Atopic Dermatitis

Pediatric patients with atopic dermatitis (AD) are more likely to experience symptoms at classical sites such as the knees and have more associated and severe signs of AD, while older adults tend to present with less flexural eczema and the fewest associated signs.

Those are key findings from a study conducted at a single academic medical center, which aimed to identify the age-related clinical phenotypes of AD.

LucaLorenzelli/Thinkstock

“Previous studies have found differences in the clinical characteristics of AD depending on age of AD onset, ethnic background, and AD severity,” senior author Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the department of dermatology at George Washington University, Washington, and his coauthor wrote in the study, which was published online in JAAD International. “However, none have prospectively compared the clinical characteristics and associated signs by age group. Improved understanding of the clinical phenotypes of AD may help guide choice of treatment and improve health outcomes,” they added.

Along with coauthor Sheena Chatrath, a dermatology research fellow in the department, Dr. Silverberg prospectively reviewed self-reported questionnaires that were completed by 380 patients prior to their visit at GWU’s eczema clinic between 2013 and 2019. Questions included age of AD onset, sociodemographics, Visual Analog Scale (VAS) itch and sleep for Scoring AD, and Numeric Rating Scale (NRS) for skin pain and itch. The researchers used the Eczema Area Severity Index to assess AD severity and a dermatologist conducted full body skin exams, noting the distribution of AD involvement as well as associated signs.

Of the 380 patients, 6.1% were younger than aged 18 years, 46.3% were young adults aged 18-39 years, and 47.6% were older adults 40 years of age and older.

Compared with pediatric patients, both young and older adults were less likely to experience AD on the ankles (adjusted odds ratio [aOR], 0.41 and 0.43, respectively), moderate to severe AD lesions on flexures (aOR, 0.47 and 0.30), pityriasis alba (aOR, 0.24 and 0.07), oozing lesions (aOR, 0.44 and 0.35), and moderate to severe excoriations (aOR, 0.49 and 0.44).

In children, severe itch was more common, reported in 47.1%, compared with 43.4% of the young adults and 38.6% of the older adults, and itch was less severe among the young and older adults. “Interestingly, despite increased itch in pediatric patients, we found no difference in the severity of skin pain across all age groups,” the researchers wrote. “Moreover, pediatric patients reported skin pain less often than adult patients. This may be due to age-related differences of pain perception.”

In other findings, compared with pediatric patients, young adults were more likely to experience AD around the eyes (aOR, 2.92), while older adults were less likely to experience AD on elbows (aOR, 0.34), nipples (aOR, 0.40), knees (aOR, 0.27), and less likely to have keratosis pilaris (aOR, 0.38), and lichenification (aOR, 0.47).

Dr. Silverberg and Ms. Chatrath used latent class analysis to identify four classes for distribution of AD lesions. In this model, class 1 had low probabilities of AD involvement at all sites examined and class 2 had low probabilities of scalp, face, and foot involvement, and intermediate probability of all other AD sites. Class 3 had low probabilities of hand and foot involvement, high probability of facial erythema, and intermediate probability of all other AD signs, while class 4 had intermediate probability of postauricular and foot involvement, and high probability of all other AD sites examined.

“Pediatric patients were most commonly in class 4 (33.3%), followed by class 1 and 2 (26.7%), and least commonly in class 3 (13.3%),” the authors wrote. “In young adults, class 4 and 1 were most common (32.4% and 29.4%), followed by class 2 (27.9%), and least commonly class 3 (10.3%). In older adults, class 1 was most common (40.3%), followed by class 4 (23.6%), and least commonly classes 2 and 3 (18.1%).”

The researchers also used latent class analysis to identify four classes for the signs and symptoms of AD. In this model, class 1 had zero-low probability of all AD signs and class 2 had low probability of all AD signs. Class 3 had high probability of oozing lesions and low probability of all other signs, while class 4 had high probability of xerosis, intermediate probability of ichthyosis and palmar hyperlinearity, and low probability of all other AD signs.

In all three groups, the most common class was class 1 (85.6% of older adults, 81.8% of younger adults, and 82.6% of pediatric patients). Among the pediatric patients, they wrote, “class 3 was the second most common (8.7%), followed by class 2 and 4 (4.4%).” Among the young adults, 9.7% were in class 2, 5.7% were in class 4, and 2.8% were in class 3; and among the older adults, 8.3% were in class 4, 4.4% were in class 2, and 1.67% were in class 3.

Zelma Chiesa Fuxench, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, who was asked to comment on the study, said that while AD is traditionally largely thought of as a disease of children primarily involving the flexural areas, “this study provides additional evidence to support that AD is more than just a disease of childhood with a fixed clinical presentation, but is a heterogeneous disease whose clinical presentation varies across different population groups.”

Pediatric patients with atopic dermatitis (AD) are more likely to experience symptoms at classical sites such as the knees and have more associated and severe signs of AD, while older adults tend to present with less flexural eczema and the fewest associated signs.

Those are key findings from a study conducted at a single academic medical center, which aimed to identify the age-related clinical phenotypes of AD.

LucaLorenzelli/Thinkstock

“Previous studies have found differences in the clinical characteristics of AD depending on age of AD onset, ethnic background, and AD severity,” senior author Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the department of dermatology at George Washington University, Washington, and his coauthor wrote in the study, which was published online in JAAD International. “However, none have prospectively compared the clinical characteristics and associated signs by age group. Improved understanding of the clinical phenotypes of AD may help guide choice of treatment and improve health outcomes,” they added.

Along with coauthor Sheena Chatrath, a dermatology research fellow in the department, Dr. Silverberg prospectively reviewed self-reported questionnaires that were completed by 380 patients prior to their visit at GWU’s eczema clinic between 2013 and 2019. Questions included age of AD onset, sociodemographics, Visual Analog Scale (VAS) itch and sleep for Scoring AD, and Numeric Rating Scale (NRS) for skin pain and itch. The researchers used the Eczema Area Severity Index to assess AD severity and a dermatologist conducted full body skin exams, noting the distribution of AD involvement as well as associated signs.

Of the 380 patients, 6.1% were younger than aged 18 years, 46.3% were young adults aged 18-39 years, and 47.6% were older adults 40 years of age and older.

Compared with pediatric patients, both young and older adults were less likely to experience AD on the ankles (adjusted odds ratio [aOR], 0.41 and 0.43, respectively), moderate to severe AD lesions on flexures (aOR, 0.47 and 0.30), pityriasis alba (aOR, 0.24 and 0.07), oozing lesions (aOR, 0.44 and 0.35), and moderate to severe excoriations (aOR, 0.49 and 0.44).

In children, severe itch was more common, reported in 47.1%, compared with 43.4% of the young adults and 38.6% of the older adults, and itch was less severe among the young and older adults. “Interestingly, despite increased itch in pediatric patients, we found no difference in the severity of skin pain across all age groups,” the researchers wrote. “Moreover, pediatric patients reported skin pain less often than adult patients. This may be due to age-related differences of pain perception.”

In other findings, compared with pediatric patients, young adults were more likely to experience AD around the eyes (aOR, 2.92), while older adults were less likely to experience AD on elbows (aOR, 0.34), nipples (aOR, 0.40), knees (aOR, 0.27), and less likely to have keratosis pilaris (aOR, 0.38), and lichenification (aOR, 0.47).

Dr. Silverberg and Ms. Chatrath used latent class analysis to identify four classes for distribution of AD lesions. In this model, class 1 had low probabilities of AD involvement at all sites examined and class 2 had low probabilities of scalp, face, and foot involvement, and intermediate probability of all other AD sites. Class 3 had low probabilities of hand and foot involvement, high probability of facial erythema, and intermediate probability of all other AD signs, while class 4 had intermediate probability of postauricular and foot involvement, and high probability of all other AD sites examined.

“Pediatric patients were most commonly in class 4 (33.3%), followed by class 1 and 2 (26.7%), and least commonly in class 3 (13.3%),” the authors wrote. “In young adults, class 4 and 1 were most common (32.4% and 29.4%), followed by class 2 (27.9%), and least commonly class 3 (10.3%). In older adults, class 1 was most common (40.3%), followed by class 4 (23.6%), and least commonly classes 2 and 3 (18.1%).”

The researchers also used latent class analysis to identify four classes for the signs and symptoms of AD. In this model, class 1 had zero-low probability of all AD signs and class 2 had low probability of all AD signs. Class 3 had high probability of oozing lesions and low probability of all other signs, while class 4 had high probability of xerosis, intermediate probability of ichthyosis and palmar hyperlinearity, and low probability of all other AD signs.

In all three groups, the most common class was class 1 (85.6% of older adults, 81.8% of younger adults, and 82.6% of pediatric patients). Among the pediatric patients, they wrote, “class 3 was the second most common (8.7%), followed by class 2 and 4 (4.4%).” Among the young adults, 9.7% were in class 2, 5.7% were in class 4, and 2.8% were in class 3; and among the older adults, 8.3% were in class 4, 4.4% were in class 2, and 1.67% were in class 3.

Zelma Chiesa Fuxench, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, who was asked to comment on the study, said that while AD is traditionally largely thought of as a disease of children primarily involving the flexural areas, “this study provides additional evidence to support that AD is more than just a disease of childhood with a fixed clinical presentation, but is a heterogeneous disease whose clinical presentation varies across different population groups.”

Pediatric patients with atopic dermatitis (AD) are more likely to experience symptoms at classical sites such as the knees and have more associated and severe signs of AD, while older adults tend to present with less flexural eczema and the fewest associated signs.

Those are key findings from a study conducted at a single academic medical center, which aimed to identify the age-related clinical phenotypes of AD.

LucaLorenzelli/Thinkstock

“Previous studies have found differences in the clinical characteristics of AD depending on age of AD onset, ethnic background, and AD severity,” senior author Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the department of dermatology at George Washington University, Washington, and his coauthor wrote in the study, which was published online in JAAD International. “However, none have prospectively compared the clinical characteristics and associated signs by age group. Improved understanding of the clinical phenotypes of AD may help guide choice of treatment and improve health outcomes,” they added.

Along with coauthor Sheena Chatrath, a dermatology research fellow in the department, Dr. Silverberg prospectively reviewed self-reported questionnaires that were completed by 380 patients prior to their visit at GWU’s eczema clinic between 2013 and 2019. Questions included age of AD onset, sociodemographics, Visual Analog Scale (VAS) itch and sleep for Scoring AD, and Numeric Rating Scale (NRS) for skin pain and itch. The researchers used the Eczema Area Severity Index to assess AD severity and a dermatologist conducted full body skin exams, noting the distribution of AD involvement as well as associated signs.

Of the 380 patients, 6.1% were younger than aged 18 years, 46.3% were young adults aged 18-39 years, and 47.6% were older adults 40 years of age and older.

Compared with pediatric patients, both young and older adults were less likely to experience AD on the ankles (adjusted odds ratio [aOR], 0.41 and 0.43, respectively), moderate to severe AD lesions on flexures (aOR, 0.47 and 0.30), pityriasis alba (aOR, 0.24 and 0.07), oozing lesions (aOR, 0.44 and 0.35), and moderate to severe excoriations (aOR, 0.49 and 0.44).

In children, severe itch was more common, reported in 47.1%, compared with 43.4% of the young adults and 38.6% of the older adults, and itch was less severe among the young and older adults. “Interestingly, despite increased itch in pediatric patients, we found no difference in the severity of skin pain across all age groups,” the researchers wrote. “Moreover, pediatric patients reported skin pain less often than adult patients. This may be due to age-related differences of pain perception.”

In other findings, compared with pediatric patients, young adults were more likely to experience AD around the eyes (aOR, 2.92), while older adults were less likely to experience AD on elbows (aOR, 0.34), nipples (aOR, 0.40), knees (aOR, 0.27), and less likely to have keratosis pilaris (aOR, 0.38), and lichenification (aOR, 0.47).

Dr. Silverberg and Ms. Chatrath used latent class analysis to identify four classes for distribution of AD lesions. In this model, class 1 had low probabilities of AD involvement at all sites examined and class 2 had low probabilities of scalp, face, and foot involvement, and intermediate probability of all other AD sites. Class 3 had low probabilities of hand and foot involvement, high probability of facial erythema, and intermediate probability of all other AD signs, while class 4 had intermediate probability of postauricular and foot involvement, and high probability of all other AD sites examined.

“Pediatric patients were most commonly in class 4 (33.3%), followed by class 1 and 2 (26.7%), and least commonly in class 3 (13.3%),” the authors wrote. “In young adults, class 4 and 1 were most common (32.4% and 29.4%), followed by class 2 (27.9%), and least commonly class 3 (10.3%). In older adults, class 1 was most common (40.3%), followed by class 4 (23.6%), and least commonly classes 2 and 3 (18.1%).”

The researchers also used latent class analysis to identify four classes for the signs and symptoms of AD. In this model, class 1 had zero-low probability of all AD signs and class 2 had low probability of all AD signs. Class 3 had high probability of oozing lesions and low probability of all other signs, while class 4 had high probability of xerosis, intermediate probability of ichthyosis and palmar hyperlinearity, and low probability of all other AD signs.

In all three groups, the most common class was class 1 (85.6% of older adults, 81.8% of younger adults, and 82.6% of pediatric patients). Among the pediatric patients, they wrote, “class 3 was the second most common (8.7%), followed by class 2 and 4 (4.4%).” Among the young adults, 9.7% were in class 2, 5.7% were in class 4, and 2.8% were in class 3; and among the older adults, 8.3% were in class 4, 4.4% were in class 2, and 1.67% were in class 3.

Zelma Chiesa Fuxench, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, who was asked to comment on the study, said that while AD is traditionally largely thought of as a disease of children primarily involving the flexural areas, “this study provides additional evidence to support that AD is more than just a disease of childhood with a fixed clinical presentation, but is a heterogeneous disease whose clinical presentation varies across different population groups.”

Adult and adolescent patients with moderate to severe atopic dermatitis (AD) showed significant improvements with the addition of lebrikizumab to topical corticosteroid (TCS) therapy, compared with TCS plus placebo, according to results of the 16-week phase 3 ADhere trial.

“Lebrikizumab, a monoclonal antibody inhibiting interleukin-13, combined with TCS was associated with reduced overall disease severity of moderate to severe AD in adolescents and adults, and had a safety profile consistent with previous lebrikizumab AD studies,” noted lead author Eric L. Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, and coauthors in their article on the study, which was published in JAMA Dermatology.

The double-blind trial, conducted at 54 sites across Germany, Poland, Canada, and the United States, included 211 patients, mean age 37.2 years, of whom 48.8% were female and roughly 22% were adolescents. Almost 15% were Asian, and about 13% were Black.

At baseline, participants had a score of 16 or higher on the Eczema Area and Severity Index (EASI), a score of 3 or higher on the Investigator’s Global Assessment (IGA) scale, AD covering a body surface area of 10% or greater, and a history of inadequate response to treatment with topical medications.

After a minimum 1-week washout period from topical and systemic therapy, participants were randomized in a 2:1 ratio to receive lebrikizumab plus TCS (n = 145) or placebo plus TCS (n = 66) for 16 weeks.

Lebrikizumab or placebo was administered by subcutaneous injection every 2 weeks; the loading and week-2 doses of lebrikizumab were 500 mg, followed by 250 mg thereafter. All patients were instructed to use low- to mid-potency TCS at their own discretion. Study sites provided a mid-potency TCS (triamcinolone acetonide 0.1% cream) and a low-potency TCS (hydrocortisone 1% cream), with topical calcineurin inhibitors permitted for sensitive skin areas.

Primary outcomes at 16 weeks included a 2-point or more reduction in IGA score from baseline and EASI-75 response. Patients in the lebrikizumab arm had superior responses on both of these outcomes, with statistical significance achieved as early as week 8 and week 4, respectively, and maintained through week 16. Specifically, 41.2% of those treated with lebrikizumab had an IGA reduction of 2 points or more, compared with 22.1% of those receiving placebo plus TCS (P = .01), and the proportion of patients achieving EASI-75 responses was 69.5% vs. 42.2%, respectively (P < .001).

Patients treated with lebrikizumab also showed statistically significant improvements, compared with TCS alone in all key secondary endpoints, “including skin clearance, improvement in itch, itch interference on sleep, and enhanced QoL [quality of life],” noted the authors. “This study captured the clinical benefit of lebrikizumab through the combined end point of physician-assessed clinical sign of skin clearance (EASI-75) and patient-reported outcome of improvement in itch (Pruritus NRS).”

The percentage of patients who achieved the combined endpoint was more than double for the lebrikizumab plus TCS group vs. the group on TCS alone, indicating that patients treated with lebrikizumab plus TCS “were more likely to experience improvement in skin symptoms and itch,” the investigators added.

The authors noted that most treatment-emergent adverse events “were nonserious, mild, or moderate in severity, and did not lead to study discontinuation.” These included conjunctivitis (4.8%), headache (4.8%), hypertension (2.8%), injection-site reactions (2.8%), and herpes infection (3.4%) – all of which occurred in 1.5% or less of patients in the placebo group.

“The higher incidence of conjunctivitis has also been reported in other biologics inhibiting IL [interleukin]–13 and/or IL-4 signaling, as well as lebrikizumab monotherapy studies,” they noted. The 4.8% rate of conjunctivitis reported in the combination study, they added, is “compared with 7.5% frequency in 16-week data from the lebrikizumab monotherapy studies. Although the mechanism remains unclear, it has been reported that conjunctival goblet cell scarcity due to IL-13 and IL-4 inhibition, and subsequent effects on the homeostasis of the conjunctival mucosal surface, results in ocular AEs [adverse events].”

“This truly is a time of great hope and promise for our patients with AD,” commented Zelma Chiesa Fuxench, MD, who was not involved in the study. “The advent of newer, targeted therapeutic agents for AD continues to revolutionize the treatment experience for our patients, offering the possibility of greater AD disease control with a favorable risk profile and less need for blood work monitoring compared to traditional systemic agents.”

On the basis of the study results, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said in an interview that “lebrikizumab represents an additional option in the treatment armamentarium for providers who care for patients with AD.” She added that, “while head-to-head trials comparing lebrikizumab to dupilumab, the first FDA-approved biologic for AD, would be beneficial, to the best of my knowledge this data is currently lacking. However, based on the results of this study, we would expect lebrikizumab to work at least similarly to dupilumab, based on the reported improvements in IGA and EASI score.”

Additionally, lebrikizumab showed a favorable safety profile, “with most treatment-emergent adverse effects reported as nonserious and not leading to drug discontinuation,” she said. “Of interest to clinicians may be the reported rates of conjunctivitis in this study. Rates of conjunctivitis for lebrikizumab appear to be lower than those reported in the LIBERTY AD CHRONOS study for dupilumab – a finding that merits further scrutiny in my opinion, as this one of the most frequent treatment-emergent adverse events that I encounter in my clinical practice.”

The study was funded by Dermira, a subsidiary of Eli Lilly. Dr. Simpson reported personal fees and grants from multiple sources, including Dermira and Eli Lilly, the companies developing lebrikizumab. Several authors were employees of Eli Lilly. Dr. Fuxench disclosed serving as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, AbbVie, and Incyte, for which she has received honoraria for AD-related work. She is the recipient of research grants through Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.

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

Adult and adolescent patients with moderate to severe atopic dermatitis (AD) showed significant improvements with the addition of lebrikizumab to topical corticosteroid (TCS) therapy, compared with TCS plus placebo, according to results of the 16-week phase 3 ADhere trial.

“Lebrikizumab, a monoclonal antibody inhibiting interleukin-13, combined with TCS was associated with reduced overall disease severity of moderate to severe AD in adolescents and adults, and had a safety profile consistent with previous lebrikizumab AD studies,” noted lead author Eric L. Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, and coauthors in their article on the study, which was published in JAMA Dermatology.

The double-blind trial, conducted at 54 sites across Germany, Poland, Canada, and the United States, included 211 patients, mean age 37.2 years, of whom 48.8% were female and roughly 22% were adolescents. Almost 15% were Asian, and about 13% were Black.

At baseline, participants had a score of 16 or higher on the Eczema Area and Severity Index (EASI), a score of 3 or higher on the Investigator’s Global Assessment (IGA) scale, AD covering a body surface area of 10% or greater, and a history of inadequate response to treatment with topical medications.

After a minimum 1-week washout period from topical and systemic therapy, participants were randomized in a 2:1 ratio to receive lebrikizumab plus TCS (n = 145) or placebo plus TCS (n = 66) for 16 weeks.

Lebrikizumab or placebo was administered by subcutaneous injection every 2 weeks; the loading and week-2 doses of lebrikizumab were 500 mg, followed by 250 mg thereafter. All patients were instructed to use low- to mid-potency TCS at their own discretion. Study sites provided a mid-potency TCS (triamcinolone acetonide 0.1% cream) and a low-potency TCS (hydrocortisone 1% cream), with topical calcineurin inhibitors permitted for sensitive skin areas.

Primary outcomes at 16 weeks included a 2-point or more reduction in IGA score from baseline and EASI-75 response. Patients in the lebrikizumab arm had superior responses on both of these outcomes, with statistical significance achieved as early as week 8 and week 4, respectively, and maintained through week 16. Specifically, 41.2% of those treated with lebrikizumab had an IGA reduction of 2 points or more, compared with 22.1% of those receiving placebo plus TCS (P = .01), and the proportion of patients achieving EASI-75 responses was 69.5% vs. 42.2%, respectively (P < .001).

Patients treated with lebrikizumab also showed statistically significant improvements, compared with TCS alone in all key secondary endpoints, “including skin clearance, improvement in itch, itch interference on sleep, and enhanced QoL [quality of life],” noted the authors. “This study captured the clinical benefit of lebrikizumab through the combined end point of physician-assessed clinical sign of skin clearance (EASI-75) and patient-reported outcome of improvement in itch (Pruritus NRS).”

The percentage of patients who achieved the combined endpoint was more than double for the lebrikizumab plus TCS group vs. the group on TCS alone, indicating that patients treated with lebrikizumab plus TCS “were more likely to experience improvement in skin symptoms and itch,” the investigators added.

The authors noted that most treatment-emergent adverse events “were nonserious, mild, or moderate in severity, and did not lead to study discontinuation.” These included conjunctivitis (4.8%), headache (4.8%), hypertension (2.8%), injection-site reactions (2.8%), and herpes infection (3.4%) – all of which occurred in 1.5% or less of patients in the placebo group.

“The higher incidence of conjunctivitis has also been reported in other biologics inhibiting IL [interleukin]–13 and/or IL-4 signaling, as well as lebrikizumab monotherapy studies,” they noted. The 4.8% rate of conjunctivitis reported in the combination study, they added, is “compared with 7.5% frequency in 16-week data from the lebrikizumab monotherapy studies. Although the mechanism remains unclear, it has been reported that conjunctival goblet cell scarcity due to IL-13 and IL-4 inhibition, and subsequent effects on the homeostasis of the conjunctival mucosal surface, results in ocular AEs [adverse events].”

“This truly is a time of great hope and promise for our patients with AD,” commented Zelma Chiesa Fuxench, MD, who was not involved in the study. “The advent of newer, targeted therapeutic agents for AD continues to revolutionize the treatment experience for our patients, offering the possibility of greater AD disease control with a favorable risk profile and less need for blood work monitoring compared to traditional systemic agents.”

On the basis of the study results, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said in an interview that “lebrikizumab represents an additional option in the treatment armamentarium for providers who care for patients with AD.” She added that, “while head-to-head trials comparing lebrikizumab to dupilumab, the first FDA-approved biologic for AD, would be beneficial, to the best of my knowledge this data is currently lacking. However, based on the results of this study, we would expect lebrikizumab to work at least similarly to dupilumab, based on the reported improvements in IGA and EASI score.”

Additionally, lebrikizumab showed a favorable safety profile, “with most treatment-emergent adverse effects reported as nonserious and not leading to drug discontinuation,” she said. “Of interest to clinicians may be the reported rates of conjunctivitis in this study. Rates of conjunctivitis for lebrikizumab appear to be lower than those reported in the LIBERTY AD CHRONOS study for dupilumab – a finding that merits further scrutiny in my opinion, as this one of the most frequent treatment-emergent adverse events that I encounter in my clinical practice.”

The study was funded by Dermira, a subsidiary of Eli Lilly. Dr. Simpson reported personal fees and grants from multiple sources, including Dermira and Eli Lilly, the companies developing lebrikizumab. Several authors were employees of Eli Lilly. Dr. Fuxench disclosed serving as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, AbbVie, and Incyte, for which she has received honoraria for AD-related work. She is the recipient of research grants through Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.

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

Adult and adolescent patients with moderate to severe atopic dermatitis (AD) showed significant improvements with the addition of lebrikizumab to topical corticosteroid (TCS) therapy, compared with TCS plus placebo, according to results of the 16-week phase 3 ADhere trial.

“Lebrikizumab, a monoclonal antibody inhibiting interleukin-13, combined with TCS was associated with reduced overall disease severity of moderate to severe AD in adolescents and adults, and had a safety profile consistent with previous lebrikizumab AD studies,” noted lead author Eric L. Simpson, MD, professor of dermatology at Oregon Health & Science University, Portland, and coauthors in their article on the study, which was published in JAMA Dermatology.

The double-blind trial, conducted at 54 sites across Germany, Poland, Canada, and the United States, included 211 patients, mean age 37.2 years, of whom 48.8% were female and roughly 22% were adolescents. Almost 15% were Asian, and about 13% were Black.

At baseline, participants had a score of 16 or higher on the Eczema Area and Severity Index (EASI), a score of 3 or higher on the Investigator’s Global Assessment (IGA) scale, AD covering a body surface area of 10% or greater, and a history of inadequate response to treatment with topical medications.

After a minimum 1-week washout period from topical and systemic therapy, participants were randomized in a 2:1 ratio to receive lebrikizumab plus TCS (n = 145) or placebo plus TCS (n = 66) for 16 weeks.

Lebrikizumab or placebo was administered by subcutaneous injection every 2 weeks; the loading and week-2 doses of lebrikizumab were 500 mg, followed by 250 mg thereafter. All patients were instructed to use low- to mid-potency TCS at their own discretion. Study sites provided a mid-potency TCS (triamcinolone acetonide 0.1% cream) and a low-potency TCS (hydrocortisone 1% cream), with topical calcineurin inhibitors permitted for sensitive skin areas.

Primary outcomes at 16 weeks included a 2-point or more reduction in IGA score from baseline and EASI-75 response. Patients in the lebrikizumab arm had superior responses on both of these outcomes, with statistical significance achieved as early as week 8 and week 4, respectively, and maintained through week 16. Specifically, 41.2% of those treated with lebrikizumab had an IGA reduction of 2 points or more, compared with 22.1% of those receiving placebo plus TCS (P = .01), and the proportion of patients achieving EASI-75 responses was 69.5% vs. 42.2%, respectively (P < .001).

Patients treated with lebrikizumab also showed statistically significant improvements, compared with TCS alone in all key secondary endpoints, “including skin clearance, improvement in itch, itch interference on sleep, and enhanced QoL [quality of life],” noted the authors. “This study captured the clinical benefit of lebrikizumab through the combined end point of physician-assessed clinical sign of skin clearance (EASI-75) and patient-reported outcome of improvement in itch (Pruritus NRS).”

The percentage of patients who achieved the combined endpoint was more than double for the lebrikizumab plus TCS group vs. the group on TCS alone, indicating that patients treated with lebrikizumab plus TCS “were more likely to experience improvement in skin symptoms and itch,” the investigators added.

The authors noted that most treatment-emergent adverse events “were nonserious, mild, or moderate in severity, and did not lead to study discontinuation.” These included conjunctivitis (4.8%), headache (4.8%), hypertension (2.8%), injection-site reactions (2.8%), and herpes infection (3.4%) – all of which occurred in 1.5% or less of patients in the placebo group.

“The higher incidence of conjunctivitis has also been reported in other biologics inhibiting IL [interleukin]–13 and/or IL-4 signaling, as well as lebrikizumab monotherapy studies,” they noted. The 4.8% rate of conjunctivitis reported in the combination study, they added, is “compared with 7.5% frequency in 16-week data from the lebrikizumab monotherapy studies. Although the mechanism remains unclear, it has been reported that conjunctival goblet cell scarcity due to IL-13 and IL-4 inhibition, and subsequent effects on the homeostasis of the conjunctival mucosal surface, results in ocular AEs [adverse events].”

“This truly is a time of great hope and promise for our patients with AD,” commented Zelma Chiesa Fuxench, MD, who was not involved in the study. “The advent of newer, targeted therapeutic agents for AD continues to revolutionize the treatment experience for our patients, offering the possibility of greater AD disease control with a favorable risk profile and less need for blood work monitoring compared to traditional systemic agents.”

On the basis of the study results, Dr. Chiesa Fuxench, of the department of dermatology at the University of Pennsylvania, Philadelphia, said in an interview that “lebrikizumab represents an additional option in the treatment armamentarium for providers who care for patients with AD.” She added that, “while head-to-head trials comparing lebrikizumab to dupilumab, the first FDA-approved biologic for AD, would be beneficial, to the best of my knowledge this data is currently lacking. However, based on the results of this study, we would expect lebrikizumab to work at least similarly to dupilumab, based on the reported improvements in IGA and EASI score.”

Additionally, lebrikizumab showed a favorable safety profile, “with most treatment-emergent adverse effects reported as nonserious and not leading to drug discontinuation,” she said. “Of interest to clinicians may be the reported rates of conjunctivitis in this study. Rates of conjunctivitis for lebrikizumab appear to be lower than those reported in the LIBERTY AD CHRONOS study for dupilumab – a finding that merits further scrutiny in my opinion, as this one of the most frequent treatment-emergent adverse events that I encounter in my clinical practice.”

The study was funded by Dermira, a subsidiary of Eli Lilly. Dr. Simpson reported personal fees and grants from multiple sources, including Dermira and Eli Lilly, the companies developing lebrikizumab. Several authors were employees of Eli Lilly. Dr. Fuxench disclosed serving as a consultant for the Asthma and Allergy Foundation of America, National Eczema Association, Pfizer, AbbVie, and Incyte, for which she has received honoraria for AD-related work. She is the recipient of research grants through Regeneron, Sanofi, Tioga, Vanda, Menlo Therapeutics, Leo Pharma, and Eli Lilly for work related to AD as well as honoraria for continuing medical education work related to AD sponsored through educational grants from Regeneron/Sanofi and Pfizer.

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

When it comes to treating atopic dermatitis (AD) in adults with topical therapies, new guidelines from the American Academy of Dermatology rate the existing evidence as “strong” for prescription moisturizers, topical calcineurin inhibitors, topical corticosteroids, and topical phosphodiesterase-4 (PDE-4) and Janus kinase (JAK) inhibitors. The guidelines also conditionally recommend the use of bathing and wet wrap therapy but recommend against the use of topical antimicrobials, antiseptics, and antihistamines.

The development updates the AAD’s 2014 recommendations for managing AD with topical therapies, published almost 9 years ago. “At that time, the only U.S. FDA–approved systemic medication for atopic dermatitis was prednisone – universally felt amongst dermatologists to be the least appropriate systemic medication for this condition, at least chronically,” Robert Sidbury, MD, MPH, who cochaired a 14-member multidisciplinary work group that assembled the updated guidelines, told this news organization in an interview.

“Since 2017, there have been two different biologic medications approved for moderate to severe AD (dupilumab and tralokinumab) with certainly a third or more right around the corner. There have been two new oral agents approved for moderate to severe AD – upadacitinib and abrocitinib – with others on the way,” he noted. While these are not topical therapies, the purview of the newly released guidelines, he said, “there have also been new topical medications approved since that time (crisaborole and ruxolitinib). It was high time for an update.”

For the new guidelines, which were published online in the Journal of the American Academy of Dermatology, Dr. Sidbury, chief of the division of dermatology at Seattle Children’s Hospital, guidelines cochair Dawn M. R. Davis, MD, a dermatologist at Mayo Clinic, Rochester, Minn., and colleagues conducted a systematic review of evidence regarding the use of nonprescription topical agents such as moisturizers, bathing practices, and wet wraps, as well as topical pharmacologic modalities such as corticosteroids, calcineurin inhibitors, JAK inhibitors, PDE-4 inhibitors, antimicrobials, and antihistamines.

Next, the work group applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for assessing the certainty of the evidence and formulating and grading clinical recommendations based on relevant randomized trials in the medical literature.
 

12 recommendations

Of the 12 recommendations made for adults with AD, the work group ranked 7 as “strong” based on the evidence reviewed, and the rest as “conditional.” The “strong” recommendations include the use of moisturizers; the use of tacrolimus 0.03% or 0.1%; the use of pimecrolimus 1% cream for mild to moderate AD; use of topical steroids; intermittent use of medium-potency topical corticosteroids as maintenance therapy to reduce flares and relapse; the use of the topical PDE-4 inhibitor crisaborole, and the use of the topical JAK inhibitor ruxolitinib.

Regarding ruxolitinib cream 1.5%, the work group advised that the treatment area “should not exceed 20% body surface area, and a maximum of 60 grams should be applied per week; these stipulations are aimed at reducing systemic absorption, as black box warnings include serious infections, mortality, malignancies (for example, lymphoma), major adverse cardiovascular events, and thrombosis.”

Conditional recommendations in the guidelines include those for bathing for treatment and maintenance and the use of wet dressings, and those against the use of topical antimicrobials, topical antihistamines, and topical antiseptics.

According to Dr. Sidbury, the topic of bathing generated robust discussion among the work group members. “Though [each group member] has strong opinions and individual practice styles, they were also able to recognize that the evidence is all that matters in a project like this, which led to a ‘conditional’ recommendation regarding bathing frequency backed by ‘low’ evidence,” he said. “While this may seem like ‘guidance’ that doesn’t ‘guide,’ I would argue it informs the guideline consumer exactly where we are in terms of this question and allows them to use their best judgment and experience as their true north here.”

In the realm of topical steroids, Dr. Sidbury said that topical steroid addiction (TSA) and topical steroid withdrawal (TSW) have been a “controversial but persistent concern” from some patients and providers. “Two systematic reviews of this topic were mentioned, and it was made clear that the evidence base [for the concepts] is weak,” he said. “With that important caveat ,the guideline committee delineated both a definition of TSW/TSA and potential risk factors.”

Dr. Sidbury marveled at the potential impact of newer medicines such as crisaborole and ruxolitinib on younger AD patients as well. Crisaborole is now Food and Drug Administration approved down to 3 months of age for mild to moderate AD. “This is extraordinary and expands treatment options for all providers at an age when parents and providers are most conservative in their practice,” he said. “Ruxolitinib, also nonsteroidal, is FDA approved for mild to moderate AD down to 12 years of age. Having spent a good percentage of my practice years either being able to offer only topical steroids, or later topical steroids and topical calcineurin inhibitors like tacrolimus or pimecrolimus, having additional options is wonderful.”

In the guidelines, the work group noted that “significant gaps remain” in current understanding of various topical AD therapies. “Studies are needed which examine quality of life and other patient-important outcomes, changes to the cutaneous microbiome, as well as long term follow-up, and use in special and diverse populations (e.g., pregnancy, lactation, immunosuppression, multiple comorbidities, skin of color, pediatric),” they wrote. “Furthermore, increased use of new systemic AD treatment options (dupilumab, tralokinumab, abrocitinib, upadacitinib) in patients with moderate to severe disease may result in a selection bias toward milder disease in current and future AD topical therapy studies.”

Use of topical therapies to manage AD in pediatric patients will be covered in a forthcoming AAD guideline. The first updated AD guideline, on comorbidities associated with AD in adults, was released in January 2022.

Dr. Sidbury reported that he serves as an advisory board member for Pfizer, a principal investigator for Regeneron, an investigator for Brickell Biotech and Galderma USA, and a consultant for Galderma Global and Microes. Other work group members reported having financial disclosures with many pharmaceutical companies.

When it comes to treating atopic dermatitis (AD) in adults with topical therapies, new guidelines from the American Academy of Dermatology rate the existing evidence as “strong” for prescription moisturizers, topical calcineurin inhibitors, topical corticosteroids, and topical phosphodiesterase-4 (PDE-4) and Janus kinase (JAK) inhibitors. The guidelines also conditionally recommend the use of bathing and wet wrap therapy but recommend against the use of topical antimicrobials, antiseptics, and antihistamines.

The development updates the AAD’s 2014 recommendations for managing AD with topical therapies, published almost 9 years ago. “At that time, the only U.S. FDA–approved systemic medication for atopic dermatitis was prednisone – universally felt amongst dermatologists to be the least appropriate systemic medication for this condition, at least chronically,” Robert Sidbury, MD, MPH, who cochaired a 14-member multidisciplinary work group that assembled the updated guidelines, told this news organization in an interview.

“Since 2017, there have been two different biologic medications approved for moderate to severe AD (dupilumab and tralokinumab) with certainly a third or more right around the corner. There have been two new oral agents approved for moderate to severe AD – upadacitinib and abrocitinib – with others on the way,” he noted. While these are not topical therapies, the purview of the newly released guidelines, he said, “there have also been new topical medications approved since that time (crisaborole and ruxolitinib). It was high time for an update.”

For the new guidelines, which were published online in the Journal of the American Academy of Dermatology, Dr. Sidbury, chief of the division of dermatology at Seattle Children’s Hospital, guidelines cochair Dawn M. R. Davis, MD, a dermatologist at Mayo Clinic, Rochester, Minn., and colleagues conducted a systematic review of evidence regarding the use of nonprescription topical agents such as moisturizers, bathing practices, and wet wraps, as well as topical pharmacologic modalities such as corticosteroids, calcineurin inhibitors, JAK inhibitors, PDE-4 inhibitors, antimicrobials, and antihistamines.

Next, the work group applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for assessing the certainty of the evidence and formulating and grading clinical recommendations based on relevant randomized trials in the medical literature.
 

12 recommendations

Of the 12 recommendations made for adults with AD, the work group ranked 7 as “strong” based on the evidence reviewed, and the rest as “conditional.” The “strong” recommendations include the use of moisturizers; the use of tacrolimus 0.03% or 0.1%; the use of pimecrolimus 1% cream for mild to moderate AD; use of topical steroids; intermittent use of medium-potency topical corticosteroids as maintenance therapy to reduce flares and relapse; the use of the topical PDE-4 inhibitor crisaborole, and the use of the topical JAK inhibitor ruxolitinib.

Regarding ruxolitinib cream 1.5%, the work group advised that the treatment area “should not exceed 20% body surface area, and a maximum of 60 grams should be applied per week; these stipulations are aimed at reducing systemic absorption, as black box warnings include serious infections, mortality, malignancies (for example, lymphoma), major adverse cardiovascular events, and thrombosis.”

Conditional recommendations in the guidelines include those for bathing for treatment and maintenance and the use of wet dressings, and those against the use of topical antimicrobials, topical antihistamines, and topical antiseptics.

According to Dr. Sidbury, the topic of bathing generated robust discussion among the work group members. “Though [each group member] has strong opinions and individual practice styles, they were also able to recognize that the evidence is all that matters in a project like this, which led to a ‘conditional’ recommendation regarding bathing frequency backed by ‘low’ evidence,” he said. “While this may seem like ‘guidance’ that doesn’t ‘guide,’ I would argue it informs the guideline consumer exactly where we are in terms of this question and allows them to use their best judgment and experience as their true north here.”

In the realm of topical steroids, Dr. Sidbury said that topical steroid addiction (TSA) and topical steroid withdrawal (TSW) have been a “controversial but persistent concern” from some patients and providers. “Two systematic reviews of this topic were mentioned, and it was made clear that the evidence base [for the concepts] is weak,” he said. “With that important caveat ,the guideline committee delineated both a definition of TSW/TSA and potential risk factors.”

Dr. Sidbury marveled at the potential impact of newer medicines such as crisaborole and ruxolitinib on younger AD patients as well. Crisaborole is now Food and Drug Administration approved down to 3 months of age for mild to moderate AD. “This is extraordinary and expands treatment options for all providers at an age when parents and providers are most conservative in their practice,” he said. “Ruxolitinib, also nonsteroidal, is FDA approved for mild to moderate AD down to 12 years of age. Having spent a good percentage of my practice years either being able to offer only topical steroids, or later topical steroids and topical calcineurin inhibitors like tacrolimus or pimecrolimus, having additional options is wonderful.”

In the guidelines, the work group noted that “significant gaps remain” in current understanding of various topical AD therapies. “Studies are needed which examine quality of life and other patient-important outcomes, changes to the cutaneous microbiome, as well as long term follow-up, and use in special and diverse populations (e.g., pregnancy, lactation, immunosuppression, multiple comorbidities, skin of color, pediatric),” they wrote. “Furthermore, increased use of new systemic AD treatment options (dupilumab, tralokinumab, abrocitinib, upadacitinib) in patients with moderate to severe disease may result in a selection bias toward milder disease in current and future AD topical therapy studies.”

Use of topical therapies to manage AD in pediatric patients will be covered in a forthcoming AAD guideline. The first updated AD guideline, on comorbidities associated with AD in adults, was released in January 2022.

Dr. Sidbury reported that he serves as an advisory board member for Pfizer, a principal investigator for Regeneron, an investigator for Brickell Biotech and Galderma USA, and a consultant for Galderma Global and Microes. Other work group members reported having financial disclosures with many pharmaceutical companies.

When it comes to treating atopic dermatitis (AD) in adults with topical therapies, new guidelines from the American Academy of Dermatology rate the existing evidence as “strong” for prescription moisturizers, topical calcineurin inhibitors, topical corticosteroids, and topical phosphodiesterase-4 (PDE-4) and Janus kinase (JAK) inhibitors. The guidelines also conditionally recommend the use of bathing and wet wrap therapy but recommend against the use of topical antimicrobials, antiseptics, and antihistamines.

The development updates the AAD’s 2014 recommendations for managing AD with topical therapies, published almost 9 years ago. “At that time, the only U.S. FDA–approved systemic medication for atopic dermatitis was prednisone – universally felt amongst dermatologists to be the least appropriate systemic medication for this condition, at least chronically,” Robert Sidbury, MD, MPH, who cochaired a 14-member multidisciplinary work group that assembled the updated guidelines, told this news organization in an interview.

“Since 2017, there have been two different biologic medications approved for moderate to severe AD (dupilumab and tralokinumab) with certainly a third or more right around the corner. There have been two new oral agents approved for moderate to severe AD – upadacitinib and abrocitinib – with others on the way,” he noted. While these are not topical therapies, the purview of the newly released guidelines, he said, “there have also been new topical medications approved since that time (crisaborole and ruxolitinib). It was high time for an update.”

For the new guidelines, which were published online in the Journal of the American Academy of Dermatology, Dr. Sidbury, chief of the division of dermatology at Seattle Children’s Hospital, guidelines cochair Dawn M. R. Davis, MD, a dermatologist at Mayo Clinic, Rochester, Minn., and colleagues conducted a systematic review of evidence regarding the use of nonprescription topical agents such as moisturizers, bathing practices, and wet wraps, as well as topical pharmacologic modalities such as corticosteroids, calcineurin inhibitors, JAK inhibitors, PDE-4 inhibitors, antimicrobials, and antihistamines.

Next, the work group applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach for assessing the certainty of the evidence and formulating and grading clinical recommendations based on relevant randomized trials in the medical literature.
 

12 recommendations

Of the 12 recommendations made for adults with AD, the work group ranked 7 as “strong” based on the evidence reviewed, and the rest as “conditional.” The “strong” recommendations include the use of moisturizers; the use of tacrolimus 0.03% or 0.1%; the use of pimecrolimus 1% cream for mild to moderate AD; use of topical steroids; intermittent use of medium-potency topical corticosteroids as maintenance therapy to reduce flares and relapse; the use of the topical PDE-4 inhibitor crisaborole, and the use of the topical JAK inhibitor ruxolitinib.

Regarding ruxolitinib cream 1.5%, the work group advised that the treatment area “should not exceed 20% body surface area, and a maximum of 60 grams should be applied per week; these stipulations are aimed at reducing systemic absorption, as black box warnings include serious infections, mortality, malignancies (for example, lymphoma), major adverse cardiovascular events, and thrombosis.”

Conditional recommendations in the guidelines include those for bathing for treatment and maintenance and the use of wet dressings, and those against the use of topical antimicrobials, topical antihistamines, and topical antiseptics.

According to Dr. Sidbury, the topic of bathing generated robust discussion among the work group members. “Though [each group member] has strong opinions and individual practice styles, they were also able to recognize that the evidence is all that matters in a project like this, which led to a ‘conditional’ recommendation regarding bathing frequency backed by ‘low’ evidence,” he said. “While this may seem like ‘guidance’ that doesn’t ‘guide,’ I would argue it informs the guideline consumer exactly where we are in terms of this question and allows them to use their best judgment and experience as their true north here.”

In the realm of topical steroids, Dr. Sidbury said that topical steroid addiction (TSA) and topical steroid withdrawal (TSW) have been a “controversial but persistent concern” from some patients and providers. “Two systematic reviews of this topic were mentioned, and it was made clear that the evidence base [for the concepts] is weak,” he said. “With that important caveat ,the guideline committee delineated both a definition of TSW/TSA and potential risk factors.”

Dr. Sidbury marveled at the potential impact of newer medicines such as crisaborole and ruxolitinib on younger AD patients as well. Crisaborole is now Food and Drug Administration approved down to 3 months of age for mild to moderate AD. “This is extraordinary and expands treatment options for all providers at an age when parents and providers are most conservative in their practice,” he said. “Ruxolitinib, also nonsteroidal, is FDA approved for mild to moderate AD down to 12 years of age. Having spent a good percentage of my practice years either being able to offer only topical steroids, or later topical steroids and topical calcineurin inhibitors like tacrolimus or pimecrolimus, having additional options is wonderful.”

In the guidelines, the work group noted that “significant gaps remain” in current understanding of various topical AD therapies. “Studies are needed which examine quality of life and other patient-important outcomes, changes to the cutaneous microbiome, as well as long term follow-up, and use in special and diverse populations (e.g., pregnancy, lactation, immunosuppression, multiple comorbidities, skin of color, pediatric),” they wrote. “Furthermore, increased use of new systemic AD treatment options (dupilumab, tralokinumab, abrocitinib, upadacitinib) in patients with moderate to severe disease may result in a selection bias toward milder disease in current and future AD topical therapy studies.”

Use of topical therapies to manage AD in pediatric patients will be covered in a forthcoming AAD guideline. The first updated AD guideline, on comorbidities associated with AD in adults, was released in January 2022.

Dr. Sidbury reported that he serves as an advisory board member for Pfizer, a principal investigator for Regeneron, an investigator for Brickell Biotech and Galderma USA, and a consultant for Galderma Global and Microes. Other work group members reported having financial disclosures with many pharmaceutical companies.

When I hear about a new drug for inflammatory skin disease that has a novel target, the first thing I do is Google what happens when you have a deficiency in that pathway. For OX40, the first thing that comes up is "inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood."¹ That doesn't make this target seem appealing to me. While I might use a new drug targeting this pathway if other options fail, drugs targeting this pathway would not be my first choice, even if clinical trial safety data looked good. Clinical trials are powered to assess efficacy and common safety issues but tend not to be large enough to fully characterize rare risks.

Black box warnings on topical calcineurin inhibitors seem dumb to me. I think black box warnings on topical calcineurin inhibitors would be truly ridiculous, even laughable, except that laughing is not appropriate because these misguided warnings may be hurting our patients. These black box warnings on topical calcineurin inhibitors may exemplify the limitations of governmental bureaucracies. There doesn't seem to be a strong rationale for why these black box warnings were placed on topical calcineurin inhibitors initially. Why regulators haven't removed these black box warnings since then is baffling, as topical calcineurin inhibitors are considerably safer for patients than the alternative, topical corticosteroids. We have good evidence that topical calcineurin inhibitors do not cause cancer in our patients. The continued presence of black box warnings on these products may undermine the credibility of FDA-mandated black box warnings on other products.

Hedderson and colleagues state, in a study of cardiovascular events and atopic dermatitis, "VTE [venous thromboembolism] and DVT [deep vein thrombosis] IRs [incidence rates] were markedly higher in this study than have been observed in the general US adult population (VTE: 2.0 [current study] vs. 1.1; DVT: 1.6 [current study] vs. 0.66 per 1000 person-years." I think that's misleading. The difference of only 1 in 1000 doesn't seem like a markedly higher rate to me and it's also unlikely to be clinically meaningful. Even if there is some increased relative risk of some type of cardiovascular event, even if the rate is doubled, that doesn't mean we need to screen or intervene. We need to be mindful of the absolute risks and not be moved by relative risks. We need to see cost-effectiveness studies showing that an intervention is valuable before we conclude that we should be doing some screening or intervention to chase down and increase the relative risk for some potential adverse event.

Additional Reference

1. Byun M, Ma CS, Akçay A et al. Inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood. J Exp Med. 2013;210(9):1743–1759. Doi: 10.1084/jem.20130592

When I hear about a new drug for inflammatory skin disease that has a novel target, the first thing I do is Google what happens when you have a deficiency in that pathway. For OX40, the first thing that comes up is "inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood."¹ That doesn't make this target seem appealing to me. While I might use a new drug targeting this pathway if other options fail, drugs targeting this pathway would not be my first choice, even if clinical trial safety data looked good. Clinical trials are powered to assess efficacy and common safety issues but tend not to be large enough to fully characterize rare risks.

Black box warnings on topical calcineurin inhibitors seem dumb to me. I think black box warnings on topical calcineurin inhibitors would be truly ridiculous, even laughable, except that laughing is not appropriate because these misguided warnings may be hurting our patients. These black box warnings on topical calcineurin inhibitors may exemplify the limitations of governmental bureaucracies. There doesn't seem to be a strong rationale for why these black box warnings were placed on topical calcineurin inhibitors initially. Why regulators haven't removed these black box warnings since then is baffling, as topical calcineurin inhibitors are considerably safer for patients than the alternative, topical corticosteroids. We have good evidence that topical calcineurin inhibitors do not cause cancer in our patients. The continued presence of black box warnings on these products may undermine the credibility of FDA-mandated black box warnings on other products.

Hedderson and colleagues state, in a study of cardiovascular events and atopic dermatitis, "VTE [venous thromboembolism] and DVT [deep vein thrombosis] IRs [incidence rates] were markedly higher in this study than have been observed in the general US adult population (VTE: 2.0 [current study] vs. 1.1; DVT: 1.6 [current study] vs. 0.66 per 1000 person-years." I think that's misleading. The difference of only 1 in 1000 doesn't seem like a markedly higher rate to me and it's also unlikely to be clinically meaningful. Even if there is some increased relative risk of some type of cardiovascular event, even if the rate is doubled, that doesn't mean we need to screen or intervene. We need to be mindful of the absolute risks and not be moved by relative risks. We need to see cost-effectiveness studies showing that an intervention is valuable before we conclude that we should be doing some screening or intervention to chase down and increase the relative risk for some potential adverse event.

Additional Reference

1. Byun M, Ma CS, Akçay A et al. Inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood. J Exp Med. 2013;210(9):1743–1759. Doi: 10.1084/jem.20130592

When I hear about a new drug for inflammatory skin disease that has a novel target, the first thing I do is Google what happens when you have a deficiency in that pathway. For OX40, the first thing that comes up is "inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood."¹ That doesn't make this target seem appealing to me. While I might use a new drug targeting this pathway if other options fail, drugs targeting this pathway would not be my first choice, even if clinical trial safety data looked good. Clinical trials are powered to assess efficacy and common safety issues but tend not to be large enough to fully characterize rare risks.

Black box warnings on topical calcineurin inhibitors seem dumb to me. I think black box warnings on topical calcineurin inhibitors would be truly ridiculous, even laughable, except that laughing is not appropriate because these misguided warnings may be hurting our patients. These black box warnings on topical calcineurin inhibitors may exemplify the limitations of governmental bureaucracies. There doesn't seem to be a strong rationale for why these black box warnings were placed on topical calcineurin inhibitors initially. Why regulators haven't removed these black box warnings since then is baffling, as topical calcineurin inhibitors are considerably safer for patients than the alternative, topical corticosteroids. We have good evidence that topical calcineurin inhibitors do not cause cancer in our patients. The continued presence of black box warnings on these products may undermine the credibility of FDA-mandated black box warnings on other products.

Hedderson and colleagues state, in a study of cardiovascular events and atopic dermatitis, "VTE [venous thromboembolism] and DVT [deep vein thrombosis] IRs [incidence rates] were markedly higher in this study than have been observed in the general US adult population (VTE: 2.0 [current study] vs. 1.1; DVT: 1.6 [current study] vs. 0.66 per 1000 person-years." I think that's misleading. The difference of only 1 in 1000 doesn't seem like a markedly higher rate to me and it's also unlikely to be clinically meaningful. Even if there is some increased relative risk of some type of cardiovascular event, even if the rate is doubled, that doesn't mean we need to screen or intervene. We need to be mindful of the absolute risks and not be moved by relative risks. We need to see cost-effectiveness studies showing that an intervention is valuable before we conclude that we should be doing some screening or intervention to chase down and increase the relative risk for some potential adverse event.

Additional Reference

1. Byun M, Ma CS, Akçay A et al. Inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood. J Exp Med. 2013;210(9):1743–1759. Doi: 10.1084/jem.20130592

An updated Cochrane Review on infant skincare interventions for preventing atopic dermatitis (AD) and food allergy has reaffirmed previous study findings indicating a lack of benefit, and strengthened the suggestion of harm associated with early use of emollients.

The document, published in November 2022, updates a February 2021 version, said Robert Boyle, MD, PhD, senior author of the Cochrane Review and a pediatric allergist at Imperial College London. “The differences were slight,” he told this news organization. “Mainly, we had a little more data about food allergy outcomes, which slightly strengthened the concern about a possible increase in food allergy with emollients; and we had some new genetic information, which allowed us to add some further interaction analyses and confirm that chromosome 11 intergenic variant rs2212434 doesn’t seem to impact the effect – or lack of effect – of emollient on eczema development.”

The updated Cochrane Review concludes that, “based on low‐ to moderate-certainty evidence, skin care interventions such as emollients during the first year of life in healthy infants are probably not effective for preventing eczema; may increase risk of food allergy; and probably increase risk of skin infection.”

The latest publication should strengthen clinicians’ confidence in not recommending emollient use for preventing AD in at-risk infants – however, that message is being diluted by a stream of contradictory conclusions from poor-quality systematic reviews, say Dr. Boyle and two coauthors. “It’s a systematic problem of people churning out endless systematic reviews without much rigor,” explained the lead author Maeve Kelleher, MD, from Children’s Health Ireland, Crumlin. There have been “misleading systematic reviews published, often in high-ranking journals,” agreed Dr. Boyle.

“I have been an advocate of systematic reviews for the last 20 years, but they have gone completely out of control,” added Hywel Williams, MD, PhD, another of the Cochrane Review coauthors, who is professor of dermato-epidemiology and codirector of the Centre of Evidence Based Dermatology, at Nottingham (England) University Hospitals NHS Trust. In an editorial, published last year, Dr. Williams even posed the question: “Are Dermatology Systematic Reviews Spinning Out of Control?” in which he blamed “the misrepresentation of study results” – which he calls “the sin of spin” – for degrading the quality of science in dermatology.

“The field has become a ‘sausage machine’ industry that undermines the value of systematic reviews in providing a summary of the best evidence to inform patient care,” he wrote. “Fewer systematic reviews are needed in dermatology,” but “better ones” are needed, he continued, calling for all systematic reviews to be registered prospectively, and reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.

Earlier this year, in a letter to the editor, Dr. Kelleher, Dr. Boyle, Dr. Williams, and several others outlined their concerns after a systemic review and meta-analysis was published, “which came to very different conclusions” than their Cochrane Review.

“It is quite common to see non-Cochrane reviews published in leading specialty journals, which interpret data in a more positive light than Cochrane reviews, which have assessed a similar dataset/topic,” Dr. Boyle said in the interview.

Such concerns also apply to the publication of another systematic review that was recently published. “Overall, early application of emollients is an effective strategy for preventing AD development in high-risk infants,” reported senior author Xiaojing Kang, MD, PhD, from People’s Hospital of Xinjiang Uygur Autonomous Region, Urumchi, China, and coauthors, who could not be reached for comment. In their discussion, the authors cite several criticisms of the Cochrane Review: that it included two meeting abstracts and two “ineligible” studies; did not do subgroup analysis of high-risk infants; did not look at different types of emollients; and did not examine the risk of food sensitization.

“A Cochrane Review can be quite a large and complex document to negotiate for those who are not very familiar with Cochrane’s methodology,” said Dr. Boyle. He dismissed the criticism, saying “we did do subgroup analysis of high risk infants, we did look at different types of emollient, and we did look at food sensitization and food allergy risk. We only included eligible studies. … Certainly we would include abstracts of trials, which are not reported in any other form, in order to capture as complete a picture.”

Ultimately, Dr. Boyle said, the discrepancy in conclusions between such systematic reviews and the Cochrane Review relates to quality of methodology. “Our Cochrane review was an individual participant data (IPD) meta-analysis, meaning that authors of the main trials in this area shared their original datasets with us,” he said in the interview. “This is the ‘gold standard’ in systematic reviews, and allowed us to check data/ query inconsistencies and to apply a single-analysis methodology across all studies. It also allowed us to undertake some analyses, which are just not possible in aggregate data analysis based on published work without IPD.”

The most recently published systematic review had no registered protocol, “so, there is no transparency about the methods used,” he noted. “It is free and simple to register a protocol – multiple websites such as PROSPERO, open science framework, and zenodo allow this,” he said “In the journal I edit, we use availability of a registered protocol as a marker of quality. We find that systematic reviews with no registered protocol are almost universally poor quality.”

Dr. Williams is a founding member and coordinating editor of the Cochrane Skin Group 1998 to 2017. Dr. Boyle was paid by Cochrane for senior editor work, until recently, and had no other relevant disclosures. