Dermatology

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.

The calendar year 2022 has been especially good for advancing acne-focused laser and light devices, most recently with the Food and Drug Administration clearance of the Accure Laser System in late November, for the treatment of mild to severe inflammatory acne vulgaris.

This was preceded by the FDA clearance of AviClear, marketed by Cutera, in March, and the commercial launch of TheraClearX, marketed by StrataSkin, in July.

“It’s an exciting time to be working with acne,” Fernanda H. Sakamoto, MD, PhD, a dermatologist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston. “We’ll see a lot of people using new devices. I’m looking forward to seeing results in the long term.”

AviClear and the Accure Laser System, marketed by Accure, are both powered by a 1,726-nm laser, but they work differently. AviClear, which was cleared for the treatment of mild, moderate, and severe acne, has a maximum fluence of 30 J/cm² in single-pulse mode and a maximum fluence of 20 J/cm² in double-pulse mode. The treatment handpiece has an integrated scanner for delivering treatment spot(s) in an operator-selected pattern. “It’s a little bit lower powered than the Accure and has a maximum pulse energy of 5 joules and a pulse duration of up to 50 milliseconds,” Dr. Sakamoto said. In the treatment of acne, laser and light treatments target the sebaceous gland.

In pivotal data submitted to the FDA, 104 patients with acne who were enrolled at 7 U.S. sites received 304 treatments with AviClear spaced 2-5 weeks apart. Each treatment took about 30 minutes. Treatment success was defined as having at least 50% fewer inflammatory acne lesions 12 weeks after the final treatment visit, compared with baseline. At the week 4 follow-up visit, there were median and mean reductions of 42% and 37%, respectively, in the inflammatory lesion counts from baseline (P < .001). The researchers found that, at the week 4 follow-up visit, 36% of patients had achieved treatment success, which increased to 78% at the 12-week follow-up visit. Treatment was considered safe and tolerable, according to the manufacturer.

The other newcomer device with a 1,726-nm wavelength is the Accure Laser System, which features a smart laser handpiece for real-time thermal monitoring and precise delivery of laser emissions. The device received CE Mark approval in 2020 for the treatment of moderate acne, and on Nov. 22, 2022, the manufacturer announced that it had been cleared by the FDA for the treatment of mild to severe inflammatory acne vulgaris.

Dr. Sakamoto and her Wellman colleagues have been working with five dermatologists to conduct clinical trials of the device: Emil Tanghetti, MD, and Mitchel Goldman, MD, in California; Roy Geronemus, MD, in New York; Joel Cohen, MD, in Colorado; and Daniel Friedmann, MD, in Texas. As of Oct. 2, 2022, more than 50 patients with mild to severe acne were enrolled in four studies and an additional 30 were enrolled in a pilot facial acne trial, Dr. Sakamoto said. In the trials, patients are followed at 4, 8, 12, and 24 weeks post treatment.

Among patients enrolled in the facial acne trial, researchers have observed a 100% responder rate for patients with more than five acne lesions at 4, 8, 12, and 24 weeks post treatment after four monthly treatment sessions. The average lesion reduction at week 12 was 82% and the mean visual analog scale score immediately after treatment was 2.09 out of 10. Each patient received more than 12,000 trigger pulls of energy from the device overall with no adverse events reported. At 12 months, they observed a 90% inflammatory lesion count reduction from baseline and a rapid response to treatment: a 73% reduction achieved after the first two treatment sessions. Histologic studies revealed selective sebaceous gland destruction with no damage to the epidermis, surrounding dermis, or other skin structures.

Dr. Sakamoto emphasized that to date no direct clinical comparisons have been made between the AviClear and Accure devices. “Are all 1,726-nm lasers made equal? That is a question that we have to keep in our mind,” she said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “They are using the same wavelength, but they are different types of lasers.”

For example, the Accure Laser treats to temperature, relies on air cooling, and is targeted to dermatologists and plastic surgeons, while the AviClear treats to fluence, relies on contact cooling, and includes med spas and other nonphysician providers as the target users. “Mathematically, the difference between the two devices is that the Accure can achieve deeper penetration in a single pulse, while the AviClear is a little more superficial,” she said. “Whether that is translated clinically is unknown at this point.”

Dr. Sakamoto also discussed the TheraClearX, which is FDA cleared for the treatment of mild, moderate, and severe acne, including comedonal, pustular, and inflammatory acne vulgaris. The device, which is a new version of the Palomar Acleara, uses a vacuum technique with up to 3 psi pressure in conjunction with broadband light with a wavelength spectrum of 500 nm–1,200 nm delivered through a liquid-cooled, handheld delivery system. The predicate device was the Aesthera Isolaz System. The vacuum extracts buildup of sebaceous material. “At the same time, it takes the blood out of the competing chromophore,” she said. “By doing so, it potentially damages the sebaceous glands and reduces the inflammatory lesions.”

Dr. Sakamoto disclosed that she is the founder of and science advisor for Lightwater Bioscience. She is also a science advisor for Accure Acne and has received portions of patent royalties from Massachusetts General Hospital.

The calendar year 2022 has been especially good for advancing acne-focused laser and light devices, most recently with the Food and Drug Administration clearance of the Accure Laser System in late November, for the treatment of mild to severe inflammatory acne vulgaris.

This was preceded by the FDA clearance of AviClear, marketed by Cutera, in March, and the commercial launch of TheraClearX, marketed by StrataSkin, in July.

“It’s an exciting time to be working with acne,” Fernanda H. Sakamoto, MD, PhD, a dermatologist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston. “We’ll see a lot of people using new devices. I’m looking forward to seeing results in the long term.”

AviClear and the Accure Laser System, marketed by Accure, are both powered by a 1,726-nm laser, but they work differently. AviClear, which was cleared for the treatment of mild, moderate, and severe acne, has a maximum fluence of 30 J/cm² in single-pulse mode and a maximum fluence of 20 J/cm² in double-pulse mode. The treatment handpiece has an integrated scanner for delivering treatment spot(s) in an operator-selected pattern. “It’s a little bit lower powered than the Accure and has a maximum pulse energy of 5 joules and a pulse duration of up to 50 milliseconds,” Dr. Sakamoto said. In the treatment of acne, laser and light treatments target the sebaceous gland.

In pivotal data submitted to the FDA, 104 patients with acne who were enrolled at 7 U.S. sites received 304 treatments with AviClear spaced 2-5 weeks apart. Each treatment took about 30 minutes. Treatment success was defined as having at least 50% fewer inflammatory acne lesions 12 weeks after the final treatment visit, compared with baseline. At the week 4 follow-up visit, there were median and mean reductions of 42% and 37%, respectively, in the inflammatory lesion counts from baseline (P < .001). The researchers found that, at the week 4 follow-up visit, 36% of patients had achieved treatment success, which increased to 78% at the 12-week follow-up visit. Treatment was considered safe and tolerable, according to the manufacturer.

The other newcomer device with a 1,726-nm wavelength is the Accure Laser System, which features a smart laser handpiece for real-time thermal monitoring and precise delivery of laser emissions. The device received CE Mark approval in 2020 for the treatment of moderate acne, and on Nov. 22, 2022, the manufacturer announced that it had been cleared by the FDA for the treatment of mild to severe inflammatory acne vulgaris.

Dr. Sakamoto and her Wellman colleagues have been working with five dermatologists to conduct clinical trials of the device: Emil Tanghetti, MD, and Mitchel Goldman, MD, in California; Roy Geronemus, MD, in New York; Joel Cohen, MD, in Colorado; and Daniel Friedmann, MD, in Texas. As of Oct. 2, 2022, more than 50 patients with mild to severe acne were enrolled in four studies and an additional 30 were enrolled in a pilot facial acne trial, Dr. Sakamoto said. In the trials, patients are followed at 4, 8, 12, and 24 weeks post treatment.

Among patients enrolled in the facial acne trial, researchers have observed a 100% responder rate for patients with more than five acne lesions at 4, 8, 12, and 24 weeks post treatment after four monthly treatment sessions. The average lesion reduction at week 12 was 82% and the mean visual analog scale score immediately after treatment was 2.09 out of 10. Each patient received more than 12,000 trigger pulls of energy from the device overall with no adverse events reported. At 12 months, they observed a 90% inflammatory lesion count reduction from baseline and a rapid response to treatment: a 73% reduction achieved after the first two treatment sessions. Histologic studies revealed selective sebaceous gland destruction with no damage to the epidermis, surrounding dermis, or other skin structures.

Dr. Sakamoto emphasized that to date no direct clinical comparisons have been made between the AviClear and Accure devices. “Are all 1,726-nm lasers made equal? That is a question that we have to keep in our mind,” she said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “They are using the same wavelength, but they are different types of lasers.”

For example, the Accure Laser treats to temperature, relies on air cooling, and is targeted to dermatologists and plastic surgeons, while the AviClear treats to fluence, relies on contact cooling, and includes med spas and other nonphysician providers as the target users. “Mathematically, the difference between the two devices is that the Accure can achieve deeper penetration in a single pulse, while the AviClear is a little more superficial,” she said. “Whether that is translated clinically is unknown at this point.”

Dr. Sakamoto also discussed the TheraClearX, which is FDA cleared for the treatment of mild, moderate, and severe acne, including comedonal, pustular, and inflammatory acne vulgaris. The device, which is a new version of the Palomar Acleara, uses a vacuum technique with up to 3 psi pressure in conjunction with broadband light with a wavelength spectrum of 500 nm–1,200 nm delivered through a liquid-cooled, handheld delivery system. The predicate device was the Aesthera Isolaz System. The vacuum extracts buildup of sebaceous material. “At the same time, it takes the blood out of the competing chromophore,” she said. “By doing so, it potentially damages the sebaceous glands and reduces the inflammatory lesions.”

Dr. Sakamoto disclosed that she is the founder of and science advisor for Lightwater Bioscience. She is also a science advisor for Accure Acne and has received portions of patent royalties from Massachusetts General Hospital.

The calendar year 2022 has been especially good for advancing acne-focused laser and light devices, most recently with the Food and Drug Administration clearance of the Accure Laser System in late November, for the treatment of mild to severe inflammatory acne vulgaris.

This was preceded by the FDA clearance of AviClear, marketed by Cutera, in March, and the commercial launch of TheraClearX, marketed by StrataSkin, in July.

“It’s an exciting time to be working with acne,” Fernanda H. Sakamoto, MD, PhD, a dermatologist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston. “We’ll see a lot of people using new devices. I’m looking forward to seeing results in the long term.”

AviClear and the Accure Laser System, marketed by Accure, are both powered by a 1,726-nm laser, but they work differently. AviClear, which was cleared for the treatment of mild, moderate, and severe acne, has a maximum fluence of 30 J/cm² in single-pulse mode and a maximum fluence of 20 J/cm² in double-pulse mode. The treatment handpiece has an integrated scanner for delivering treatment spot(s) in an operator-selected pattern. “It’s a little bit lower powered than the Accure and has a maximum pulse energy of 5 joules and a pulse duration of up to 50 milliseconds,” Dr. Sakamoto said. In the treatment of acne, laser and light treatments target the sebaceous gland.

In pivotal data submitted to the FDA, 104 patients with acne who were enrolled at 7 U.S. sites received 304 treatments with AviClear spaced 2-5 weeks apart. Each treatment took about 30 minutes. Treatment success was defined as having at least 50% fewer inflammatory acne lesions 12 weeks after the final treatment visit, compared with baseline. At the week 4 follow-up visit, there were median and mean reductions of 42% and 37%, respectively, in the inflammatory lesion counts from baseline (P < .001). The researchers found that, at the week 4 follow-up visit, 36% of patients had achieved treatment success, which increased to 78% at the 12-week follow-up visit. Treatment was considered safe and tolerable, according to the manufacturer.

The other newcomer device with a 1,726-nm wavelength is the Accure Laser System, which features a smart laser handpiece for real-time thermal monitoring and precise delivery of laser emissions. The device received CE Mark approval in 2020 for the treatment of moderate acne, and on Nov. 22, 2022, the manufacturer announced that it had been cleared by the FDA for the treatment of mild to severe inflammatory acne vulgaris.

Dr. Sakamoto and her Wellman colleagues have been working with five dermatologists to conduct clinical trials of the device: Emil Tanghetti, MD, and Mitchel Goldman, MD, in California; Roy Geronemus, MD, in New York; Joel Cohen, MD, in Colorado; and Daniel Friedmann, MD, in Texas. As of Oct. 2, 2022, more than 50 patients with mild to severe acne were enrolled in four studies and an additional 30 were enrolled in a pilot facial acne trial, Dr. Sakamoto said. In the trials, patients are followed at 4, 8, 12, and 24 weeks post treatment.

Among patients enrolled in the facial acne trial, researchers have observed a 100% responder rate for patients with more than five acne lesions at 4, 8, 12, and 24 weeks post treatment after four monthly treatment sessions. The average lesion reduction at week 12 was 82% and the mean visual analog scale score immediately after treatment was 2.09 out of 10. Each patient received more than 12,000 trigger pulls of energy from the device overall with no adverse events reported. At 12 months, they observed a 90% inflammatory lesion count reduction from baseline and a rapid response to treatment: a 73% reduction achieved after the first two treatment sessions. Histologic studies revealed selective sebaceous gland destruction with no damage to the epidermis, surrounding dermis, or other skin structures.

Dr. Sakamoto emphasized that to date no direct clinical comparisons have been made between the AviClear and Accure devices. “Are all 1,726-nm lasers made equal? That is a question that we have to keep in our mind,” she said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “They are using the same wavelength, but they are different types of lasers.”

For example, the Accure Laser treats to temperature, relies on air cooling, and is targeted to dermatologists and plastic surgeons, while the AviClear treats to fluence, relies on contact cooling, and includes med spas and other nonphysician providers as the target users. “Mathematically, the difference between the two devices is that the Accure can achieve deeper penetration in a single pulse, while the AviClear is a little more superficial,” she said. “Whether that is translated clinically is unknown at this point.”

Dr. Sakamoto also discussed the TheraClearX, which is FDA cleared for the treatment of mild, moderate, and severe acne, including comedonal, pustular, and inflammatory acne vulgaris. The device, which is a new version of the Palomar Acleara, uses a vacuum technique with up to 3 psi pressure in conjunction with broadband light with a wavelength spectrum of 500 nm–1,200 nm delivered through a liquid-cooled, handheld delivery system. The predicate device was the Aesthera Isolaz System. The vacuum extracts buildup of sebaceous material. “At the same time, it takes the blood out of the competing chromophore,” she said. “By doing so, it potentially damages the sebaceous glands and reduces the inflammatory lesions.”

Dr. Sakamoto disclosed that she is the founder of and science advisor for Lightwater Bioscience. She is also a science advisor for Accure Acne and has received portions of patent royalties from Massachusetts General Hospital.

Contact allergy to cobalt, chromium, and especially nickel, may be higher in European metalworkers than in all European male patients with allergic contact dermatitis, a systematic review and meta-analysis reports.

“Metal allergy to all three metals was significantly more common in European metalworkers with dermatitis attending patch test clinics as compared to ESSCA [European Surveillance System on Contact Allergies] data, indicating a relationship to occupational exposures,” senior study author Jeanne D. Johansen, MD, professor, department of dermatology and allergy, Copenhagen University Hospital, Hellerup, Denmark, and colleagues at the University of Copenhagen wrote in Contact Dermatitis. “However, confounders could not be accounted for.”

How common is metal allergy in metalworkers?

Occupational hand eczema is known to be common in metalworkers. Touching oils, greases, metals, leather gloves, rubber materials, and metalworking fluids as they repeatedly cut, shape, and process raw metals and minerals derived from ore mining exposes metalworkers to allergens and skin irritants, the authors wrote. But the prevalence of allergy to certain metals has not been well characterized.

So they searched PubMed for full-text studies in English that reported metal allergy prevalence in metalworkers, from the database’s inception through April 2022.

They included studies with absolute numbers or proportions of metal allergy to cobalt, chromium, or nickel, in all metalworkers with suspected allergic contact dermatitis who attended outpatient clinics or who worked at metalworking plants participating in workplace studies.

The researchers performed a random-effects meta-analysis to calculate the pooled prevalence of metal allergy. Because 85%-90% of metalworkers in Denmark are male, they compared the estimates they found with ESSCA data on 13,382 consecutively patch-tested males with dermatitis between 2015 and 2018.

Of the 1,667 records they screened, they analyzed data from 29 that met their inclusion criteria: 22 patient studies and 7 workplace studies involving 5,691 patients overall from 22 studies from Europe, 5 studies from Asia, and 1 from Africa. Regarding European metalworkers, the authors found:

• Pooled proportions of allergy in European metalworkers with dermatitis referred to patch test clinics were 8.2% to cobalt (95% confidence interval, 5.3%-11.7%), 8.0% to chromium (95% CI, 5.1%-11.4%), and 11.0% to nickel (95% CI, 7.3%-15.4%).
• In workplace studies, the pooled proportions of allergy in unselected European metalworkers were 4.9% to cobalt, (95% CI, 2.4%-8.1%), 5.2% to chromium (95% CI, 1.0% - 12.6%), and 7.6% to nickel (95% CI, 3.8%-12.6%).
• By comparison, ESSCA data on metal allergy prevalence showed 3.9% allergic to cobalt (95% CI, 3.6%-4.2%), 4.4% allergic to chromium (95% CI, 4.1%-4.8%), and 6.7% allergic to nickel (95% CI, 6.3%-7.0%).
• Data on sex, age, body piercings, and atopic dermatitis were scant.

Thorough histories, protective regulations and equipment

Providers need to ask their dermatitis patients about current and past occupations and hobbies, and employers need to provide employees with equipment that protects them from exposure, Kelly Tyler, MD, associate professor of dermatology, Ohio State University Wexner Medical Center, Columbus, said in an interview.

“Repeated exposure to an allergen is required for sensitization to develop,” said Dr. Tyler, who was not involved in the study. “Metalworkers, who are continually exposed to metals and metalworking fluids, have a higher risk of allergic contact dermatitis to cobalt, chromium, and nickel.”

“The primary treatment for allergic contact dermatitis is preventing continued exposure to the allergen,” she added. “This study highlights the importance of asking about metal or metalworking fluid in the workplace and of elucidating whether the employer is providing appropriate protective gear.”

To prevent occupational dermatitis, workplaces need to apply regulatory measures and provide their employees with protective equipment, Dr. Tyler advised.

“Body piercings are a common sensitizer in patients with metal allergy, and the prevalence of body piercings among metalworkers was not included in the study,” she noted.

The results of the study may not be generalizable to patients in the United States, she added, because regulations and requirements to provide protective gear here may differ.

“Taking a thorough patient history is crucial when investigating potential causes of dermatitis, especially in patients with suspected allergic contact dermatitis,” Dr. Tyler urged.

Funding and conflict-of-interest details were not provided. Dr. Tyler reported no relevant financial relationships.

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

Contact allergy to cobalt, chromium, and especially nickel, may be higher in European metalworkers than in all European male patients with allergic contact dermatitis, a systematic review and meta-analysis reports.

“Metal allergy to all three metals was significantly more common in European metalworkers with dermatitis attending patch test clinics as compared to ESSCA [European Surveillance System on Contact Allergies] data, indicating a relationship to occupational exposures,” senior study author Jeanne D. Johansen, MD, professor, department of dermatology and allergy, Copenhagen University Hospital, Hellerup, Denmark, and colleagues at the University of Copenhagen wrote in Contact Dermatitis. “However, confounders could not be accounted for.”

How common is metal allergy in metalworkers?

Occupational hand eczema is known to be common in metalworkers. Touching oils, greases, metals, leather gloves, rubber materials, and metalworking fluids as they repeatedly cut, shape, and process raw metals and minerals derived from ore mining exposes metalworkers to allergens and skin irritants, the authors wrote. But the prevalence of allergy to certain metals has not been well characterized.

So they searched PubMed for full-text studies in English that reported metal allergy prevalence in metalworkers, from the database’s inception through April 2022.

They included studies with absolute numbers or proportions of metal allergy to cobalt, chromium, or nickel, in all metalworkers with suspected allergic contact dermatitis who attended outpatient clinics or who worked at metalworking plants participating in workplace studies.

The researchers performed a random-effects meta-analysis to calculate the pooled prevalence of metal allergy. Because 85%-90% of metalworkers in Denmark are male, they compared the estimates they found with ESSCA data on 13,382 consecutively patch-tested males with dermatitis between 2015 and 2018.

Of the 1,667 records they screened, they analyzed data from 29 that met their inclusion criteria: 22 patient studies and 7 workplace studies involving 5,691 patients overall from 22 studies from Europe, 5 studies from Asia, and 1 from Africa. Regarding European metalworkers, the authors found:

• Pooled proportions of allergy in European metalworkers with dermatitis referred to patch test clinics were 8.2% to cobalt (95% confidence interval, 5.3%-11.7%), 8.0% to chromium (95% CI, 5.1%-11.4%), and 11.0% to nickel (95% CI, 7.3%-15.4%).
• In workplace studies, the pooled proportions of allergy in unselected European metalworkers were 4.9% to cobalt, (95% CI, 2.4%-8.1%), 5.2% to chromium (95% CI, 1.0% - 12.6%), and 7.6% to nickel (95% CI, 3.8%-12.6%).
• By comparison, ESSCA data on metal allergy prevalence showed 3.9% allergic to cobalt (95% CI, 3.6%-4.2%), 4.4% allergic to chromium (95% CI, 4.1%-4.8%), and 6.7% allergic to nickel (95% CI, 6.3%-7.0%).
• Data on sex, age, body piercings, and atopic dermatitis were scant.

Thorough histories, protective regulations and equipment

Providers need to ask their dermatitis patients about current and past occupations and hobbies, and employers need to provide employees with equipment that protects them from exposure, Kelly Tyler, MD, associate professor of dermatology, Ohio State University Wexner Medical Center, Columbus, said in an interview.

“Repeated exposure to an allergen is required for sensitization to develop,” said Dr. Tyler, who was not involved in the study. “Metalworkers, who are continually exposed to metals and metalworking fluids, have a higher risk of allergic contact dermatitis to cobalt, chromium, and nickel.”

“The primary treatment for allergic contact dermatitis is preventing continued exposure to the allergen,” she added. “This study highlights the importance of asking about metal or metalworking fluid in the workplace and of elucidating whether the employer is providing appropriate protective gear.”

To prevent occupational dermatitis, workplaces need to apply regulatory measures and provide their employees with protective equipment, Dr. Tyler advised.

“Body piercings are a common sensitizer in patients with metal allergy, and the prevalence of body piercings among metalworkers was not included in the study,” she noted.

The results of the study may not be generalizable to patients in the United States, she added, because regulations and requirements to provide protective gear here may differ.

“Taking a thorough patient history is crucial when investigating potential causes of dermatitis, especially in patients with suspected allergic contact dermatitis,” Dr. Tyler urged.

Funding and conflict-of-interest details were not provided. Dr. Tyler reported no relevant financial relationships.

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

Contact allergy to cobalt, chromium, and especially nickel, may be higher in European metalworkers than in all European male patients with allergic contact dermatitis, a systematic review and meta-analysis reports.

“Metal allergy to all three metals was significantly more common in European metalworkers with dermatitis attending patch test clinics as compared to ESSCA [European Surveillance System on Contact Allergies] data, indicating a relationship to occupational exposures,” senior study author Jeanne D. Johansen, MD, professor, department of dermatology and allergy, Copenhagen University Hospital, Hellerup, Denmark, and colleagues at the University of Copenhagen wrote in Contact Dermatitis. “However, confounders could not be accounted for.”

How common is metal allergy in metalworkers?

Occupational hand eczema is known to be common in metalworkers. Touching oils, greases, metals, leather gloves, rubber materials, and metalworking fluids as they repeatedly cut, shape, and process raw metals and minerals derived from ore mining exposes metalworkers to allergens and skin irritants, the authors wrote. But the prevalence of allergy to certain metals has not been well characterized.

So they searched PubMed for full-text studies in English that reported metal allergy prevalence in metalworkers, from the database’s inception through April 2022.

They included studies with absolute numbers or proportions of metal allergy to cobalt, chromium, or nickel, in all metalworkers with suspected allergic contact dermatitis who attended outpatient clinics or who worked at metalworking plants participating in workplace studies.

The researchers performed a random-effects meta-analysis to calculate the pooled prevalence of metal allergy. Because 85%-90% of metalworkers in Denmark are male, they compared the estimates they found with ESSCA data on 13,382 consecutively patch-tested males with dermatitis between 2015 and 2018.

Of the 1,667 records they screened, they analyzed data from 29 that met their inclusion criteria: 22 patient studies and 7 workplace studies involving 5,691 patients overall from 22 studies from Europe, 5 studies from Asia, and 1 from Africa. Regarding European metalworkers, the authors found:

• Pooled proportions of allergy in European metalworkers with dermatitis referred to patch test clinics were 8.2% to cobalt (95% confidence interval, 5.3%-11.7%), 8.0% to chromium (95% CI, 5.1%-11.4%), and 11.0% to nickel (95% CI, 7.3%-15.4%).
• In workplace studies, the pooled proportions of allergy in unselected European metalworkers were 4.9% to cobalt, (95% CI, 2.4%-8.1%), 5.2% to chromium (95% CI, 1.0% - 12.6%), and 7.6% to nickel (95% CI, 3.8%-12.6%).
• By comparison, ESSCA data on metal allergy prevalence showed 3.9% allergic to cobalt (95% CI, 3.6%-4.2%), 4.4% allergic to chromium (95% CI, 4.1%-4.8%), and 6.7% allergic to nickel (95% CI, 6.3%-7.0%).
• Data on sex, age, body piercings, and atopic dermatitis were scant.

Thorough histories, protective regulations and equipment

Providers need to ask their dermatitis patients about current and past occupations and hobbies, and employers need to provide employees with equipment that protects them from exposure, Kelly Tyler, MD, associate professor of dermatology, Ohio State University Wexner Medical Center, Columbus, said in an interview.

“Repeated exposure to an allergen is required for sensitization to develop,” said Dr. Tyler, who was not involved in the study. “Metalworkers, who are continually exposed to metals and metalworking fluids, have a higher risk of allergic contact dermatitis to cobalt, chromium, and nickel.”

“The primary treatment for allergic contact dermatitis is preventing continued exposure to the allergen,” she added. “This study highlights the importance of asking about metal or metalworking fluid in the workplace and of elucidating whether the employer is providing appropriate protective gear.”

To prevent occupational dermatitis, workplaces need to apply regulatory measures and provide their employees with protective equipment, Dr. Tyler advised.

“Body piercings are a common sensitizer in patients with metal allergy, and the prevalence of body piercings among metalworkers was not included in the study,” she noted.

The results of the study may not be generalizable to patients in the United States, she added, because regulations and requirements to provide protective gear here may differ.

“Taking a thorough patient history is crucial when investigating potential causes of dermatitis, especially in patients with suspected allergic contact dermatitis,” Dr. Tyler urged.

