dr. Soung advised.

Systemic treatments with demonstrated effectiveness on scalp psoriasis in post hoc analyses of patients with moderate to severe plaque psoriasis include adalimumab, etanercept, ixekizumab, and secukinumab. Studies specifically focused on treatment of scalp psoriasis have shown success with secukinumab and apremilast, she noted.

Roflumilast foam, 0.3%, is in development and is an emerging option for scalp psoriasis. (A cream formulation of roflumilast, a topical phosphodiesterase 4 inhibitor, was approved for treatment of plaque psoriasis in July 2022.) A phase 2b study of roflumilast foam showed that approximately one-third of patients with scalp psoriasis achieved a status of clear based on scalp-investigator global assessment, compared with approximately 3% of those on vehicle, and similar results were seen in a recently completed phase 3 trial for scalp and body psoriasis, she added.
 

Facial psoriasis

Patients with facial psoriasis tend to be younger, and they may have more severe disease overall, Dr. Soung said. Given the sensitivity of facial skin, “it is nice to have a nonsteroidal option,” she noted. Current novel nonsteroidal therapies include a cream formulation of tapinarof, an aryl hydrocarbon receptor agonist, which was approved earlier this year for plaque psoriasis in adults, and roflumilast cream. Vitamin D and topical calcineurin inhibitors are options as well, she said.

Intertriginous tricks

Intertriginous (inverse) psoriasis is distinct from other areas in that the plaques are usually smooth and well-demarcated, with little or no scaling, Dr. Soung said. Erosions or signs of maceration may be present. The prevalence of inverse psoriasis is approximately 30%, but the prevalence on external genitalia is 80%, she noted. For inverse psoriasis, topical corticosteroids can result in adverse events such as poor wound healing and skin fragility, and some patients resist the idea of a steroid and don’t adhere to the medication, she added. Dr. Soung recommended topical corticosteroids for the short term, and topical calcineurin inhibitors or calcipotriol for the long term.

New topical options for inverse psoriasis include tapinarof and roflumilast, Dr. Soung said. For tapinarof, the phase 3 PSOARING program included assessment of tolerability in sensitive skin areas and found little to no irritation. Similarly, treatment with roflumilast cream was effective and well tolerated by patients with intertriginous plaque psoriasis in the DERMIS-1 and DERMIS-2 studies, she said.
 

Genital psoriasis

Ask patients with psoriasis about genital psoriasis, because they often are too embarrassed to provide that information on their own, said Dr. Soung. In fact, 63% of patients with psoriasis report ever experiencing genital psoriasis, but it often goes undiagnosed and undertreated, which has a significant impact on patient quality of life and sexual health.

A differential diagnosis of genital psoriasis should include dermatitis, tinea or candidiasis, and even squamous cell carcinoma, she noted. Other considerations include fixed drug eruption, lichen nitidus, lichen sclerosus, and scabies.

Dr. Soung’s first line of treatment for genital psoriasis is low-potency topical corticosteroids for 2-4 weeks. If long-term topical therapy is needed, alternatives include calcineurin inhibitors and vitamin D analogs, she said. The new topicals roflumilast and tapinarof are options as well, she said.

For those patients with severe and extensive genital psoriasis, consider systemic therapy, possibly with ixekizumab or secukinumab, she added. Patients with moderate to severe genital psoriasis treated with apremilast have shown improvement at week 16, in an ongoing clinical trial, she noted.

Palmoplantar involvement

For patients with palmar plantar psoriasis, “don’t underestimate the impact on quality of life,” said Dr. Soung. Approximately 12%-16% of patients with psoriasis report palmoplantar involvement, she noted.

Palmoplantar psoriasis can be stubborn, and many patients will need combination therapy with topicals and systemics, she said. “I am very curious about how well our new topical nonsteroidals will work in these areas,” she added.

Dr. Soung starts patients with palmoplantar psoriasis with a “potent to super-potent” twice daily topical corticosteroid, with or without occlusion. Her first-line systemic therapy is acitretin, 10-50 mg daily. However, keep in mind that acitretin is contraindicated in pregnancy, and also may cause side effects including cheilitis, alopecia, and peeling skin, she cautioned.

During the question and answer session, Dr. Soung was asked whether she routinely biopsies patients with palmoplantar psoriasis. “Not always,” was her answer. Instead, she looks for clues elsewhere on the body to confirm the diagnosis.
 

Nail know-how

Approximately 23%-27% of patients with psoriasis experience nail involvement, said Dr. Soung. Nail psoriasis can appear on the nail plate as pitting, onycholysis, or subungual hyperkeratosis, or in the nail bed as splinter hemorrhages or oil spots, she said.

For patients with psoriasis of the nails only, Dr. Soung described the use of high-potency topical corticosteroids, with or without calcipotriol. In her experience, she said that intralesional steroids for nail psoriasis are torturous to patients. For patients who have failed topical therapy or have psoriasis in other areas, with or without psoriatic arthritis, she advised the use of either IL-17 antagonists (secukinumab, ixekizumab, brodalumab) or IL-23 antagonists (risankizumab, guselkumab).

Dr. Soung disclosed serving as a consultant or advisor for Arcutis, Bristol Myers Squibb Company, Dermavant, and Novartis. She also disclosed serving as a speaker or member of the speakers’ bureau for AbbVie, Amgen, Arcutis, Bristol Myers Squibb Company, Celgene, Leo Pharma, Eli Lilly, Novartis, Ortho Dermatologics, Pfizer, Regeneron, and Sanofi, as well as research funding from AbbVie, Amgen, Arcutis, Castle Biosciences, Dermavant, KoBio, Kyowa Kirin, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB.

MedscapeLive and this news organization are owned by the same parent company.
 

Vedolizumab (Entyvio) and ustekinumab (Stelara) appear to be equally effective for extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD), according to results of a retrospective study published online in Digestive and Liver Disease.

Between 25% and 40% of patients with IBD experience EIM, which reduces quality of life, according to the Crohn’s & Colitis Foundation. EIM commonly involves the joints, skin, bones, eyes, kidney, and liver. Anemia is another extraintestinal complication.

Until now, it’s been unclear whether vedolizumab and ustekinumab are equally effective for treating EIM.

Vedolizumab specifically targets the gastrointestinal tract, a potential disadvantage in reducing EIM, while ustekinumab is thought to have a systemic effect, a potential treatment advantage, Moran Livne-Margolin, MD, and colleagues, Chaim Sheba Medical Center, Ramat Gan, Israel, point out.

To investigate, they included 111 adults with IBD who were treated at the medical center between 2015 and 2021 – 53 with vedolizumab and 58 with ustekinumab. Before starting treatment, all of them had active EIM, most commonly arthralgia (84%).

After 6 weeks of treatment, 66% of patients in both groups had a clinical response to their intestinal disease.

After 14 and 26 weeks of treatment, clinical response rates were 59% and 50%, respectively, with vedolizumab, and 48% and 41%, respectively, with ustekinumab.

Over 52 weeks, both biologics were equally effective against the intestinal disease, with clinical response rates of 42% with vedolizumab and 44% with ustekinumab.

A similar pattern emerged when looking at improvement in EIM.

At week 6, 44% of patients taking vedolizumab and 35% taking ustekinumab had improvement in EIM, with no significant difference between the two biologics (P = .4).

At week 14, rates of improvement in EIM were 43% for vedolizumab and 33% for ustekinumab (P = .39); at 26 weeks, rates were 39% and 33%, respectively (P = .6); and at 52 weeks, rates were 34% and 36% (P = .9).

Researchers also found a significant positive correlation between improvement of the intestinal disease and clinical improvement of EIM at each time point.

Ustekinumab is usually preferred in patients with EIM, Dr. Livne-Margolin and colleagues note. But their findings “may raise some questions whether ustekinumab is, in fact, a better choice in those specific patients.”

Limitations of the study include its retrospective design and small cohort size.

Additionally, vedolizumab is given intravenously in the clinic and mandates patients to have a routine checkup every 1-2 months, whereas ustekinumab can be given at home. As a result, data were missing on some of the patients treated with ustekinumab during the follow-up.

Another limitation is that most of the patients had articular complaints with a small presentation of other EIM.

Also, most of the patients had Crohn’s disease, with only one patient with ulcerative colitis in the ustekinumab group, compared with 12 in the vedolizumab group.

Finally, patients treated with ustekinumab had more experience with anti-TNF treatment, compared with the vedolizumab group, which might have influenced the results with a negative bias toward ustekinumab.

The study had no specific funding. Three authors have disclosed relationships with Janssen, which makes ustekinumab.

A version of this article first appeared on Medscape.com.

Vedolizumab (Entyvio) and ustekinumab (Stelara) appear to be equally effective for extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD), according to results of a retrospective study published online in Digestive and Liver Disease.

Between 25% and 40% of patients with IBD experience EIM, which reduces quality of life, according to the Crohn’s & Colitis Foundation. EIM commonly involves the joints, skin, bones, eyes, kidney, and liver. Anemia is another extraintestinal complication.

Until now, it’s been unclear whether vedolizumab and ustekinumab are equally effective for treating EIM.

Vedolizumab specifically targets the gastrointestinal tract, a potential disadvantage in reducing EIM, while ustekinumab is thought to have a systemic effect, a potential treatment advantage, Moran Livne-Margolin, MD, and colleagues, Chaim Sheba Medical Center, Ramat Gan, Israel, point out.

To investigate, they included 111 adults with IBD who were treated at the medical center between 2015 and 2021 – 53 with vedolizumab and 58 with ustekinumab. Before starting treatment, all of them had active EIM, most commonly arthralgia (84%).

After 6 weeks of treatment, 66% of patients in both groups had a clinical response to their intestinal disease.

After 14 and 26 weeks of treatment, clinical response rates were 59% and 50%, respectively, with vedolizumab, and 48% and 41%, respectively, with ustekinumab.

Over 52 weeks, both biologics were equally effective against the intestinal disease, with clinical response rates of 42% with vedolizumab and 44% with ustekinumab.

A similar pattern emerged when looking at improvement in EIM.

At week 6, 44% of patients taking vedolizumab and 35% taking ustekinumab had improvement in EIM, with no significant difference between the two biologics (P = .4).

At week 14, rates of improvement in EIM were 43% for vedolizumab and 33% for ustekinumab (P = .39); at 26 weeks, rates were 39% and 33%, respectively (P = .6); and at 52 weeks, rates were 34% and 36% (P = .9).

Researchers also found a significant positive correlation between improvement of the intestinal disease and clinical improvement of EIM at each time point.

Ustekinumab is usually preferred in patients with EIM, Dr. Livne-Margolin and colleagues note. But their findings “may raise some questions whether ustekinumab is, in fact, a better choice in those specific patients.”

Limitations of the study include its retrospective design and small cohort size.

Additionally, vedolizumab is given intravenously in the clinic and mandates patients to have a routine checkup every 1-2 months, whereas ustekinumab can be given at home. As a result, data were missing on some of the patients treated with ustekinumab during the follow-up.

Another limitation is that most of the patients had articular complaints with a small presentation of other EIM.

Also, most of the patients had Crohn’s disease, with only one patient with ulcerative colitis in the ustekinumab group, compared with 12 in the vedolizumab group.

