Dermatology

The U.S. Food and Drug Administration on May 22 approved a new autoinjection option for adalimumab-adbm (Cyltezo), a biosimilar to AbbVie’s adalimumab (Humira), ahead of Cyltezo’s commercial launch on July 1, 2023.

Cyltezo was approved by the FDA in 2017 as a prefilled syringe and was the first biosimilar deemed to be interchangeable with Humira in 2021. It is indicated to treat multiple chronic inflammatory conditions, including rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and hidradenitis suppurativa. This new design, which features one-button, three-step activation, has been certified as an “Ease of Use” product by the Arthritis Foundation, Boehringer Ingelheim said in a press release. The 40-mg, prefilled Cyltezo Pen will be available in two-, four-, and six-pack options.

“The FDA approval of the Cyltezo Pen is great news for patients living with chronic inflammatory diseases who may prefer administering the medication needed to manage their conditions via an autoinjector,” said Stephen Pagnotta, the executive director and biosimilar commercial lead at Boehringer Ingelheim in a statement; “we’re excited to be able to offer the Cyltezo Pen as an additional option to patients at Cyltezo’s launch on July 1.”

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

The U.S. Food and Drug Administration on May 22 approved a new autoinjection option for adalimumab-adbm (Cyltezo), a biosimilar to AbbVie’s adalimumab (Humira), ahead of Cyltezo’s commercial launch on July 1, 2023.

Cyltezo was approved by the FDA in 2017 as a prefilled syringe and was the first biosimilar deemed to be interchangeable with Humira in 2021. It is indicated to treat multiple chronic inflammatory conditions, including rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and hidradenitis suppurativa. This new design, which features one-button, three-step activation, has been certified as an “Ease of Use” product by the Arthritis Foundation, Boehringer Ingelheim said in a press release. The 40-mg, prefilled Cyltezo Pen will be available in two-, four-, and six-pack options.

“The FDA approval of the Cyltezo Pen is great news for patients living with chronic inflammatory diseases who may prefer administering the medication needed to manage their conditions via an autoinjector,” said Stephen Pagnotta, the executive director and biosimilar commercial lead at Boehringer Ingelheim in a statement; “we’re excited to be able to offer the Cyltezo Pen as an additional option to patients at Cyltezo’s launch on July 1.”

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

The U.S. Food and Drug Administration on May 22 approved a new autoinjection option for adalimumab-adbm (Cyltezo), a biosimilar to AbbVie’s adalimumab (Humira), ahead of Cyltezo’s commercial launch on July 1, 2023.

Cyltezo was approved by the FDA in 2017 as a prefilled syringe and was the first biosimilar deemed to be interchangeable with Humira in 2021. It is indicated to treat multiple chronic inflammatory conditions, including rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and hidradenitis suppurativa. This new design, which features one-button, three-step activation, has been certified as an “Ease of Use” product by the Arthritis Foundation, Boehringer Ingelheim said in a press release. The 40-mg, prefilled Cyltezo Pen will be available in two-, four-, and six-pack options.

“The FDA approval of the Cyltezo Pen is great news for patients living with chronic inflammatory diseases who may prefer administering the medication needed to manage their conditions via an autoinjector,” said Stephen Pagnotta, the executive director and biosimilar commercial lead at Boehringer Ingelheim in a statement; “we’re excited to be able to offer the Cyltezo Pen as an additional option to patients at Cyltezo’s launch on July 1.”

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

WASHINGTON – Atopic dermatitis (AD) in childhood presents most commonly by age 1 and typically begins on the face, and while it can make infants “miserable,” caregiver and provider concerns about treatment on the face and at such a young age mean it is often “woefully undertreated,” Robert Sidbury, MD, MPH, said at the annual Revolutionizing Atopic Dermatitis conference.

Identifying and mitigating triggers – such as irritation, contact allergy, and infection – is a cornerstone of treatment in infants, but tailored therapy with topical corticosteroids, topical calcineurin inhibitors (TCIs), and topical phosphodiesterase 4 (PDE4) inhibitors also have roles to play, said Dr. Sidbury, chief of dermatology at Seattle Children’s Hospital and professor in the department of pediatrics at the University of Washington, Seattle.

Views on the use of dupilumab as a systemic agent for severe infantile AD, meanwhile, have shifted significantly in the past year with the Food and Drug Administration approval of the biologic for children aged 6 months to 5 years and with extended experience with the biologic in all ages, including children, Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, said at the meeting.

The pediatric dermatologists spoke during a session devoted to AD in infants, during which the diagnosis of AD and the role – and risks – of food allergy testing were also discussed. Diagnosis, said Elaine C. Siegfried, MD, who also spoke during the session, requires careful consideration of mimicking conditions and a broader list of differential diagnoses in those infants with poor growth or frequent infections.

Here are some of the experts’ pearls for practice.
 

Diagnosing AD in infants

Among infants who are growing well and otherwise healthy, the infantile eczema phenotype encompasses AD, seborrheic dermatitis, contact dermatitis, psoriasis – and overlap of more than one of these conditions. “Overlap is common,” said Dr. Siegfried, professor of pediatrics and dermatology at Saint Louis University, and director of the division of pediatric dermatology at Cardinal Glennon Children’s Hospital.

(Initial topical treatment for all these conditions is similar, but optimal treatment may differ for young children with moderate to severe disease that requires systemic treatment, she said in an interview after the meeting.)

Sparing of the diaper area that reflects skin barrier integrity is a classic feature of AD in infants and can be a useful diagnostic sign. In addition, “hypopigmentation is more characteristic of psoriasis” than AD, whereas AD tends to be hyperpigmented, which is most obvious in skin-of-color patients, Dr. Siegfried said.

Disease-specific pigment changes may be related to microbial colonization – such as Malassezia-associated hypopigmentation – or cell turnover, which is faster in psoriasis and slower in AD – with corresponding differences in pigment retention, and may be more obvious in children than adults, she said.

A less common scenario is dermatitis in infants who are not growing well. For these patients, she noted, the differential diagnosis includes metabolic or immune deficiency dermatitis as well as a variety of genodermatoses.

Generalized redness and scaling present on the first day of life is suggestive of non-atopic dermatitis. “If you’re born with red scaly skin, that’s very different than if you develop red skin in the first month or two of life,” Dr. Siegfried said.

When there is diaper area involvement with AD, contact dermatitis, impetigo, and Candida may be complicating factors. And in infants with other morbidities – especially those who are not growing well – diaper area involvement suggests a broader differential diagnosis. “I implore you, if you see children, make sure you weigh and measure them at every appointment,” she said.

Dr. Siegfried has seen infants with Netherton syndrome, and those with cystic fibrosis with zinc deficiency, for instance, presenting with “an eczematous-like picture,” diaper-area involvement, and other morbidities.

For infants with AD, she maintains a high index of suspicion for secondary infections such as molluscum, herpes simplex virus (HSV) with or without streptococci, scabies, tinea, and group A streptococci. “Secondary infections ... may be incognito,” she said. “Look for subtle signs. Even molluscum can be very subtle.”

Secondary allergic contact dermatitis is also common although it’s “technically difficult to confirm the diagnosis,” she said. Patch testing in infants is technically challenging, sensitivity is low, and monosensitization is uncommon. “So I do initial empiric topical allergen avoidance,” she said, keeping in mind ubiquitous and avoidable topical allergens such as Kathon, cocamidopropyl betaine, propylene glycol, disperse blue, and adhesives.
 

Treating AD in infancy

Irritation “is probably one of the biggest triggers” of AD in infants, and the often “pristine” diaper area compared with inflamed eczema elsewhere can demonstrate the importance of moisturization for healthy skin in atopic infants, Dr. Sidbury said.

Among treatments that “punch above their weight” for AD in infants is an ointment-based barrier applied around the mouth, chin, and chest – where the wet/dry impact of drooling is maximal – before and after meals, he said.

Another is hydrocortisone 2.5% mixed 1:1 with mupirocin for those infants who have secondary infections and “that exudative, weepy-looking appearance on the face,” he said. The topical antibiotic in the combination cream “lessens the potency of the steroid and oftentimes by synergy, makes it more effective” by simultaneously treating inflammation, he said. He cautions against products containing neomycin, which can be an allergen.

A combination antibiotic-steroid-emollient cream (the Aron Regimen) can also “sometimes punch above its weight,” Dr. Sidbury said.

Infections typically involve Staphylococcus aureus, but in up to 16% of cases Streptococcus is involved. And notably, lurking underneath the honey-colored crusting of S. aureus infections may be the grouped vesicles that characterize eczema herpeticum, Dr. Sidbury said.

“Counsel [parents] preemptively to treat cold sores immediately [in order to] decrease HSV shedding and minimize risk to their baby,” Dr. Sidbury said.

For treating AD-associated inflammation in skin not affected by secondary infections, over-the-counter 1% hydrocortisone cream is often sufficient, and “for very young babies and preemies in particular, I generally don’t use anything stronger because their skin barrier isn’t fully complete yet, so they absorb more than an older child does,” he said, referring to ages 2 months corrected as a marker for considering a stronger formulation if needed.

Many parents are “very concerned” about topical corticosteroid (TCS) use and pediatricians are also “often concerned,” Dr. Sidbury said. Addressing this concern, he tries to provide context and promote adherence by pointing out that infants have an easily visible vein at the temple area where the skin is naturally thin. If parents were to see this appearance for the first time in other areas while using topical steroids, he tells them, it may be the first sign of skin thinning, but “it’s entirely reversible at that stage.”

He also stressed the cost of not treating. It’s unknown whether “treating aggressively early on prevents any future development or manifestation of eczema, or future comorbidities, but we don’t know that it doesn’t,” Dr. Sidbury said. “And we certainly know how miserable that baby with eczema can be in the short term. So we need to use these medicines.”

Dr. Sidbury utilizes tacrolimus 0.03% ointment, a topical calcineurin inhibitor (TCI), only if he is worried about overuse of steroids, and uses a regimen that alternates the TCI (used in infants off-label because it is approved for ages 2 years and older) with TCS in periods of similar duration (for example, treatment with TCS for 1 week and TCI for 1 week, or rotations of 2 weeks each or 3 days each). “And these rotations may be dynamic depending on severity of the flare at any given time,” he said after the meeting.

Preapproval data from the pivotal trials of tacrolimus are reassuring and can be shared with parents. “Two-year-olds had 90% of BSA [body surface area] treated for 12 weeks” with no signs of systemic risks, Dr. Sidbury said at the meeting.

Crisaborole, a topical phosphodiesterase 4 (PDE4) inhibitor approved for AD down to age 3 months, does not, like tacrolimus, have a boxed warning about a possible risk for cancer, and may also be alternated with TCSs. It will cause stinging in some children, but TCSs and TCIs can also sting in some children, he said, noting that samples can be helpful to predict what will or won’t sting each infant.
 

Systemic treatment in infants

The Liberty AD PRESCHOOL phase 3 trial that supported the FDA’s approval of dupilumab down to 6 months of age, published in 2022 in The Lancet, covered ages 6 months to 5 years but included only six children under the age of 2, “leaving us with a very limited dataset in this age group,” Dr. Eichenfield said at the meeting.

University of California, San Diego

Other data and analyses that have provided reassurance, such as a laboratory safety analysis published online in 2022 showing no meaningful changes in laboratory safety parameters in children as young as 6 months, and pediatric data (not including infants) presented at a RAD meeting in 2022 showing that dupilumab, an interleukin-4 receptor alpha antagonist, may have positive effects on bone mineral density.

Data from the Liberty AD PRESCHOOL open-label extension study presented at the American Academy of Dermatology meeting in 2023, meanwhile, show that “the adverse event profile is not looking much different than what we see in older children,” Dr. Eichenfield said. “There are low rates of severe adverse events and a very low rate of discontinuations.”

At Rady Children’s Hospital, where Dr. Eichenfield is chief of pediatric and adolescent dermatology, dupilumab has become a first-line systemic agent for severe infantile AD, supplanting prior traditional but little used systemic agents such as oral corticosteroids, cyclosporine, methotrexate, azathioprine, or mycophenolate, he said after the meeting.

The decision to use systemics in the first 2 years of life is “a comprehensive one,” requiring knowledge of the child’s history, disease course, and assessment of response to prior therapies, comorbidities and severity, he said.
 

Food allergy in infants with AD

Food allergy is common in children with moderate to severe AD, but true food-triggered AD, with AD being the only symptom of food allergy, is rare, said Anne Marie Singh, MD, associate professor in the division of allergy and immunology and rheumatology at the University of Wisconsin, Madison, who focuses on pediatrics.

Over the years, studies of double-blind placebo-controlled food challenge tests in children with AD have tended to conflate immediate IgE hypersensitivity (and skin symptoms like urticaria) with AD, said Dr. Singh, who directs the university’s Food Allergy Research and Education Center of Excellence. In a recently published study she led involving 374 children with AD referred to allergy and/or dermatology subspecialty clinics at the University of Wisconsin, Madison, 55% had a food allergy but only 2% had food-triggered AD “where eczema is the only symptom and removal of the food cleared up the eczema and its return brought it back,” Dr. Singh said at the meeting. Another 4% had combined IgE-mediated food allergy and food-triggered AD. Almost half of the children with food-triggered AD were under 1 year of age, and egg was the most common trigger, she noted.

Food should be implicated largely by history, Dr. Singh emphasized.

Food allergy testing in the context of AD can be done but is challenging, with the clinical relevance of skin prick testing and food-specific immunoglobulin E (sIgE) difficult to predict. Predictive values of sIgE levels are established for immediate IgE mediated food allergy, but “cut-offs” for food-triggered AD are not established, she explained, noting that “cut-offs are likely higher for our children with AD.”

Elimination diets, moreover, pose significant risks of future oral tolerance and risks of nutritional deficiencies and poor growth, Dr. Singh said. New and immediate reactions to foods that are reintroduced after an elimination diet are common, and research has shown that 20% or more of such reactions involve anaphylaxis. “If an elimination diet is undertaken, you need emergency action plans, injectable epinephrine, and nutrition counseling,” she said.

A recent systematic review and meta-analysis conditionally recommended against elimination diets for the treatment of AD, Dr. Singh noted.

Asked by Dr. Sidbury whether there “is a sweet spot where you can eliminate [foods] without going all the way,” Dr. Singh said she will sometimes do a “diagnostic elimination trial” with food elimination for 2-4 weeks only – a time period after which “I’ll feel really comfortable reintroducing the food.”

Dr. Singh urged dermatologists to “know your allergist” because “patients respond best with a consistent message.”