Funding and conflict-of-interest details were not provided. Dr. Tyler reported no relevant financial relationships.

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

A 12-YEAR-OLD BOY presented to the hospital with a 2-day history of fever, cough, and painful blisters on swollen lips. On examination, he had multiple tense blisters with clear fluid on the buccal mucosa and inner lips (FIGURE 1A), as well as multiple discrete ulcers on his posterior pharynx. The patient had no other skin, eye, or urogenital involvement, but he was dehydrated. Respiratory examination was unremarkable. A complete blood count and metabolic panel were normal, as was a ­C-reactive protein (CRP) test (0.8 mg/L).

The preliminary diagnosis was primary herpetic gingivostomatitis, and treatment was initiated with intravenous (IV) acyclovir (10 mg/kg every 8 hours), IV fluids, and topical lidocaine gel and topical steroids for analgesia. However, the patient’s fever persisted over the next 4 days, with his temperature fluctuating between 101.3 °F and 104 °F, and he had a worsening productive cough. The blisters ruptured on Day 6 of illness, leaving hemorrhagic crusting on his lips (FIGURE 1B). Herpes simplex virus types 1 and 2 and polymerase chain reaction (PCR) testing were negative.

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

 

 

Dx: Mycoplasma pneumoniae–induced rash and mucositis

Further follow-up on Day 6 of illness revealed bibasilar crepitations along with an elevated CRP level of 40.5 mg/L and a positive mycoplasma antibody serology (titer > 1:1280; ­normal, < 1:80). The patient was given a diagnosis of pneumonia (due to infection with Mycoplasma pneumoniae) and M ­pneumoniae–induced rash and mucositis (MIRM).

MIRM was first proposed as a distinct clinical entity in 2015 to distinguish it from Stevens-Johnson syndrome and erythema multiforme.¹ MIRM is seen more commonly in children and young adults, with a male preponderance.¹

Within 3 days of initiating treatment with IV ceftriaxone, azithromycin, and methylprednisolone, our patient experienced marked improvement of his symptoms.

A small longitudinal study found that approximately 22.7% of children who have M pneumoniae infections present with mucocutaneous lesions, and of those cases, 6.8% are MIRM.² Chlamydia pneumoniae is another potential causal organism of mucositis resembling MIRM.³

Pathogenesis. The commonly accepted mechanism of MIRM is an immune response triggered by a distant infection. This leads to tissue damage via polyclonal B cell proliferation and subsequent immune complex deposition, complement activation, and cytokine overproduction. Molecular mimicry between M pneumoniae P1-adhesion molecules and keratinocyte antigens may also contribute to this pathway.

3 criteria to make the diagnosis

Canavan et al¹ have proposed the following criteria for the diagnosis of MIRM:

• Clinical symptoms, such as fever and cough, and laboratory findings of M pneumoniae infection (elevated M pneumoniae immunoglobulin M antibodies, positive cultures or PCR for M pneumoniae from oropharyngeal samples or bullae, and/or serial cold agglutinins) AND
• a rash to the mucosa that usually affects ≥ 2 sites (although rare cases may have fewer than 2 mucosal sites involved) AND
• skin detachment of less than 10% of the body surface area.

Continue to: The 3 variants of MIRM include...

The 3 variants of MIRM include:

• Classic MIRM has evidence of all 3 diagnostic criteria plus a nonmucosal rash, such as vesiculobullous lesions (77%), scattered target lesions (48%), papules (14%), macules (12%), and morbilliform eruptions (9%).⁴
• MIRM sine rash includes all 3 criteria but there is no significant cutaneous, nonmucosal rash. There may be “few fleeting morbilliform lesions or a few vesicles.”⁴
• Severe MIRM includes the first 2 criteria listed, but the cutaneous rash is extensive, with widespread nonmucosal blisters or flat atypical target lesions.⁴

Our patient had definitive clinical symptoms, laboratory evidence, and severe oral mucositis without significant cutaneous rash, thereby fulfilling the criteria for a diagnosis of MIRM sine rash variant.

These skin conditions were considered in the differential

The differential diagnosis for sudden onset of severe oral mucosal blisters in children includes herpes gingivostomatitis; hand, foot, and mouth disease; erythema multiforme; and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). The presence of pulmonary symptoms and oropharyngeal mucositis, together with the laboratory markers currently proposed as MIRM diagnostic criteria, are important in helping differentiate MIRM from other items in the differential diagnosis.

Herpes gingivostomatitis would involve numerous ulcerations of the oral mucosa and tongue, as well as gum hypertrophy.

Hand, foot, and mouth disease is characterized by vesicular exanthems of the hands, legs, and buttocks.

Continue to: Erythema multiforme

Erythema multiforme appears as cutaneous target lesions on the limbs that spread in a centripetal manner following herpes simplex virus infection.

SJS/TEN manifests with severe mucositis and is commonly triggered by medications (eg, sulphonamides, beta-lactams, nonsteroidal anti-inflammatory drugs, and antiepileptics).

With antibiotics, the prognosis is good

There are no established guidelines for the treatment of MIRM. Antibiotics and supportive care are universally accepted. Immunosuppressive therapy (eg, systemic steroids) is frequently used in patients with MIRM who have extensive mucosal involvement, in an attempt to decrease inflammation and pain; however, evidence for such an approach is lacking. The hyperimmune reactions of the host to M pneumoniae infection include cytokine overproduction and T-cell activation, which promote both pulmonary and extrapulmonary manifestations. This forms the basis of immunosuppressive therapy, such as systemic corticosteroids, IV immunoglobulin, and cyclosporin A, particularly when MIRM is associated with pneumonia caused by infection with M pneumoniae.^1,5,6

The overall prognosis of MIRM is good. Recurrence has been reported in up to 8% of cases, the treatment of which remains the same. Mucocutaneous and ocular sequelae (oral or genital synechiae, corneal ulcerations, dry eyes, loss of eye lashes) have been reported in less than 9% of patients.¹ Other rare reported complications following the occurrence of MIRM include persistent cutaneous lesions, B cell lymphopenia, and restrictive lung disease or chronic obliterative bronchitis.

Our patient was started on IV ­ceftriaxone (50 mg/kg/d), azithromycin (10 mg/kg/d on the first day, then 5 mg/kg/d on the sub­sequent 5 days), and methylprednisolone (3 mg/kg/d) on Day 6 of illness. Within 3 days, there was marked improvement of mucositis and respiratory symptoms with resolution of fever. He was discharged on Day 10. At his outpatient follow-up 2 weeks later, the patient had made a complete recovery.

A 12-YEAR-OLD BOY presented to the hospital with a 2-day history of fever, cough, and painful blisters on swollen lips. On examination, he had multiple tense blisters with clear fluid on the buccal mucosa and inner lips (FIGURE 1A), as well as multiple discrete ulcers on his posterior pharynx. The patient had no other skin, eye, or urogenital involvement, but he was dehydrated. Respiratory examination was unremarkable. A complete blood count and metabolic panel were normal, as was a ­C-reactive protein (CRP) test (0.8 mg/L).

The preliminary diagnosis was primary herpetic gingivostomatitis, and treatment was initiated with intravenous (IV) acyclovir (10 mg/kg every 8 hours), IV fluids, and topical lidocaine gel and topical steroids for analgesia. However, the patient’s fever persisted over the next 4 days, with his temperature fluctuating between 101.3 °F and 104 °F, and he had a worsening productive cough. The blisters ruptured on Day 6 of illness, leaving hemorrhagic crusting on his lips (FIGURE 1B). Herpes simplex virus types 1 and 2 and polymerase chain reaction (PCR) testing were negative.

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

 

 

Dx: Mycoplasma pneumoniae–induced rash and mucositis

Further follow-up on Day 6 of illness revealed bibasilar crepitations along with an elevated CRP level of 40.5 mg/L and a positive mycoplasma antibody serology (titer > 1:1280; ­normal, < 1:80). The patient was given a diagnosis of pneumonia (due to infection with Mycoplasma pneumoniae) and M ­pneumoniae–induced rash and mucositis (MIRM).

MIRM was first proposed as a distinct clinical entity in 2015 to distinguish it from Stevens-Johnson syndrome and erythema multiforme.¹ MIRM is seen more commonly in children and young adults, with a male preponderance.¹

Within 3 days of initiating treatment with IV ceftriaxone, azithromycin, and methylprednisolone, our patient experienced marked improvement of his symptoms.

A small longitudinal study found that approximately 22.7% of children who have M pneumoniae infections present with mucocutaneous lesions, and of those cases, 6.8% are MIRM.² Chlamydia pneumoniae is another potential causal organism of mucositis resembling MIRM.³

Pathogenesis. The commonly accepted mechanism of MIRM is an immune response triggered by a distant infection. This leads to tissue damage via polyclonal B cell proliferation and subsequent immune complex deposition, complement activation, and cytokine overproduction. Molecular mimicry between M pneumoniae P1-adhesion molecules and keratinocyte antigens may also contribute to this pathway.

3 criteria to make the diagnosis

Canavan et al¹ have proposed the following criteria for the diagnosis of MIRM:

• Clinical symptoms, such as fever and cough, and laboratory findings of M pneumoniae infection (elevated M pneumoniae immunoglobulin M antibodies, positive cultures or PCR for M pneumoniae from oropharyngeal samples or bullae, and/or serial cold agglutinins) AND
• a rash to the mucosa that usually affects ≥ 2 sites (although rare cases may have fewer than 2 mucosal sites involved) AND
• skin detachment of less than 10% of the body surface area.

Continue to: The 3 variants of MIRM include...

The 3 variants of MIRM include:

• Classic MIRM has evidence of all 3 diagnostic criteria plus a nonmucosal rash, such as vesiculobullous lesions (77%), scattered target lesions (48%), papules (14%), macules (12%), and morbilliform eruptions (9%).⁴
• MIRM sine rash includes all 3 criteria but there is no significant cutaneous, nonmucosal rash. There may be “few fleeting morbilliform lesions or a few vesicles.”⁴
• Severe MIRM includes the first 2 criteria listed, but the cutaneous rash is extensive, with widespread nonmucosal blisters or flat atypical target lesions.⁴

Our patient had definitive clinical symptoms, laboratory evidence, and severe oral mucositis without significant cutaneous rash, thereby fulfilling the criteria for a diagnosis of MIRM sine rash variant.

These skin conditions were considered in the differential

The differential diagnosis for sudden onset of severe oral mucosal blisters in children includes herpes gingivostomatitis; hand, foot, and mouth disease; erythema multiforme; and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). The presence of pulmonary symptoms and oropharyngeal mucositis, together with the laboratory markers currently proposed as MIRM diagnostic criteria, are important in helping differentiate MIRM from other items in the differential diagnosis.

Herpes gingivostomatitis would involve numerous ulcerations of the oral mucosa and tongue, as well as gum hypertrophy.

Hand, foot, and mouth disease is characterized by vesicular exanthems of the hands, legs, and buttocks.

Continue to: Erythema multiforme

Erythema multiforme appears as cutaneous target lesions on the limbs that spread in a centripetal manner following herpes simplex virus infection.

SJS/TEN manifests with severe mucositis and is commonly triggered by medications (eg, sulphonamides, beta-lactams, nonsteroidal anti-inflammatory drugs, and antiepileptics).

With antibiotics, the prognosis is good

There are no established guidelines for the treatment of MIRM. Antibiotics and supportive care are universally accepted. Immunosuppressive therapy (eg, systemic steroids) is frequently used in patients with MIRM who have extensive mucosal involvement, in an attempt to decrease inflammation and pain; however, evidence for such an approach is lacking. The hyperimmune reactions of the host to M pneumoniae infection include cytokine overproduction and T-cell activation, which promote both pulmonary and extrapulmonary manifestations. This forms the basis of immunosuppressive therapy, such as systemic corticosteroids, IV immunoglobulin, and cyclosporin A, particularly when MIRM is associated with pneumonia caused by infection with M pneumoniae.^1,5,6

The overall prognosis of MIRM is good. Recurrence has been reported in up to 8% of cases, the treatment of which remains the same. Mucocutaneous and ocular sequelae (oral or genital synechiae, corneal ulcerations, dry eyes, loss of eye lashes) have been reported in less than 9% of patients.¹ Other rare reported complications following the occurrence of MIRM include persistent cutaneous lesions, B cell lymphopenia, and restrictive lung disease or chronic obliterative bronchitis.

Our patient was started on IV ­ceftriaxone (50 mg/kg/d), azithromycin (10 mg/kg/d on the first day, then 5 mg/kg/d on the sub­sequent 5 days), and methylprednisolone (3 mg/kg/d) on Day 6 of illness. Within 3 days, there was marked improvement of mucositis and respiratory symptoms with resolution of fever. He was discharged on Day 10. At his outpatient follow-up 2 weeks later, the patient had made a complete recovery.

A 12-YEAR-OLD BOY presented to the hospital with a 2-day history of fever, cough, and painful blisters on swollen lips. On examination, he had multiple tense blisters with clear fluid on the buccal mucosa and inner lips (FIGURE 1A), as well as multiple discrete ulcers on his posterior pharynx. The patient had no other skin, eye, or urogenital involvement, but he was dehydrated. Respiratory examination was unremarkable. A complete blood count and metabolic panel were normal, as was a ­C-reactive protein (CRP) test (0.8 mg/L).

The preliminary diagnosis was primary herpetic gingivostomatitis, and treatment was initiated with intravenous (IV) acyclovir (10 mg/kg every 8 hours), IV fluids, and topical lidocaine gel and topical steroids for analgesia. However, the patient’s fever persisted over the next 4 days, with his temperature fluctuating between 101.3 °F and 104 °F, and he had a worsening productive cough. The blisters ruptured on Day 6 of illness, leaving hemorrhagic crusting on his lips (FIGURE 1B). Herpes simplex virus types 1 and 2 and polymerase chain reaction (PCR) testing were negative.