Finally, patients treated with ustekinumab had more experience with anti-TNF treatment, compared with the vedolizumab group, which might have influenced the results with a negative bias toward ustekinumab.

The study had no specific funding. Three authors have disclosed relationships with Janssen, which makes ustekinumab.

A version of this article first appeared on Medscape.com.

Vedolizumab (Entyvio) and ustekinumab (Stelara) appear to be equally effective for extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD), according to results of a retrospective study published online in Digestive and Liver Disease.

Between 25% and 40% of patients with IBD experience EIM, which reduces quality of life, according to the Crohn’s & Colitis Foundation. EIM commonly involves the joints, skin, bones, eyes, kidney, and liver. Anemia is another extraintestinal complication.

Until now, it’s been unclear whether vedolizumab and ustekinumab are equally effective for treating EIM.

Vedolizumab specifically targets the gastrointestinal tract, a potential disadvantage in reducing EIM, while ustekinumab is thought to have a systemic effect, a potential treatment advantage, Moran Livne-Margolin, MD, and colleagues, Chaim Sheba Medical Center, Ramat Gan, Israel, point out.

To investigate, they included 111 adults with IBD who were treated at the medical center between 2015 and 2021 – 53 with vedolizumab and 58 with ustekinumab. Before starting treatment, all of them had active EIM, most commonly arthralgia (84%).

After 6 weeks of treatment, 66% of patients in both groups had a clinical response to their intestinal disease.

After 14 and 26 weeks of treatment, clinical response rates were 59% and 50%, respectively, with vedolizumab, and 48% and 41%, respectively, with ustekinumab.

Over 52 weeks, both biologics were equally effective against the intestinal disease, with clinical response rates of 42% with vedolizumab and 44% with ustekinumab.

A similar pattern emerged when looking at improvement in EIM.

At week 6, 44% of patients taking vedolizumab and 35% taking ustekinumab had improvement in EIM, with no significant difference between the two biologics (P = .4).

At week 14, rates of improvement in EIM were 43% for vedolizumab and 33% for ustekinumab (P = .39); at 26 weeks, rates were 39% and 33%, respectively (P = .6); and at 52 weeks, rates were 34% and 36% (P = .9).

Researchers also found a significant positive correlation between improvement of the intestinal disease and clinical improvement of EIM at each time point.

Ustekinumab is usually preferred in patients with EIM, Dr. Livne-Margolin and colleagues note. But their findings “may raise some questions whether ustekinumab is, in fact, a better choice in those specific patients.”

Limitations of the study include its retrospective design and small cohort size.

Additionally, vedolizumab is given intravenously in the clinic and mandates patients to have a routine checkup every 1-2 months, whereas ustekinumab can be given at home. As a result, data were missing on some of the patients treated with ustekinumab during the follow-up.

Another limitation is that most of the patients had articular complaints with a small presentation of other EIM.

Also, most of the patients had Crohn’s disease, with only one patient with ulcerative colitis in the ustekinumab group, compared with 12 in the vedolizumab group.

Finally, patients treated with ustekinumab had more experience with anti-TNF treatment, compared with the vedolizumab group, which might have influenced the results with a negative bias toward ustekinumab.

The study had no specific funding. Three authors have disclosed relationships with Janssen, which makes ustekinumab.

A version of this article first appeared on Medscape.com.

Case Report

A 47-year-old man presented with a sudden-onset rash consisting of red bumps on the abdomen and legs that had been ongoing for several days. He had known psoriasis and psoriatic arthritis that had been well controlled with adalimumab for the last 18 months. He reported concurrent onset of nausea but denied fevers, chills, night sweats, unintentional weight loss, abdominal pain, and pruritus. He endorsed prior cutaneous infections of methicillin-resistant Staphylococcus aureus (MRSA). His medical history also included diabetes mellitus, hypertension, and obesity. His other medications included oral losartan-hydrochlorothiazide, amlodipine, naproxen, and atorvastatin.

Physical examination revealed numerous thin purpuric papules—some with adherent scale—distributed on the lower legs, extensor forearms, and abdomen. Abdominal lesions were confined to weight-related striae (Figure 1). The palms, soles, oral mucosa, and face were spared. Three punch biopsies were performed, including 1 for direct immunofluorescence (DIF), and the patient was instructed to apply clobetasol to the affected areas twice daily until further notice.

Pathology showed perivascular extravasation of erythrocytes, neutrophils, eosinophils, and leukocytoclasis surrounding blood vessels associated with fibrin (Figure 2). Direct immunofluorescence showed granular deposition of IgA, complement component 3, and fibrinogen in a superficial dermal vascular pattern (Figure 3). These results were consistent with IgA small-vessel vasculitis. One specimen was consistent with the patient’s known psoriasis.  

Urinalysis revealed moderate hemoglobinuria, and urine microscopy showed 174 red blood cells per high-power field. Creatinine was high at 1.87 mg/dL (reference range, <1.34 mg/dL; patient’s baseline, 0.81 mg/dL) and glomerular filtration rate was low (42 mL/min, patient’s baseline, >60 mL/min [reference range, 90–120 mL/min]). Erythrocyte sedimentation rate (21 mm/h [reference range, 0–22 mm/h]) and C-reactive protein were elevated (2.2 mg/dL [reference range, 0.3–1.0 mg/dL]). Given his history of cutaneous MRSA infections, a bacterial culture swab was collected from the skin surface to check for colonization, which showed moderate growth of MRSA. Naproxen was discontinued over concern of worsening the patient’s renal status. The patient was instructed to rest at home with his legs elevated, wear compression socks when ambulatory, use chlorhexidine antiseptic daily as a body wash when showering, and apply mupirocin three times daily to the biopsy sites. He was referred to urology for his microhematuria, where cystoscopy revealed no abnormalities.A month passed with no improvement of the patient’s cutaneous vasculitis, and his psoriatic arthritis worsened without his usual use of naproxen. He developed abdominal pain and loss of appetite. A prednisone taper was ordered starting at 40 mg/d (28.8 mg/kg), which provided relief of the skin and joint symptoms only until the course was completed 12 days later. 

Five weeks after the initial presentation, the patient returned with a more severe eruption consisting of innumerable purpuric papules that coalesced in plaques on the abdomen, arms, and legs. He also had erythematous facial pustules and mild palmar petechiae (Figure 4). Three biopsies were performed, including 1 for DIF and 1 from a pustule on the forehead. Histology and DIF were again consistent with IgA small-vessel vasculitis. The forehead biopsy was compatible with steroid acne (attributed to recent prednisone use) and psoriasis.   

Rheumatology was consulted, and adalimumab was discontinued 6 weeks after the initial presentation out of concern for drug-induced cutaneous vasculitis. Vasculitis work-up was unremarkable, including antineutrophil cytoplasmic antibodies, rheumatoid factor, cyclic citrullinated peptide, and serum protein electrophoresis. Oral dapsone was started at 100 mg/d, with the tentative plan of starting secukinumab if cutaneous symptoms improved. For 3 weeks, the patient’s cutaneous symptoms steadily improved.

Nine weeks after initial presentation to dermatology (3 weeks after discontinuing adalimumab) the patient self-administered his first dose of secukinumab at home. Several hours later, he reported sudden reappearance of vasculitis. He denied diarrhea, abdominal pain, bowel movement urgency, fevers, fatigue, and unintentional weight loss. Antistreptolysin O and hepatitis A antibodies were negative. He was instructed to hold secukinumab indefinitely.

Four weeks after his only secukinumab injection, the patient reported another episode of acute worsening cutaneous symptoms. A 4-week prednisone taper starting at 40 mg/d was ordered. Computed tomography of the chest, abdomen, and pelvis to rule out internal malignancy was unremarkable. Around this time, the patient reported major emotional distress related to an unexpected death in his family, which added to a gradual increase in his stress level related to the COVID-19 pandemic. 

Three weeks later, dapsone was increased to 100 mg twice daily on account of the patient’s adiposity and lack of cutaneous improvement on the lower dose. Subsequently, the vasculitis rapidly improved for 2 weeks. The patient then reported symptoms of headache, dizziness, and chills. He was tested for COVID-19 and was negative. Six weeks after increasing the dapsone dose (5 months after initial presentation), the skin was normalizing, showing only faintly hyperpigmented macules confined to areas of resolved vasculitis (forearms, abdomen, legs). 

The patient had been on dapsone 100 mg twice daily for 3 months when he was started on ustekinumab (90 mg at weeks 0 and 4, with planned doses every 12 weeks) for psoriatic arthritis in hopes of withdrawing dapsone. His cutaneous symptoms have remained well controlled on this regimen for 18 months. Lowering of dapsone below 100 mg daily has resulted in recurrent mild vasculitis symptoms; he now maintains the once-daily dosing without negative side effects.

Comment

IgA vasculitis is a form of cutaneous small-vessel leukocytoclastic vasculitis (LCV) characterized by episodes of palpable purpura on the extensor surfaces of the arms and legs that may be associated with arthritis, abdominal pain, and/or hematuria. Although vasculitis is a known potential adverse effect of anti–tumor necrosis factor (TNF) α therapy, cases of adalimumab-induced IgA vasculitis are uncommon. As use of more targeted therapies for psoriasis and psoriatic arthritis, such as the IL-17 inhibitor secukinumab, increases so do reports of associated adverse events. Of 6 previously reported cases of secukinumab-associated vasculitis, at least 4 were IgA vasculitis (Table).^1-6 Another case described one patient with rheumatoid arthritis undergoing secukinumab treatment who experienced necrotizing glomerulonephritis; however, the authors concluded secukinumab likely was not causative in that case, as serologies and urinalyses suggested gradual onset of the process prior to initiating the medication.⁷

The exact pathogenesis of IgA vasculitis is unclear, but a prevailing theory involves the dysregulation of IgA synthesis and metabolism. Other than increased serum levels of transforming growth factor β, which is a major stimulating factor for IgA production, it also has been hypothesized that the presence of aberrantly hypoglycosylated IgA exposes an autoepitope for recognition by other pathogenic IgG and IgA, leading to the formation of large immune complexes that can readily deposit in postcapillary venules. The deposition of IgA immune complexes in postcapillary venules and the subsequent activation of the complement system causes direct damage to the endothelial cells of vessel walls. This complement activation is evidenced by vascular complement component 3 deposition on DIF (a nonspecific feature of LCV). Chemotaxis of neutrophils ensues, followed by their firm adherence and transendothelial migration (mediated by monocyte chemoattractant protein 1 [MCP-1]). Neutrophil degranulation releases reactive oxygen species and cytokines, which in turn recruit additional leukocytes to the area of inflammation, subsequently undergoing degeneration (leukocytoclasis). Microvascular permeability also is enhanced by MCP-1, allowing exudation of serum, erythrocytes, and fibrin. In the setting of elevated circulating TNF and IL-1, endothelium is stimulated to activate the intrinsic and extrinsic coagulation pathways. This decreases endothelial fibrinolytic activity, leading to thrombosis. The high venous pressure and low fibrinolytic activity in the lower legs explains why vasculitic lesions often are confined to or begin in this distribution.^1,8-10