Dr. Sidbury reported ties with Regeneron, UCB, Pfizer, Leo Pharma, Lilly, and Beiersdorf. Dr. Siegfried reported ties with Pfizer, Regeneron, Sanofi Genzyme, Pfizer, UCB, Novan and Leo Pharma. Dr. Singh reported ties with Incyte and Siolta Therapeutics. Dr. Eichenfield reported ties with Pfizer, Regeneron, Sanofi Genzyme, Incyte, and Pfizer.

WASHINGTON – Atopic dermatitis (AD) in childhood presents most commonly by age 1 and typically begins on the face, and while it can make infants “miserable,” caregiver and provider concerns about treatment on the face and at such a young age mean it is often “woefully undertreated,” Robert Sidbury, MD, MPH, said at the annual Revolutionizing Atopic Dermatitis conference.

Identifying and mitigating triggers – such as irritation, contact allergy, and infection – is a cornerstone of treatment in infants, but tailored therapy with topical corticosteroids, topical calcineurin inhibitors (TCIs), and topical phosphodiesterase 4 (PDE4) inhibitors also have roles to play, said Dr. Sidbury, chief of dermatology at Seattle Children’s Hospital and professor in the department of pediatrics at the University of Washington, Seattle.

Views on the use of dupilumab as a systemic agent for severe infantile AD, meanwhile, have shifted significantly in the past year with the Food and Drug Administration approval of the biologic for children aged 6 months to 5 years and with extended experience with the biologic in all ages, including children, Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, said at the meeting.

The pediatric dermatologists spoke during a session devoted to AD in infants, during which the diagnosis of AD and the role – and risks – of food allergy testing were also discussed. Diagnosis, said Elaine C. Siegfried, MD, who also spoke during the session, requires careful consideration of mimicking conditions and a broader list of differential diagnoses in those infants with poor growth or frequent infections.

Here are some of the experts’ pearls for practice.
 

Diagnosing AD in infants

Among infants who are growing well and otherwise healthy, the infantile eczema phenotype encompasses AD, seborrheic dermatitis, contact dermatitis, psoriasis – and overlap of more than one of these conditions. “Overlap is common,” said Dr. Siegfried, professor of pediatrics and dermatology at Saint Louis University, and director of the division of pediatric dermatology at Cardinal Glennon Children’s Hospital.

(Initial topical treatment for all these conditions is similar, but optimal treatment may differ for young children with moderate to severe disease that requires systemic treatment, she said in an interview after the meeting.)

Sparing of the diaper area that reflects skin barrier integrity is a classic feature of AD in infants and can be a useful diagnostic sign. In addition, “hypopigmentation is more characteristic of psoriasis” than AD, whereas AD tends to be hyperpigmented, which is most obvious in skin-of-color patients, Dr. Siegfried said.

Disease-specific pigment changes may be related to microbial colonization – such as Malassezia-associated hypopigmentation – or cell turnover, which is faster in psoriasis and slower in AD – with corresponding differences in pigment retention, and may be more obvious in children than adults, she said.

A less common scenario is dermatitis in infants who are not growing well. For these patients, she noted, the differential diagnosis includes metabolic or immune deficiency dermatitis as well as a variety of genodermatoses.

Generalized redness and scaling present on the first day of life is suggestive of non-atopic dermatitis. “If you’re born with red scaly skin, that’s very different than if you develop red skin in the first month or two of life,” Dr. Siegfried said.

When there is diaper area involvement with AD, contact dermatitis, impetigo, and Candida may be complicating factors. And in infants with other morbidities – especially those who are not growing well – diaper area involvement suggests a broader differential diagnosis. “I implore you, if you see children, make sure you weigh and measure them at every appointment,” she said.

Dr. Siegfried has seen infants with Netherton syndrome, and those with cystic fibrosis with zinc deficiency, for instance, presenting with “an eczematous-like picture,” diaper-area involvement, and other morbidities.

For infants with AD, she maintains a high index of suspicion for secondary infections such as molluscum, herpes simplex virus (HSV) with or without streptococci, scabies, tinea, and group A streptococci. “Secondary infections ... may be incognito,” she said. “Look for subtle signs. Even molluscum can be very subtle.”

Secondary allergic contact dermatitis is also common although it’s “technically difficult to confirm the diagnosis,” she said. Patch testing in infants is technically challenging, sensitivity is low, and monosensitization is uncommon. “So I do initial empiric topical allergen avoidance,” she said, keeping in mind ubiquitous and avoidable topical allergens such as Kathon, cocamidopropyl betaine, propylene glycol, disperse blue, and adhesives.
 

Treating AD in infancy

Irritation “is probably one of the biggest triggers” of AD in infants, and the often “pristine” diaper area compared with inflamed eczema elsewhere can demonstrate the importance of moisturization for healthy skin in atopic infants, Dr. Sidbury said.

Among treatments that “punch above their weight” for AD in infants is an ointment-based barrier applied around the mouth, chin, and chest – where the wet/dry impact of drooling is maximal – before and after meals, he said.

Another is hydrocortisone 2.5% mixed 1:1 with mupirocin for those infants who have secondary infections and “that exudative, weepy-looking appearance on the face,” he said. The topical antibiotic in the combination cream “lessens the potency of the steroid and oftentimes by synergy, makes it more effective” by simultaneously treating inflammation, he said. He cautions against products containing neomycin, which can be an allergen.

A combination antibiotic-steroid-emollient cream (the Aron Regimen) can also “sometimes punch above its weight,” Dr. Sidbury said.

Infections typically involve Staphylococcus aureus, but in up to 16% of cases Streptococcus is involved. And notably, lurking underneath the honey-colored crusting of S. aureus infections may be the grouped vesicles that characterize eczema herpeticum, Dr. Sidbury said.

“Counsel [parents] preemptively to treat cold sores immediately [in order to] decrease HSV shedding and minimize risk to their baby,” Dr. Sidbury said.

For treating AD-associated inflammation in skin not affected by secondary infections, over-the-counter 1% hydrocortisone cream is often sufficient, and “for very young babies and preemies in particular, I generally don’t use anything stronger because their skin barrier isn’t fully complete yet, so they absorb more than an older child does,” he said, referring to ages 2 months corrected as a marker for considering a stronger formulation if needed.

Many parents are “very concerned” about topical corticosteroid (TCS) use and pediatricians are also “often concerned,” Dr. Sidbury said. Addressing this concern, he tries to provide context and promote adherence by pointing out that infants have an easily visible vein at the temple area where the skin is naturally thin. If parents were to see this appearance for the first time in other areas while using topical steroids, he tells them, it may be the first sign of skin thinning, but “it’s entirely reversible at that stage.”

He also stressed the cost of not treating. It’s unknown whether “treating aggressively early on prevents any future development or manifestation of eczema, or future comorbidities, but we don’t know that it doesn’t,” Dr. Sidbury said. “And we certainly know how miserable that baby with eczema can be in the short term. So we need to use these medicines.”

Dr. Sidbury utilizes tacrolimus 0.03% ointment, a topical calcineurin inhibitor (TCI), only if he is worried about overuse of steroids, and uses a regimen that alternates the TCI (used in infants off-label because it is approved for ages 2 years and older) with TCS in periods of similar duration (for example, treatment with TCS for 1 week and TCI for 1 week, or rotations of 2 weeks each or 3 days each). “And these rotations may be dynamic depending on severity of the flare at any given time,” he said after the meeting.

Preapproval data from the pivotal trials of tacrolimus are reassuring and can be shared with parents. “Two-year-olds had 90% of BSA [body surface area] treated for 12 weeks” with no signs of systemic risks, Dr. Sidbury said at the meeting.

Crisaborole, a topical phosphodiesterase 4 (PDE4) inhibitor approved for AD down to age 3 months, does not, like tacrolimus, have a boxed warning about a possible risk for cancer, and may also be alternated with TCSs. It will cause stinging in some children, but TCSs and TCIs can also sting in some children, he said, noting that samples can be helpful to predict what will or won’t sting each infant.
 

Systemic treatment in infants

The Liberty AD PRESCHOOL phase 3 trial that supported the FDA’s approval of dupilumab down to 6 months of age, published in 2022 in The Lancet, covered ages 6 months to 5 years but included only six children under the age of 2, “leaving us with a very limited dataset in this age group,” Dr. Eichenfield said at the meeting.

University of California, San Diego

Other data and analyses that have provided reassurance, such as a laboratory safety analysis published online in 2022 showing no meaningful changes in laboratory safety parameters in children as young as 6 months, and pediatric data (not including infants) presented at a RAD meeting in 2022 showing that dupilumab, an interleukin-4 receptor alpha antagonist, may have positive effects on bone mineral density.

Data from the Liberty AD PRESCHOOL open-label extension study presented at the American Academy of Dermatology meeting in 2023, meanwhile, show that “the adverse event profile is not looking much different than what we see in older children,” Dr. Eichenfield said. “There are low rates of severe adverse events and a very low rate of discontinuations.”

At Rady Children’s Hospital, where Dr. Eichenfield is chief of pediatric and adolescent dermatology, dupilumab has become a first-line systemic agent for severe infantile AD, supplanting prior traditional but little used systemic agents such as oral corticosteroids, cyclosporine, methotrexate, azathioprine, or mycophenolate, he said after the meeting.

The decision to use systemics in the first 2 years of life is “a comprehensive one,” requiring knowledge of the child’s history, disease course, and assessment of response to prior therapies, comorbidities and severity, he said.
 

Food allergy in infants with AD

Food allergy is common in children with moderate to severe AD, but true food-triggered AD, with AD being the only symptom of food allergy, is rare, said Anne Marie Singh, MD, associate professor in the division of allergy and immunology and rheumatology at the University of Wisconsin, Madison, who focuses on pediatrics.

Over the years, studies of double-blind placebo-controlled food challenge tests in children with AD have tended to conflate immediate IgE hypersensitivity (and skin symptoms like urticaria) with AD, said Dr. Singh, who directs the university’s Food Allergy Research and Education Center of Excellence. In a recently published study she led involving 374 children with AD referred to allergy and/or dermatology subspecialty clinics at the University of Wisconsin, Madison, 55% had a food allergy but only 2% had food-triggered AD “where eczema is the only symptom and removal of the food cleared up the eczema and its return brought it back,” Dr. Singh said at the meeting. Another 4% had combined IgE-mediated food allergy and food-triggered AD. Almost half of the children with food-triggered AD were under 1 year of age, and egg was the most common trigger, she noted.

Food should be implicated largely by history, Dr. Singh emphasized.

Food allergy testing in the context of AD can be done but is challenging, with the clinical relevance of skin prick testing and food-specific immunoglobulin E (sIgE) difficult to predict. Predictive values of sIgE levels are established for immediate IgE mediated food allergy, but “cut-offs” for food-triggered AD are not established, she explained, noting that “cut-offs are likely higher for our children with AD.”

Elimination diets, moreover, pose significant risks of future oral tolerance and risks of nutritional deficiencies and poor growth, Dr. Singh said. New and immediate reactions to foods that are reintroduced after an elimination diet are common, and research has shown that 20% or more of such reactions involve anaphylaxis. “If an elimination diet is undertaken, you need emergency action plans, injectable epinephrine, and nutrition counseling,” she said.

A recent systematic review and meta-analysis conditionally recommended against elimination diets for the treatment of AD, Dr. Singh noted.

Asked by Dr. Sidbury whether there “is a sweet spot where you can eliminate [foods] without going all the way,” Dr. Singh said she will sometimes do a “diagnostic elimination trial” with food elimination for 2-4 weeks only – a time period after which “I’ll feel really comfortable reintroducing the food.”

Dr. Singh urged dermatologists to “know your allergist” because “patients respond best with a consistent message.”

Dr. Sidbury reported ties with Regeneron, UCB, Pfizer, Leo Pharma, Lilly, and Beiersdorf. Dr. Siegfried reported ties with Pfizer, Regeneron, Sanofi Genzyme, Pfizer, UCB, Novan and Leo Pharma. Dr. Singh reported ties with Incyte and Siolta Therapeutics. Dr. Eichenfield reported ties with Pfizer, Regeneron, Sanofi Genzyme, Incyte, and Pfizer.

WASHINGTON – Atopic dermatitis (AD) in childhood presents most commonly by age 1 and typically begins on the face, and while it can make infants “miserable,” caregiver and provider concerns about treatment on the face and at such a young age mean it is often “woefully undertreated,” Robert Sidbury, MD, MPH, said at the annual Revolutionizing Atopic Dermatitis conference.

Identifying and mitigating triggers – such as irritation, contact allergy, and infection – is a cornerstone of treatment in infants, but tailored therapy with topical corticosteroids, topical calcineurin inhibitors (TCIs), and topical phosphodiesterase 4 (PDE4) inhibitors also have roles to play, said Dr. Sidbury, chief of dermatology at Seattle Children’s Hospital and professor in the department of pediatrics at the University of Washington, Seattle.

Views on the use of dupilumab as a systemic agent for severe infantile AD, meanwhile, have shifted significantly in the past year with the Food and Drug Administration approval of the biologic for children aged 6 months to 5 years and with extended experience with the biologic in all ages, including children, Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, said at the meeting.

The pediatric dermatologists spoke during a session devoted to AD in infants, during which the diagnosis of AD and the role – and risks – of food allergy testing were also discussed. Diagnosis, said Elaine C. Siegfried, MD, who also spoke during the session, requires careful consideration of mimicking conditions and a broader list of differential diagnoses in those infants with poor growth or frequent infections.

Here are some of the experts’ pearls for practice.
 

Diagnosing AD in infants

Among infants who are growing well and otherwise healthy, the infantile eczema phenotype encompasses AD, seborrheic dermatitis, contact dermatitis, psoriasis – and overlap of more than one of these conditions. “Overlap is common,” said Dr. Siegfried, professor of pediatrics and dermatology at Saint Louis University, and director of the division of pediatric dermatology at Cardinal Glennon Children’s Hospital.

(Initial topical treatment for all these conditions is similar, but optimal treatment may differ for young children with moderate to severe disease that requires systemic treatment, she said in an interview after the meeting.)

Sparing of the diaper area that reflects skin barrier integrity is a classic feature of AD in infants and can be a useful diagnostic sign. In addition, “hypopigmentation is more characteristic of psoriasis” than AD, whereas AD tends to be hyperpigmented, which is most obvious in skin-of-color patients, Dr. Siegfried said.

Disease-specific pigment changes may be related to microbial colonization – such as Malassezia-associated hypopigmentation – or cell turnover, which is faster in psoriasis and slower in AD – with corresponding differences in pigment retention, and may be more obvious in children than adults, she said.

A less common scenario is dermatitis in infants who are not growing well. For these patients, she noted, the differential diagnosis includes metabolic or immune deficiency dermatitis as well as a variety of genodermatoses.

Generalized redness and scaling present on the first day of life is suggestive of non-atopic dermatitis. “If you’re born with red scaly skin, that’s very different than if you develop red skin in the first month or two of life,” Dr. Siegfried said.

When there is diaper area involvement with AD, contact dermatitis, impetigo, and Candida may be complicating factors. And in infants with other morbidities – especially those who are not growing well – diaper area involvement suggests a broader differential diagnosis. “I implore you, if you see children, make sure you weigh and measure them at every appointment,” she said.

Dr. Siegfried has seen infants with Netherton syndrome, and those with cystic fibrosis with zinc deficiency, for instance, presenting with “an eczematous-like picture,” diaper-area involvement, and other morbidities.

For infants with AD, she maintains a high index of suspicion for secondary infections such as molluscum, herpes simplex virus (HSV) with or without streptococci, scabies, tinea, and group A streptococci. “Secondary infections ... may be incognito,” she said. “Look for subtle signs. Even molluscum can be very subtle.”

Secondary allergic contact dermatitis is also common although it’s “technically difficult to confirm the diagnosis,” she said. Patch testing in infants is technically challenging, sensitivity is low, and monosensitization is uncommon. “So I do initial empiric topical allergen avoidance,” she said, keeping in mind ubiquitous and avoidable topical allergens such as Kathon, cocamidopropyl betaine, propylene glycol, disperse blue, and adhesives.
 

Treating AD in infancy

Irritation “is probably one of the biggest triggers” of AD in infants, and the often “pristine” diaper area compared with inflamed eczema elsewhere can demonstrate the importance of moisturization for healthy skin in atopic infants, Dr. Sidbury said.

Among treatments that “punch above their weight” for AD in infants is an ointment-based barrier applied around the mouth, chin, and chest – where the wet/dry impact of drooling is maximal – before and after meals, he said.

Another is hydrocortisone 2.5% mixed 1:1 with mupirocin for those infants who have secondary infections and “that exudative, weepy-looking appearance on the face,” he said. The topical antibiotic in the combination cream “lessens the potency of the steroid and oftentimes by synergy, makes it more effective” by simultaneously treating inflammation, he said. He cautions against products containing neomycin, which can be an allergen.

A combination antibiotic-steroid-emollient cream (the Aron Regimen) can also “sometimes punch above its weight,” Dr. Sidbury said.

Infections typically involve Staphylococcus aureus, but in up to 16% of cases Streptococcus is involved. And notably, lurking underneath the honey-colored crusting of S. aureus infections may be the grouped vesicles that characterize eczema herpeticum, Dr. Sidbury said.

“Counsel [parents] preemptively to treat cold sores immediately [in order to] decrease HSV shedding and minimize risk to their baby,” Dr. Sidbury said.

For treating AD-associated inflammation in skin not affected by secondary infections, over-the-counter 1% hydrocortisone cream is often sufficient, and “for very young babies and preemies in particular, I generally don’t use anything stronger because their skin barrier isn’t fully complete yet, so they absorb more than an older child does,” he said, referring to ages 2 months corrected as a marker for considering a stronger formulation if needed.

Many parents are “very concerned” about topical corticosteroid (TCS) use and pediatricians are also “often concerned,” Dr. Sidbury said. Addressing this concern, he tries to provide context and promote adherence by pointing out that infants have an easily visible vein at the temple area where the skin is naturally thin. If parents were to see this appearance for the first time in other areas while using topical steroids, he tells them, it may be the first sign of skin thinning, but “it’s entirely reversible at that stage.”

He also stressed the cost of not treating. It’s unknown whether “treating aggressively early on prevents any future development or manifestation of eczema, or future comorbidities, but we don’t know that it doesn’t,” Dr. Sidbury said. “And we certainly know how miserable that baby with eczema can be in the short term. So we need to use these medicines.”

Dr. Sidbury utilizes tacrolimus 0.03% ointment, a topical calcineurin inhibitor (TCI), only if he is worried about overuse of steroids, and uses a regimen that alternates the TCI (used in infants off-label because it is approved for ages 2 years and older) with TCS in periods of similar duration (for example, treatment with TCS for 1 week and TCI for 1 week, or rotations of 2 weeks each or 3 days each). “And these rotations may be dynamic depending on severity of the flare at any given time,” he said after the meeting.

Preapproval data from the pivotal trials of tacrolimus are reassuring and can be shared with parents. “Two-year-olds had 90% of BSA [body surface area] treated for 12 weeks” with no signs of systemic risks, Dr. Sidbury said at the meeting.

Crisaborole, a topical phosphodiesterase 4 (PDE4) inhibitor approved for AD down to age 3 months, does not, like tacrolimus, have a boxed warning about a possible risk for cancer, and may also be alternated with TCSs. It will cause stinging in some children, but TCSs and TCIs can also sting in some children, he said, noting that samples can be helpful to predict what will or won’t sting each infant.
 

Systemic treatment in infants

The Liberty AD PRESCHOOL phase 3 trial that supported the FDA’s approval of dupilumab down to 6 months of age, published in 2022 in The Lancet, covered ages 6 months to 5 years but included only six children under the age of 2, “leaving us with a very limited dataset in this age group,” Dr. Eichenfield said at the meeting.

University of California, San Diego

Other data and analyses that have provided reassurance, such as a laboratory safety analysis published online in 2022 showing no meaningful changes in laboratory safety parameters in children as young as 6 months, and pediatric data (not including infants) presented at a RAD meeting in 2022 showing that dupilumab, an interleukin-4 receptor alpha antagonist, may have positive effects on bone mineral density.

Data from the Liberty AD PRESCHOOL open-label extension study presented at the American Academy of Dermatology meeting in 2023, meanwhile, show that “the adverse event profile is not looking much different than what we see in older children,” Dr. Eichenfield said. “There are low rates of severe adverse events and a very low rate of discontinuations.”

At Rady Children’s Hospital, where Dr. Eichenfield is chief of pediatric and adolescent dermatology, dupilumab has become a first-line systemic agent for severe infantile AD, supplanting prior traditional but little used systemic agents such as oral corticosteroids, cyclosporine, methotrexate, azathioprine, or mycophenolate, he said after the meeting.

The decision to use systemics in the first 2 years of life is “a comprehensive one,” requiring knowledge of the child’s history, disease course, and assessment of response to prior therapies, comorbidities and severity, he said.
 

Food allergy in infants with AD

Food allergy is common in children with moderate to severe AD, but true food-triggered AD, with AD being the only symptom of food allergy, is rare, said Anne Marie Singh, MD, associate professor in the division of allergy and immunology and rheumatology at the University of Wisconsin, Madison, who focuses on pediatrics.

Over the years, studies of double-blind placebo-controlled food challenge tests in children with AD have tended to conflate immediate IgE hypersensitivity (and skin symptoms like urticaria) with AD, said Dr. Singh, who directs the university’s Food Allergy Research and Education Center of Excellence. In a recently published study she led involving 374 children with AD referred to allergy and/or dermatology subspecialty clinics at the University of Wisconsin, Madison, 55% had a food allergy but only 2% had food-triggered AD “where eczema is the only symptom and removal of the food cleared up the eczema and its return brought it back,” Dr. Singh said at the meeting. Another 4% had combined IgE-mediated food allergy and food-triggered AD. Almost half of the children with food-triggered AD were under 1 year of age, and egg was the most common trigger, she noted.

Food should be implicated largely by history, Dr. Singh emphasized.

Food allergy testing in the context of AD can be done but is challenging, with the clinical relevance of skin prick testing and food-specific immunoglobulin E (sIgE) difficult to predict. Predictive values of sIgE levels are established for immediate IgE mediated food allergy, but “cut-offs” for food-triggered AD are not established, she explained, noting that “cut-offs are likely higher for our children with AD.”

Elimination diets, moreover, pose significant risks of future oral tolerance and risks of nutritional deficiencies and poor growth, Dr. Singh said. New and immediate reactions to foods that are reintroduced after an elimination diet are common, and research has shown that 20% or more of such reactions involve anaphylaxis. “If an elimination diet is undertaken, you need emergency action plans, injectable epinephrine, and nutrition counseling,” she said.

A recent systematic review and meta-analysis conditionally recommended against elimination diets for the treatment of AD, Dr. Singh noted.

Asked by Dr. Sidbury whether there “is a sweet spot where you can eliminate [foods] without going all the way,” Dr. Singh said she will sometimes do a “diagnostic elimination trial” with food elimination for 2-4 weeks only – a time period after which “I’ll feel really comfortable reintroducing the food.”

Dr. Singh urged dermatologists to “know your allergist” because “patients respond best with a consistent message.”

Dr. Sidbury reported ties with Regeneron, UCB, Pfizer, Leo Pharma, Lilly, and Beiersdorf. Dr. Siegfried reported ties with Pfizer, Regeneron, Sanofi Genzyme, Pfizer, UCB, Novan and Leo Pharma. Dr. Singh reported ties with Incyte and Siolta Therapeutics. Dr. Eichenfield reported ties with Pfizer, Regeneron, Sanofi Genzyme, Incyte, and Pfizer.

Last month, I described a 28-year-old patient with a history of injection drug use who presented with pain in his left forearm. His history showed that, within the past 2 years, he’d been seen for cutaneous infections multiple times as an outpatient and in the emergency department. His records indicated that he was diagnosed with a penicillin allergy as a child when he developed a rash after receiving amoxicillin. I believed the next course of action should be to test for a penicillin allergy with an oral amoxicillin challenge.
 

Thank you for your excellent questions regarding this case. Great to hear the enthusiasm for testing for penicillin allergy!

One question focused on the course of action in the case of a mild or moderate IgE-mediated reaction after a single dose test with amoxicillin. Treatment for these reactions should include an antihistamine. I would reserve intravenous antihistamines for more severe cases, which also require treatment with a course of corticosteroids. However, the risk for a moderate to severe reaction to amoxicillin on retesting is quite low.

Clinicians need to exercise caution in the use of systemic corticosteroids. These drugs can be lifesaving, but even short courses of corticosteroids are associated with potentially serious adverse events. In a review of adverse events associated with short-course systemic corticosteroids among children, the rate of vomiting was 5.4%; behavioral change, 4.7%; and sleep disturbance, 4.3%. One child died after contracting herpes zoster, more than one-third of children developed elevated blood pressure, and 81.1% had evidence of suppression of the hypothalamic-pituitary-adrenal axis.

Among adults, short courses of systemic corticosteroids are associated with acute increases in the risks for gastrointestinal bleeding and hypertension. Cumulative exposure to short courses of corticosteroids over time results in higher risks for obesity, type 2 diabetes, and osteoporosis.

Another question prompted by this young man’s case focused on the durability of IgE reactions against penicillin. The IgE response to penicillin does indeed wane over time; 80% of patients with a previous true penicillin allergy can tolerate the antibiotic after 10 years. Thus, about 95% of patients with a remote history of penicillin allergy are tolerant of penicillin, and testing can be performed using the algorithm described.

Clinicians should avoid applying current guidelines for the evaluation of patients with penicillin allergy to other common drug allergies. The overall prevalence of sulfonamide allergy is 3%-8%, and the vast majority of these reactions follow treatment with trimethoprim-sulfamethoxazole. Sulfa allergy is even more common among persons living with HIV infection. The natural history of sulfa allergy is not as well established as penicillin allergy. Allergy testing is encouraged in these cases. Graded oral challenge testing is best reserved for patients who are unlikely to have a true sulfa allergy based on their history.

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

Last month, I described a 28-year-old patient with a history of injection drug use who presented with pain in his left forearm. His history showed that, within the past 2 years, he’d been seen for cutaneous infections multiple times as an outpatient and in the emergency department. His records indicated that he was diagnosed with a penicillin allergy as a child when he developed a rash after receiving amoxicillin. I believed the next course of action should be to test for a penicillin allergy with an oral amoxicillin challenge.
 

Thank you for your excellent questions regarding this case. Great to hear the enthusiasm for testing for penicillin allergy!

One question focused on the course of action in the case of a mild or moderate IgE-mediated reaction after a single dose test with amoxicillin. Treatment for these reactions should include an antihistamine. I would reserve intravenous antihistamines for more severe cases, which also require treatment with a course of corticosteroids. However, the risk for a moderate to severe reaction to amoxicillin on retesting is quite low.

Clinicians need to exercise caution in the use of systemic corticosteroids. These drugs can be lifesaving, but even short courses of corticosteroids are associated with potentially serious adverse events. In a review of adverse events associated with short-course systemic corticosteroids among children, the rate of vomiting was 5.4%; behavioral change, 4.7%; and sleep disturbance, 4.3%. One child died after contracting herpes zoster, more than one-third of children developed elevated blood pressure, and 81.1% had evidence of suppression of the hypothalamic-pituitary-adrenal axis.

Among adults, short courses of systemic corticosteroids are associated with acute increases in the risks for gastrointestinal bleeding and hypertension. Cumulative exposure to short courses of corticosteroids over time results in higher risks for obesity, type 2 diabetes, and osteoporosis.

Another question prompted by this young man’s case focused on the durability of IgE reactions against penicillin. The IgE response to penicillin does indeed wane over time; 80% of patients with a previous true penicillin allergy can tolerate the antibiotic after 10 years. Thus, about 95% of patients with a remote history of penicillin allergy are tolerant of penicillin, and testing can be performed using the algorithm described.

Clinicians should avoid applying current guidelines for the evaluation of patients with penicillin allergy to other common drug allergies. The overall prevalence of sulfonamide allergy is 3%-8%, and the vast majority of these reactions follow treatment with trimethoprim-sulfamethoxazole. Sulfa allergy is even more common among persons living with HIV infection. The natural history of sulfa allergy is not as well established as penicillin allergy. Allergy testing is encouraged in these cases. Graded oral challenge testing is best reserved for patients who are unlikely to have a true sulfa allergy based on their history.

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

Last month, I described a 28-year-old patient with a history of injection drug use who presented with pain in his left forearm. His history showed that, within the past 2 years, he’d been seen for cutaneous infections multiple times as an outpatient and in the emergency department. His records indicated that he was diagnosed with a penicillin allergy as a child when he developed a rash after receiving amoxicillin. I believed the next course of action should be to test for a penicillin allergy with an oral amoxicillin challenge.
 

Thank you for your excellent questions regarding this case. Great to hear the enthusiasm for testing for penicillin allergy!

One question focused on the course of action in the case of a mild or moderate IgE-mediated reaction after a single dose test with amoxicillin. Treatment for these reactions should include an antihistamine. I would reserve intravenous antihistamines for more severe cases, which also require treatment with a course of corticosteroids. However, the risk for a moderate to severe reaction to amoxicillin on retesting is quite low.