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

 

 

Dx: Mycoplasma pneumoniae–induced rash and mucositis

Further follow-up on Day 6 of illness revealed bibasilar crepitations along with an elevated CRP level of 40.5 mg/L and a positive mycoplasma antibody serology (titer > 1:1280; ­normal, < 1:80). The patient was given a diagnosis of pneumonia (due to infection with Mycoplasma pneumoniae) and M ­pneumoniae–induced rash and mucositis (MIRM).

MIRM was first proposed as a distinct clinical entity in 2015 to distinguish it from Stevens-Johnson syndrome and erythema multiforme.¹ MIRM is seen more commonly in children and young adults, with a male preponderance.¹

Within 3 days of initiating treatment with IV ceftriaxone, azithromycin, and methylprednisolone, our patient experienced marked improvement of his symptoms.

A small longitudinal study found that approximately 22.7% of children who have M pneumoniae infections present with mucocutaneous lesions, and of those cases, 6.8% are MIRM.² Chlamydia pneumoniae is another potential causal organism of mucositis resembling MIRM.³

Pathogenesis. The commonly accepted mechanism of MIRM is an immune response triggered by a distant infection. This leads to tissue damage via polyclonal B cell proliferation and subsequent immune complex deposition, complement activation, and cytokine overproduction. Molecular mimicry between M pneumoniae P1-adhesion molecules and keratinocyte antigens may also contribute to this pathway.

3 criteria to make the diagnosis

Canavan et al¹ have proposed the following criteria for the diagnosis of MIRM:

• Clinical symptoms, such as fever and cough, and laboratory findings of M pneumoniae infection (elevated M pneumoniae immunoglobulin M antibodies, positive cultures or PCR for M pneumoniae from oropharyngeal samples or bullae, and/or serial cold agglutinins) AND
• a rash to the mucosa that usually affects ≥ 2 sites (although rare cases may have fewer than 2 mucosal sites involved) AND
• skin detachment of less than 10% of the body surface area.

Continue to: The 3 variants of MIRM include...

The 3 variants of MIRM include:

• Classic MIRM has evidence of all 3 diagnostic criteria plus a nonmucosal rash, such as vesiculobullous lesions (77%), scattered target lesions (48%), papules (14%), macules (12%), and morbilliform eruptions (9%).⁴
• MIRM sine rash includes all 3 criteria but there is no significant cutaneous, nonmucosal rash. There may be “few fleeting morbilliform lesions or a few vesicles.”⁴
• Severe MIRM includes the first 2 criteria listed, but the cutaneous rash is extensive, with widespread nonmucosal blisters or flat atypical target lesions.⁴

Our patient had definitive clinical symptoms, laboratory evidence, and severe oral mucositis without significant cutaneous rash, thereby fulfilling the criteria for a diagnosis of MIRM sine rash variant.

These skin conditions were considered in the differential

The differential diagnosis for sudden onset of severe oral mucosal blisters in children includes herpes gingivostomatitis; hand, foot, and mouth disease; erythema multiforme; and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). The presence of pulmonary symptoms and oropharyngeal mucositis, together with the laboratory markers currently proposed as MIRM diagnostic criteria, are important in helping differentiate MIRM from other items in the differential diagnosis.

Herpes gingivostomatitis would involve numerous ulcerations of the oral mucosa and tongue, as well as gum hypertrophy.

Hand, foot, and mouth disease is characterized by vesicular exanthems of the hands, legs, and buttocks.

Continue to: Erythema multiforme

Erythema multiforme appears as cutaneous target lesions on the limbs that spread in a centripetal manner following herpes simplex virus infection.

SJS/TEN manifests with severe mucositis and is commonly triggered by medications (eg, sulphonamides, beta-lactams, nonsteroidal anti-inflammatory drugs, and antiepileptics).

With antibiotics, the prognosis is good

There are no established guidelines for the treatment of MIRM. Antibiotics and supportive care are universally accepted. Immunosuppressive therapy (eg, systemic steroids) is frequently used in patients with MIRM who have extensive mucosal involvement, in an attempt to decrease inflammation and pain; however, evidence for such an approach is lacking. The hyperimmune reactions of the host to M pneumoniae infection include cytokine overproduction and T-cell activation, which promote both pulmonary and extrapulmonary manifestations. This forms the basis of immunosuppressive therapy, such as systemic corticosteroids, IV immunoglobulin, and cyclosporin A, particularly when MIRM is associated with pneumonia caused by infection with M pneumoniae.^1,5,6

The overall prognosis of MIRM is good. Recurrence has been reported in up to 8% of cases, the treatment of which remains the same. Mucocutaneous and ocular sequelae (oral or genital synechiae, corneal ulcerations, dry eyes, loss of eye lashes) have been reported in less than 9% of patients.¹ Other rare reported complications following the occurrence of MIRM include persistent cutaneous lesions, B cell lymphopenia, and restrictive lung disease or chronic obliterative bronchitis.

Our patient was started on IV ­ceftriaxone (50 mg/kg/d), azithromycin (10 mg/kg/d on the first day, then 5 mg/kg/d on the sub­sequent 5 days), and methylprednisolone (3 mg/kg/d) on Day 6 of illness. Within 3 days, there was marked improvement of mucositis and respiratory symptoms with resolution of fever. He was discharged on Day 10. At his outpatient follow-up 2 weeks later, the patient had made a complete recovery.

This is a digital mucous cyst, also known as a myxoid cyst. The clear to translucent appearance over a finger or toe joint is usually diagnosed clinically. If uncertain, a biopsy can confirm the diagnosis.

Digital mucous cysts are a type of ganglion cyst that is associated with trauma or arthritis in the toe joint. A microscopic opening in the joint capsule results in a fluid filled cyst in the surrounding tissue. If the cyst is ruptured, thick, gelatinous (sometimes blood-tinged) hyaluronic acid–rich fluid may escape. Sometimes, the cyst applies pressure to the nail matrix, causing a scooped out longitudinal nail deformity.

Digital mucous cysts more commonly affect the fingers than the toes. Although benign, patients may be bothered by the appearance of these cysts and their effect on nails. Observation is a reasonable approach. Rarely, digital mucous cysts resolve spontaneously.

Treatment options include cryotherapy, needle draining and scarification, and surgical excision with flap repair. Surgical excision may be performed quickly in the office and offers the highest cure rate of 95% in 1 study on fingers.¹ Cryotherapy is successful in 70% of cases and needle drainage is successful in 39% of cases, but these modalities are quick and require minimal downtime.¹

In this case, the patient was not significantly bothered by the lesion and was happy to forego treatment.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

This is a digital mucous cyst, also known as a myxoid cyst. The clear to translucent appearance over a finger or toe joint is usually diagnosed clinically. If uncertain, a biopsy can confirm the diagnosis.

Digital mucous cysts are a type of ganglion cyst that is associated with trauma or arthritis in the toe joint. A microscopic opening in the joint capsule results in a fluid filled cyst in the surrounding tissue. If the cyst is ruptured, thick, gelatinous (sometimes blood-tinged) hyaluronic acid–rich fluid may escape. Sometimes, the cyst applies pressure to the nail matrix, causing a scooped out longitudinal nail deformity.

Digital mucous cysts more commonly affect the fingers than the toes. Although benign, patients may be bothered by the appearance of these cysts and their effect on nails. Observation is a reasonable approach. Rarely, digital mucous cysts resolve spontaneously.

Treatment options include cryotherapy, needle draining and scarification, and surgical excision with flap repair. Surgical excision may be performed quickly in the office and offers the highest cure rate of 95% in 1 study on fingers.¹ Cryotherapy is successful in 70% of cases and needle drainage is successful in 39% of cases, but these modalities are quick and require minimal downtime.¹

In this case, the patient was not significantly bothered by the lesion and was happy to forego treatment.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

This is a digital mucous cyst, also known as a myxoid cyst. The clear to translucent appearance over a finger or toe joint is usually diagnosed clinically. If uncertain, a biopsy can confirm the diagnosis.

Digital mucous cysts are a type of ganglion cyst that is associated with trauma or arthritis in the toe joint. A microscopic opening in the joint capsule results in a fluid filled cyst in the surrounding tissue. If the cyst is ruptured, thick, gelatinous (sometimes blood-tinged) hyaluronic acid–rich fluid may escape. Sometimes, the cyst applies pressure to the nail matrix, causing a scooped out longitudinal nail deformity.

Digital mucous cysts more commonly affect the fingers than the toes. Although benign, patients may be bothered by the appearance of these cysts and their effect on nails. Observation is a reasonable approach. Rarely, digital mucous cysts resolve spontaneously.

Treatment options include cryotherapy, needle draining and scarification, and surgical excision with flap repair. Surgical excision may be performed quickly in the office and offers the highest cure rate of 95% in 1 study on fingers.¹ Cryotherapy is successful in 70% of cases and needle drainage is successful in 39% of cases, but these modalities are quick and require minimal downtime.¹

In this case, the patient was not significantly bothered by the lesion and was happy to forego treatment.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Dermoscopy revealed a keratotic, 2.5-cm scaly plaque with linearly arranged dotted vessels, ulceration, and shiny white lines. A shave biopsy was consistent with a squamous cell carcinoma in situ (SCC in situ)—a pre-invasive keratinocyte carcinoma.

SCC in situ, also known as Bowen’s disease, is a very common skin cancer that can be easily treated. Lesions may manifest anywhere on the skin but are most often found on sun-damaged areas. Actinic keratoses are a pre-malignant precursor of SCC in situ; both are characterized by a sandpapery rough surface on a pink or brown background. Histologically, SCC in situ has atypia of keratinocytes over the full thickness of the epidermis, while actinic keratoses have limited atypia of the upper epidermis only. With this in mind, suspect SCC in situ (over actinic keratosis) when a lesion is thicker than 1 mm, larger in diameter than 5 mm, or painful.¹

Treatment options include surgical and nonsurgical modalities. Excision and electrodessication and curettage (EDC) are both effective surgical procedures, with cure rates greater than 90%.² Nonsurgical options include cryotherapy, 5-fluorouracil (5FU), imiquimod, and photodynamic therapy. Treatment with 5FU or imiquimod involves the application of cream to the lesion for 4 to 6 weeks. Marked inflammation during treatment is to be expected.

In the case described here, the patient underwent EDC in the office and was counseled to continue with complete skin exams twice a year for the next 2 years.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Dermoscopy revealed a keratotic, 2.5-cm scaly plaque with linearly arranged dotted vessels, ulceration, and shiny white lines. A shave biopsy was consistent with a squamous cell carcinoma in situ (SCC in situ)—a pre-invasive keratinocyte carcinoma.

SCC in situ, also known as Bowen’s disease, is a very common skin cancer that can be easily treated. Lesions may manifest anywhere on the skin but are most often found on sun-damaged areas. Actinic keratoses are a pre-malignant precursor of SCC in situ; both are characterized by a sandpapery rough surface on a pink or brown background. Histologically, SCC in situ has atypia of keratinocytes over the full thickness of the epidermis, while actinic keratoses have limited atypia of the upper epidermis only. With this in mind, suspect SCC in situ (over actinic keratosis) when a lesion is thicker than 1 mm, larger in diameter than 5 mm, or painful.¹

Treatment options include surgical and nonsurgical modalities. Excision and electrodessication and curettage (EDC) are both effective surgical procedures, with cure rates greater than 90%.² Nonsurgical options include cryotherapy, 5-fluorouracil (5FU), imiquimod, and photodynamic therapy. Treatment with 5FU or imiquimod involves the application of cream to the lesion for 4 to 6 weeks. Marked inflammation during treatment is to be expected.

In the case described here, the patient underwent EDC in the office and was counseled to continue with complete skin exams twice a year for the next 2 years.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Dermoscopy revealed a keratotic, 2.5-cm scaly plaque with linearly arranged dotted vessels, ulceration, and shiny white lines. A shave biopsy was consistent with a squamous cell carcinoma in situ (SCC in situ)—a pre-invasive keratinocyte carcinoma.

SCC in situ, also known as Bowen’s disease, is a very common skin cancer that can be easily treated. Lesions may manifest anywhere on the skin but are most often found on sun-damaged areas. Actinic keratoses are a pre-malignant precursor of SCC in situ; both are characterized by a sandpapery rough surface on a pink or brown background. Histologically, SCC in situ has atypia of keratinocytes over the full thickness of the epidermis, while actinic keratoses have limited atypia of the upper epidermis only. With this in mind, suspect SCC in situ (over actinic keratosis) when a lesion is thicker than 1 mm, larger in diameter than 5 mm, or painful.¹

Treatment options include surgical and nonsurgical modalities. Excision and electrodessication and curettage (EDC) are both effective surgical procedures, with cure rates greater than 90%.² Nonsurgical options include cryotherapy, 5-fluorouracil (5FU), imiquimod, and photodynamic therapy. Treatment with 5FU or imiquimod involves the application of cream to the lesion for 4 to 6 weeks. Marked inflammation during treatment is to be expected.

In the case described here, the patient underwent EDC in the office and was counseled to continue with complete skin exams twice a year for the next 2 years.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

PHILADELPHIA – Combining the immunomodulatory agent mycophenolate with the antifibrotic pirfenidone led to more rapid improvement and showed a trend to be more effective than mycophenolate mofetil alone for treating the signs and symptoms of scleroderma-related interstitial lung disease, but the combination therapy came with an increase in side effects, according to results from the Scleroderma Lung Study III.

Dinesh Khanna, MBBS, MSc, of the University of Michigan, Ann Arbor, presented the results at the annual meeting of the American College of Rheumatology. He noted some problems with the study – namely its small size, enrolling only 51 patients, about one-third of its original goal. But he also said it showed a potential signal for efficacy and that the study itself could serve as a “template” for future studies of combination mycophenolate mofetil (MMF) plus pirfenidone therapy for scleroderma-related interstitial lung disease (SSc-ILD).

“The pirfenidone patients had quite a bit more GI side effects and photosensitivity, and those are known side effects,” Dr. Khanna said in an interview. “So the combination therapy had more side effects but trends to higher efficacy.”

The design of SLS-III, a phase 2 clinical trial, was a challenge, Dr. Khanna explained. The goal was to enroll 150 SSc-ILD patients who hadn’t had any previous treatment for their disease. Finding those patients proved difficult. “In fact, if you look at the recent history, 70% of the patients with early diffuse scleroderma are on MMF,” he said in his presentation. Compounding low study enrollment was the intervening COVID-19 pandemic, he added.
 

Testing a faster-acting combination

Nonetheless, the trial managed to enroll 27 patients in the combination therapy group and 24 in the MMF-plus-placebo group and compared their outcomes over 18 months. Study dosing was 1,500 mg MMF twice daily and pirfenidone 801 mg three times daily, titrated to the tolerable dose.

Despite the study’s being underpowered, Dr. Khanna said, it still reported some notable outcomes that merit further investigation. “I think what was intriguing in the study was the long-term benefit in the patient-reported outcomes and the structural changes,” he said in the interview.

Among those notable outcomes was a clinically significant change in forced vital capacity (FVC) percentage for the combination vs. the placebo groups: 2.24% vs. 2.09%. He also noted that the combination group saw a somewhat more robust improvement in FVC at six months: 2.59% (± 0.98%) vs. 0.92% (± 1.1%) in the placebo group.

The combination group showed greater improvements in high-resolution computed tomography-evaluated lung involvement and lung fibrosis and patient-reported outcomes, including a statistically significant 3.67-point greater improvement in PROMIS-29 physical function score (4.42 vs. 0.75).

The patients on combination therapy had higher rates of serious adverse events (SAEs), and seven discontinued one or both study drugs early, all in the combined arm. Four combination therapy patients had six SAEs, compared to two placebo patients with three SAEs. In the combination group, SAEs included chest pain, herpes zoster ophthalmicus, nodular basal cell cancer, marginal zone B cell lymphoma, renal crisis, and dyspnea. SAEs in the placebo group were colitis, COVID-19 and hypoxic respiratory failure.

Study design challenges

Nonetheless, Dr. Khanna said the SLS-III data are consistent with the SLS-II findings, with mean improvements in FVC of 2.24% and 2.1%, respectively.

“The next study may be able to replicate what we tried to do, keeping in mind that there are really no MMF-naive patients who are walking around,” Dr. Khanna said. “So the challenge is about the feasibility of recruiting within a trial vs. trying to show a statistical difference between the drug and placebo.”

This study could serve as a foundation for future studies of MMF in patients with SSc-ILD, Robert Spiera, MD, of the Hospital for Special Surgery in New York, said in an interview. “There are lessons to be learned both from the study but also from prior studies looking at MMF use in the background in patients treated with other drugs in clinical trials,” he said.

Dr. Spiera noted that the study had other challenges besides the difficulty in recruiting patients who hadn’t been on MMF therapy. “A great challenge is that the benefit with regard to the impact on the lungs from MMF seems most prominent in the first 6 months to a year to even 2 years that somebody is on the drug,” he said.

The other challenge with this study is that a large proportion of patients had limited systemic disease and relatively lower levels of skin disease compared with other studies of patients on MMF, Dr. Spiera said.

“The optimal treatment of scleroderma-associated lung disease remains a very important and not-adequately met need,” he said. “Particularly, we’re looking for drugs that are tolerable in a patient population that are very prone to GI side effects in general. This study and others have taught us a lot about trial design, and I think more globally this will allow us to move this field forward.”

Dr. Khanna disclosed relationships with Actelion, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Horizon Therapeutics USA, Janssen Global Services, Prometheus Biosciences, Mitsubishi Tanabe Pharma Corp., Genentech/Roche, Theraly, and Pfizer. Genentech provided funding for the study and pirfenidone and placebo drugs at no cost.

Dr. Spiera disclosed relationships with GlaxoSmithKline, Boehringer-Ingelheim, Corbus Pharmaceutical, InflaRx, AbbVie/Abbott, Sanofi, Novartis, Chemocentryx, Roche and Vera.

PHILADELPHIA – Combining the immunomodulatory agent mycophenolate with the antifibrotic pirfenidone led to more rapid improvement and showed a trend to be more effective than mycophenolate mofetil alone for treating the signs and symptoms of scleroderma-related interstitial lung disease, but the combination therapy came with an increase in side effects, according to results from the Scleroderma Lung Study III.

Dinesh Khanna, MBBS, MSc, of the University of Michigan, Ann Arbor, presented the results at the annual meeting of the American College of Rheumatology. He noted some problems with the study – namely its small size, enrolling only 51 patients, about one-third of its original goal. But he also said it showed a potential signal for efficacy and that the study itself could serve as a “template” for future studies of combination mycophenolate mofetil (MMF) plus pirfenidone therapy for scleroderma-related interstitial lung disease (SSc-ILD).

“The pirfenidone patients had quite a bit more GI side effects and photosensitivity, and those are known side effects,” Dr. Khanna said in an interview. “So the combination therapy had more side effects but trends to higher efficacy.”

The design of SLS-III, a phase 2 clinical trial, was a challenge, Dr. Khanna explained. The goal was to enroll 150 SSc-ILD patients who hadn’t had any previous treatment for their disease. Finding those patients proved difficult. “In fact, if you look at the recent history, 70% of the patients with early diffuse scleroderma are on MMF,” he said in his presentation. Compounding low study enrollment was the intervening COVID-19 pandemic, he added.
 

Testing a faster-acting combination

Nonetheless, the trial managed to enroll 27 patients in the combination therapy group and 24 in the MMF-plus-placebo group and compared their outcomes over 18 months. Study dosing was 1,500 mg MMF twice daily and pirfenidone 801 mg three times daily, titrated to the tolerable dose.

Despite the study’s being underpowered, Dr. Khanna said, it still reported some notable outcomes that merit further investigation. “I think what was intriguing in the study was the long-term benefit in the patient-reported outcomes and the structural changes,” he said in the interview.

Among those notable outcomes was a clinically significant change in forced vital capacity (FVC) percentage for the combination vs. the placebo groups: 2.24% vs. 2.09%. He also noted that the combination group saw a somewhat more robust improvement in FVC at six months: 2.59% (± 0.98%) vs. 0.92% (± 1.1%) in the placebo group.

The combination group showed greater improvements in high-resolution computed tomography-evaluated lung involvement and lung fibrosis and patient-reported outcomes, including a statistically significant 3.67-point greater improvement in PROMIS-29 physical function score (4.42 vs. 0.75).

The patients on combination therapy had higher rates of serious adverse events (SAEs), and seven discontinued one or both study drugs early, all in the combined arm. Four combination therapy patients had six SAEs, compared to two placebo patients with three SAEs. In the combination group, SAEs included chest pain, herpes zoster ophthalmicus, nodular basal cell cancer, marginal zone B cell lymphoma, renal crisis, and dyspnea. SAEs in the placebo group were colitis, COVID-19 and hypoxic respiratory failure.

Study design challenges

Nonetheless, Dr. Khanna said the SLS-III data are consistent with the SLS-II findings, with mean improvements in FVC of 2.24% and 2.1%, respectively.

“The next study may be able to replicate what we tried to do, keeping in mind that there are really no MMF-naive patients who are walking around,” Dr. Khanna said. “So the challenge is about the feasibility of recruiting within a trial vs. trying to show a statistical difference between the drug and placebo.”

This study could serve as a foundation for future studies of MMF in patients with SSc-ILD, Robert Spiera, MD, of the Hospital for Special Surgery in New York, said in an interview. “There are lessons to be learned both from the study but also from prior studies looking at MMF use in the background in patients treated with other drugs in clinical trials,” he said.

Dr. Spiera noted that the study had other challenges besides the difficulty in recruiting patients who hadn’t been on MMF therapy. “A great challenge is that the benefit with regard to the impact on the lungs from MMF seems most prominent in the first 6 months to a year to even 2 years that somebody is on the drug,” he said.

The other challenge with this study is that a large proportion of patients had limited systemic disease and relatively lower levels of skin disease compared with other studies of patients on MMF, Dr. Spiera said.

“The optimal treatment of scleroderma-associated lung disease remains a very important and not-adequately met need,” he said. “Particularly, we’re looking for drugs that are tolerable in a patient population that are very prone to GI side effects in general. This study and others have taught us a lot about trial design, and I think more globally this will allow us to move this field forward.”

Dr. Khanna disclosed relationships with Actelion, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Horizon Therapeutics USA, Janssen Global Services, Prometheus Biosciences, Mitsubishi Tanabe Pharma Corp., Genentech/Roche, Theraly, and Pfizer. Genentech provided funding for the study and pirfenidone and placebo drugs at no cost.

Dr. Spiera disclosed relationships with GlaxoSmithKline, Boehringer-Ingelheim, Corbus Pharmaceutical, InflaRx, AbbVie/Abbott, Sanofi, Novartis, Chemocentryx, Roche and Vera.

PHILADELPHIA – Combining the immunomodulatory agent mycophenolate with the antifibrotic pirfenidone led to more rapid improvement and showed a trend to be more effective than mycophenolate mofetil alone for treating the signs and symptoms of scleroderma-related interstitial lung disease, but the combination therapy came with an increase in side effects, according to results from the Scleroderma Lung Study III.

Dinesh Khanna, MBBS, MSc, of the University of Michigan, Ann Arbor, presented the results at the annual meeting of the American College of Rheumatology. He noted some problems with the study – namely its small size, enrolling only 51 patients, about one-third of its original goal. But he also said it showed a potential signal for efficacy and that the study itself could serve as a “template” for future studies of combination mycophenolate mofetil (MMF) plus pirfenidone therapy for scleroderma-related interstitial lung disease (SSc-ILD).

“The pirfenidone patients had quite a bit more GI side effects and photosensitivity, and those are known side effects,” Dr. Khanna said in an interview. “So the combination therapy had more side effects but trends to higher efficacy.”

The design of SLS-III, a phase 2 clinical trial, was a challenge, Dr. Khanna explained. The goal was to enroll 150 SSc-ILD patients who hadn’t had any previous treatment for their disease. Finding those patients proved difficult. “In fact, if you look at the recent history, 70% of the patients with early diffuse scleroderma are on MMF,” he said in his presentation. Compounding low study enrollment was the intervening COVID-19 pandemic, he added.
 

Testing a faster-acting combination

Nonetheless, the trial managed to enroll 27 patients in the combination therapy group and 24 in the MMF-plus-placebo group and compared their outcomes over 18 months. Study dosing was 1,500 mg MMF twice daily and pirfenidone 801 mg three times daily, titrated to the tolerable dose.

Despite the study’s being underpowered, Dr. Khanna said, it still reported some notable outcomes that merit further investigation. “I think what was intriguing in the study was the long-term benefit in the patient-reported outcomes and the structural changes,” he said in the interview.

Among those notable outcomes was a clinically significant change in forced vital capacity (FVC) percentage for the combination vs. the placebo groups: 2.24% vs. 2.09%. He also noted that the combination group saw a somewhat more robust improvement in FVC at six months: 2.59% (± 0.98%) vs. 0.92% (± 1.1%) in the placebo group.

The combination group showed greater improvements in high-resolution computed tomography-evaluated lung involvement and lung fibrosis and patient-reported outcomes, including a statistically significant 3.67-point greater improvement in PROMIS-29 physical function score (4.42 vs. 0.75).

The patients on combination therapy had higher rates of serious adverse events (SAEs), and seven discontinued one or both study drugs early, all in the combined arm. Four combination therapy patients had six SAEs, compared to two placebo patients with three SAEs. In the combination group, SAEs included chest pain, herpes zoster ophthalmicus, nodular basal cell cancer, marginal zone B cell lymphoma, renal crisis, and dyspnea. SAEs in the placebo group were colitis, COVID-19 and hypoxic respiratory failure.

Study design challenges

Nonetheless, Dr. Khanna said the SLS-III data are consistent with the SLS-II findings, with mean improvements in FVC of 2.24% and 2.1%, respectively.

“The next study may be able to replicate what we tried to do, keeping in mind that there are really no MMF-naive patients who are walking around,” Dr. Khanna said. “So the challenge is about the feasibility of recruiting within a trial vs. trying to show a statistical difference between the drug and placebo.”

This study could serve as a foundation for future studies of MMF in patients with SSc-ILD, Robert Spiera, MD, of the Hospital for Special Surgery in New York, said in an interview. “There are lessons to be learned both from the study but also from prior studies looking at MMF use in the background in patients treated with other drugs in clinical trials,” he said.

Dr. Spiera noted that the study had other challenges besides the difficulty in recruiting patients who hadn’t been on MMF therapy. “A great challenge is that the benefit with regard to the impact on the lungs from MMF seems most prominent in the first 6 months to a year to even 2 years that somebody is on the drug,” he said.

The other challenge with this study is that a large proportion of patients had limited systemic disease and relatively lower levels of skin disease compared with other studies of patients on MMF, Dr. Spiera said.

“The optimal treatment of scleroderma-associated lung disease remains a very important and not-adequately met need,” he said. “Particularly, we’re looking for drugs that are tolerable in a patient population that are very prone to GI side effects in general. This study and others have taught us a lot about trial design, and I think more globally this will allow us to move this field forward.”

Dr. Khanna disclosed relationships with Actelion, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Horizon Therapeutics USA, Janssen Global Services, Prometheus Biosciences, Mitsubishi Tanabe Pharma Corp., Genentech/Roche, Theraly, and Pfizer. Genentech provided funding for the study and pirfenidone and placebo drugs at no cost.

Dr. Spiera disclosed relationships with GlaxoSmithKline, Boehringer-Ingelheim, Corbus Pharmaceutical, InflaRx, AbbVie/Abbott, Sanofi, Novartis, Chemocentryx, Roche and Vera.

The finding that serum dupilumab levels in patients with atopic dermatitis (AD) do not predict long-term response levels or adverse events (AEs) suggests that factors beyond interpatient variability of the interleukin-4 receptor subunit-alpha (IL-4R-alpha) may drive response levels, according to a study published in JAMA Dermatology.

The study results mean that researchers should continue exploring potential AD drugs with novel mechanisms to help patients who fail type 2 inflammatory inhibition, experts told this news organization. The search for accurate augurs of clinical performance also must continue.

Addressing inadequate response

Quantifying nonresponse and incomplete response levels with dupilumab is difficult, said Jonathan I. Silverberg, MD, PhD, MPH, offering perspective on the study. “True nonresponse is probably less than 20%, but many other patients are inadequate responders even if they are having partial response.” Dr. Silverberg, professor of dermatology and director of clinical research, at George Washington University, Washington, was not an investigator.

Robert Sidbury, MD, MPH, added, “When a patient doesn’t respond to a medication that you expect they should, we always ask ourselves why.” Dermatologists have long assumed that, as with biologics for psoriasis, low blood levels were to blame for dupilumab nonresponse, said Dr. Sidbury, who is division chief of dermatology at Seattle Children’s Hospital and was not involved with the study. “This study showed that there was no correlation between response and blood levels.”

In the study, Lotte S. Spekhorst, MD, of National Expertise Center for Atopic Dermatitis, department of dermatology and allergology, University Medical Center Utrecht (the Netherlands) and coinvestigators prospectively followed 295 consecutive adult patients with moderate AD who were treated with dupilumab for 1 year. All patients received the same loading (600 mg) and biweekly (300 mg) doses.

The median dupilumab level at 16 weeks was 86.6 mcg/mL, which is higher than serum levels observed with other monoclonal antibodies used for other indications, such as psoriasis and inflammatory bowel disease, the authors noted. More importantly, researchers found no significant relationship between median week 16 dupilumab levels and 1-year clinical responses measured either discretely (Eczema Area and Severity Index [EASI] < 50, 50, 75, or 90; P = .18) or as quartiles (P = .06).

“It may be that response is dependent on target availability of the IL-4R-alpha, with an interpatient variability producing heterogeneity in response,” the authors wrote. But because serum dupilumab levels were relatively high, they said, all patients’ IL-4R-alpha “was likely fully saturated” at 16 weeks.

“This would explain why serum dupilumab levels were not related to effectiveness,” they noted, “although we cannot rule out differential effects in the tissue associated with heterogeneity in serum dupilumab levels.”

The study helps explain why some patients do not fully respond to dupilumab, said Eric L. Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, who was not involved with the study.

“One hypothesis would be that drug serum levels differ due to metabolism or absorption reasons,” Dr. Simpson said in an interview. Results also suggest that heterogeneity in disease biology, such as other uninhibited cytokine pathways, might explain differences in clinical results. “Thus, more therapeutics that target different inflammatory pathways are needed to capture responses in patients not adequately responding to type 2 inflammatory blockade,” he said.
 

Assessing AEs

As with response levels, serum dupilumab levels at week 16 did not predict AEs including dupilumab-associated ocular surface disease (DAOSD), which impacted 46.4% of 216 patients who reported AEs. These findings also contradict what happens with biologics in other diseases such as psoriasis and inflammatory bowel disease, said Dr. Sidbury, wherein serum drug levels may predict both clinical response and side-effect risks.

A previous study showed that lowering dupilumab levels led to improvement in DAOSD. Authors of the current study therefore surmised that DAOSD development might be more associated with interpatient variability in IL-4R-alpha expression than with serum drug levels. “More research is necessary to confirm the hypothesis of interpatient variability of the IL-4Ra and the pharmacokinetics of dupilumab,” they concluded.

For now, said Dr. Sidbury, the study helps clinicians look beyond serum drug levels when patients respond inadequately to dupilumab. Moreover, added Dr. Silverberg, study results mean that physicians must find other ways to predict dupilumab response levels. “We need better predictors of clinical response – theranostic markers that we could test the patient to and understand how well they’re going to do,” he said.

Be it dupilumab or any other medication, he said, physicians lack even confirmatory biomarkers to reflect when a drug is working well. “Right now, we go with clinical assessments. But if it’s not drug levels, we have to figure out why some patients do markedly better than others.”

It was not unreasonable, Dr. Silverberg said, for the investigators to seek a biomarker in blood rather than tissue. “But in this disease, we believe that the more important place to look for biomarkers and drug levels would be in the skin itself. So we are still left with the issue” that drug levels in tissue might reflect response when serum levels do not.

The study was supported by grants from AbbVie, Eli Lilly, Leo Pharma, Pfizer, and Sanofi. Study patients participated in the BioDay Registry, which is sponsored by Sanofi, Regeneron, AbbVie, Eli Lilly, LEO Pharma, and Pfizer; the sponsors had no role in the study design and conduct. Dr. Spekhorst discloses receiving speaking fees from Abbvie outside the work; disclosures of other authors included receiving advisory, speaking consulting, and/or investigator fees from Sanofi Genzyme during the study. Several authors had no disclosures.

Dr. Simpson has been an investigator and consultant for Regeneron and Sanofi, makers of dupilumab. Dr. Silverberg has been an investigator, consultant, and speaker for Regeneron and Sanofi. Dr. Sidbury has been a clinical investigator for all dupilumab pediatric trials. (His institution has a contract with Regeneron and Sanofi, but he receives no money from the arrangement.)

The finding that serum dupilumab levels in patients with atopic dermatitis (AD) do not predict long-term response levels or adverse events (AEs) suggests that factors beyond interpatient variability of the interleukin-4 receptor subunit-alpha (IL-4R-alpha) may drive response levels, according to a study published in JAMA Dermatology.

The study results mean that researchers should continue exploring potential AD drugs with novel mechanisms to help patients who fail type 2 inflammatory inhibition, experts told this news organization. The search for accurate augurs of clinical performance also must continue.

Addressing inadequate response

Quantifying nonresponse and incomplete response levels with dupilumab is difficult, said Jonathan I. Silverberg, MD, PhD, MPH, offering perspective on the study. “True nonresponse is probably less than 20%, but many other patients are inadequate responders even if they are having partial response.” Dr. Silverberg, professor of dermatology and director of clinical research, at George Washington University, Washington, was not an investigator.

Robert Sidbury, MD, MPH, added, “When a patient doesn’t respond to a medication that you expect they should, we always ask ourselves why.” Dermatologists have long assumed that, as with biologics for psoriasis, low blood levels were to blame for dupilumab nonresponse, said Dr. Sidbury, who is division chief of dermatology at Seattle Children’s Hospital and was not involved with the study. “This study showed that there was no correlation between response and blood levels.”

In the study, Lotte S. Spekhorst, MD, of National Expertise Center for Atopic Dermatitis, department of dermatology and allergology, University Medical Center Utrecht (the Netherlands) and coinvestigators prospectively followed 295 consecutive adult patients with moderate AD who were treated with dupilumab for 1 year. All patients received the same loading (600 mg) and biweekly (300 mg) doses.

The median dupilumab level at 16 weeks was 86.6 mcg/mL, which is higher than serum levels observed with other monoclonal antibodies used for other indications, such as psoriasis and inflammatory bowel disease, the authors noted. More importantly, researchers found no significant relationship between median week 16 dupilumab levels and 1-year clinical responses measured either discretely (Eczema Area and Severity Index [EASI] < 50, 50, 75, or 90; P = .18) or as quartiles (P = .06).

“It may be that response is dependent on target availability of the IL-4R-alpha, with an interpatient variability producing heterogeneity in response,” the authors wrote. But because serum dupilumab levels were relatively high, they said, all patients’ IL-4R-alpha “was likely fully saturated” at 16 weeks.

“This would explain why serum dupilumab levels were not related to effectiveness,” they noted, “although we cannot rule out differential effects in the tissue associated with heterogeneity in serum dupilumab levels.”

The study helps explain why some patients do not fully respond to dupilumab, said Eric L. Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, who was not involved with the study.

“One hypothesis would be that drug serum levels differ due to metabolism or absorption reasons,” Dr. Simpson said in an interview. Results also suggest that heterogeneity in disease biology, such as other uninhibited cytokine pathways, might explain differences in clinical results. “Thus, more therapeutics that target different inflammatory pathways are needed to capture responses in patients not adequately responding to type 2 inflammatory blockade,” he said.
 

Assessing AEs

As with response levels, serum dupilumab levels at week 16 did not predict AEs including dupilumab-associated ocular surface disease (DAOSD), which impacted 46.4% of 216 patients who reported AEs. These findings also contradict what happens with biologics in other diseases such as psoriasis and inflammatory bowel disease, said Dr. Sidbury, wherein serum drug levels may predict both clinical response and side-effect risks.

A previous study showed that lowering dupilumab levels led to improvement in DAOSD. Authors of the current study therefore surmised that DAOSD development might be more associated with interpatient variability in IL-4R-alpha expression than with serum drug levels. “More research is necessary to confirm the hypothesis of interpatient variability of the IL-4Ra and the pharmacokinetics of dupilumab,” they concluded.

For now, said Dr. Sidbury, the study helps clinicians look beyond serum drug levels when patients respond inadequately to dupilumab. Moreover, added Dr. Silverberg, study results mean that physicians must find other ways to predict dupilumab response levels. “We need better predictors of clinical response – theranostic markers that we could test the patient to and understand how well they’re going to do,” he said.

Be it dupilumab or any other medication, he said, physicians lack even confirmatory biomarkers to reflect when a drug is working well. “Right now, we go with clinical assessments. But if it’s not drug levels, we have to figure out why some patients do markedly better than others.”

It was not unreasonable, Dr. Silverberg said, for the investigators to seek a biomarker in blood rather than tissue. “But in this disease, we believe that the more important place to look for biomarkers and drug levels would be in the skin itself. So we are still left with the issue” that drug levels in tissue might reflect response when serum levels do not.

The study was supported by grants from AbbVie, Eli Lilly, Leo Pharma, Pfizer, and Sanofi. Study patients participated in the BioDay Registry, which is sponsored by Sanofi, Regeneron, AbbVie, Eli Lilly, LEO Pharma, and Pfizer; the sponsors had no role in the study design and conduct. Dr. Spekhorst discloses receiving speaking fees from Abbvie outside the work; disclosures of other authors included receiving advisory, speaking consulting, and/or investigator fees from Sanofi Genzyme during the study. Several authors had no disclosures.

Dr. Simpson has been an investigator and consultant for Regeneron and Sanofi, makers of dupilumab. Dr. Silverberg has been an investigator, consultant, and speaker for Regeneron and Sanofi. Dr. Sidbury has been a clinical investigator for all dupilumab pediatric trials. (His institution has a contract with Regeneron and Sanofi, but he receives no money from the arrangement.)

The finding that serum dupilumab levels in patients with atopic dermatitis (AD) do not predict long-term response levels or adverse events (AEs) suggests that factors beyond interpatient variability of the interleukin-4 receptor subunit-alpha (IL-4R-alpha) may drive response levels, according to a study published in JAMA Dermatology.

The study results mean that researchers should continue exploring potential AD drugs with novel mechanisms to help patients who fail type 2 inflammatory inhibition, experts told this news organization. The search for accurate augurs of clinical performance also must continue.

Addressing inadequate response

Quantifying nonresponse and incomplete response levels with dupilumab is difficult, said Jonathan I. Silverberg, MD, PhD, MPH, offering perspective on the study. “True nonresponse is probably less than 20%, but many other patients are inadequate responders even if they are having partial response.” Dr. Silverberg, professor of dermatology and director of clinical research, at George Washington University, Washington, was not an investigator.

Robert Sidbury, MD, MPH, added, “When a patient doesn’t respond to a medication that you expect they should, we always ask ourselves why.” Dermatologists have long assumed that, as with biologics for psoriasis, low blood levels were to blame for dupilumab nonresponse, said Dr. Sidbury, who is division chief of dermatology at Seattle Children’s Hospital and was not involved with the study. “This study showed that there was no correlation between response and blood levels.”

In the study, Lotte S. Spekhorst, MD, of National Expertise Center for Atopic Dermatitis, department of dermatology and allergology, University Medical Center Utrecht (the Netherlands) and coinvestigators prospectively followed 295 consecutive adult patients with moderate AD who were treated with dupilumab for 1 year. All patients received the same loading (600 mg) and biweekly (300 mg) doses.

The median dupilumab level at 16 weeks was 86.6 mcg/mL, which is higher than serum levels observed with other monoclonal antibodies used for other indications, such as psoriasis and inflammatory bowel disease, the authors noted. More importantly, researchers found no significant relationship between median week 16 dupilumab levels and 1-year clinical responses measured either discretely (Eczema Area and Severity Index [EASI] < 50, 50, 75, or 90; P = .18) or as quartiles (P = .06).

“It may be that response is dependent on target availability of the IL-4R-alpha, with an interpatient variability producing heterogeneity in response,” the authors wrote. But because serum dupilumab levels were relatively high, they said, all patients’ IL-4R-alpha “was likely fully saturated” at 16 weeks.

“This would explain why serum dupilumab levels were not related to effectiveness,” they noted, “although we cannot rule out differential effects in the tissue associated with heterogeneity in serum dupilumab levels.”

The study helps explain why some patients do not fully respond to dupilumab, said Eric L. Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, who was not involved with the study.

“One hypothesis would be that drug serum levels differ due to metabolism or absorption reasons,” Dr. Simpson said in an interview. Results also suggest that heterogeneity in disease biology, such as other uninhibited cytokine pathways, might explain differences in clinical results. “Thus, more therapeutics that target different inflammatory pathways are needed to capture responses in patients not adequately responding to type 2 inflammatory blockade,” he said.
 

Assessing AEs

As with response levels, serum dupilumab levels at week 16 did not predict AEs including dupilumab-associated ocular surface disease (DAOSD), which impacted 46.4% of 216 patients who reported AEs. These findings also contradict what happens with biologics in other diseases such as psoriasis and inflammatory bowel disease, said Dr. Sidbury, wherein serum drug levels may predict both clinical response and side-effect risks.

A previous study showed that lowering dupilumab levels led to improvement in DAOSD. Authors of the current study therefore surmised that DAOSD development might be more associated with interpatient variability in IL-4R-alpha expression than with serum drug levels. “More research is necessary to confirm the hypothesis of interpatient variability of the IL-4Ra and the pharmacokinetics of dupilumab,” they concluded.

For now, said Dr. Sidbury, the study helps clinicians look beyond serum drug levels when patients respond inadequately to dupilumab. Moreover, added Dr. Silverberg, study results mean that physicians must find other ways to predict dupilumab response levels. “We need better predictors of clinical response – theranostic markers that we could test the patient to and understand how well they’re going to do,” he said.

Be it dupilumab or any other medication, he said, physicians lack even confirmatory biomarkers to reflect when a drug is working well. “Right now, we go with clinical assessments. But if it’s not drug levels, we have to figure out why some patients do markedly better than others.”

It was not unreasonable, Dr. Silverberg said, for the investigators to seek a biomarker in blood rather than tissue. “But in this disease, we believe that the more important place to look for biomarkers and drug levels would be in the skin itself. So we are still left with the issue” that drug levels in tissue might reflect response when serum levels do not.

The study was supported by grants from AbbVie, Eli Lilly, Leo Pharma, Pfizer, and Sanofi. Study patients participated in the BioDay Registry, which is sponsored by Sanofi, Regeneron, AbbVie, Eli Lilly, LEO Pharma, and Pfizer; the sponsors had no role in the study design and conduct. Dr. Spekhorst discloses receiving speaking fees from Abbvie outside the work; disclosures of other authors included receiving advisory, speaking consulting, and/or investigator fees from Sanofi Genzyme during the study. Several authors had no disclosures.

Dr. Simpson has been an investigator and consultant for Regeneron and Sanofi, makers of dupilumab. Dr. Silverberg has been an investigator, consultant, and speaker for Regeneron and Sanofi. Dr. Sidbury has been a clinical investigator for all dupilumab pediatric trials. (His institution has a contract with Regeneron and Sanofi, but he receives no money from the arrangement.)

Monkeypox virus infections in children and adolescents in the United States are rare, and young patients with known infections have all recovered, according to a study from the Centers for Disease Control and Prevention.

In addition, evidence suggests that secondary transmission in schools or childcare facilities may be unlikely.

The study was the first comprehensive study on the impact of monkeypox on children during the 2022 outbreak, according to a statement emailed to this news organization from the California Department of Public Health, one of the state health departments that partnered with the CDC to share information.

News of low infection rates and relatively mild disease was welcome to clinicians, who had braced for severe findings on the basis of sparse prior data, according to Peter Chin-Hong, MD, a professor of medicine and an infectious diseases physician at the University of California, San Francisco.

“We were on heightened alert that kids may do poorly,” said Dr. Chin-Hong, who was not involved in the study but who cared for monkeypox patients during the outbreak. “I think this study is reassuring.

“The other silver lining about it is that most of the kids got infected in the household setting from ways that you would expect them to get [infected],” Dr. Chin-Hong said in an interview.

However, Black and Hispanic children were more likely to contract the disease, underscoring troubling inequities.

“Early on, individuals of color were much less likely to be able to successfully access vaccination,” said first author Ian Hennessee, PhD, MPH, an epidemic intelligence service officer with the CDC and a member of the Special Case Investigation Unit of the Multinational Monkeypox Response Team at the CDC. “We think those kinds of structural inequities really trickled down towards the children and adolescents that have been affected by this outbreak.”

The study was published  in Morbidity and Mortality Weekly Report.
 

A nationwide look at the data

The researchers discussed 83 children and adolescents with monkeypox who came to the CDC’s attention between May 17 and Sept. 24, 2022.

The 83 cases represent 0.3% of the 25,038 reported monkeypox cases in the United States over that period. Of the 28 children aged 12 years or younger, 18 (64%) were boys. Sixteen children were younger than 4 years.

Exposure data were available for 20 (71%) of those aged 0-12. In that group, 19 were exposed at home; 17 cases were due to routine skin-to-skin contact with a household caregiver; and one case was suspected to be caused by fomites (such as a shared towel). Exposure information was unavailable for the remaining case.

Most of the children experienced lesions on the trunk. No lesions were anogenital. Two patients in the youngest age group were hospitalized because of widespread rash that involved the eyelids, and a patient in the 5- to 12-year-old group was hospitalized because of periorbital cellulitis and conjunctivitis.

Among those aged 13-17, there were 55 cases. Of these patients, 89% were boys. Exposure data were available for 35 (64%). In 32 of these patients, the infection occurred from presumed sexual contact. Twenty-three of those adolescents reported male-to-male sexual contact. No case was found to be connected with sexual abuse.

Lesions in the adolescents were mostly truncal or anogenital. Six in this group were hospitalized, and all of them recovered. One adolescent was found to be HIV positive.

Black and Hispanic children accounted for 47% and 35% of all cases, respectively.

Eleven percent of all the children and adolescents were hospitalized, and none received intensive care.

Treatments, when given, included the antiviral drug tecovirimat, intravenous vaccinia immune globulin, and topical trifluridine. There were no deaths.

Ten symptomatic patients attended school or daycare. Among these patients, no secondary transmissions were found to have occurred. Some contacts were offered the JYNNEOS monkeypox vaccine as postexposure prophylaxis.

Limitations of the study included potentially overlooked cases. Data were collected through routine surveillance, children frequently experience rashes, and access to testing has been a challenge, Dr. Hennessee explained.

In addition, data on exposure characteristics were missing for some children.
 

Inequities and the risks of being judged

The outbreak in the United States has eased in recent months. However, though uncommon in children, monkeypox has affected some racial groups disproportionately.

“Especially in the later course of the outbreak, the majority of cases were among Black and Hispanic individuals,” said co-author Rachel E. Harold, MD, an infectious diseases specialist and supervisory medical officer with the District of Columbia Department of Health’s HIV/AIDS, Hepatitis, STDs, and TB Administration.

“Unfortunately, the pediatric cases do reflect the outbreak overall,” she told this news organization.

Dr. Harold noted there have been efforts in D.C. and other jurisdictions, as well as by the White House monkeypox response team, to reach populations at greatest risk and that they were “really trying to make vaccine available to people of color.”

Vaccination clinics often popped up in unexpected locations at short notice, and that made it hard for some people to get to them, Dr. Chin-Hong pointed out.

Another factor was “the public aspect of accessing diagnostics and vaccines and the way that that’s linked to potential judgment or sexual risk,” he added.

“Not everybody’s out,” Dr. Chin-Hong said, referring to members of the LGBTQ community. “In many communities of color, going to get a test or going to get a vaccine essentially means that you’re out.”

For clinicians who suspect monkeypox in a child, Dr. Harold suggests keeping a broad differential diagnosis, looking for an epidemiologic link, and contacting the CDC for assistance. Infected children should be encouraged to avoid touching their own eyes or mucous membranes, she added.

In addition, she said, tecovirimat is a reasonable treatment and is well tolerated by pediatric monkeypox patients with eczema, an underlying condition that could lead to severe disease.

For infected caregivers, Dr. Hennessee said, measures to prevent infecting children at home include isolation, contact precautions, and in some cases, postexposure prophylaxis via vaccination.

For sexually active adolescents, he advised that clinicians offer vaccination, education on sexual health, and testing for HIV and other sexually transmitted infections.

“It’s important to remember that adolescents may be sexually active, and clinicians should do a thorough and nonjudgmental sexual history,” Dr. Harold added. “That is always true, but especially if there is concern for [monkeypox].”

Dr. Hennessee, Dr. Chin-Hong, and Dr. Harold have disclosed no relevant financial relationships.

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

Monkeypox virus infections in children and adolescents in the United States are rare, and young patients with known infections have all recovered, according to a study from the Centers for Disease Control and Prevention.

In addition, evidence suggests that secondary transmission in schools or childcare facilities may be unlikely.

The study was the first comprehensive study on the impact of monkeypox on children during the 2022 outbreak, according to a statement emailed to this news organization from the California Department of Public Health, one of the state health departments that partnered with the CDC to share information.

News of low infection rates and relatively mild disease was welcome to clinicians, who had braced for severe findings on the basis of sparse prior data, according to Peter Chin-Hong, MD, a professor of medicine and an infectious diseases physician at the University of California, San Francisco.

“We were on heightened alert that kids may do poorly,” said Dr. Chin-Hong, who was not involved in the study but who cared for monkeypox patients during the outbreak. “I think this study is reassuring.

“The other silver lining about it is that most of the kids got infected in the household setting from ways that you would expect them to get [infected],” Dr. Chin-Hong said in an interview.

However, Black and Hispanic children were more likely to contract the disease, underscoring troubling inequities.

“Early on, individuals of color were much less likely to be able to successfully access vaccination,” said first author Ian Hennessee, PhD, MPH, an epidemic intelligence service officer with the CDC and a member of the Special Case Investigation Unit of the Multinational Monkeypox Response Team at the CDC. “We think those kinds of structural inequities really trickled down towards the children and adolescents that have been affected by this outbreak.”

The study was published  in Morbidity and Mortality Weekly Report.
 

A nationwide look at the data

The researchers discussed 83 children and adolescents with monkeypox who came to the CDC’s attention between May 17 and Sept. 24, 2022.

The 83 cases represent 0.3% of the 25,038 reported monkeypox cases in the United States over that period. Of the 28 children aged 12 years or younger, 18 (64%) were boys. Sixteen children were younger than 4 years.

Exposure data were available for 20 (71%) of those aged 0-12. In that group, 19 were exposed at home; 17 cases were due to routine skin-to-skin contact with a household caregiver; and one case was suspected to be caused by fomites (such as a shared towel). Exposure information was unavailable for the remaining case.

Most of the children experienced lesions on the trunk. No lesions were anogenital. Two patients in the youngest age group were hospitalized because of widespread rash that involved the eyelids, and a patient in the 5- to 12-year-old group was hospitalized because of periorbital cellulitis and conjunctivitis.

Among those aged 13-17, there were 55 cases. Of these patients, 89% were boys. Exposure data were available for 35 (64%). In 32 of these patients, the infection occurred from presumed sexual contact. Twenty-three of those adolescents reported male-to-male sexual contact. No case was found to be connected with sexual abuse.

Lesions in the adolescents were mostly truncal or anogenital. Six in this group were hospitalized, and all of them recovered. One adolescent was found to be HIV positive.

Black and Hispanic children accounted for 47% and 35% of all cases, respectively.

Eleven percent of all the children and adolescents were hospitalized, and none received intensive care.

Treatments, when given, included the antiviral drug tecovirimat, intravenous vaccinia immune globulin, and topical trifluridine. There were no deaths.

Ten symptomatic patients attended school or daycare. Among these patients, no secondary transmissions were found to have occurred. Some contacts were offered the JYNNEOS monkeypox vaccine as postexposure prophylaxis.

Limitations of the study included potentially overlooked cases. Data were collected through routine surveillance, children frequently experience rashes, and access to testing has been a challenge, Dr. Hennessee explained.

In addition, data on exposure characteristics were missing for some children.
 

Inequities and the risks of being judged

The outbreak in the United States has eased in recent months. However, though uncommon in children, monkeypox has affected some racial groups disproportionately.

“Especially in the later course of the outbreak, the majority of cases were among Black and Hispanic individuals,” said co-author Rachel E. Harold, MD, an infectious diseases specialist and supervisory medical officer with the District of Columbia Department of Health’s HIV/AIDS, Hepatitis, STDs, and TB Administration.

“Unfortunately, the pediatric cases do reflect the outbreak overall,” she told this news organization.

Dr. Harold noted there have been efforts in D.C. and other jurisdictions, as well as by the White House monkeypox response team, to reach populations at greatest risk and that they were “really trying to make vaccine available to people of color.”

Vaccination clinics often popped up in unexpected locations at short notice, and that made it hard for some people to get to them, Dr. Chin-Hong pointed out.

Another factor was “the public aspect of accessing diagnostics and vaccines and the way that that’s linked to potential judgment or sexual risk,” he added.

“Not everybody’s out,” Dr. Chin-Hong said, referring to members of the LGBTQ community. “In many communities of color, going to get a test or going to get a vaccine essentially means that you’re out.”

For clinicians who suspect monkeypox in a child, Dr. Harold suggests keeping a broad differential diagnosis, looking for an epidemiologic link, and contacting the CDC for assistance. Infected children should be encouraged to avoid touching their own eyes or mucous membranes, she added.

In addition, she said, tecovirimat is a reasonable treatment and is well tolerated by pediatric monkeypox patients with eczema, an underlying condition that could lead to severe disease.

For infected caregivers, Dr. Hennessee said, measures to prevent infecting children at home include isolation, contact precautions, and in some cases, postexposure prophylaxis via vaccination.

For sexually active adolescents, he advised that clinicians offer vaccination, education on sexual health, and testing for HIV and other sexually transmitted infections.

“It’s important to remember that adolescents may be sexually active, and clinicians should do a thorough and nonjudgmental sexual history,” Dr. Harold added. “That is always true, but especially if there is concern for [monkeypox].”

Dr. Hennessee, Dr. Chin-Hong, and Dr. Harold have disclosed no relevant financial relationships.

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

Monkeypox virus infections in children and adolescents in the United States are rare, and young patients with known infections have all recovered, according to a study from the Centers for Disease Control and Prevention.

In addition, evidence suggests that secondary transmission in schools or childcare facilities may be unlikely.

The study was the first comprehensive study on the impact of monkeypox on children during the 2022 outbreak, according to a statement emailed to this news organization from the California Department of Public Health, one of the state health departments that partnered with the CDC to share information.

News of low infection rates and relatively mild disease was welcome to clinicians, who had braced for severe findings on the basis of sparse prior data, according to Peter Chin-Hong, MD, a professor of medicine and an infectious diseases physician at the University of California, San Francisco.

“We were on heightened alert that kids may do poorly,” said Dr. Chin-Hong, who was not involved in the study but who cared for monkeypox patients during the outbreak. “I think this study is reassuring.

“The other silver lining about it is that most of the kids got infected in the household setting from ways that you would expect them to get [infected],” Dr. Chin-Hong said in an interview.

However, Black and Hispanic children were more likely to contract the disease, underscoring troubling inequities.

“Early on, individuals of color were much less likely to be able to successfully access vaccination,” said first author Ian Hennessee, PhD, MPH, an epidemic intelligence service officer with the CDC and a member of the Special Case Investigation Unit of the Multinational Monkeypox Response Team at the CDC. “We think those kinds of structural inequities really trickled down towards the children and adolescents that have been affected by this outbreak.”

The study was published  in Morbidity and Mortality Weekly Report.
 

A nationwide look at the data

The researchers discussed 83 children and adolescents with monkeypox who came to the CDC’s attention between May 17 and Sept. 24, 2022.

The 83 cases represent 0.3% of the 25,038 reported monkeypox cases in the United States over that period. Of the 28 children aged 12 years or younger, 18 (64%) were boys. Sixteen children were younger than 4 years.

Exposure data were available for 20 (71%) of those aged 0-12. In that group, 19 were exposed at home; 17 cases were due to routine skin-to-skin contact with a household caregiver; and one case was suspected to be caused by fomites (such as a shared towel). Exposure information was unavailable for the remaining case.

Most of the children experienced lesions on the trunk. No lesions were anogenital. Two patients in the youngest age group were hospitalized because of widespread rash that involved the eyelids, and a patient in the 5- to 12-year-old group was hospitalized because of periorbital cellulitis and conjunctivitis.

Among those aged 13-17, there were 55 cases. Of these patients, 89% were boys. Exposure data were available for 35 (64%). In 32 of these patients, the infection occurred from presumed sexual contact. Twenty-three of those adolescents reported male-to-male sexual contact. No case was found to be connected with sexual abuse.

Lesions in the adolescents were mostly truncal or anogenital. Six in this group were hospitalized, and all of them recovered. One adolescent was found to be HIV positive.

Black and Hispanic children accounted for 47% and 35% of all cases, respectively.

Eleven percent of all the children and adolescents were hospitalized, and none received intensive care.

Treatments, when given, included the antiviral drug tecovirimat, intravenous vaccinia immune globulin, and topical trifluridine. There were no deaths.

Ten symptomatic patients attended school or daycare. Among these patients, no secondary transmissions were found to have occurred. Some contacts were offered the JYNNEOS monkeypox vaccine as postexposure prophylaxis.

Limitations of the study included potentially overlooked cases. Data were collected through routine surveillance, children frequently experience rashes, and access to testing has been a challenge, Dr. Hennessee explained.

In addition, data on exposure characteristics were missing for some children.
 

Inequities and the risks of being judged

The outbreak in the United States has eased in recent months. However, though uncommon in children, monkeypox has affected some racial groups disproportionately.

“Especially in the later course of the outbreak, the majority of cases were among Black and Hispanic individuals,” said co-author Rachel E. Harold, MD, an infectious diseases specialist and supervisory medical officer with the District of Columbia Department of Health’s HIV/AIDS, Hepatitis, STDs, and TB Administration.

“Unfortunately, the pediatric cases do reflect the outbreak overall,” she told this news organization.

Dr. Harold noted there have been efforts in D.C. and other jurisdictions, as well as by the White House monkeypox response team, to reach populations at greatest risk and that they were “really trying to make vaccine available to people of color.”

Vaccination clinics often popped up in unexpected locations at short notice, and that made it hard for some people to get to them, Dr. Chin-Hong pointed out.

Another factor was “the public aspect of accessing diagnostics and vaccines and the way that that’s linked to potential judgment or sexual risk,” he added.

“Not everybody’s out,” Dr. Chin-Hong said, referring to members of the LGBTQ community. “In many communities of color, going to get a test or going to get a vaccine essentially means that you’re out.”

For clinicians who suspect monkeypox in a child, Dr. Harold suggests keeping a broad differential diagnosis, looking for an epidemiologic link, and contacting the CDC for assistance. Infected children should be encouraged to avoid touching their own eyes or mucous membranes, she added.

In addition, she said, tecovirimat is a reasonable treatment and is well tolerated by pediatric monkeypox patients with eczema, an underlying condition that could lead to severe disease.

For infected caregivers, Dr. Hennessee said, measures to prevent infecting children at home include isolation, contact precautions, and in some cases, postexposure prophylaxis via vaccination.

For sexually active adolescents, he advised that clinicians offer vaccination, education on sexual health, and testing for HIV and other sexually transmitted infections.

“It’s important to remember that adolescents may be sexually active, and clinicians should do a thorough and nonjudgmental sexual history,” Dr. Harold added. “That is always true, but especially if there is concern for [monkeypox].”

Dr. Hennessee, Dr. Chin-Hong, and Dr. Harold have disclosed no relevant financial relationships.

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

The correct answer is (D), molluscum contagiosum. Upon surgical excision, the pathology indicated the lesion was consistent with molluscum contagiosum.

Molluscum contagiosum is a benign skin disorder caused by a pox virus and is frequently seen in children. This disease is transmitted primarily through direct skin contact with an infected individual.¹ Contaminated fomites have been suggested as another source of infection.² The typical lesion appears dome-shaped, round, and pinkish-purple in color.¹ The incubation period ranges from 2 weeks to 6 months and is typically self-limited in immunocompetent hosts; however, in immunocompromised persons, molluscum contagiosum lesions may present atypically such that they are larger in size and/or resemble malignancies, such as basal cell carcinoma or keratoacanthoma (for single lesions), or other infectious diseases, such as cryptococcosis and histoplasmosis (for more numerous lesions).^{3,4 A} giant atypical molluscum contagiosum is rarely seen in healthy individuals.
 

What’s on the differential?

The recent episode of bleeding raises concern for other neoplastic processes of the skin including squamous cell carcinoma or basal cell carcinoma as well as cutaneous metastatic rhabdoid tumor, given the patient’s history.

Eruptive keratoacanthomas are also reported in patients taking nivolumab, an anti-PD-1 immunotherapy, which the patient has received for treatment of his recurrent metastatic rhabdoid tumor.⁵ More common entities such as a pyogenic granuloma or verruca are also included on the differential. The initial presentation of the lesion, however, is more consistent with the pearly umbilicated papules associated with molluscum contagiosum.

Comments from Dr. Eichenfield

This is a very hard diagnosis to make with the clinical findings and history.

Molluscum contagiosum infections are common, but with this patient’s medical history, biopsy and excision with pathologic examination was an appropriate approach to make a certain diagnosis.

Ms. Moyal is a research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego.

References

1. Brown J et al. Int J Dermatol. 2006 Feb;45(2):93-9.

2. Hanson D and Diven DG. Dermatol Online J. 2003 Mar;9(2).

3. Badri T and Gandhi GR. Molluscum contagiosum. 2022. In: StatPearls [Internet]. Treasure Island, Fla.: StatPearls Publishing.

4. Schwartz JJ and Myskowski PL. J Am Acad Dermatol. 1992 Oct 1;27(4):583-8.

5. Antonov NK et al. JAAD Case Rep. 2019 Apr 5;5(4):342-5.

The correct answer is (D), molluscum contagiosum. Upon surgical excision, the pathology indicated the lesion was consistent with molluscum contagiosum.

Molluscum contagiosum is a benign skin disorder caused by a pox virus and is frequently seen in children. This disease is transmitted primarily through direct skin contact with an infected individual.¹ Contaminated fomites have been suggested as another source of infection.² The typical lesion appears dome-shaped, round, and pinkish-purple in color.¹ The incubation period ranges from 2 weeks to 6 months and is typically self-limited in immunocompetent hosts; however, in immunocompromised persons, molluscum contagiosum lesions may present atypically such that they are larger in size and/or resemble malignancies, such as basal cell carcinoma or keratoacanthoma (for single lesions), or other infectious diseases, such as cryptococcosis and histoplasmosis (for more numerous lesions).^{3,4 A} giant atypical molluscum contagiosum is rarely seen in healthy individuals.
 

What’s on the differential?

The recent episode of bleeding raises concern for other neoplastic processes of the skin including squamous cell carcinoma or basal cell carcinoma as well as cutaneous metastatic rhabdoid tumor, given the patient’s history.

Eruptive keratoacanthomas are also reported in patients taking nivolumab, an anti-PD-1 immunotherapy, which the patient has received for treatment of his recurrent metastatic rhabdoid tumor.⁵ More common entities such as a pyogenic granuloma or verruca are also included on the differential. The initial presentation of the lesion, however, is more consistent with the pearly umbilicated papules associated with molluscum contagiosum.

Comments from Dr. Eichenfield

This is a very hard diagnosis to make with the clinical findings and history.

Molluscum contagiosum infections are common, but with this patient’s medical history, biopsy and excision with pathologic examination was an appropriate approach to make a certain diagnosis.

Ms. Moyal is a research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego.

References

1. Brown J et al. Int J Dermatol. 2006 Feb;45(2):93-9.

2. Hanson D and Diven DG. Dermatol Online J. 2003 Mar;9(2).

3. Badri T and Gandhi GR. Molluscum contagiosum. 2022. In: StatPearls [Internet]. Treasure Island, Fla.: StatPearls Publishing.

4. Schwartz JJ and Myskowski PL. J Am Acad Dermatol. 1992 Oct 1;27(4):583-8.

5. Antonov NK et al. JAAD Case Rep. 2019 Apr 5;5(4):342-5.

The correct answer is (D), molluscum contagiosum. Upon surgical excision, the pathology indicated the lesion was consistent with molluscum contagiosum.

Molluscum contagiosum is a benign skin disorder caused by a pox virus and is frequently seen in children. This disease is transmitted primarily through direct skin contact with an infected individual.¹ Contaminated fomites have been suggested as another source of infection.² The typical lesion appears dome-shaped, round, and pinkish-purple in color.¹ The incubation period ranges from 2 weeks to 6 months and is typically self-limited in immunocompetent hosts; however, in immunocompromised persons, molluscum contagiosum lesions may present atypically such that they are larger in size and/or resemble malignancies, such as basal cell carcinoma or keratoacanthoma (for single lesions), or other infectious diseases, such as cryptococcosis and histoplasmosis (for more numerous lesions).^{3,4 A} giant atypical molluscum contagiosum is rarely seen in healthy individuals.
 

What’s on the differential?

The recent episode of bleeding raises concern for other neoplastic processes of the skin including squamous cell carcinoma or basal cell carcinoma as well as cutaneous metastatic rhabdoid tumor, given the patient’s history.

Eruptive keratoacanthomas are also reported in patients taking nivolumab, an anti-PD-1 immunotherapy, which the patient has received for treatment of his recurrent metastatic rhabdoid tumor.⁵ More common entities such as a pyogenic granuloma or verruca are also included on the differential. The initial presentation of the lesion, however, is more consistent with the pearly umbilicated papules associated with molluscum contagiosum.

Comments from Dr. Eichenfield

This is a very hard diagnosis to make with the clinical findings and history.

Molluscum contagiosum infections are common, but with this patient’s medical history, biopsy and excision with pathologic examination was an appropriate approach to make a certain diagnosis.

Ms. Moyal is a research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego.

References

1. Brown J et al. Int J Dermatol. 2006 Feb;45(2):93-9.

2. Hanson D and Diven DG. Dermatol Online J. 2003 Mar;9(2).

3. Badri T and Gandhi GR. Molluscum contagiosum. 2022. In: StatPearls [Internet]. Treasure Island, Fla.: StatPearls Publishing.

4. Schwartz JJ and Myskowski PL. J Am Acad Dermatol. 1992 Oct 1;27(4):583-8.

5. Antonov NK et al. JAAD Case Rep. 2019 Apr 5;5(4):342-5.