There also are noteworthy roles for cytokines in LCV. Circulating transforming growth factor β and IL-6—which are necessary for development of T helper 17 (T_H17) cells and production of IL-17—are higher in patients with LCV compared to controls. Peripheral blood monocytes in patients with LCV demonstrate higher production of IL-17. Once T_H17 cells develop, their survival and phenotype are maintained by IL-23 (considered the master regulator of T_H17 differentiation). IL-17 is a potent chemoattractant of IL-8 (CXCL8) and MCP-1, both of which promote neutrophil-mediated perivascular inflammation. The IL-23 and IL-17 pathways implicated in the pathogenesis of psoriasis also cause neutrophil activation and upregulate transcription of proinflammatory cytokines (IL-1, IL-6, IL-8, and TNF-α), which overlap with those implicated in LCV. Autoimmune disease generally entails some positive feedback loop of progressively severe self-recognition and tissue destruction by the immune system. These shared cytokinetic processes may explain how the internal environment of psoriasis could perpetuate IgA vasculitis.^1,2,8,10-12

The mechanisms underlying vasculitis associated with adalimumab are unclear, but hypotheses involve direct toxicity on vessels, capillary deposition of anti-TNF/TNF immune complexes, or an inflammatory process resulting in autoantibodies. Similar hypotheses are posited for secukinumab-associated vasculitis, including deposition of secukinumab–IL-17 complexes. Anti–TNF-α medications may increase T_H17 cell numbers, leading to increased production of IL-22 and a resultant immunologic microenvironment conducive to vasculitis. All 6 published cases of secukinumab-associated vasculitis that we found had received prior treatment with a TNF-α blocker, but only 1 had occurrence of vasculitis during that treatment.^1-6,10

In the 6 cases we reviewed, the time from starting secukinumab to onset of vasculitis ranged from 1 to 18 months. Our patient’s same-day re-emergence of vasculitis after his first secukinumab dose was so acute that we were skeptical of secukinumab as a potential trigger; this may simply have been coincident to the natural waxing and waning of the vasculitis (although onset of IgA vasculitis within 1 day of starting anti–TNF-α therapy has been reported).^1-6,13  

Specific associations of IgA vasculitis are many and can include bacterial organisms such as Helicobacter pylori, streptococci, and staphylococci. Although internal mucous membrane infections are considered more linked because of the surveillance role of IgA predominantly in mucosal tissues, it is possible that our patient with cutaneous MRSA harbored the same within the nasal mucosa. Our patient also received multiple vaccinations outside our department throughout his clinical course (2 hepatitis B and 1 pneumococcal conjugate), which are known potential triggers for vasculitis. Psychological stress is a known trigger for psoriasis, and given the cytokinetic relationship of psoriasis to vasculitis described previously, it may have indirectly contributed to vasculitis in our case. The anxiety associated with being immunosuppressed during the COVID-19 pandemic and bereavement of losing a family member may have contributed to the refractory nature of our patient’s condition. Renal involvement is relatively common in adults with IgA vasculitis and so should be ruled out, as should occult internal malignancy.^8,10,14

It is unclear which of the above factors was causative in our case, but a multifactorial process is likely. Treatment of monoclonal antibody–associated vasculitis entails investigating for triggers and systemic involvement, removing the most likely culprit, quelling the vasculitis acutely, avoiding known potential exacerbators, and introducing an alternative long-term immunomodulant. In all 6 reported similar cases, discontinuation of secukinumab and initiation of prednisone or colchicine led to resolution.^1-6 Dapsone also is acceptable for acute control of IgA vasculitis, although this medication is highly lipid soluble and penetrates well into various tissues.¹⁵ Thus, lower doses may prove ineffective for obese patients, as was demonstrated in our case. Given the known potential of vaccinations, infections, and other factors (eg, alcohol, penicillin) to trigger IgA vasculitis, these should be avoided.¹⁰

Blockade of IL-23 with ustekinumab has been suggested by other authors encountering secukinumab-associated vasculitis, as IL-23 is the main driver and sustainer of T_H17 cell differentiation.⁸ Although 6 previously reported cases of secukinumab-associated vasculitis achieved resolution without long-term recurrence, none did so using an IL-23 inhibitor (nor had any of the described patients received IL-23 inhibitors previously).^1-6 Given the established safety of IL-23 inhibitors and that they theoretically are well suited for this unique circumstance (by ceasing the main causative cytokine cascades “upstream”) and were efficacious in quickly resolving our patient’s vasculitis, we suggest that ustekinumab may represent an ideal treatment option for patients in whom adalimumab- or secukinumab-associated vasculitis is suspected. Further research is needed given the complex interplay of so many variables and the increasingly common reports of adverse cutaneous events associated with these drugs.^1-6,10 

Case Report

A 47-year-old man presented with a sudden-onset rash consisting of red bumps on the abdomen and legs that had been ongoing for several days. He had known psoriasis and psoriatic arthritis that had been well controlled with adalimumab for the last 18 months. He reported concurrent onset of nausea but denied fevers, chills, night sweats, unintentional weight loss, abdominal pain, and pruritus. He endorsed prior cutaneous infections of methicillin-resistant Staphylococcus aureus (MRSA). His medical history also included diabetes mellitus, hypertension, and obesity. His other medications included oral losartan-hydrochlorothiazide, amlodipine, naproxen, and atorvastatin.

Physical examination revealed numerous thin purpuric papules—some with adherent scale—distributed on the lower legs, extensor forearms, and abdomen. Abdominal lesions were confined to weight-related striae (Figure 1). The palms, soles, oral mucosa, and face were spared. Three punch biopsies were performed, including 1 for direct immunofluorescence (DIF), and the patient was instructed to apply clobetasol to the affected areas twice daily until further notice.

Pathology showed perivascular extravasation of erythrocytes, neutrophils, eosinophils, and leukocytoclasis surrounding blood vessels associated with fibrin (Figure 2). Direct immunofluorescence showed granular deposition of IgA, complement component 3, and fibrinogen in a superficial dermal vascular pattern (Figure 3). These results were consistent with IgA small-vessel vasculitis. One specimen was consistent with the patient’s known psoriasis.  

Urinalysis revealed moderate hemoglobinuria, and urine microscopy showed 174 red blood cells per high-power field. Creatinine was high at 1.87 mg/dL (reference range, <1.34 mg/dL; patient’s baseline, 0.81 mg/dL) and glomerular filtration rate was low (42 mL/min, patient’s baseline, >60 mL/min [reference range, 90–120 mL/min]). Erythrocyte sedimentation rate (21 mm/h [reference range, 0–22 mm/h]) and C-reactive protein were elevated (2.2 mg/dL [reference range, 0.3–1.0 mg/dL]). Given his history of cutaneous MRSA infections, a bacterial culture swab was collected from the skin surface to check for colonization, which showed moderate growth of MRSA. Naproxen was discontinued over concern of worsening the patient’s renal status. The patient was instructed to rest at home with his legs elevated, wear compression socks when ambulatory, use chlorhexidine antiseptic daily as a body wash when showering, and apply mupirocin three times daily to the biopsy sites. He was referred to urology for his microhematuria, where cystoscopy revealed no abnormalities.A month passed with no improvement of the patient’s cutaneous vasculitis, and his psoriatic arthritis worsened without his usual use of naproxen. He developed abdominal pain and loss of appetite. A prednisone taper was ordered starting at 40 mg/d (28.8 mg/kg), which provided relief of the skin and joint symptoms only until the course was completed 12 days later. 

Five weeks after the initial presentation, the patient returned with a more severe eruption consisting of innumerable purpuric papules that coalesced in plaques on the abdomen, arms, and legs. He also had erythematous facial pustules and mild palmar petechiae (Figure 4). Three biopsies were performed, including 1 for DIF and 1 from a pustule on the forehead. Histology and DIF were again consistent with IgA small-vessel vasculitis. The forehead biopsy was compatible with steroid acne (attributed to recent prednisone use) and psoriasis.   

Rheumatology was consulted, and adalimumab was discontinued 6 weeks after the initial presentation out of concern for drug-induced cutaneous vasculitis. Vasculitis work-up was unremarkable, including antineutrophil cytoplasmic antibodies, rheumatoid factor, cyclic citrullinated peptide, and serum protein electrophoresis. Oral dapsone was started at 100 mg/d, with the tentative plan of starting secukinumab if cutaneous symptoms improved. For 3 weeks, the patient’s cutaneous symptoms steadily improved.

Nine weeks after initial presentation to dermatology (3 weeks after discontinuing adalimumab) the patient self-administered his first dose of secukinumab at home. Several hours later, he reported sudden reappearance of vasculitis. He denied diarrhea, abdominal pain, bowel movement urgency, fevers, fatigue, and unintentional weight loss. Antistreptolysin O and hepatitis A antibodies were negative. He was instructed to hold secukinumab indefinitely.

Four weeks after his only secukinumab injection, the patient reported another episode of acute worsening cutaneous symptoms. A 4-week prednisone taper starting at 40 mg/d was ordered. Computed tomography of the chest, abdomen, and pelvis to rule out internal malignancy was unremarkable. Around this time, the patient reported major emotional distress related to an unexpected death in his family, which added to a gradual increase in his stress level related to the COVID-19 pandemic. 

Three weeks later, dapsone was increased to 100 mg twice daily on account of the patient’s adiposity and lack of cutaneous improvement on the lower dose. Subsequently, the vasculitis rapidly improved for 2 weeks. The patient then reported symptoms of headache, dizziness, and chills. He was tested for COVID-19 and was negative. Six weeks after increasing the dapsone dose (5 months after initial presentation), the skin was normalizing, showing only faintly hyperpigmented macules confined to areas of resolved vasculitis (forearms, abdomen, legs). 

The patient had been on dapsone 100 mg twice daily for 3 months when he was started on ustekinumab (90 mg at weeks 0 and 4, with planned doses every 12 weeks) for psoriatic arthritis in hopes of withdrawing dapsone. His cutaneous symptoms have remained well controlled on this regimen for 18 months. Lowering of dapsone below 100 mg daily has resulted in recurrent mild vasculitis symptoms; he now maintains the once-daily dosing without negative side effects.

Comment

IgA vasculitis is a form of cutaneous small-vessel leukocytoclastic vasculitis (LCV) characterized by episodes of palpable purpura on the extensor surfaces of the arms and legs that may be associated with arthritis, abdominal pain, and/or hematuria. Although vasculitis is a known potential adverse effect of anti–tumor necrosis factor (TNF) α therapy, cases of adalimumab-induced IgA vasculitis are uncommon. As use of more targeted therapies for psoriasis and psoriatic arthritis, such as the IL-17 inhibitor secukinumab, increases so do reports of associated adverse events. Of 6 previously reported cases of secukinumab-associated vasculitis, at least 4 were IgA vasculitis (Table).^1-6 Another case described one patient with rheumatoid arthritis undergoing secukinumab treatment who experienced necrotizing glomerulonephritis; however, the authors concluded secukinumab likely was not causative in that case, as serologies and urinalyses suggested gradual onset of the process prior to initiating the medication.⁷

The exact pathogenesis of IgA vasculitis is unclear, but a prevailing theory involves the dysregulation of IgA synthesis and metabolism. Other than increased serum levels of transforming growth factor β, which is a major stimulating factor for IgA production, it also has been hypothesized that the presence of aberrantly hypoglycosylated IgA exposes an autoepitope for recognition by other pathogenic IgG and IgA, leading to the formation of large immune complexes that can readily deposit in postcapillary venules. The deposition of IgA immune complexes in postcapillary venules and the subsequent activation of the complement system causes direct damage to the endothelial cells of vessel walls. This complement activation is evidenced by vascular complement component 3 deposition on DIF (a nonspecific feature of LCV). Chemotaxis of neutrophils ensues, followed by their firm adherence and transendothelial migration (mediated by monocyte chemoattractant protein 1 [MCP-1]). Neutrophil degranulation releases reactive oxygen species and cytokines, which in turn recruit additional leukocytes to the area of inflammation, subsequently undergoing degeneration (leukocytoclasis). Microvascular permeability also is enhanced by MCP-1, allowing exudation of serum, erythrocytes, and fibrin. In the setting of elevated circulating TNF and IL-1, endothelium is stimulated to activate the intrinsic and extrinsic coagulation pathways. This decreases endothelial fibrinolytic activity, leading to thrombosis. The high venous pressure and low fibrinolytic activity in the lower legs explains why vasculitic lesions often are confined to or begin in this distribution.^1,8-10

There also are noteworthy roles for cytokines in LCV. Circulating transforming growth factor β and IL-6—which are necessary for development of T helper 17 (T_H17) cells and production of IL-17—are higher in patients with LCV compared to controls. Peripheral blood monocytes in patients with LCV demonstrate higher production of IL-17. Once T_H17 cells develop, their survival and phenotype are maintained by IL-23 (considered the master regulator of T_H17 differentiation). IL-17 is a potent chemoattractant of IL-8 (CXCL8) and MCP-1, both of which promote neutrophil-mediated perivascular inflammation. The IL-23 and IL-17 pathways implicated in the pathogenesis of psoriasis also cause neutrophil activation and upregulate transcription of proinflammatory cytokines (IL-1, IL-6, IL-8, and TNF-α), which overlap with those implicated in LCV. Autoimmune disease generally entails some positive feedback loop of progressively severe self-recognition and tissue destruction by the immune system. These shared cytokinetic processes may explain how the internal environment of psoriasis could perpetuate IgA vasculitis.^1,2,8,10-12

The mechanisms underlying vasculitis associated with adalimumab are unclear, but hypotheses involve direct toxicity on vessels, capillary deposition of anti-TNF/TNF immune complexes, or an inflammatory process resulting in autoantibodies. Similar hypotheses are posited for secukinumab-associated vasculitis, including deposition of secukinumab–IL-17 complexes. Anti–TNF-α medications may increase T_H17 cell numbers, leading to increased production of IL-22 and a resultant immunologic microenvironment conducive to vasculitis. All 6 published cases of secukinumab-associated vasculitis that we found had received prior treatment with a TNF-α blocker, but only 1 had occurrence of vasculitis during that treatment.^1-6,10

In the 6 cases we reviewed, the time from starting secukinumab to onset of vasculitis ranged from 1 to 18 months. Our patient’s same-day re-emergence of vasculitis after his first secukinumab dose was so acute that we were skeptical of secukinumab as a potential trigger; this may simply have been coincident to the natural waxing and waning of the vasculitis (although onset of IgA vasculitis within 1 day of starting anti–TNF-α therapy has been reported).^1-6,13  

Specific associations of IgA vasculitis are many and can include bacterial organisms such as Helicobacter pylori, streptococci, and staphylococci. Although internal mucous membrane infections are considered more linked because of the surveillance role of IgA predominantly in mucosal tissues, it is possible that our patient with cutaneous MRSA harbored the same within the nasal mucosa. Our patient also received multiple vaccinations outside our department throughout his clinical course (2 hepatitis B and 1 pneumococcal conjugate), which are known potential triggers for vasculitis. Psychological stress is a known trigger for psoriasis, and given the cytokinetic relationship of psoriasis to vasculitis described previously, it may have indirectly contributed to vasculitis in our case. The anxiety associated with being immunosuppressed during the COVID-19 pandemic and bereavement of losing a family member may have contributed to the refractory nature of our patient’s condition. Renal involvement is relatively common in adults with IgA vasculitis and so should be ruled out, as should occult internal malignancy.^8,10,14

It is unclear which of the above factors was causative in our case, but a multifactorial process is likely. Treatment of monoclonal antibody–associated vasculitis entails investigating for triggers and systemic involvement, removing the most likely culprit, quelling the vasculitis acutely, avoiding known potential exacerbators, and introducing an alternative long-term immunomodulant. In all 6 reported similar cases, discontinuation of secukinumab and initiation of prednisone or colchicine led to resolution.^1-6 Dapsone also is acceptable for acute control of IgA vasculitis, although this medication is highly lipid soluble and penetrates well into various tissues.¹⁵ Thus, lower doses may prove ineffective for obese patients, as was demonstrated in our case. Given the known potential of vaccinations, infections, and other factors (eg, alcohol, penicillin) to trigger IgA vasculitis, these should be avoided.¹⁰

Blockade of IL-23 with ustekinumab has been suggested by other authors encountering secukinumab-associated vasculitis, as IL-23 is the main driver and sustainer of T_H17 cell differentiation.⁸ Although 6 previously reported cases of secukinumab-associated vasculitis achieved resolution without long-term recurrence, none did so using an IL-23 inhibitor (nor had any of the described patients received IL-23 inhibitors previously).^1-6 Given the established safety of IL-23 inhibitors and that they theoretically are well suited for this unique circumstance (by ceasing the main causative cytokine cascades “upstream”) and were efficacious in quickly resolving our patient’s vasculitis, we suggest that ustekinumab may represent an ideal treatment option for patients in whom adalimumab- or secukinumab-associated vasculitis is suspected. Further research is needed given the complex interplay of so many variables and the increasingly common reports of adverse cutaneous events associated with these drugs.^1-6,10 

Case Report

A 47-year-old man presented with a sudden-onset rash consisting of red bumps on the abdomen and legs that had been ongoing for several days. He had known psoriasis and psoriatic arthritis that had been well controlled with adalimumab for the last 18 months. He reported concurrent onset of nausea but denied fevers, chills, night sweats, unintentional weight loss, abdominal pain, and pruritus. He endorsed prior cutaneous infections of methicillin-resistant Staphylococcus aureus (MRSA). His medical history also included diabetes mellitus, hypertension, and obesity. His other medications included oral losartan-hydrochlorothiazide, amlodipine, naproxen, and atorvastatin.

Physical examination revealed numerous thin purpuric papules—some with adherent scale—distributed on the lower legs, extensor forearms, and abdomen. Abdominal lesions were confined to weight-related striae (Figure 1). The palms, soles, oral mucosa, and face were spared. Three punch biopsies were performed, including 1 for direct immunofluorescence (DIF), and the patient was instructed to apply clobetasol to the affected areas twice daily until further notice.

Pathology showed perivascular extravasation of erythrocytes, neutrophils, eosinophils, and leukocytoclasis surrounding blood vessels associated with fibrin (Figure 2). Direct immunofluorescence showed granular deposition of IgA, complement component 3, and fibrinogen in a superficial dermal vascular pattern (Figure 3). These results were consistent with IgA small-vessel vasculitis. One specimen was consistent with the patient’s known psoriasis.  

Urinalysis revealed moderate hemoglobinuria, and urine microscopy showed 174 red blood cells per high-power field. Creatinine was high at 1.87 mg/dL (reference range, <1.34 mg/dL; patient’s baseline, 0.81 mg/dL) and glomerular filtration rate was low (42 mL/min, patient’s baseline, >60 mL/min [reference range, 90–120 mL/min]). Erythrocyte sedimentation rate (21 mm/h [reference range, 0–22 mm/h]) and C-reactive protein were elevated (2.2 mg/dL [reference range, 0.3–1.0 mg/dL]). Given his history of cutaneous MRSA infections, a bacterial culture swab was collected from the skin surface to check for colonization, which showed moderate growth of MRSA. Naproxen was discontinued over concern of worsening the patient’s renal status. The patient was instructed to rest at home with his legs elevated, wear compression socks when ambulatory, use chlorhexidine antiseptic daily as a body wash when showering, and apply mupirocin three times daily to the biopsy sites. He was referred to urology for his microhematuria, where cystoscopy revealed no abnormalities.A month passed with no improvement of the patient’s cutaneous vasculitis, and his psoriatic arthritis worsened without his usual use of naproxen. He developed abdominal pain and loss of appetite. A prednisone taper was ordered starting at 40 mg/d (28.8 mg/kg), which provided relief of the skin and joint symptoms only until the course was completed 12 days later. 

Five weeks after the initial presentation, the patient returned with a more severe eruption consisting of innumerable purpuric papules that coalesced in plaques on the abdomen, arms, and legs. He also had erythematous facial pustules and mild palmar petechiae (Figure 4). Three biopsies were performed, including 1 for DIF and 1 from a pustule on the forehead. Histology and DIF were again consistent with IgA small-vessel vasculitis. The forehead biopsy was compatible with steroid acne (attributed to recent prednisone use) and psoriasis.   

Rheumatology was consulted, and adalimumab was discontinued 6 weeks after the initial presentation out of concern for drug-induced cutaneous vasculitis. Vasculitis work-up was unremarkable, including antineutrophil cytoplasmic antibodies, rheumatoid factor, cyclic citrullinated peptide, and serum protein electrophoresis. Oral dapsone was started at 100 mg/d, with the tentative plan of starting secukinumab if cutaneous symptoms improved. For 3 weeks, the patient’s cutaneous symptoms steadily improved.

Nine weeks after initial presentation to dermatology (3 weeks after discontinuing adalimumab) the patient self-administered his first dose of secukinumab at home. Several hours later, he reported sudden reappearance of vasculitis. He denied diarrhea, abdominal pain, bowel movement urgency, fevers, fatigue, and unintentional weight loss. Antistreptolysin O and hepatitis A antibodies were negative. He was instructed to hold secukinumab indefinitely.

Four weeks after his only secukinumab injection, the patient reported another episode of acute worsening cutaneous symptoms. A 4-week prednisone taper starting at 40 mg/d was ordered. Computed tomography of the chest, abdomen, and pelvis to rule out internal malignancy was unremarkable. Around this time, the patient reported major emotional distress related to an unexpected death in his family, which added to a gradual increase in his stress level related to the COVID-19 pandemic. 

Three weeks later, dapsone was increased to 100 mg twice daily on account of the patient’s adiposity and lack of cutaneous improvement on the lower dose. Subsequently, the vasculitis rapidly improved for 2 weeks. The patient then reported symptoms of headache, dizziness, and chills. He was tested for COVID-19 and was negative. Six weeks after increasing the dapsone dose (5 months after initial presentation), the skin was normalizing, showing only faintly hyperpigmented macules confined to areas of resolved vasculitis (forearms, abdomen, legs). 

The patient had been on dapsone 100 mg twice daily for 3 months when he was started on ustekinumab (90 mg at weeks 0 and 4, with planned doses every 12 weeks) for psoriatic arthritis in hopes of withdrawing dapsone. His cutaneous symptoms have remained well controlled on this regimen for 18 months. Lowering of dapsone below 100 mg daily has resulted in recurrent mild vasculitis symptoms; he now maintains the once-daily dosing without negative side effects.

Comment

IgA vasculitis is a form of cutaneous small-vessel leukocytoclastic vasculitis (LCV) characterized by episodes of palpable purpura on the extensor surfaces of the arms and legs that may be associated with arthritis, abdominal pain, and/or hematuria. Although vasculitis is a known potential adverse effect of anti–tumor necrosis factor (TNF) α therapy, cases of adalimumab-induced IgA vasculitis are uncommon. As use of more targeted therapies for psoriasis and psoriatic arthritis, such as the IL-17 inhibitor secukinumab, increases so do reports of associated adverse events. Of 6 previously reported cases of secukinumab-associated vasculitis, at least 4 were IgA vasculitis (Table).^1-6 Another case described one patient with rheumatoid arthritis undergoing secukinumab treatment who experienced necrotizing glomerulonephritis; however, the authors concluded secukinumab likely was not causative in that case, as serologies and urinalyses suggested gradual onset of the process prior to initiating the medication.⁷

The exact pathogenesis of IgA vasculitis is unclear, but a prevailing theory involves the dysregulation of IgA synthesis and metabolism. Other than increased serum levels of transforming growth factor β, which is a major stimulating factor for IgA production, it also has been hypothesized that the presence of aberrantly hypoglycosylated IgA exposes an autoepitope for recognition by other pathogenic IgG and IgA, leading to the formation of large immune complexes that can readily deposit in postcapillary venules. The deposition of IgA immune complexes in postcapillary venules and the subsequent activation of the complement system causes direct damage to the endothelial cells of vessel walls. This complement activation is evidenced by vascular complement component 3 deposition on DIF (a nonspecific feature of LCV). Chemotaxis of neutrophils ensues, followed by their firm adherence and transendothelial migration (mediated by monocyte chemoattractant protein 1 [MCP-1]). Neutrophil degranulation releases reactive oxygen species and cytokines, which in turn recruit additional leukocytes to the area of inflammation, subsequently undergoing degeneration (leukocytoclasis). Microvascular permeability also is enhanced by MCP-1, allowing exudation of serum, erythrocytes, and fibrin. In the setting of elevated circulating TNF and IL-1, endothelium is stimulated to activate the intrinsic and extrinsic coagulation pathways. This decreases endothelial fibrinolytic activity, leading to thrombosis. The high venous pressure and low fibrinolytic activity in the lower legs explains why vasculitic lesions often are confined to or begin in this distribution.^1,8-10

There also are noteworthy roles for cytokines in LCV. Circulating transforming growth factor β and IL-6—which are necessary for development of T helper 17 (T_H17) cells and production of IL-17—are higher in patients with LCV compared to controls. Peripheral blood monocytes in patients with LCV demonstrate higher production of IL-17. Once T_H17 cells develop, their survival and phenotype are maintained by IL-23 (considered the master regulator of T_H17 differentiation). IL-17 is a potent chemoattractant of IL-8 (CXCL8) and MCP-1, both of which promote neutrophil-mediated perivascular inflammation. The IL-23 and IL-17 pathways implicated in the pathogenesis of psoriasis also cause neutrophil activation and upregulate transcription of proinflammatory cytokines (IL-1, IL-6, IL-8, and TNF-α), which overlap with those implicated in LCV. Autoimmune disease generally entails some positive feedback loop of progressively severe self-recognition and tissue destruction by the immune system. These shared cytokinetic processes may explain how the internal environment of psoriasis could perpetuate IgA vasculitis.^1,2,8,10-12

The mechanisms underlying vasculitis associated with adalimumab are unclear, but hypotheses involve direct toxicity on vessels, capillary deposition of anti-TNF/TNF immune complexes, or an inflammatory process resulting in autoantibodies. Similar hypotheses are posited for secukinumab-associated vasculitis, including deposition of secukinumab–IL-17 complexes. Anti–TNF-α medications may increase T_H17 cell numbers, leading to increased production of IL-22 and a resultant immunologic microenvironment conducive to vasculitis. All 6 published cases of secukinumab-associated vasculitis that we found had received prior treatment with a TNF-α blocker, but only 1 had occurrence of vasculitis during that treatment.^1-6,10

In the 6 cases we reviewed, the time from starting secukinumab to onset of vasculitis ranged from 1 to 18 months. Our patient’s same-day re-emergence of vasculitis after his first secukinumab dose was so acute that we were skeptical of secukinumab as a potential trigger; this may simply have been coincident to the natural waxing and waning of the vasculitis (although onset of IgA vasculitis within 1 day of starting anti–TNF-α therapy has been reported).^1-6,13  

Specific associations of IgA vasculitis are many and can include bacterial organisms such as Helicobacter pylori, streptococci, and staphylococci. Although internal mucous membrane infections are considered more linked because of the surveillance role of IgA predominantly in mucosal tissues, it is possible that our patient with cutaneous MRSA harbored the same within the nasal mucosa. Our patient also received multiple vaccinations outside our department throughout his clinical course (2 hepatitis B and 1 pneumococcal conjugate), which are known potential triggers for vasculitis. Psychological stress is a known trigger for psoriasis, and given the cytokinetic relationship of psoriasis to vasculitis described previously, it may have indirectly contributed to vasculitis in our case. The anxiety associated with being immunosuppressed during the COVID-19 pandemic and bereavement of losing a family member may have contributed to the refractory nature of our patient’s condition. Renal involvement is relatively common in adults with IgA vasculitis and so should be ruled out, as should occult internal malignancy.^8,10,14

It is unclear which of the above factors was causative in our case, but a multifactorial process is likely. Treatment of monoclonal antibody–associated vasculitis entails investigating for triggers and systemic involvement, removing the most likely culprit, quelling the vasculitis acutely, avoiding known potential exacerbators, and introducing an alternative long-term immunomodulant. In all 6 reported similar cases, discontinuation of secukinumab and initiation of prednisone or colchicine led to resolution.^1-6 Dapsone also is acceptable for acute control of IgA vasculitis, although this medication is highly lipid soluble and penetrates well into various tissues.¹⁵ Thus, lower doses may prove ineffective for obese patients, as was demonstrated in our case. Given the known potential of vaccinations, infections, and other factors (eg, alcohol, penicillin) to trigger IgA vasculitis, these should be avoided.¹⁰

Blockade of IL-23 with ustekinumab has been suggested by other authors encountering secukinumab-associated vasculitis, as IL-23 is the main driver and sustainer of T_H17 cell differentiation.⁸ Although 6 previously reported cases of secukinumab-associated vasculitis achieved resolution without long-term recurrence, none did so using an IL-23 inhibitor (nor had any of the described patients received IL-23 inhibitors previously).^1-6 Given the established safety of IL-23 inhibitors and that they theoretically are well suited for this unique circumstance (by ceasing the main causative cytokine cascades “upstream”) and were efficacious in quickly resolving our patient’s vasculitis, we suggest that ustekinumab may represent an ideal treatment option for patients in whom adalimumab- or secukinumab-associated vasculitis is suspected. Further research is needed given the complex interplay of so many variables and the increasingly common reports of adverse cutaneous events associated with these drugs.^1-6,10 

Janus kinase inhibitors tofacitinib (Xeljanz) and baricitinib (Olumiant) may pose no greater risk than does adalimumab (Humira and biosimilars) for major adverse cardiovascular events (MACEs) or venous thromboembolism (VTE) on the basis of a nationwide cohort study.

The French data, which included almost 16,000 patients with rheumatoid arthritis, revealed similar safety across subgroups, including older patients with at least one preexisting cardiovascular risk factor, reported lead author Léa Hoisnard, MD, of Henri Mondor Hospital, Paris, and colleagues.

These findings arrive 1 year after the U.S. Food and Drug Administration imposed class-wide boxed warnings on three Janus kinase (JAK) inhibitors, citing increased risks for both cancer and serious cardiac events detected by the open-label, randomized ORAL Surveillance postmarketing trial, which compared tofacitinib against adalimumab and etanercept.

More recently, the observational STAR-RA study, relying upon private insurance and Medicare claims in the United States, found no significant increase in cardiovascular events among patients taking tofacitinib, adding some uncertainty to the conversation.

“In this context, observational studies of unselected populations outside of North America are still needed to assess other JAK inhibitor agents,” Dr. Hoisnard and colleagues write in Annals of the Rheumatic Diseases.

Their retrospective study included 8,481 patients who received baricitinib or tofacitinib, and 7,354 patients who received adalimumab. Almost all patients in the tofacitinib group received 5 mg twice daily instead of 10 mg twice daily (99.4% vs. 0.6%), so cardiovascular safety was assessed only for the 5-mg dose. Baricitinib was prescribed at 4-mg and 2-mg doses (79.5% vs. 20.5%), allowing inclusion of both dose levels. The investigators accounted for a range of covariates, including concurrent therapy, comorbidities, and other patient characteristics.

Median follow-up durations were 440 days in the JAK inhibitor group and 344 days in the adalimumab group. The JAK inhibitor group had numerically more MACEs than did the adalimumab group, but the difference in risk was not statistically significant (54 vs. 35 MACEs; weighted hazard ratio, 1.0; 95% confidence interval, 0.7-1.5; P = .99). Similarly, more patients taking JAK inhibitors had VTEs, but relative risk was, again, not significant (75 vs. 32 VTEs; HRw, 1.1; 95% CI, 0.7-1.6; P = .63).

These findings were consistent for all subgroups, including patients aged 50 years or older and patients aged 65 years or older, although the investigators noted that statistical power was lacking for subgroup analyses.
 

Findings from Echo ORAL Surveillance

“I think the baricitinib data are important,” Kevin Winthrop, MD, MPH, professor of infectious diseases and epidemiology at Oregon Health & Science University, Portland, told this news organization. “There’s no difference between 2 mg and 4 mg [dose levels] in this analysis. And there doesn’t really seem to be a difference between baricitinib and tofacitinib. Most of the results are pretty consistent with ORAL Surveillance, which was a randomized, controlled trial.”

Dr. Winthrop, who has been active in JAK inhibitor clinical trials, recently coauthored an article in Nature Reviews Rheumatology encouraging clinicians to remember that the cardiovascular risks of JAK inhibitors are relative to adalimumab, and safety should be framed within the context of risk-to-benefit ratios.

He and his coauthor also called into question the FDA’s “better to be safe than sorry” approach, which resulted in boxed warnings across all JAK inhibitors, despite differences in target specificity.

“There are pros and cons of taking that approach,” Dr. Winthrop said in an interview. “The FDA might ultimately be right. Certainly, these drugs appear similar for some types of events, like herpes zoster, for example. But whether they’re similar with regard to malignancy or cardiovascular events, I don’t think we know.”

Dr. Winthrop noted that deucravacitinib was recently approved for psoriasis sans boxed warning, suggesting inconsistency in the FDA’s approach. The agent headlines as a “TYK2 inhibitor,” but TYK2 is a member of the JAK family.

“I don’t know why the FDA decided to treat them differently,” Dr. Winthrop said.

Boxed warnings encourage caution, lock treatment sequence

Michael Thakor, MD, of Arthritis & Rheumatology Clinic of Northern Colorado, Fort Collins, supports the boxed warnings because they encourage caution and transparency.

“It forces you to have that discussion with your patient, which may take some time, but it’s actually a very good thing,” Dr. Thakor said in an interview. “Some patients will say, ‘Oh my gosh, I don’t want to take that drug.’ But most patients, considering the level of risk that you’re talking about, are actually okay going ahead with the medication.”

If these risks aren’t discussed, he noted, patient trust may falter.

“They’re going to go online, and they’re going to be reading about it,” Dr. Thakor said. “And then they tend to get more spooked. They also may question your advice from then on, if you’re not telling them the possible risk.”

Reflecting on the present study, Dr. Thakor said that the findings initially appeared reassuring, but he became concerned about the lack of power and how adverse events trended higher in the JAK inhibitor group, particularly for VTEs, most of which occurred with baricitinib. This latter finding is challenging to interpret, however, because the 4-mg dose is not used in the United States, he added.

Dr. Thakor described how JAK inhibitors once seemed poised to assume a frontline role in RA until the boxed warnings came out. These safety concerns don’t take JAK inhibitors off the table, he said, but they do keep the class further down the treatment sequence, and the present data don’t alter this picture in daily practice.

“If I had a patient who was over the age of 50 with at least one cardiovascular risk factor, I might have a little bit of concern, but if they need their RA treated, I would definitely discuss the possibility of using a JAK inhibitor,” Dr. Thakor said. “If the patient is comfortable with it, then I would feel comfortable going ahead.”

The investigators disclosed no outside funding or conflicts of interest. Dr. Winthrop disclosed relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, and others. Dr. Thakor disclosed no conflicts of interest.

A version of this article first appeared on Medscape.com.

Janus kinase inhibitors tofacitinib (Xeljanz) and baricitinib (Olumiant) may pose no greater risk than does adalimumab (Humira and biosimilars) for major adverse cardiovascular events (MACEs) or venous thromboembolism (VTE) on the basis of a nationwide cohort study.

The French data, which included almost 16,000 patients with rheumatoid arthritis, revealed similar safety across subgroups, including older patients with at least one preexisting cardiovascular risk factor, reported lead author Léa Hoisnard, MD, of Henri Mondor Hospital, Paris, and colleagues.

These findings arrive 1 year after the U.S. Food and Drug Administration imposed class-wide boxed warnings on three Janus kinase (JAK) inhibitors, citing increased risks for both cancer and serious cardiac events detected by the open-label, randomized ORAL Surveillance postmarketing trial, which compared tofacitinib against adalimumab and etanercept.

More recently, the observational STAR-RA study, relying upon private insurance and Medicare claims in the United States, found no significant increase in cardiovascular events among patients taking tofacitinib, adding some uncertainty to the conversation.

“In this context, observational studies of unselected populations outside of North America are still needed to assess other JAK inhibitor agents,” Dr. Hoisnard and colleagues write in Annals of the Rheumatic Diseases.

Their retrospective study included 8,481 patients who received baricitinib or tofacitinib, and 7,354 patients who received adalimumab. Almost all patients in the tofacitinib group received 5 mg twice daily instead of 10 mg twice daily (99.4% vs. 0.6%), so cardiovascular safety was assessed only for the 5-mg dose. Baricitinib was prescribed at 4-mg and 2-mg doses (79.5% vs. 20.5%), allowing inclusion of both dose levels. The investigators accounted for a range of covariates, including concurrent therapy, comorbidities, and other patient characteristics.

Median follow-up durations were 440 days in the JAK inhibitor group and 344 days in the adalimumab group. The JAK inhibitor group had numerically more MACEs than did the adalimumab group, but the difference in risk was not statistically significant (54 vs. 35 MACEs; weighted hazard ratio, 1.0; 95% confidence interval, 0.7-1.5; P = .99). Similarly, more patients taking JAK inhibitors had VTEs, but relative risk was, again, not significant (75 vs. 32 VTEs; HRw, 1.1; 95% CI, 0.7-1.6; P = .63).

These findings were consistent for all subgroups, including patients aged 50 years or older and patients aged 65 years or older, although the investigators noted that statistical power was lacking for subgroup analyses.
 

Findings from Echo ORAL Surveillance

“I think the baricitinib data are important,” Kevin Winthrop, MD, MPH, professor of infectious diseases and epidemiology at Oregon Health & Science University, Portland, told this news organization. “There’s no difference between 2 mg and 4 mg [dose levels] in this analysis. And there doesn’t really seem to be a difference between baricitinib and tofacitinib. Most of the results are pretty consistent with ORAL Surveillance, which was a randomized, controlled trial.”

Dr. Winthrop, who has been active in JAK inhibitor clinical trials, recently coauthored an article in Nature Reviews Rheumatology encouraging clinicians to remember that the cardiovascular risks of JAK inhibitors are relative to adalimumab, and safety should be framed within the context of risk-to-benefit ratios.

He and his coauthor also called into question the FDA’s “better to be safe than sorry” approach, which resulted in boxed warnings across all JAK inhibitors, despite differences in target specificity.

“There are pros and cons of taking that approach,” Dr. Winthrop said in an interview. “The FDA might ultimately be right. Certainly, these drugs appear similar for some types of events, like herpes zoster, for example. But whether they’re similar with regard to malignancy or cardiovascular events, I don’t think we know.”

Dr. Winthrop noted that deucravacitinib was recently approved for psoriasis sans boxed warning, suggesting inconsistency in the FDA’s approach. The agent headlines as a “TYK2 inhibitor,” but TYK2 is a member of the JAK family.

“I don’t know why the FDA decided to treat them differently,” Dr. Winthrop said.

Boxed warnings encourage caution, lock treatment sequence

Michael Thakor, MD, of Arthritis & Rheumatology Clinic of Northern Colorado, Fort Collins, supports the boxed warnings because they encourage caution and transparency.

“It forces you to have that discussion with your patient, which may take some time, but it’s actually a very good thing,” Dr. Thakor said in an interview. “Some patients will say, ‘Oh my gosh, I don’t want to take that drug.’ But most patients, considering the level of risk that you’re talking about, are actually okay going ahead with the medication.”

If these risks aren’t discussed, he noted, patient trust may falter.

“They’re going to go online, and they’re going to be reading about it,” Dr. Thakor said. “And then they tend to get more spooked. They also may question your advice from then on, if you’re not telling them the possible risk.”

Reflecting on the present study, Dr. Thakor said that the findings initially appeared reassuring, but he became concerned about the lack of power and how adverse events trended higher in the JAK inhibitor group, particularly for VTEs, most of which occurred with baricitinib. This latter finding is challenging to interpret, however, because the 4-mg dose is not used in the United States, he added.

Dr. Thakor described how JAK inhibitors once seemed poised to assume a frontline role in RA until the boxed warnings came out. These safety concerns don’t take JAK inhibitors off the table, he said, but they do keep the class further down the treatment sequence, and the present data don’t alter this picture in daily practice.

“If I had a patient who was over the age of 50 with at least one cardiovascular risk factor, I might have a little bit of concern, but if they need their RA treated, I would definitely discuss the possibility of using a JAK inhibitor,” Dr. Thakor said. “If the patient is comfortable with it, then I would feel comfortable going ahead.”

The investigators disclosed no outside funding or conflicts of interest. Dr. Winthrop disclosed relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, and others. Dr. Thakor disclosed no conflicts of interest.

A version of this article first appeared on Medscape.com.

Janus kinase inhibitors tofacitinib (Xeljanz) and baricitinib (Olumiant) may pose no greater risk than does adalimumab (Humira and biosimilars) for major adverse cardiovascular events (MACEs) or venous thromboembolism (VTE) on the basis of a nationwide cohort study.

The French data, which included almost 16,000 patients with rheumatoid arthritis, revealed similar safety across subgroups, including older patients with at least one preexisting cardiovascular risk factor, reported lead author Léa Hoisnard, MD, of Henri Mondor Hospital, Paris, and colleagues.

These findings arrive 1 year after the U.S. Food and Drug Administration imposed class-wide boxed warnings on three Janus kinase (JAK) inhibitors, citing increased risks for both cancer and serious cardiac events detected by the open-label, randomized ORAL Surveillance postmarketing trial, which compared tofacitinib against adalimumab and etanercept.

More recently, the observational STAR-RA study, relying upon private insurance and Medicare claims in the United States, found no significant increase in cardiovascular events among patients taking tofacitinib, adding some uncertainty to the conversation.

“In this context, observational studies of unselected populations outside of North America are still needed to assess other JAK inhibitor agents,” Dr. Hoisnard and colleagues write in Annals of the Rheumatic Diseases.

Their retrospective study included 8,481 patients who received baricitinib or tofacitinib, and 7,354 patients who received adalimumab. Almost all patients in the tofacitinib group received 5 mg twice daily instead of 10 mg twice daily (99.4% vs. 0.6%), so cardiovascular safety was assessed only for the 5-mg dose. Baricitinib was prescribed at 4-mg and 2-mg doses (79.5% vs. 20.5%), allowing inclusion of both dose levels. The investigators accounted for a range of covariates, including concurrent therapy, comorbidities, and other patient characteristics.

Median follow-up durations were 440 days in the JAK inhibitor group and 344 days in the adalimumab group. The JAK inhibitor group had numerically more MACEs than did the adalimumab group, but the difference in risk was not statistically significant (54 vs. 35 MACEs; weighted hazard ratio, 1.0; 95% confidence interval, 0.7-1.5; P = .99). Similarly, more patients taking JAK inhibitors had VTEs, but relative risk was, again, not significant (75 vs. 32 VTEs; HRw, 1.1; 95% CI, 0.7-1.6; P = .63).

These findings were consistent for all subgroups, including patients aged 50 years or older and patients aged 65 years or older, although the investigators noted that statistical power was lacking for subgroup analyses.
 

Findings from Echo ORAL Surveillance

“I think the baricitinib data are important,” Kevin Winthrop, MD, MPH, professor of infectious diseases and epidemiology at Oregon Health & Science University, Portland, told this news organization. “There’s no difference between 2 mg and 4 mg [dose levels] in this analysis. And there doesn’t really seem to be a difference between baricitinib and tofacitinib. Most of the results are pretty consistent with ORAL Surveillance, which was a randomized, controlled trial.”

Dr. Winthrop, who has been active in JAK inhibitor clinical trials, recently coauthored an article in Nature Reviews Rheumatology encouraging clinicians to remember that the cardiovascular risks of JAK inhibitors are relative to adalimumab, and safety should be framed within the context of risk-to-benefit ratios.

He and his coauthor also called into question the FDA’s “better to be safe than sorry” approach, which resulted in boxed warnings across all JAK inhibitors, despite differences in target specificity.

“There are pros and cons of taking that approach,” Dr. Winthrop said in an interview. “The FDA might ultimately be right. Certainly, these drugs appear similar for some types of events, like herpes zoster, for example. But whether they’re similar with regard to malignancy or cardiovascular events, I don’t think we know.”

Dr. Winthrop noted that deucravacitinib was recently approved for psoriasis sans boxed warning, suggesting inconsistency in the FDA’s approach. The agent headlines as a “TYK2 inhibitor,” but TYK2 is a member of the JAK family.

“I don’t know why the FDA decided to treat them differently,” Dr. Winthrop said.

Boxed warnings encourage caution, lock treatment sequence

Michael Thakor, MD, of Arthritis & Rheumatology Clinic of Northern Colorado, Fort Collins, supports the boxed warnings because they encourage caution and transparency.

“It forces you to have that discussion with your patient, which may take some time, but it’s actually a very good thing,” Dr. Thakor said in an interview. “Some patients will say, ‘Oh my gosh, I don’t want to take that drug.’ But most patients, considering the level of risk that you’re talking about, are actually okay going ahead with the medication.”

If these risks aren’t discussed, he noted, patient trust may falter.

“They’re going to go online, and they’re going to be reading about it,” Dr. Thakor said. “And then they tend to get more spooked. They also may question your advice from then on, if you’re not telling them the possible risk.”

Reflecting on the present study, Dr. Thakor said that the findings initially appeared reassuring, but he became concerned about the lack of power and how adverse events trended higher in the JAK inhibitor group, particularly for VTEs, most of which occurred with baricitinib. This latter finding is challenging to interpret, however, because the 4-mg dose is not used in the United States, he added.

Dr. Thakor described how JAK inhibitors once seemed poised to assume a frontline role in RA until the boxed warnings came out. These safety concerns don’t take JAK inhibitors off the table, he said, but they do keep the class further down the treatment sequence, and the present data don’t alter this picture in daily practice.

“If I had a patient who was over the age of 50 with at least one cardiovascular risk factor, I might have a little bit of concern, but if they need their RA treated, I would definitely discuss the possibility of using a JAK inhibitor,” Dr. Thakor said. “If the patient is comfortable with it, then I would feel comfortable going ahead.”

The investigators disclosed no outside funding or conflicts of interest. Dr. Winthrop disclosed relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, and others. Dr. Thakor disclosed no conflicts of interest.

A version of this article first appeared on Medscape.com.

A commentary published across four dermatology journals in September urges dermatologists and their medical societies to “engage more meaningfully” on climate change issues, “moving beyond merely discussing skin-related impacts” and toward prioritizing both patient and planetary health.

Dermatologists must make emissions-saving changes in everyday practice, for instance, and the specialty must enlist key stakeholders in public health, nonprofits, and industry – that is, pharmaceutical and medical supply companies – in finding solutions to help mitigate and adapt to climate change, wrote Eva Rawlings Parker, MD, and Markus D. Boos, MD, PhD.

“We have an ethical imperative to act,” they wrote. “The time is now for dermatologists and our medical societies to collectively rise to meet this crisis.”

Their commentary was published online in the International Journal of Dermatology , Journal of the European Academy of Dermatology and Venereology, British Journal of Dermatology, and Pediatric Dermatology.

In an interview, Dr. Parker, assistant professor of dermatology at Vanderbilt University, Nashville, Tenn., said that she and Dr. Boos, associate professor in the division of dermatology and department of pediatrics at the University of Washington, Seattle, were motivated to write the editorial upon finding that dermatology was not represented among more than 230 medical journals that published an editorial in September 2021 calling for emergency action to limit global warming and protect health. In addition to the New England Journal of Medicine and The Lancet, the copublishing journals represented numerous specialties, from nursing and pediatrics, to cardiology, rheumatology, and gastroenterology.

The editorial was not published in any dermatology journals, Dr. Parker said. “It was incredibly disappointing for me along with many of my colleagues who advocate for climate action because we realized it was a missed opportunity for dermatology to align with other medical specialties and be on the forefront of leading climate action to protect health.”
 

‘A threat multiplier’

The impact of climate change on skin disease is “an incredibly important part of our conversation as dermatologists because many cutaneous diseases are climate sensitive and we’re often seeing the effects of climate change every day in our clinical practices,” Dr. Parker said.

In fact, the impact on skin disease needs to be explored much further through more robust research funding, so that dermatology can better understand not only the incidence and severity of climate-induced changes in skin diseases – including and beyond atopic dermatitis, acne, and psoriasis – but also the mechanisms and pathophysiology involved, she said.

However, the impacts are much broader, she and Dr. Boos, a pediatric dermatologist at Seattle Children’s Hospital, maintain in their commentary. “An essential concept to broker among dermatologists is that the impacts of climate change extend well beyond skin disease by also placing broad pressure” on infrastructure, the economy, financial markets, global supply chains, food and water insecurity, and more, they wrote, noting the deep inequities of climate change.

Climate change is a “threat multiplier for public health, equity, and health systems,” the commentary says. “The confluence of these climate-related pressures should sound alarm bells as they place enormous jeopardy on the practice of dermatology across all scales and regions.”

Health care is among the most carbon-intensive service sectors worldwide, contributing to almost 5% of greenhouse gas emissions globally, the commentary says. And nationally, of the estimated greenhouse gas emissions from the United States, the health care sector contributes 10%, Dr. Parker said in the interview, referring to a 2016 report.

In addition, according to a 2019 report, the United States is the top contributor to health care’s global climate footprint, contributing 27% of health care’s global emissions, Dr. Parker noted.

Petmal/iStock/Getty Images

In their commentary, she and Dr. Boos wrote that individually and practice wide, dermatologists can impact decarbonization through measures such as virtual attendance at medical meetings and greater utilization of telehealth services. Reductions in carbon emissions were demonstrated for virtual isotretinoin follow-up visits in a recent study, and these savings could be extrapolated to other routine follow-up visits for conditions such as rosacea, monitoring of biologics in patients with well-controlled disease, and postoperative wound checks, they said.

But when it comes to measures such as significantly reducing packaging and waste and “curating supply chains to make them more sustainable,” it is medical societies that have the “larger voice and broader relationship with the pharmaceutical industry” and with medical supply manufacturers and distributors, Dr. Parker explained in the interview, noting the potential for reducing the extensive amount of packaging used for drug samples.

Dr. Parker cochairs the American Academy of Dermatology’s Expert Resource Group for Climate Change and Environmental Issues, which was established several years ago, and Dr. Boos is a member of the group’s executive committee.


 

AAD actions

In its 2018 Position Statement on Climate and Health, the American Academy of Dermatology resolved to raise awareness of the effects of climate change on the skin and educate patients about this, and to “work with other medical societies in ongoing and future efforts to educate the public and mitigate the effects of climate change on global health.”

Asked about the commentary’s call for more collaboration with industry and other stakeholders – and the impact that organized dermatology can have on planetary health – Mark D. Kaufmann, MD, president of the AAD, said in an email that the AAD is “first and foremost an organization focused on providing gold-standard educational resources for dermatologists.”

The academy recognizes that “there are many dermatologic consequences of climate change that will increasingly affect our patients and challenge our membership,” and it has provided education on climate change in forums such as articles, podcasts, and sessions at AAD meetings, said Dr. Kaufmann, clinical professor in the department of dermatology, Icahn School of Medicine at Mount Sinai, New York.

Regarding collaboration with other societies, he said that the AAD’s “focus to date has been on how to provide our members with educational resources to understand and prepare for how climate change may impact their practices and the dermatologic health of their patients,” he said.

The AAD has also sought to address its own carbon footprint and improve sustainability of its operations, including taking steps to reduce plastic and paper waste at its educational events, and to eliminate plastic waste associated with mailing resources like its member magazine, Dr. Kaufmann noted.

And in keeping with the Academy pledge – also articulated in the 2018 position statement – to support and facilitate dermatologists’ efforts to decrease their carbon footprint “in a cost effective (or cost-saving) manner,” Dr. Kaufmann said that the AAD has been offering a program called My Green Doctor as a free benefit of membership.
 

‘Be part of the solution’

In an interview, Mary E. Maloney, MD, professor of medicine and director of dermatologic surgery at the University of Massachusetts, Worcester, said her practice did an audit of their surgical area and found ways to increase the use of paper-packaged gauze – and decrease use of gauze in hard plastic containers – and otherwise decrease the amount of disposables, all of which take “huge amounts of resources” to create.

In the process, “we found significant savings,” she said. “Little things can turn out, in the long run, to be big things.”

Asked about the commentary, Dr. Maloney, who is involved in the AAD’s climate change resource group, said “the message is that yes, we need to be aware of the diseases affected by climate change. But our greater imperative is to be part of the solution and not part of the problem as far as doing things that affect climate change.”

Organized dermatology needs to broaden its advocacy, she said. “I don’t want us to stop advocating for things for our patients, but I do want us to start advocating for the world ... If we don’t try to [mitigate] climate change, we won’t have patients to advocate for.”

Dr. Parker, an associate editor of The Journal of Climate Change and Health, and Dr. Boos declared no conflicts of interest and no funding source for their commentary. Dr. Maloney said she has no conflicts of interest.

A commentary published across four dermatology journals in September urges dermatologists and their medical societies to “engage more meaningfully” on climate change issues, “moving beyond merely discussing skin-related impacts” and toward prioritizing both patient and planetary health.

Dermatologists must make emissions-saving changes in everyday practice, for instance, and the specialty must enlist key stakeholders in public health, nonprofits, and industry – that is, pharmaceutical and medical supply companies – in finding solutions to help mitigate and adapt to climate change, wrote Eva Rawlings Parker, MD, and Markus D. Boos, MD, PhD.

“We have an ethical imperative to act,” they wrote. “The time is now for dermatologists and our medical societies to collectively rise to meet this crisis.”

Their commentary was published online in the International Journal of Dermatology , Journal of the European Academy of Dermatology and Venereology, British Journal of Dermatology, and Pediatric Dermatology.

In an interview, Dr. Parker, assistant professor of dermatology at Vanderbilt University, Nashville, Tenn., said that she and Dr. Boos, associate professor in the division of dermatology and department of pediatrics at the University of Washington, Seattle, were motivated to write the editorial upon finding that dermatology was not represented among more than 230 medical journals that published an editorial in September 2021 calling for emergency action to limit global warming and protect health. In addition to the New England Journal of Medicine and The Lancet, the copublishing journals represented numerous specialties, from nursing and pediatrics, to cardiology, rheumatology, and gastroenterology.

The editorial was not published in any dermatology journals, Dr. Parker said. “It was incredibly disappointing for me along with many of my colleagues who advocate for climate action because we realized it was a missed opportunity for dermatology to align with other medical specialties and be on the forefront of leading climate action to protect health.”
 

‘A threat multiplier’

The impact of climate change on skin disease is “an incredibly important part of our conversation as dermatologists because many cutaneous diseases are climate sensitive and we’re often seeing the effects of climate change every day in our clinical practices,” Dr. Parker said.

In fact, the impact on skin disease needs to be explored much further through more robust research funding, so that dermatology can better understand not only the incidence and severity of climate-induced changes in skin diseases – including and beyond atopic dermatitis, acne, and psoriasis – but also the mechanisms and pathophysiology involved, she said.

However, the impacts are much broader, she and Dr. Boos, a pediatric dermatologist at Seattle Children’s Hospital, maintain in their commentary. “An essential concept to broker among dermatologists is that the impacts of climate change extend well beyond skin disease by also placing broad pressure” on infrastructure, the economy, financial markets, global supply chains, food and water insecurity, and more, they wrote, noting the deep inequities of climate change.

Climate change is a “threat multiplier for public health, equity, and health systems,” the commentary says. “The confluence of these climate-related pressures should sound alarm bells as they place enormous jeopardy on the practice of dermatology across all scales and regions.”

Health care is among the most carbon-intensive service sectors worldwide, contributing to almost 5% of greenhouse gas emissions globally, the commentary says. And nationally, of the estimated greenhouse gas emissions from the United States, the health care sector contributes 10%, Dr. Parker said in the interview, referring to a 2016 report.

In addition, according to a 2019 report, the United States is the top contributor to health care’s global climate footprint, contributing 27% of health care’s global emissions, Dr. Parker noted.

Petmal/iStock/Getty Images

In their commentary, she and Dr. Boos wrote that individually and practice wide, dermatologists can impact decarbonization through measures such as virtual attendance at medical meetings and greater utilization of telehealth services. Reductions in carbon emissions were demonstrated for virtual isotretinoin follow-up visits in a recent study, and these savings could be extrapolated to other routine follow-up visits for conditions such as rosacea, monitoring of biologics in patients with well-controlled disease, and postoperative wound checks, they said.

But when it comes to measures such as significantly reducing packaging and waste and “curating supply chains to make them more sustainable,” it is medical societies that have the “larger voice and broader relationship with the pharmaceutical industry” and with medical supply manufacturers and distributors, Dr. Parker explained in the interview, noting the potential for reducing the extensive amount of packaging used for drug samples.

Dr. Parker cochairs the American Academy of Dermatology’s Expert Resource Group for Climate Change and Environmental Issues, which was established several years ago, and Dr. Boos is a member of the group’s executive committee.


 

AAD actions

In its 2018 Position Statement on Climate and Health, the American Academy of Dermatology resolved to raise awareness of the effects of climate change on the skin and educate patients about this, and to “work with other medical societies in ongoing and future efforts to educate the public and mitigate the effects of climate change on global health.”

Asked about the commentary’s call for more collaboration with industry and other stakeholders – and the impact that organized dermatology can have on planetary health – Mark D. Kaufmann, MD, president of the AAD, said in an email that the AAD is “first and foremost an organization focused on providing gold-standard educational resources for dermatologists.”

The academy recognizes that “there are many dermatologic consequences of climate change that will increasingly affect our patients and challenge our membership,” and it has provided education on climate change in forums such as articles, podcasts, and sessions at AAD meetings, said Dr. Kaufmann, clinical professor in the department of dermatology, Icahn School of Medicine at Mount Sinai, New York.

Regarding collaboration with other societies, he said that the AAD’s “focus to date has been on how to provide our members with educational resources to understand and prepare for how climate change may impact their practices and the dermatologic health of their patients,” he said.

The AAD has also sought to address its own carbon footprint and improve sustainability of its operations, including taking steps to reduce plastic and paper waste at its educational events, and to eliminate plastic waste associated with mailing resources like its member magazine, Dr. Kaufmann noted.

And in keeping with the Academy pledge – also articulated in the 2018 position statement – to support and facilitate dermatologists’ efforts to decrease their carbon footprint “in a cost effective (or cost-saving) manner,” Dr. Kaufmann said that the AAD has been offering a program called My Green Doctor as a free benefit of membership.
 

‘Be part of the solution’

In an interview, Mary E. Maloney, MD, professor of medicine and director of dermatologic surgery at the University of Massachusetts, Worcester, said her practice did an audit of their surgical area and found ways to increase the use of paper-packaged gauze – and decrease use of gauze in hard plastic containers – and otherwise decrease the amount of disposables, all of which take “huge amounts of resources” to create.

In the process, “we found significant savings,” she said. “Little things can turn out, in the long run, to be big things.”

Asked about the commentary, Dr. Maloney, who is involved in the AAD’s climate change resource group, said “the message is that yes, we need to be aware of the diseases affected by climate change. But our greater imperative is to be part of the solution and not part of the problem as far as doing things that affect climate change.”

Organized dermatology needs to broaden its advocacy, she said. “I don’t want us to stop advocating for things for our patients, but I do want us to start advocating for the world ... If we don’t try to [mitigate] climate change, we won’t have patients to advocate for.”

Dr. Parker, an associate editor of The Journal of Climate Change and Health, and Dr. Boos declared no conflicts of interest and no funding source for their commentary. Dr. Maloney said she has no conflicts of interest.

A commentary published across four dermatology journals in September urges dermatologists and their medical societies to “engage more meaningfully” on climate change issues, “moving beyond merely discussing skin-related impacts” and toward prioritizing both patient and planetary health.

Dermatologists must make emissions-saving changes in everyday practice, for instance, and the specialty must enlist key stakeholders in public health, nonprofits, and industry – that is, pharmaceutical and medical supply companies – in finding solutions to help mitigate and adapt to climate change, wrote Eva Rawlings Parker, MD, and Markus D. Boos, MD, PhD.

“We have an ethical imperative to act,” they wrote. “The time is now for dermatologists and our medical societies to collectively rise to meet this crisis.”

Their commentary was published online in the International Journal of Dermatology , Journal of the European Academy of Dermatology and Venereology, British Journal of Dermatology, and Pediatric Dermatology.

In an interview, Dr. Parker, assistant professor of dermatology at Vanderbilt University, Nashville, Tenn., said that she and Dr. Boos, associate professor in the division of dermatology and department of pediatrics at the University of Washington, Seattle, were motivated to write the editorial upon finding that dermatology was not represented among more than 230 medical journals that published an editorial in September 2021 calling for emergency action to limit global warming and protect health. In addition to the New England Journal of Medicine and The Lancet, the copublishing journals represented numerous specialties, from nursing and pediatrics, to cardiology, rheumatology, and gastroenterology.

The editorial was not published in any dermatology journals, Dr. Parker said. “It was incredibly disappointing for me along with many of my colleagues who advocate for climate action because we realized it was a missed opportunity for dermatology to align with other medical specialties and be on the forefront of leading climate action to protect health.”
 

‘A threat multiplier’

The impact of climate change on skin disease is “an incredibly important part of our conversation as dermatologists because many cutaneous diseases are climate sensitive and we’re often seeing the effects of climate change every day in our clinical practices,” Dr. Parker said.

In fact, the impact on skin disease needs to be explored much further through more robust research funding, so that dermatology can better understand not only the incidence and severity of climate-induced changes in skin diseases – including and beyond atopic dermatitis, acne, and psoriasis – but also the mechanisms and pathophysiology involved, she said.

However, the impacts are much broader, she and Dr. Boos, a pediatric dermatologist at Seattle Children’s Hospital, maintain in their commentary. “An essential concept to broker among dermatologists is that the impacts of climate change extend well beyond skin disease by also placing broad pressure” on infrastructure, the economy, financial markets, global supply chains, food and water insecurity, and more, they wrote, noting the deep inequities of climate change.

Climate change is a “threat multiplier for public health, equity, and health systems,” the commentary says. “The confluence of these climate-related pressures should sound alarm bells as they place enormous jeopardy on the practice of dermatology across all scales and regions.”

Health care is among the most carbon-intensive service sectors worldwide, contributing to almost 5% of greenhouse gas emissions globally, the commentary says. And nationally, of the estimated greenhouse gas emissions from the United States, the health care sector contributes 10%, Dr. Parker said in the interview, referring to a 2016 report.

In addition, according to a 2019 report, the United States is the top contributor to health care’s global climate footprint, contributing 27% of health care’s global emissions, Dr. Parker noted.

Petmal/iStock/Getty Images

In their commentary, she and Dr. Boos wrote that individually and practice wide, dermatologists can impact decarbonization through measures such as virtual attendance at medical meetings and greater utilization of telehealth services. Reductions in carbon emissions were demonstrated for virtual isotretinoin follow-up visits in a recent study, and these savings could be extrapolated to other routine follow-up visits for conditions such as rosacea, monitoring of biologics in patients with well-controlled disease, and postoperative wound checks, they said.

But when it comes to measures such as significantly reducing packaging and waste and “curating supply chains to make them more sustainable,” it is medical societies that have the “larger voice and broader relationship with the pharmaceutical industry” and with medical supply manufacturers and distributors, Dr. Parker explained in the interview, noting the potential for reducing the extensive amount of packaging used for drug samples.

Dr. Parker cochairs the American Academy of Dermatology’s Expert Resource Group for Climate Change and Environmental Issues, which was established several years ago, and Dr. Boos is a member of the group’s executive committee.


 

AAD actions

In its 2018 Position Statement on Climate and Health, the American Academy of Dermatology resolved to raise awareness of the effects of climate change on the skin and educate patients about this, and to “work with other medical societies in ongoing and future efforts to educate the public and mitigate the effects of climate change on global health.”

Asked about the commentary’s call for more collaboration with industry and other stakeholders – and the impact that organized dermatology can have on planetary health – Mark D. Kaufmann, MD, president of the AAD, said in an email that the AAD is “first and foremost an organization focused on providing gold-standard educational resources for dermatologists.”

The academy recognizes that “there are many dermatologic consequences of climate change that will increasingly affect our patients and challenge our membership,” and it has provided education on climate change in forums such as articles, podcasts, and sessions at AAD meetings, said Dr. Kaufmann, clinical professor in the department of dermatology, Icahn School of Medicine at Mount Sinai, New York.

Regarding collaboration with other societies, he said that the AAD’s “focus to date has been on how to provide our members with educational resources to understand and prepare for how climate change may impact their practices and the dermatologic health of their patients,” he said.

The AAD has also sought to address its own carbon footprint and improve sustainability of its operations, including taking steps to reduce plastic and paper waste at its educational events, and to eliminate plastic waste associated with mailing resources like its member magazine, Dr. Kaufmann noted.

And in keeping with the Academy pledge – also articulated in the 2018 position statement – to support and facilitate dermatologists’ efforts to decrease their carbon footprint “in a cost effective (or cost-saving) manner,” Dr. Kaufmann said that the AAD has been offering a program called My Green Doctor as a free benefit of membership.
 

‘Be part of the solution’

In an interview, Mary E. Maloney, MD, professor of medicine and director of dermatologic surgery at the University of Massachusetts, Worcester, said her practice did an audit of their surgical area and found ways to increase the use of paper-packaged gauze – and decrease use of gauze in hard plastic containers – and otherwise decrease the amount of disposables, all of which take “huge amounts of resources” to create.

In the process, “we found significant savings,” she said. “Little things can turn out, in the long run, to be big things.”

Asked about the commentary, Dr. Maloney, who is involved in the AAD’s climate change resource group, said “the message is that yes, we need to be aware of the diseases affected by climate change. But our greater imperative is to be part of the solution and not part of the problem as far as doing things that affect climate change.”

Organized dermatology needs to broaden its advocacy, she said. “I don’t want us to stop advocating for things for our patients, but I do want us to start advocating for the world ... If we don’t try to [mitigate] climate change, we won’t have patients to advocate for.”

Dr. Parker, an associate editor of The Journal of Climate Change and Health, and Dr. Boos declared no conflicts of interest and no funding source for their commentary. Dr. Maloney said she has no conflicts of interest.