Clinicians need to exercise caution in the use of systemic corticosteroids. These drugs can be lifesaving, but even short courses of corticosteroids are associated with potentially serious adverse events. In a review of adverse events associated with short-course systemic corticosteroids among children, the rate of vomiting was 5.4%; behavioral change, 4.7%; and sleep disturbance, 4.3%. One child died after contracting herpes zoster, more than one-third of children developed elevated blood pressure, and 81.1% had evidence of suppression of the hypothalamic-pituitary-adrenal axis.

Among adults, short courses of systemic corticosteroids are associated with acute increases in the risks for gastrointestinal bleeding and hypertension. Cumulative exposure to short courses of corticosteroids over time results in higher risks for obesity, type 2 diabetes, and osteoporosis.

Another question prompted by this young man’s case focused on the durability of IgE reactions against penicillin. The IgE response to penicillin does indeed wane over time; 80% of patients with a previous true penicillin allergy can tolerate the antibiotic after 10 years. Thus, about 95% of patients with a remote history of penicillin allergy are tolerant of penicillin, and testing can be performed using the algorithm described.

Clinicians should avoid applying current guidelines for the evaluation of patients with penicillin allergy to other common drug allergies. The overall prevalence of sulfonamide allergy is 3%-8%, and the vast majority of these reactions follow treatment with trimethoprim-sulfamethoxazole. Sulfa allergy is even more common among persons living with HIV infection. The natural history of sulfa allergy is not as well established as penicillin allergy. Allergy testing is encouraged in these cases. Graded oral challenge testing is best reserved for patients who are unlikely to have a true sulfa allergy based on their history.

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

A broad shave biopsy was performed at the base of the lesion and the results were consistent with a thick nodular melanoma with a Breslow depth of 5.5 mm.

Melanoma is the deadliest skin cancer in the United States with mortality risk corresponding with the depth of the tumor.¹ Nodular melanomas grow faster than all other types of melanoma. For this reason, a concerning raised lesion with a risk of melanoma should not be observed for change over time; it should be biopsied promptly. In this case, a depth of 5.5 mm was cause for quick action. Patients with tumors > 1 mm in depth (and some tumors > 0.8 mm) should be offered sentinel lymph node biopsy (SLNB) along with wide local excision to evaluate for lymphatic spread. Patients with thinner tumors may undergo wide local excision without SLNB.

In this case, National Comprehensive Cancer Network guidelines would dictate a 2-cm margin for a wide local incision; the patient underwent a modified version of this with Surgical Oncology to accommodate maintenance of hand function. This patient’s SLNB was negative, so the melanoma was classified as Stage IIC.

In the recent past, there were no additional treatments for patients with late Stage II disease (thick tumors without evidence of metastasis). However, in December 2021, the US Food and Drug Administration approved the use of immunotherapy with pembrolizumab in patients with node-negative late Stage II melanoma after demonstration of improved recurrence-free survival in the KEYNOTE trial.² Evidence of improved long-term survival is mixed with adjuvant therapy, and studies evaluating the best role of adjuvant therapy are ongoing.

This patient was started on a regimen of pembrolizumab 200 mg IV every 3 weeks, which he will continue for as long as 1 year. He has tolerated this regimen without difficulty and has no evidence of disease.

‌

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.

A broad shave biopsy was performed at the base of the lesion and the results were consistent with a thick nodular melanoma with a Breslow depth of 5.5 mm.

Melanoma is the deadliest skin cancer in the United States with mortality risk corresponding with the depth of the tumor.¹ Nodular melanomas grow faster than all other types of melanoma. For this reason, a concerning raised lesion with a risk of melanoma should not be observed for change over time; it should be biopsied promptly. In this case, a depth of 5.5 mm was cause for quick action. Patients with tumors > 1 mm in depth (and some tumors > 0.8 mm) should be offered sentinel lymph node biopsy (SLNB) along with wide local excision to evaluate for lymphatic spread. Patients with thinner tumors may undergo wide local excision without SLNB.

In this case, National Comprehensive Cancer Network guidelines would dictate a 2-cm margin for a wide local incision; the patient underwent a modified version of this with Surgical Oncology to accommodate maintenance of hand function. This patient’s SLNB was negative, so the melanoma was classified as Stage IIC.

In the recent past, there were no additional treatments for patients with late Stage II disease (thick tumors without evidence of metastasis). However, in December 2021, the US Food and Drug Administration approved the use of immunotherapy with pembrolizumab in patients with node-negative late Stage II melanoma after demonstration of improved recurrence-free survival in the KEYNOTE trial.² Evidence of improved long-term survival is mixed with adjuvant therapy, and studies evaluating the best role of adjuvant therapy are ongoing.

This patient was started on a regimen of pembrolizumab 200 mg IV every 3 weeks, which he will continue for as long as 1 year. He has tolerated this regimen without difficulty and has no evidence of disease.

‌

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.

A broad shave biopsy was performed at the base of the lesion and the results were consistent with a thick nodular melanoma with a Breslow depth of 5.5 mm.

Melanoma is the deadliest skin cancer in the United States with mortality risk corresponding with the depth of the tumor.¹ Nodular melanomas grow faster than all other types of melanoma. For this reason, a concerning raised lesion with a risk of melanoma should not be observed for change over time; it should be biopsied promptly. In this case, a depth of 5.5 mm was cause for quick action. Patients with tumors > 1 mm in depth (and some tumors > 0.8 mm) should be offered sentinel lymph node biopsy (SLNB) along with wide local excision to evaluate for lymphatic spread. Patients with thinner tumors may undergo wide local excision without SLNB.

In this case, National Comprehensive Cancer Network guidelines would dictate a 2-cm margin for a wide local incision; the patient underwent a modified version of this with Surgical Oncology to accommodate maintenance of hand function. This patient’s SLNB was negative, so the melanoma was classified as Stage IIC.

In the recent past, there were no additional treatments for patients with late Stage II disease (thick tumors without evidence of metastasis). However, in December 2021, the US Food and Drug Administration approved the use of immunotherapy with pembrolizumab in patients with node-negative late Stage II melanoma after demonstration of improved recurrence-free survival in the KEYNOTE trial.² Evidence of improved long-term survival is mixed with adjuvant therapy, and studies evaluating the best role of adjuvant therapy are ongoing.

This patient was started on a regimen of pembrolizumab 200 mg IV every 3 weeks, which he will continue for as long as 1 year. He has tolerated this regimen without difficulty and has no evidence of disease.

‌

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.

The biopsy revealed abundant lymphocytes, neutrophils, and eosinophils consistent with a diagnosis of cutaneous B cell pseudolymphoma. The pseudolymphoma was caused by an exaggerated response to a tick bite.

As the name implies, B cell pseudolymphomas clinically and histologically mimic the various patterns of cutaneous lymphoma, often appearing as a firm, pink to dark violet nodule. A biopsy is mandatory to distinguish between pseudolymphoma and true lymphoma. There is an association between pseudolymphomas and Borrelia burgdorferi, the organism responsible for Lyme disease. Thus, testing for Lyme disease is recommended for patients with pseudolymphomas who live in endemic areas. Patients who test positive should be treated with doxycycline 100 mg bid for 10 days.

In the absence of Lyme disease, a pseudolymphoma may resolve spontaneously over weeks or months. Resolution can be hastened with topical superpotent steroids, intralesional steroids, or systemic steroids. Treatment can begin with topical clobetasol 0.05% bid. If the lesion does not resolve, the next step would be intralesional triamcinolone 10 mg/mL injected directly into the nodule until it blanches slightly. Injections should be repeated every 3 to 4 weeks for a total of 2 to 3 injections.

The patient in this case had negative Lyme serology and was treated with 2 injections of triamcinolone 10 mg/mL administered 3 weeks apart. She experienced complete resolution.

‌

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.

The biopsy revealed abundant lymphocytes, neutrophils, and eosinophils consistent with a diagnosis of cutaneous B cell pseudolymphoma. The pseudolymphoma was caused by an exaggerated response to a tick bite.

As the name implies, B cell pseudolymphomas clinically and histologically mimic the various patterns of cutaneous lymphoma, often appearing as a firm, pink to dark violet nodule. A biopsy is mandatory to distinguish between pseudolymphoma and true lymphoma. There is an association between pseudolymphomas and Borrelia burgdorferi, the organism responsible for Lyme disease. Thus, testing for Lyme disease is recommended for patients with pseudolymphomas who live in endemic areas. Patients who test positive should be treated with doxycycline 100 mg bid for 10 days.

In the absence of Lyme disease, a pseudolymphoma may resolve spontaneously over weeks or months. Resolution can be hastened with topical superpotent steroids, intralesional steroids, or systemic steroids. Treatment can begin with topical clobetasol 0.05% bid. If the lesion does not resolve, the next step would be intralesional triamcinolone 10 mg/mL injected directly into the nodule until it blanches slightly. Injections should be repeated every 3 to 4 weeks for a total of 2 to 3 injections.

The patient in this case had negative Lyme serology and was treated with 2 injections of triamcinolone 10 mg/mL administered 3 weeks apart. She experienced complete resolution.

‌

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.

The biopsy revealed abundant lymphocytes, neutrophils, and eosinophils consistent with a diagnosis of cutaneous B cell pseudolymphoma. The pseudolymphoma was caused by an exaggerated response to a tick bite.

As the name implies, B cell pseudolymphomas clinically and histologically mimic the various patterns of cutaneous lymphoma, often appearing as a firm, pink to dark violet nodule. A biopsy is mandatory to distinguish between pseudolymphoma and true lymphoma. There is an association between pseudolymphomas and Borrelia burgdorferi, the organism responsible for Lyme disease. Thus, testing for Lyme disease is recommended for patients with pseudolymphomas who live in endemic areas. Patients who test positive should be treated with doxycycline 100 mg bid for 10 days.

In the absence of Lyme disease, a pseudolymphoma may resolve spontaneously over weeks or months. Resolution can be hastened with topical superpotent steroids, intralesional steroids, or systemic steroids. Treatment can begin with topical clobetasol 0.05% bid. If the lesion does not resolve, the next step would be intralesional triamcinolone 10 mg/mL injected directly into the nodule until it blanches slightly. Injections should be repeated every 3 to 4 weeks for a total of 2 to 3 injections.

The patient in this case had negative Lyme serology and was treated with 2 injections of triamcinolone 10 mg/mL administered 3 weeks apart. She experienced complete resolution.

‌

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.

BY ALICIA AULT

The Centers for Disease Control and Prevention is alerting clinicians to be on the lookout for a severe antifungal-resistant form of tinea, as it was recently detected in two patients in New York.

Tinea, or ringworm, one of the most common fungal infections, is responsible for almost 5 million outpatient visits and 690 hospitalizations annually, according to the CDC.

Over the past 10 years, severe, antifungal-resistant tinea has spread in South Asia, in part because of the rise of a new dermatophyte species known as Trichophyton indotineae, wrote the authors of a report on the two patients with the drug-resistant strain. This epidemic “has likely been driven by misuse and overuse of topical antifungals and corticosteroids,” added the authors, in Morbidity and Mortality Weekly Report.

The cases were detected by a New York City dermatologist. In the first case, a 28-year-old woman developed a widespread pruritic eruption in the summer of 2021. She did not consult a dermatologist until December, when she was in the third trimester of pregnancy. She had large, annular, scaly, pruritic plaques on her neck, abdomen, pubic region, and buttocks, but had no underlying medical conditions, no known exposures to someone with a similar rash, and no recent international travel history.

After she gave birth in January, she started oral terbinafine therapy but had no improvement after 2 weeks. Clinicians administered a 4-week course of itraconazole, which resolved the infection.

The second patient, a 47-year-old woman with no medical conditions, developed a rash while in Bangladesh in the summer of 2022. Other family members had a similar rash. She was treated with topical antifungal and steroid combination creams but had no resolution. Back in the United States, she was prescribed hydrocortisone 2.5% ointment and diphenhydramine, clotrimazole cream, and terbinafine cream in three successive emergency department visits. In December 2022, dermatologists, observing widespread, discrete, scaly, annular, pruritic plaques on the thighs and buttocks, prescribed a 4-week course of oral terbinafine. When the rash did not resolve, she was given 4 weeks of griseofulvin. The rash persisted, although there was 80% improvement. Clinicians are now considering itraconazole. The woman’s son and husband are also being evaluated, as they have similar rashes.

In both cases, skin culture isolates were initially identified as Trichophyton mentagrophytes. Further analysis at the New York State Department of Health’s lab, using Sanger sequencing of the internal transcribed spacer region of the ribosomal gene, followed by phylogenetic analysis, identified the isolates as T. indotineae.

The authors note that culture-based techniques used by most clinical laboratories typically misidentify T. indotineae as T. mentagrophytes or T. interdigitale. Genomic sequencing must be used to properly identify T. indotineae, they wrote.

Clinicians should consider T. indotineae in patients with widespread ringworm, especially if they do not improve with topical antifungals or oral terbinafine, said the authors. If T. indotineae is suspected, state or local public health departments can direct clinicians to testing.

The authors report no relevant financial relationships.

BY ALICIA AULT

The Centers for Disease Control and Prevention is alerting clinicians to be on the lookout for a severe antifungal-resistant form of tinea, as it was recently detected in two patients in New York.

Tinea, or ringworm, one of the most common fungal infections, is responsible for almost 5 million outpatient visits and 690 hospitalizations annually, according to the CDC.

Over the past 10 years, severe, antifungal-resistant tinea has spread in South Asia, in part because of the rise of a new dermatophyte species known as Trichophyton indotineae, wrote the authors of a report on the two patients with the drug-resistant strain. This epidemic “has likely been driven by misuse and overuse of topical antifungals and corticosteroids,” added the authors, in Morbidity and Mortality Weekly Report.

The cases were detected by a New York City dermatologist. In the first case, a 28-year-old woman developed a widespread pruritic eruption in the summer of 2021. She did not consult a dermatologist until December, when she was in the third trimester of pregnancy. She had large, annular, scaly, pruritic plaques on her neck, abdomen, pubic region, and buttocks, but had no underlying medical conditions, no known exposures to someone with a similar rash, and no recent international travel history.

After she gave birth in January, she started oral terbinafine therapy but had no improvement after 2 weeks. Clinicians administered a 4-week course of itraconazole, which resolved the infection.

The second patient, a 47-year-old woman with no medical conditions, developed a rash while in Bangladesh in the summer of 2022. Other family members had a similar rash. She was treated with topical antifungal and steroid combination creams but had no resolution. Back in the United States, she was prescribed hydrocortisone 2.5% ointment and diphenhydramine, clotrimazole cream, and terbinafine cream in three successive emergency department visits. In December 2022, dermatologists, observing widespread, discrete, scaly, annular, pruritic plaques on the thighs and buttocks, prescribed a 4-week course of oral terbinafine. When the rash did not resolve, she was given 4 weeks of griseofulvin. The rash persisted, although there was 80% improvement. Clinicians are now considering itraconazole. The woman’s son and husband are also being evaluated, as they have similar rashes.

In both cases, skin culture isolates were initially identified as Trichophyton mentagrophytes. Further analysis at the New York State Department of Health’s lab, using Sanger sequencing of the internal transcribed spacer region of the ribosomal gene, followed by phylogenetic analysis, identified the isolates as T. indotineae.

The authors note that culture-based techniques used by most clinical laboratories typically misidentify T. indotineae as T. mentagrophytes or T. interdigitale. Genomic sequencing must be used to properly identify T. indotineae, they wrote.

Clinicians should consider T. indotineae in patients with widespread ringworm, especially if they do not improve with topical antifungals or oral terbinafine, said the authors. If T. indotineae is suspected, state or local public health departments can direct clinicians to testing.

The authors report no relevant financial relationships.

BY ALICIA AULT

The Centers for Disease Control and Prevention is alerting clinicians to be on the lookout for a severe antifungal-resistant form of tinea, as it was recently detected in two patients in New York.

Tinea, or ringworm, one of the most common fungal infections, is responsible for almost 5 million outpatient visits and 690 hospitalizations annually, according to the CDC.

Over the past 10 years, severe, antifungal-resistant tinea has spread in South Asia, in part because of the rise of a new dermatophyte species known as Trichophyton indotineae, wrote the authors of a report on the two patients with the drug-resistant strain. This epidemic “has likely been driven by misuse and overuse of topical antifungals and corticosteroids,” added the authors, in Morbidity and Mortality Weekly Report.

The cases were detected by a New York City dermatologist. In the first case, a 28-year-old woman developed a widespread pruritic eruption in the summer of 2021. She did not consult a dermatologist until December, when she was in the third trimester of pregnancy. She had large, annular, scaly, pruritic plaques on her neck, abdomen, pubic region, and buttocks, but had no underlying medical conditions, no known exposures to someone with a similar rash, and no recent international travel history.

After she gave birth in January, she started oral terbinafine therapy but had no improvement after 2 weeks. Clinicians administered a 4-week course of itraconazole, which resolved the infection.

The second patient, a 47-year-old woman with no medical conditions, developed a rash while in Bangladesh in the summer of 2022. Other family members had a similar rash. She was treated with topical antifungal and steroid combination creams but had no resolution. Back in the United States, she was prescribed hydrocortisone 2.5% ointment and diphenhydramine, clotrimazole cream, and terbinafine cream in three successive emergency department visits. In December 2022, dermatologists, observing widespread, discrete, scaly, annular, pruritic plaques on the thighs and buttocks, prescribed a 4-week course of oral terbinafine. When the rash did not resolve, she was given 4 weeks of griseofulvin. The rash persisted, although there was 80% improvement. Clinicians are now considering itraconazole. The woman’s son and husband are also being evaluated, as they have similar rashes.

In both cases, skin culture isolates were initially identified as Trichophyton mentagrophytes. Further analysis at the New York State Department of Health’s lab, using Sanger sequencing of the internal transcribed spacer region of the ribosomal gene, followed by phylogenetic analysis, identified the isolates as T. indotineae.

The authors note that culture-based techniques used by most clinical laboratories typically misidentify T. indotineae as T. mentagrophytes or T. interdigitale. Genomic sequencing must be used to properly identify T. indotineae, they wrote.

Clinicians should consider T. indotineae in patients with widespread ringworm, especially if they do not improve with topical antifungals or oral terbinafine, said the authors. If T. indotineae is suspected, state or local public health departments can direct clinicians to testing.

The authors report no relevant financial relationships.

Lebrikizumab, an interleukin (IL)–13 inhibitor under investigation for adult and adolescents with moderate to severe atopic dermatitis (AD), was efficacious in improving facial and hand dermatitis in a secondary analysis of randomized, double-blind, placebo-controlled phase 3 trials of the drug, Jenny E. Murase, MD, reported at the annual Revolutionizing Atopic Dermatitis conference.

At week 16 in the ADvocate 1, ADvocate 2, and ADhere trials, with and without concomitant topical corticosteroid (TCS) use, at least 58% of treated patients experienced improvement in facial dermatitis, and 62% or more experienced improvement in hand dermatitis – statistically significant differences over placebo.

Injenerker/Getty Images

“Lebrikizumab was efficacious in clearing and improving facial and hand dermatitis, burdensome and difficult-to-treat areas, in most patients with moderate to severe AD,” said Dr. Murase, of the department of dermatology at the University of California, San Francisco, and director of medical dermatology consultative services and patch testing for the Palo Alto (Calf.) Foundation Medical Group.

In another late-breaking abstract presented at the RAD conference, the injectable biologic dupilumab – now in its 6th year on the market – was reported by Jonathan I. Silverberg, MD, PhD, MPH, to “rapidly and significantly” improve the signs, symptoms, and quality of life in some adults and adolescents with moderate to severe hand and foot AD in a recently completed phase 3 trial of dupilumab.
 

Lebrikizumab results for facial, hand dermatitis

The ADvocate 1 and ADvocate 2 trials evaluated lebrikizumab monotherapy and randomized patients to receive 250 mg subcutaneously every 2 weeks (after a 500-mg loading dose at baseline and week 2) or placebo. (Patients who received any corticosteroid as a rescue medication were considered nonresponders.) The ADhere trial compared low to mid–potency TCS plus lebrikizumab, using the same dosing of lebrikizumab as in the ADvocate studies, versus TCS plus placebo.

In all three trials, with a total of more than 1,000 participants, clinicians assessed for the presence or absence of facial or hand dermatitis at baseline. At week 16, they then assessed the change from baseline based on a 4-point scale of cleared, improved, no change, and worsened. “Improvement” was defined as cleared or improved.

Both facial and hand dermatitis were identified in a majority of patients at baseline. For instance, in ADvocate 1, facial dermatitis was identified in 71.4% of patients in the lebrikizumab group and 80.9% of those in the placebo group. Hand dermatitis was identified in 72% and 73% of the treatment and placebo groups, respectively.

Across the trials, at 16 weeks, 58%-69% of adult and adolescent patients receiving lebrikizumab had improvement in facial dermatitis, compared with 22%-46% on placebo. For hand dermatitis, 62%-73% experienced improvement, compared with 19%-43% on placebo, respectively. Proportions of improved patients in both the lebrikizumab and placebo groups were highest in the ADhere trial, Dr. Murase reported.

In the ADvocate trials, 16 weeks marked the end of the induction phase and the start of a 36-week maintenance period. The ADhere trial was a 16-week study. Overall results from ADhere were published in January in JAMA Dermatology, and results from the 16-week induction period of the ADvocate trials were published in March in the New England Journal of Medicine.

Lebrikizumab received fast-track designation for AD by the Food and Drug Administration in 2019. Regulatory decisions in the United States and the European Union are expected later this year, according to a press release from Eli Lilly, the drug’s developer.

Asked to comment on the study results, Zelma Chiesa Fuxench, MD, MSCE, assistant professor of dermatology at the University of Pennsylvania, Philadelphia, called the post-hoc results promising. “While newer, more targeted treatments for AD offer the possibility of overall improvement and long-term disease control, we do not have sufficient data to help guide us when it comes to selecting treatment based on which area of the body is affected,” she explained. Most published findings have used “overall scores and not scores stratified by body region.”

The new findings, “help expand our current understanding of how the drug works for different areas of the body,” which can help inform treatment discussions with patients, she added.

AD can be especially challenging to treat when it involves “what are considered to be more sensitive areas such as the face or hands,” said Dr. Chiesa Fuxench. Challenges may include poor tolerance to topical medications, concerns for safety with long-term use, and the need for constant reapplication.

“Those of us who treat a large number of AD patients suspect that the impact and/or burden of AD may be different depending on what areas of the body are affected,” but more data are needed, she added. Limitations of the study, she noted, include “that the study may not have been adequately powered and that the sample size was small.”
 

Dupilumab result for hand, foot dermatitis

The phase 3 LIBERTY-AD-HAFT trial randomized 133 patients with moderate to severe atopic hand and/or foot dermatitis to a 16-week course of dupilumab (Dupixent) monotherapy, 300 mg every 2 weeks in adults and 200 or 300 mg every 2 weeks in adolescents, or placebo. Patients were then followed during a 12-week safety follow-up period.

Significantly more patients in the dupilumab group achieved the primary endpoint of a hand and foot Investigator Global Assessment (IGA) score of 0/1 at 16 weeks: 40.3% vs. 16.7% in the placebo group (P = .003). Statistical significance was reached at week 8, reported Dr. Silverberg, professor of dermatology and director of clinical research at George Washington University, Washington. Dupilumab, a human monoclonal IgG4 antibody that inhibits IL-4 and IL-13 signaling, is FDA approved for treating moderate to severe AD in patients age 6 months and older, among other indications.

In addition, the proportion of patients achieving a 4-point or greater improvement in the weekly average of daily hand and foot Peak Pruritus Numerical Rating Scale (PPNRS), the key secondary endpoint, was about fourfold greater with dupilumab: 52.2%, compared with 13.6% on placebo (P < .0001). This reduction in itch reached statistical significance by week 1. Dupilumab-treated patients also experienced significant improvement in other lesion measures and in Quality of Life in Hand Eczema Questionnaire scores, Dr. Silverberg noted.

The patients had a mean age in their 30s and a mean duration of atopic hand and/or foot dermatitis of 15-16 years. For more than one-quarter of patients, morphology was hyperkeratotic, which “has to be one of the toughest subsets to affect positive change in,” he said.

About 40% of patients had lesions on the hands only, and more than half had lesions on both hands and feet. “This is pretty realistic – we generally don’t see much isolated foot dermatitis in the AD population,” Dr. Silverberg said.

About 70%-75% had concomitant AD outside of the hands and feet, mostly of moderate severity. Patients with positive patch tests or whose hand and foot eczema was believed to be driven by irritants were excluded from the trial, as were patients who had used TCS or other topical treatments within 2 weeks of the baseline visit.

Rescue medication use was low (3% with dupilumab vs. 21% with placebo), and adverse events were “pretty consistent with everything we’ve seen with dupilumab,” said Dr. Silverberg.

Commenting on this study, Dr. Chiesa Fuxench said she was “excited to see [the findings], as hand and foot AD can often be quite challenging to treat in clinic.” The improvements in overall disease scores, itch, and quality of life scores – with fairly good tolerance – are “reassuring and what we would expect based on our current experience with dupilumab,” she said.

The lebrikizumab study was funded by Dermira, a wholly owned subsidiary of Eli Lilly. The dupilumab study was sponsored by Sanofi and Regeneron Pharmaceuticals. Some of the data were also reported by lead investigator Eric Simpson, MD, of Oregon Health and Science University at the annual meeting of the American Academy of Dermatology in March 2023.

Dr. Murase reported consulting/advising for Eli Lilly, Leo Pharma, UCB, Sanofi-Genzyme, and non-CME speaking/honoraria for UCB and Regeneron. Dr. Silverberg reported consulting fees and fees for non-CME services from Sanofi Genzyme, Regeneron, Pfizer, and other companies. Dr. Chiesa Fuxench, who was a speaker at the RAD meeting but was not involved in the studies, disclosed receiving honoraria for CME work in AD sponsored by education grants from Regeneron/Sanofi, and grant/research support from Lilly, Regeneron, and Sanofi, among other disclosures.

Lebrikizumab, an interleukin (IL)–13 inhibitor under investigation for adult and adolescents with moderate to severe atopic dermatitis (AD), was efficacious in improving facial and hand dermatitis in a secondary analysis of randomized, double-blind, placebo-controlled phase 3 trials of the drug, Jenny E. Murase, MD, reported at the annual Revolutionizing Atopic Dermatitis conference.

At week 16 in the ADvocate 1, ADvocate 2, and ADhere trials, with and without concomitant topical corticosteroid (TCS) use, at least 58% of treated patients experienced improvement in facial dermatitis, and 62% or more experienced improvement in hand dermatitis – statistically significant differences over placebo.

Injenerker/Getty Images

“Lebrikizumab was efficacious in clearing and improving facial and hand dermatitis, burdensome and difficult-to-treat areas, in most patients with moderate to severe AD,” said Dr. Murase, of the department of dermatology at the University of California, San Francisco, and director of medical dermatology consultative services and patch testing for the Palo Alto (Calf.) Foundation Medical Group.

In another late-breaking abstract presented at the RAD conference, the injectable biologic dupilumab – now in its 6th year on the market – was reported by Jonathan I. Silverberg, MD, PhD, MPH, to “rapidly and significantly” improve the signs, symptoms, and quality of life in some adults and adolescents with moderate to severe hand and foot AD in a recently completed phase 3 trial of dupilumab.
 

Lebrikizumab results for facial, hand dermatitis

The ADvocate 1 and ADvocate 2 trials evaluated lebrikizumab monotherapy and randomized patients to receive 250 mg subcutaneously every 2 weeks (after a 500-mg loading dose at baseline and week 2) or placebo. (Patients who received any corticosteroid as a rescue medication were considered nonresponders.) The ADhere trial compared low to mid–potency TCS plus lebrikizumab, using the same dosing of lebrikizumab as in the ADvocate studies, versus TCS plus placebo.

In all three trials, with a total of more than 1,000 participants, clinicians assessed for the presence or absence of facial or hand dermatitis at baseline. At week 16, they then assessed the change from baseline based on a 4-point scale of cleared, improved, no change, and worsened. “Improvement” was defined as cleared or improved.

Both facial and hand dermatitis were identified in a majority of patients at baseline. For instance, in ADvocate 1, facial dermatitis was identified in 71.4% of patients in the lebrikizumab group and 80.9% of those in the placebo group. Hand dermatitis was identified in 72% and 73% of the treatment and placebo groups, respectively.

Across the trials, at 16 weeks, 58%-69% of adult and adolescent patients receiving lebrikizumab had improvement in facial dermatitis, compared with 22%-46% on placebo. For hand dermatitis, 62%-73% experienced improvement, compared with 19%-43% on placebo, respectively. Proportions of improved patients in both the lebrikizumab and placebo groups were highest in the ADhere trial, Dr. Murase reported.

In the ADvocate trials, 16 weeks marked the end of the induction phase and the start of a 36-week maintenance period. The ADhere trial was a 16-week study. Overall results from ADhere were published in January in JAMA Dermatology, and results from the 16-week induction period of the ADvocate trials were published in March in the New England Journal of Medicine.

Lebrikizumab received fast-track designation for AD by the Food and Drug Administration in 2019. Regulatory decisions in the United States and the European Union are expected later this year, according to a press release from Eli Lilly, the drug’s developer.

Asked to comment on the study results, Zelma Chiesa Fuxench, MD, MSCE, assistant professor of dermatology at the University of Pennsylvania, Philadelphia, called the post-hoc results promising. “While newer, more targeted treatments for AD offer the possibility of overall improvement and long-term disease control, we do not have sufficient data to help guide us when it comes to selecting treatment based on which area of the body is affected,” she explained. Most published findings have used “overall scores and not scores stratified by body region.”

The new findings, “help expand our current understanding of how the drug works for different areas of the body,” which can help inform treatment discussions with patients, she added.

AD can be especially challenging to treat when it involves “what are considered to be more sensitive areas such as the face or hands,” said Dr. Chiesa Fuxench. Challenges may include poor tolerance to topical medications, concerns for safety with long-term use, and the need for constant reapplication.

“Those of us who treat a large number of AD patients suspect that the impact and/or burden of AD may be different depending on what areas of the body are affected,” but more data are needed, she added. Limitations of the study, she noted, include “that the study may not have been adequately powered and that the sample size was small.”
 

Dupilumab result for hand, foot dermatitis

The phase 3 LIBERTY-AD-HAFT trial randomized 133 patients with moderate to severe atopic hand and/or foot dermatitis to a 16-week course of dupilumab (Dupixent) monotherapy, 300 mg every 2 weeks in adults and 200 or 300 mg every 2 weeks in adolescents, or placebo. Patients were then followed during a 12-week safety follow-up period.

Significantly more patients in the dupilumab group achieved the primary endpoint of a hand and foot Investigator Global Assessment (IGA) score of 0/1 at 16 weeks: 40.3% vs. 16.7% in the placebo group (P = .003). Statistical significance was reached at week 8, reported Dr. Silverberg, professor of dermatology and director of clinical research at George Washington University, Washington. Dupilumab, a human monoclonal IgG4 antibody that inhibits IL-4 and IL-13 signaling, is FDA approved for treating moderate to severe AD in patients age 6 months and older, among other indications.

In addition, the proportion of patients achieving a 4-point or greater improvement in the weekly average of daily hand and foot Peak Pruritus Numerical Rating Scale (PPNRS), the key secondary endpoint, was about fourfold greater with dupilumab: 52.2%, compared with 13.6% on placebo (P < .0001). This reduction in itch reached statistical significance by week 1. Dupilumab-treated patients also experienced significant improvement in other lesion measures and in Quality of Life in Hand Eczema Questionnaire scores, Dr. Silverberg noted.

The patients had a mean age in their 30s and a mean duration of atopic hand and/or foot dermatitis of 15-16 years. For more than one-quarter of patients, morphology was hyperkeratotic, which “has to be one of the toughest subsets to affect positive change in,” he said.

About 40% of patients had lesions on the hands only, and more than half had lesions on both hands and feet. “This is pretty realistic – we generally don’t see much isolated foot dermatitis in the AD population,” Dr. Silverberg said.

About 70%-75% had concomitant AD outside of the hands and feet, mostly of moderate severity. Patients with positive patch tests or whose hand and foot eczema was believed to be driven by irritants were excluded from the trial, as were patients who had used TCS or other topical treatments within 2 weeks of the baseline visit.

Rescue medication use was low (3% with dupilumab vs. 21% with placebo), and adverse events were “pretty consistent with everything we’ve seen with dupilumab,” said Dr. Silverberg.

Commenting on this study, Dr. Chiesa Fuxench said she was “excited to see [the findings], as hand and foot AD can often be quite challenging to treat in clinic.” The improvements in overall disease scores, itch, and quality of life scores – with fairly good tolerance – are “reassuring and what we would expect based on our current experience with dupilumab,” she said.

The lebrikizumab study was funded by Dermira, a wholly owned subsidiary of Eli Lilly. The dupilumab study was sponsored by Sanofi and Regeneron Pharmaceuticals. Some of the data were also reported by lead investigator Eric Simpson, MD, of Oregon Health and Science University at the annual meeting of the American Academy of Dermatology in March 2023.

Dr. Murase reported consulting/advising for Eli Lilly, Leo Pharma, UCB, Sanofi-Genzyme, and non-CME speaking/honoraria for UCB and Regeneron. Dr. Silverberg reported consulting fees and fees for non-CME services from Sanofi Genzyme, Regeneron, Pfizer, and other companies. Dr. Chiesa Fuxench, who was a speaker at the RAD meeting but was not involved in the studies, disclosed receiving honoraria for CME work in AD sponsored by education grants from Regeneron/Sanofi, and grant/research support from Lilly, Regeneron, and Sanofi, among other disclosures.

Lebrikizumab, an interleukin (IL)–13 inhibitor under investigation for adult and adolescents with moderate to severe atopic dermatitis (AD), was efficacious in improving facial and hand dermatitis in a secondary analysis of randomized, double-blind, placebo-controlled phase 3 trials of the drug, Jenny E. Murase, MD, reported at the annual Revolutionizing Atopic Dermatitis conference.

At week 16 in the ADvocate 1, ADvocate 2, and ADhere trials, with and without concomitant topical corticosteroid (TCS) use, at least 58% of treated patients experienced improvement in facial dermatitis, and 62% or more experienced improvement in hand dermatitis – statistically significant differences over placebo.

Injenerker/Getty Images

“Lebrikizumab was efficacious in clearing and improving facial and hand dermatitis, burdensome and difficult-to-treat areas, in most patients with moderate to severe AD,” said Dr. Murase, of the department of dermatology at the University of California, San Francisco, and director of medical dermatology consultative services and patch testing for the Palo Alto (Calf.) Foundation Medical Group.

In another late-breaking abstract presented at the RAD conference, the injectable biologic dupilumab – now in its 6th year on the market – was reported by Jonathan I. Silverberg, MD, PhD, MPH, to “rapidly and significantly” improve the signs, symptoms, and quality of life in some adults and adolescents with moderate to severe hand and foot AD in a recently completed phase 3 trial of dupilumab.
 

Lebrikizumab results for facial, hand dermatitis

The ADvocate 1 and ADvocate 2 trials evaluated lebrikizumab monotherapy and randomized patients to receive 250 mg subcutaneously every 2 weeks (after a 500-mg loading dose at baseline and week 2) or placebo. (Patients who received any corticosteroid as a rescue medication were considered nonresponders.) The ADhere trial compared low to mid–potency TCS plus lebrikizumab, using the same dosing of lebrikizumab as in the ADvocate studies, versus TCS plus placebo.

In all three trials, with a total of more than 1,000 participants, clinicians assessed for the presence or absence of facial or hand dermatitis at baseline. At week 16, they then assessed the change from baseline based on a 4-point scale of cleared, improved, no change, and worsened. “Improvement” was defined as cleared or improved.

Both facial and hand dermatitis were identified in a majority of patients at baseline. For instance, in ADvocate 1, facial dermatitis was identified in 71.4% of patients in the lebrikizumab group and 80.9% of those in the placebo group. Hand dermatitis was identified in 72% and 73% of the treatment and placebo groups, respectively.

Across the trials, at 16 weeks, 58%-69% of adult and adolescent patients receiving lebrikizumab had improvement in facial dermatitis, compared with 22%-46% on placebo. For hand dermatitis, 62%-73% experienced improvement, compared with 19%-43% on placebo, respectively. Proportions of improved patients in both the lebrikizumab and placebo groups were highest in the ADhere trial, Dr. Murase reported.

In the ADvocate trials, 16 weeks marked the end of the induction phase and the start of a 36-week maintenance period. The ADhere trial was a 16-week study. Overall results from ADhere were published in January in JAMA Dermatology, and results from the 16-week induction period of the ADvocate trials were published in March in the New England Journal of Medicine.

Lebrikizumab received fast-track designation for AD by the Food and Drug Administration in 2019. Regulatory decisions in the United States and the European Union are expected later this year, according to a press release from Eli Lilly, the drug’s developer.

Asked to comment on the study results, Zelma Chiesa Fuxench, MD, MSCE, assistant professor of dermatology at the University of Pennsylvania, Philadelphia, called the post-hoc results promising. “While newer, more targeted treatments for AD offer the possibility of overall improvement and long-term disease control, we do not have sufficient data to help guide us when it comes to selecting treatment based on which area of the body is affected,” she explained. Most published findings have used “overall scores and not scores stratified by body region.”

The new findings, “help expand our current understanding of how the drug works for different areas of the body,” which can help inform treatment discussions with patients, she added.

AD can be especially challenging to treat when it involves “what are considered to be more sensitive areas such as the face or hands,” said Dr. Chiesa Fuxench. Challenges may include poor tolerance to topical medications, concerns for safety with long-term use, and the need for constant reapplication.

“Those of us who treat a large number of AD patients suspect that the impact and/or burden of AD may be different depending on what areas of the body are affected,” but more data are needed, she added. Limitations of the study, she noted, include “that the study may not have been adequately powered and that the sample size was small.”
 

Dupilumab result for hand, foot dermatitis

The phase 3 LIBERTY-AD-HAFT trial randomized 133 patients with moderate to severe atopic hand and/or foot dermatitis to a 16-week course of dupilumab (Dupixent) monotherapy, 300 mg every 2 weeks in adults and 200 or 300 mg every 2 weeks in adolescents, or placebo. Patients were then followed during a 12-week safety follow-up period.

Significantly more patients in the dupilumab group achieved the primary endpoint of a hand and foot Investigator Global Assessment (IGA) score of 0/1 at 16 weeks: 40.3% vs. 16.7% in the placebo group (P = .003). Statistical significance was reached at week 8, reported Dr. Silverberg, professor of dermatology and director of clinical research at George Washington University, Washington. Dupilumab, a human monoclonal IgG4 antibody that inhibits IL-4 and IL-13 signaling, is FDA approved for treating moderate to severe AD in patients age 6 months and older, among other indications.

In addition, the proportion of patients achieving a 4-point or greater improvement in the weekly average of daily hand and foot Peak Pruritus Numerical Rating Scale (PPNRS), the key secondary endpoint, was about fourfold greater with dupilumab: 52.2%, compared with 13.6% on placebo (P < .0001). This reduction in itch reached statistical significance by week 1. Dupilumab-treated patients also experienced significant improvement in other lesion measures and in Quality of Life in Hand Eczema Questionnaire scores, Dr. Silverberg noted.

The patients had a mean age in their 30s and a mean duration of atopic hand and/or foot dermatitis of 15-16 years. For more than one-quarter of patients, morphology was hyperkeratotic, which “has to be one of the toughest subsets to affect positive change in,” he said.

About 40% of patients had lesions on the hands only, and more than half had lesions on both hands and feet. “This is pretty realistic – we generally don’t see much isolated foot dermatitis in the AD population,” Dr. Silverberg said.

About 70%-75% had concomitant AD outside of the hands and feet, mostly of moderate severity. Patients with positive patch tests or whose hand and foot eczema was believed to be driven by irritants were excluded from the trial, as were patients who had used TCS or other topical treatments within 2 weeks of the baseline visit.

Rescue medication use was low (3% with dupilumab vs. 21% with placebo), and adverse events were “pretty consistent with everything we’ve seen with dupilumab,” said Dr. Silverberg.

Commenting on this study, Dr. Chiesa Fuxench said she was “excited to see [the findings], as hand and foot AD can often be quite challenging to treat in clinic.” The improvements in overall disease scores, itch, and quality of life scores – with fairly good tolerance – are “reassuring and what we would expect based on our current experience with dupilumab,” she said.

The lebrikizumab study was funded by Dermira, a wholly owned subsidiary of Eli Lilly. The dupilumab study was sponsored by Sanofi and Regeneron Pharmaceuticals. Some of the data were also reported by lead investigator Eric Simpson, MD, of Oregon Health and Science University at the annual meeting of the American Academy of Dermatology in March 2023.

Dr. Murase reported consulting/advising for Eli Lilly, Leo Pharma, UCB, Sanofi-Genzyme, and non-CME speaking/honoraria for UCB and Regeneron. Dr. Silverberg reported consulting fees and fees for non-CME services from Sanofi Genzyme, Regeneron, Pfizer, and other companies. Dr. Chiesa Fuxench, who was a speaker at the RAD meeting but was not involved in the studies, disclosed receiving honoraria for CME work in AD sponsored by education grants from Regeneron/Sanofi, and grant/research support from Lilly, Regeneron, and Sanofi, among other disclosures.

In this patient, bacterial and viral cultures were taken and varicella zoster virus (VZV) was isolated. Additionally, Orthopox DNA by PCR and Monkeypox (mpox) virus DNA by PCR were detected. Herpes simplex virus and bacterial viral cultures were negative. Valacyclovir was started at the time of presentation and the patient’s lesions resolved without sequelae.

Mpox is a zoonotic double-stranded DNA virus that is part of the Orthopoxvirus family, including the West African and Central African variants. This disease presents similarly to smallpox, so most mpox research was conducted around the time smallpox was eradicated. It was not until 1970, when the disease was isolated from a patient with suspected smallpox in the Democratic Republic of the Congo (DRC), that human mpox was considered a distinct disease. An epidemic outbreak in the United States occurred in 2003 related to infected prairie dogs, and travel-related outbreaks have been more recently reported up until May 2022, in which mpox was reported in nonendemic areas including North America, Europe, and Australia. Most cases in this outbreak occurred in men who have sex with men (MSM), but this is not always the case, and mpox is not necessarily considered a sexually transmitted infection. Mpox presents similarly to smallpox and VZV, so using laboratory tests is important in diagnosing and tracking this disease.

Although it is not easily transmitted, the disease can spread through bodily secretions both directly and indirectly. Mpox typically begins with a prodrome that includes fever, headache, myalgia, and fatigue. This is followed by lymphadenopathy that precedes and coincides with rash development. The lymph nodes are firm, tender, may be painful, and are a defining factor in presentation that differs from smallpox and varicella. The rash typically starts on the face, then presents on the body in a centrifugal distribution. However, cases related to sexual transmission present with anogenital lesions. The lesions are characterized by a progression from maculopapular to vesiculopustular, and can vary widely in quantity.

Notably, individuals are contagious from the onset of the prodrome until the lesions have scabbed over and fallen off. The eruptive nature of the later lesions poses a threat of secondary infection, and is often accompanied by a second febrile period that signifies deterioration of the patient’s condition. Other signs of secondary infection are variable and include pulmonary symptoms, vomiting, diarrhea, ocular infections, and in rare cases, encephalitis. These sequelae are more common in unvaccinated and immunocompromised individuals. Long-term complications of mpox include pitted scarring from cutaneous lesions with children being more susceptible to severe disease. The mortality rate for the disease is very low. (As of May 10, 2023, there have been 30,395 mpox cases reported in the United States, and 42 deaths, according to the Centers for Disease Control and Prevention.)

There are a variety of diagnostic tests that can aid in mpox identification, but they are most strongly supported when combined with clinical and epidemiological data. The best, least invasive method includes collection of lesion exudate or crust on a swab, and viral DNA is best preserved by keeping the specimen in a cool, dry, and dark environment. PCR is considered the standard, and electron microscopy and immunohistochemistry are valid tests, but all modalities require sophisticated technicians with the proper laboratory equipment. This is limiting because many cases present in underserved areas that lack the facilities for proper, real-time analysis. Antigen and antibody-based tests can be used, but cross-reactivity of other orthopoxviridae limits confirmation of mpox infection. Vaccination status, history and location must be considered.

Vaccination is the chief form of prevention for mpox, although it is not considered entirely protective. Smallpox vaccination provides protection, but widespread administration of the vaccine is no longer practiced, and an estimated 70% of the global population is no longer vaccinated. Vaccination is recommended for anyone at risk of exposure, but as this is a live, attenuated vaccine, the immune status of the patient is important to keep in mind. Tecovirimat and other antiviral medications including cidofovir and brincidofovir may be considered in severe cases.

This case is unique as our patient, who had no known risk factors for mpox, presented with mpox and VZV, simultaneously. Although clinical presentation and epidemiological patterns between these diseases differ, there have been a limited number of cases of coinfection reported in the literature, mainly in the DRC where mpox is endemic. Diagnosis must be made by separate laboratory tests and there are differences in presentation between independent and coinfection for these viruses. Notably, patients with mpox/VZV coinfection may be less likely to present with lesions on the face, thorax, arms, palms, and soles than those with only mpox but experience a higher lesion burden than those afflicted by only VZV. Coinfection may be related to reactivation of dormant VZV, or increased susceptibility to secondary infection when infected with one virus.

This case and photo were submitted by Lucas Shapiro, BS, of the Dr. Kiran C. Patel College of Osteopathic Medicine at Nova Southeastern University, Fort Lauderdale, Fla., and Donna Bilu Martin, MD.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Macneil A et al. Clin Infect Dis. 2009 Jan 1;48(1):e6-8.

2. Di Gennaro F et al. Microorganisms. 2022 Aug 12;10(8):1633.

3. Hughes CM et al. Am J Trop Med Hyg. 2020 Dec 7;104(2):604-11.

In this patient, bacterial and viral cultures were taken and varicella zoster virus (VZV) was isolated. Additionally, Orthopox DNA by PCR and Monkeypox (mpox) virus DNA by PCR were detected. Herpes simplex virus and bacterial viral cultures were negative. Valacyclovir was started at the time of presentation and the patient’s lesions resolved without sequelae.

Mpox is a zoonotic double-stranded DNA virus that is part of the Orthopoxvirus family, including the West African and Central African variants. This disease presents similarly to smallpox, so most mpox research was conducted around the time smallpox was eradicated. It was not until 1970, when the disease was isolated from a patient with suspected smallpox in the Democratic Republic of the Congo (DRC), that human mpox was considered a distinct disease. An epidemic outbreak in the United States occurred in 2003 related to infected prairie dogs, and travel-related outbreaks have been more recently reported up until May 2022, in which mpox was reported in nonendemic areas including North America, Europe, and Australia. Most cases in this outbreak occurred in men who have sex with men (MSM), but this is not always the case, and mpox is not necessarily considered a sexually transmitted infection. Mpox presents similarly to smallpox and VZV, so using laboratory tests is important in diagnosing and tracking this disease.

Although it is not easily transmitted, the disease can spread through bodily secretions both directly and indirectly. Mpox typically begins with a prodrome that includes fever, headache, myalgia, and fatigue. This is followed by lymphadenopathy that precedes and coincides with rash development. The lymph nodes are firm, tender, may be painful, and are a defining factor in presentation that differs from smallpox and varicella. The rash typically starts on the face, then presents on the body in a centrifugal distribution. However, cases related to sexual transmission present with anogenital lesions. The lesions are characterized by a progression from maculopapular to vesiculopustular, and can vary widely in quantity.

Notably, individuals are contagious from the onset of the prodrome until the lesions have scabbed over and fallen off. The eruptive nature of the later lesions poses a threat of secondary infection, and is often accompanied by a second febrile period that signifies deterioration of the patient’s condition. Other signs of secondary infection are variable and include pulmonary symptoms, vomiting, diarrhea, ocular infections, and in rare cases, encephalitis. These sequelae are more common in unvaccinated and immunocompromised individuals. Long-term complications of mpox include pitted scarring from cutaneous lesions with children being more susceptible to severe disease. The mortality rate for the disease is very low. (As of May 10, 2023, there have been 30,395 mpox cases reported in the United States, and 42 deaths, according to the Centers for Disease Control and Prevention.)

There are a variety of diagnostic tests that can aid in mpox identification, but they are most strongly supported when combined with clinical and epidemiological data. The best, least invasive method includes collection of lesion exudate or crust on a swab, and viral DNA is best preserved by keeping the specimen in a cool, dry, and dark environment. PCR is considered the standard, and electron microscopy and immunohistochemistry are valid tests, but all modalities require sophisticated technicians with the proper laboratory equipment. This is limiting because many cases present in underserved areas that lack the facilities for proper, real-time analysis. Antigen and antibody-based tests can be used, but cross-reactivity of other orthopoxviridae limits confirmation of mpox infection. Vaccination status, history and location must be considered.

Vaccination is the chief form of prevention for mpox, although it is not considered entirely protective. Smallpox vaccination provides protection, but widespread administration of the vaccine is no longer practiced, and an estimated 70% of the global population is no longer vaccinated. Vaccination is recommended for anyone at risk of exposure, but as this is a live, attenuated vaccine, the immune status of the patient is important to keep in mind. Tecovirimat and other antiviral medications including cidofovir and brincidofovir may be considered in severe cases.

This case is unique as our patient, who had no known risk factors for mpox, presented with mpox and VZV, simultaneously. Although clinical presentation and epidemiological patterns between these diseases differ, there have been a limited number of cases of coinfection reported in the literature, mainly in the DRC where mpox is endemic. Diagnosis must be made by separate laboratory tests and there are differences in presentation between independent and coinfection for these viruses. Notably, patients with mpox/VZV coinfection may be less likely to present with lesions on the face, thorax, arms, palms, and soles than those with only mpox but experience a higher lesion burden than those afflicted by only VZV. Coinfection may be related to reactivation of dormant VZV, or increased susceptibility to secondary infection when infected with one virus.

This case and photo were submitted by Lucas Shapiro, BS, of the Dr. Kiran C. Patel College of Osteopathic Medicine at Nova Southeastern University, Fort Lauderdale, Fla., and Donna Bilu Martin, MD.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Macneil A et al. Clin Infect Dis. 2009 Jan 1;48(1):e6-8.

2. Di Gennaro F et al. Microorganisms. 2022 Aug 12;10(8):1633.

3. Hughes CM et al. Am J Trop Med Hyg. 2020 Dec 7;104(2):604-11.

In this patient, bacterial and viral cultures were taken and varicella zoster virus (VZV) was isolated. Additionally, Orthopox DNA by PCR and Monkeypox (mpox) virus DNA by PCR were detected. Herpes simplex virus and bacterial viral cultures were negative. Valacyclovir was started at the time of presentation and the patient’s lesions resolved without sequelae.

Mpox is a zoonotic double-stranded DNA virus that is part of the Orthopoxvirus family, including the West African and Central African variants. This disease presents similarly to smallpox, so most mpox research was conducted around the time smallpox was eradicated. It was not until 1970, when the disease was isolated from a patient with suspected smallpox in the Democratic Republic of the Congo (DRC), that human mpox was considered a distinct disease. An epidemic outbreak in the United States occurred in 2003 related to infected prairie dogs, and travel-related outbreaks have been more recently reported up until May 2022, in which mpox was reported in nonendemic areas including North America, Europe, and Australia. Most cases in this outbreak occurred in men who have sex with men (MSM), but this is not always the case, and mpox is not necessarily considered a sexually transmitted infection. Mpox presents similarly to smallpox and VZV, so using laboratory tests is important in diagnosing and tracking this disease.

Although it is not easily transmitted, the disease can spread through bodily secretions both directly and indirectly. Mpox typically begins with a prodrome that includes fever, headache, myalgia, and fatigue. This is followed by lymphadenopathy that precedes and coincides with rash development. The lymph nodes are firm, tender, may be painful, and are a defining factor in presentation that differs from smallpox and varicella. The rash typically starts on the face, then presents on the body in a centrifugal distribution. However, cases related to sexual transmission present with anogenital lesions. The lesions are characterized by a progression from maculopapular to vesiculopustular, and can vary widely in quantity.

Notably, individuals are contagious from the onset of the prodrome until the lesions have scabbed over and fallen off. The eruptive nature of the later lesions poses a threat of secondary infection, and is often accompanied by a second febrile period that signifies deterioration of the patient’s condition. Other signs of secondary infection are variable and include pulmonary symptoms, vomiting, diarrhea, ocular infections, and in rare cases, encephalitis. These sequelae are more common in unvaccinated and immunocompromised individuals. Long-term complications of mpox include pitted scarring from cutaneous lesions with children being more susceptible to severe disease. The mortality rate for the disease is very low. (As of May 10, 2023, there have been 30,395 mpox cases reported in the United States, and 42 deaths, according to the Centers for Disease Control and Prevention.)

There are a variety of diagnostic tests that can aid in mpox identification, but they are most strongly supported when combined with clinical and epidemiological data. The best, least invasive method includes collection of lesion exudate or crust on a swab, and viral DNA is best preserved by keeping the specimen in a cool, dry, and dark environment. PCR is considered the standard, and electron microscopy and immunohistochemistry are valid tests, but all modalities require sophisticated technicians with the proper laboratory equipment. This is limiting because many cases present in underserved areas that lack the facilities for proper, real-time analysis. Antigen and antibody-based tests can be used, but cross-reactivity of other orthopoxviridae limits confirmation of mpox infection. Vaccination status, history and location must be considered.

Vaccination is the chief form of prevention for mpox, although it is not considered entirely protective. Smallpox vaccination provides protection, but widespread administration of the vaccine is no longer practiced, and an estimated 70% of the global population is no longer vaccinated. Vaccination is recommended for anyone at risk of exposure, but as this is a live, attenuated vaccine, the immune status of the patient is important to keep in mind. Tecovirimat and other antiviral medications including cidofovir and brincidofovir may be considered in severe cases.

This case is unique as our patient, who had no known risk factors for mpox, presented with mpox and VZV, simultaneously. Although clinical presentation and epidemiological patterns between these diseases differ, there have been a limited number of cases of coinfection reported in the literature, mainly in the DRC where mpox is endemic. Diagnosis must be made by separate laboratory tests and there are differences in presentation between independent and coinfection for these viruses. Notably, patients with mpox/VZV coinfection may be less likely to present with lesions on the face, thorax, arms, palms, and soles than those with only mpox but experience a higher lesion burden than those afflicted by only VZV. Coinfection may be related to reactivation of dormant VZV, or increased susceptibility to secondary infection when infected with one virus.

This case and photo were submitted by Lucas Shapiro, BS, of the Dr. Kiran C. Patel College of Osteopathic Medicine at Nova Southeastern University, Fort Lauderdale, Fla., and Donna Bilu Martin, MD.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

1. Macneil A et al. Clin Infect Dis. 2009 Jan 1;48(1):e6-8.

2. Di Gennaro F et al. Microorganisms. 2022 Aug 12;10(8):1633.

3. Hughes CM et al. Am J Trop Med Hyg. 2020 Dec 7;104(2):604-11.

Adults with cutaneous vasculitis experience a significantly diminished quality of life across physical, symptom, and emotional domains, and its measurement with an organ-specific instrument may catch important disease outcomes better than a generic health-related quality of life index, according to survey responses from participants in the Vasculitis Patient-Powered Research Network (VPPRN).

Although cutaneous vasculitis often causes itching, pain, and ulceration, the impact of the disease on specific health-related quality of life (HRQOL) outcomes has not been systematically assessed, wrote Sarah Mann, MD, of the University of Pittsburgh, and colleagues.

In a study published in JAMA Dermatology, the researchers used the VPPRN to conduct an online survey of adults aged 18 years and older with cutaneous manifestations of vasculitis. The survey was conducted between January 2020 and August 2021.

The primary outcomes of HRQOL were determined using two validated measures. One measured skin-related HRQOL (the Effects of Skin Disease on Quality-of-Life Survey [Skindex-29]), and the other measured general health and well-being (36-Item Short Form Health Survey [SF-36]).

The final analysis included 190 survey responses. The mean age of the respondents was 50.5 years, 84.1% were female, and approximately two-thirds reported a duration of vasculitis of at least 5 years. Respondents’ vasculitides included cutaneous small-vessel vasculitis (14%), IgA vasculitis (6.5%), urticarial vasculitis (8.4%), granulomatosis with polyangiitis (17.6%), microscopic polyangiitis (10.3%), eosinophilic vasculitis (15%), polyarteritis nodosa (3.7%), and other vasculitis types (24.2%).

On the Skindex-29 domains, severely or very severely diminished HRQOL was reported by 77.6% of respondents for emotions, 78.5% for symptoms, 60.7% for functioning, and 75.7% for overall HRQOL.

On the SF-36, the HRQOL was below average on six of eight domains, and approximately half of the patients had summative physical component scores (56%) and mental component scores (52%) below 50.

The HRQOL outcomes of cutaneous vasculitis were worse on the Skindex-29 than the SF-36, the researchers noted. “This discordance may reflect the value of disease or organ-specific measures, which may be able to capture important outcomes of disease even when generic measures do not,” they said.

The study findings were limited by several factors, including the potential lack of generalizability to broader populations of vasculitis patients, the researchers noted. Other limitations included the underrepresentation of male patients and the lack of a disease-specific patient-reported outcome measure, they said.

In addition, “Because half of patients reported having disease which was in remission or mildly active, the study findings may underestimate the true role of active cutaneous vasculitis on HRQOL,” the researchers said.

More studies are needed to assess how HRQOL measures respond to disease treatment and control, the researchers wrote in their discussion. However, the results suggest that cutaneous vasculitis has a significant effect on patients’ perception of their health, as well as on their well-being and symptoms, they said.

The study was supported by the Patient-Centered Outcomes Research Institute and GlaxoSmithKline. Dr. Mann had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies, including GlaxoSmithKline.

Adults with cutaneous vasculitis experience a significantly diminished quality of life across physical, symptom, and emotional domains, and its measurement with an organ-specific instrument may catch important disease outcomes better than a generic health-related quality of life index, according to survey responses from participants in the Vasculitis Patient-Powered Research Network (VPPRN).

Although cutaneous vasculitis often causes itching, pain, and ulceration, the impact of the disease on specific health-related quality of life (HRQOL) outcomes has not been systematically assessed, wrote Sarah Mann, MD, of the University of Pittsburgh, and colleagues.

In a study published in JAMA Dermatology, the researchers used the VPPRN to conduct an online survey of adults aged 18 years and older with cutaneous manifestations of vasculitis. The survey was conducted between January 2020 and August 2021.

The primary outcomes of HRQOL were determined using two validated measures. One measured skin-related HRQOL (the Effects of Skin Disease on Quality-of-Life Survey [Skindex-29]), and the other measured general health and well-being (36-Item Short Form Health Survey [SF-36]).

The final analysis included 190 survey responses. The mean age of the respondents was 50.5 years, 84.1% were female, and approximately two-thirds reported a duration of vasculitis of at least 5 years. Respondents’ vasculitides included cutaneous small-vessel vasculitis (14%), IgA vasculitis (6.5%), urticarial vasculitis (8.4%), granulomatosis with polyangiitis (17.6%), microscopic polyangiitis (10.3%), eosinophilic vasculitis (15%), polyarteritis nodosa (3.7%), and other vasculitis types (24.2%).

On the Skindex-29 domains, severely or very severely diminished HRQOL was reported by 77.6% of respondents for emotions, 78.5% for symptoms, 60.7% for functioning, and 75.7% for overall HRQOL.

On the SF-36, the HRQOL was below average on six of eight domains, and approximately half of the patients had summative physical component scores (56%) and mental component scores (52%) below 50.

The HRQOL outcomes of cutaneous vasculitis were worse on the Skindex-29 than the SF-36, the researchers noted. “This discordance may reflect the value of disease or organ-specific measures, which may be able to capture important outcomes of disease even when generic measures do not,” they said.

The study findings were limited by several factors, including the potential lack of generalizability to broader populations of vasculitis patients, the researchers noted. Other limitations included the underrepresentation of male patients and the lack of a disease-specific patient-reported outcome measure, they said.

In addition, “Because half of patients reported having disease which was in remission or mildly active, the study findings may underestimate the true role of active cutaneous vasculitis on HRQOL,” the researchers said.

More studies are needed to assess how HRQOL measures respond to disease treatment and control, the researchers wrote in their discussion. However, the results suggest that cutaneous vasculitis has a significant effect on patients’ perception of their health, as well as on their well-being and symptoms, they said.

The study was supported by the Patient-Centered Outcomes Research Institute and GlaxoSmithKline. Dr. Mann had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies, including GlaxoSmithKline.

Adults with cutaneous vasculitis experience a significantly diminished quality of life across physical, symptom, and emotional domains, and its measurement with an organ-specific instrument may catch important disease outcomes better than a generic health-related quality of life index, according to survey responses from participants in the Vasculitis Patient-Powered Research Network (VPPRN).

Although cutaneous vasculitis often causes itching, pain, and ulceration, the impact of the disease on specific health-related quality of life (HRQOL) outcomes has not been systematically assessed, wrote Sarah Mann, MD, of the University of Pittsburgh, and colleagues.

In a study published in JAMA Dermatology, the researchers used the VPPRN to conduct an online survey of adults aged 18 years and older with cutaneous manifestations of vasculitis. The survey was conducted between January 2020 and August 2021.

The primary outcomes of HRQOL were determined using two validated measures. One measured skin-related HRQOL (the Effects of Skin Disease on Quality-of-Life Survey [Skindex-29]), and the other measured general health and well-being (36-Item Short Form Health Survey [SF-36]).

The final analysis included 190 survey responses. The mean age of the respondents was 50.5 years, 84.1% were female, and approximately two-thirds reported a duration of vasculitis of at least 5 years. Respondents’ vasculitides included cutaneous small-vessel vasculitis (14%), IgA vasculitis (6.5%), urticarial vasculitis (8.4%), granulomatosis with polyangiitis (17.6%), microscopic polyangiitis (10.3%), eosinophilic vasculitis (15%), polyarteritis nodosa (3.7%), and other vasculitis types (24.2%).

On the Skindex-29 domains, severely or very severely diminished HRQOL was reported by 77.6% of respondents for emotions, 78.5% for symptoms, 60.7% for functioning, and 75.7% for overall HRQOL.

On the SF-36, the HRQOL was below average on six of eight domains, and approximately half of the patients had summative physical component scores (56%) and mental component scores (52%) below 50.

The HRQOL outcomes of cutaneous vasculitis were worse on the Skindex-29 than the SF-36, the researchers noted. “This discordance may reflect the value of disease or organ-specific measures, which may be able to capture important outcomes of disease even when generic measures do not,” they said.

The study findings were limited by several factors, including the potential lack of generalizability to broader populations of vasculitis patients, the researchers noted. Other limitations included the underrepresentation of male patients and the lack of a disease-specific patient-reported outcome measure, they said.

In addition, “Because half of patients reported having disease which was in remission or mildly active, the study findings may underestimate the true role of active cutaneous vasculitis on HRQOL,” the researchers said.

More studies are needed to assess how HRQOL measures respond to disease treatment and control, the researchers wrote in their discussion. However, the results suggest that cutaneous vasculitis has a significant effect on patients’ perception of their health, as well as on their well-being and symptoms, they said.

The study was supported by the Patient-Centered Outcomes Research Institute and GlaxoSmithKline. Dr. Mann had no financial conflicts to disclose. Several coauthors disclosed relationships with multiple companies, including GlaxoSmithKline.

Pediatricians may have a new aid to better predict peanut allergies among infants with atopic dermatitis.

Researchers have developed a scorecard to help pediatricians identify and assess the severity of atopic dermatitis in infants of various skin tones and to then predict risk of allergies to peanuts. Their study of the implementation of the scorecard was presented at the Pediatric Academic Societies annual meeting.

Infants with atopic dermatitis or eczema are six times more likely to have an egg allergy and eleven times more likely to have a peanut allergy at age 12 months than are infants without atopic dermatitis.

The scorecard reflects recent directives from the National Institute of Allergy and Infectious Diseases to help combat the public health problem.

“When the NIAID prevention of peanut allergy guidelines first came out, it asked pediatricians to serve as frontline practitioners in implementing them by identifying children at risk for peanut allergy and guiding families on what to do next,” said Waheeda Samady, MD, professor of pediatrics at Northwestern University, Chicago. “The impetus for the study was to further support pediatricians in this role.”

Although pediatricians are trained to identify and even treat mild to moderate cases of atopic dermatitis, little emphasis has gone to categorizing the condition on the basis of severity and to correlating peanut allergy risk.

The predictive scorecard captures 14 images from one infant of mixed race, two White infants, two Black infants, and two Hispanic infants.

To create the card, two in-house pediatric dermatologists assessed 58 images from 13 children and categorized images from 0 (no signs of atopic dermatitis) to 4 (severe signs of atopic dermatitis). After a first pass on categorization, the doctors agreed on 84% of images.

Of 189 pediatricians who used the card, fewer than half reported that they “sometimes,” “very often,” or “always” used the scorecard for atopic dermatitis evaluation. A little fewer than three-quarters reported that their ability to diagnose and categorize atopic dermatitis improved.

“Severity staging of atopic dermatitis is not something that the general pediatrician necessarily performs on a day-to-day basis,” said Kawaljit Brar, MD, professor of pediatrics in the division of allergy and immunology at Hassenfeld Children’s Hospital in New York.

Dr. Brar explained that children who are identified as being at high risk are often referred to specialists such as her, who then perform allergy screenings and can determine whether introduction of food at home is safe or whether office feedings supervised by an allergist are necessary. Researchers have found that early introduction to peanuts for children with moderate to severe atopic dermatitis could prevent peanut allergy.

“This represents a wonderful initiative to educate pediatricians so that they understand which patients require screening for peanut allergy and which patients don’t and can just get introduced to peanuts at home,” Dr. Brar said.

The atopic dermatitis scorecard reflects a growing recognition that varying skin tones show levels of severity incongruously.

“Many of us in clinical practice have recognized that our education has not always been inclusive of patients with varying skin tones,” Dr. Samady said. “When we looked for photos of patients with different skin tones, we simply could not find any that we thought were appropriate. So we decided to take some ourselves, and we’re currently continuing to take photos in order to improve the scorecard we currently have.”

The study was funded by the National Institute of Health and Food Allergy Research and Education. Dr. Samady and Dr. Brar reported no relevant financial relationships.

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

Pediatricians may have a new aid to better predict peanut allergies among infants with atopic dermatitis.

Researchers have developed a scorecard to help pediatricians identify and assess the severity of atopic dermatitis in infants of various skin tones and to then predict risk of allergies to peanuts. Their study of the implementation of the scorecard was presented at the Pediatric Academic Societies annual meeting.

Infants with atopic dermatitis or eczema are six times more likely to have an egg allergy and eleven times more likely to have a peanut allergy at age 12 months than are infants without atopic dermatitis.

The scorecard reflects recent directives from the National Institute of Allergy and Infectious Diseases to help combat the public health problem.

“When the NIAID prevention of peanut allergy guidelines first came out, it asked pediatricians to serve as frontline practitioners in implementing them by identifying children at risk for peanut allergy and guiding families on what to do next,” said Waheeda Samady, MD, professor of pediatrics at Northwestern University, Chicago. “The impetus for the study was to further support pediatricians in this role.”

Although pediatricians are trained to identify and even treat mild to moderate cases of atopic dermatitis, little emphasis has gone to categorizing the condition on the basis of severity and to correlating peanut allergy risk.

The predictive scorecard captures 14 images from one infant of mixed race, two White infants, two Black infants, and two Hispanic infants.

To create the card, two in-house pediatric dermatologists assessed 58 images from 13 children and categorized images from 0 (no signs of atopic dermatitis) to 4 (severe signs of atopic dermatitis). After a first pass on categorization, the doctors agreed on 84% of images.

Of 189 pediatricians who used the card, fewer than half reported that they “sometimes,” “very often,” or “always” used the scorecard for atopic dermatitis evaluation. A little fewer than three-quarters reported that their ability to diagnose and categorize atopic dermatitis improved.

“Severity staging of atopic dermatitis is not something that the general pediatrician necessarily performs on a day-to-day basis,” said Kawaljit Brar, MD, professor of pediatrics in the division of allergy and immunology at Hassenfeld Children’s Hospital in New York.

Dr. Brar explained that children who are identified as being at high risk are often referred to specialists such as her, who then perform allergy screenings and can determine whether introduction of food at home is safe or whether office feedings supervised by an allergist are necessary. Researchers have found that early introduction to peanuts for children with moderate to severe atopic dermatitis could prevent peanut allergy.

“This represents a wonderful initiative to educate pediatricians so that they understand which patients require screening for peanut allergy and which patients don’t and can just get introduced to peanuts at home,” Dr. Brar said.

The atopic dermatitis scorecard reflects a growing recognition that varying skin tones show levels of severity incongruously.

“Many of us in clinical practice have recognized that our education has not always been inclusive of patients with varying skin tones,” Dr. Samady said. “When we looked for photos of patients with different skin tones, we simply could not find any that we thought were appropriate. So we decided to take some ourselves, and we’re currently continuing to take photos in order to improve the scorecard we currently have.”

The study was funded by the National Institute of Health and Food Allergy Research and Education. Dr. Samady and Dr. Brar reported no relevant financial relationships.

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

Pediatricians may have a new aid to better predict peanut allergies among infants with atopic dermatitis.

Researchers have developed a scorecard to help pediatricians identify and assess the severity of atopic dermatitis in infants of various skin tones and to then predict risk of allergies to peanuts. Their study of the implementation of the scorecard was presented at the Pediatric Academic Societies annual meeting.

Infants with atopic dermatitis or eczema are six times more likely to have an egg allergy and eleven times more likely to have a peanut allergy at age 12 months than are infants without atopic dermatitis.

The scorecard reflects recent directives from the National Institute of Allergy and Infectious Diseases to help combat the public health problem.

“When the NIAID prevention of peanut allergy guidelines first came out, it asked pediatricians to serve as frontline practitioners in implementing them by identifying children at risk for peanut allergy and guiding families on what to do next,” said Waheeda Samady, MD, professor of pediatrics at Northwestern University, Chicago. “The impetus for the study was to further support pediatricians in this role.”

Although pediatricians are trained to identify and even treat mild to moderate cases of atopic dermatitis, little emphasis has gone to categorizing the condition on the basis of severity and to correlating peanut allergy risk.

The predictive scorecard captures 14 images from one infant of mixed race, two White infants, two Black infants, and two Hispanic infants.

To create the card, two in-house pediatric dermatologists assessed 58 images from 13 children and categorized images from 0 (no signs of atopic dermatitis) to 4 (severe signs of atopic dermatitis). After a first pass on categorization, the doctors agreed on 84% of images.

Of 189 pediatricians who used the card, fewer than half reported that they “sometimes,” “very often,” or “always” used the scorecard for atopic dermatitis evaluation. A little fewer than three-quarters reported that their ability to diagnose and categorize atopic dermatitis improved.

“Severity staging of atopic dermatitis is not something that the general pediatrician necessarily performs on a day-to-day basis,” said Kawaljit Brar, MD, professor of pediatrics in the division of allergy and immunology at Hassenfeld Children’s Hospital in New York.

Dr. Brar explained that children who are identified as being at high risk are often referred to specialists such as her, who then perform allergy screenings and can determine whether introduction of food at home is safe or whether office feedings supervised by an allergist are necessary. Researchers have found that early introduction to peanuts for children with moderate to severe atopic dermatitis could prevent peanut allergy.

“This represents a wonderful initiative to educate pediatricians so that they understand which patients require screening for peanut allergy and which patients don’t and can just get introduced to peanuts at home,” Dr. Brar said.

The atopic dermatitis scorecard reflects a growing recognition that varying skin tones show levels of severity incongruously.

“Many of us in clinical practice have recognized that our education has not always been inclusive of patients with varying skin tones,” Dr. Samady said. “When we looked for photos of patients with different skin tones, we simply could not find any that we thought were appropriate. So we decided to take some ourselves, and we’re currently continuing to take photos in order to improve the scorecard we currently have.”

The study was funded by the National Institute of Health and Food Allergy Research and Education. Dr. Samady and Dr. Brar reported no relevant financial relationships.

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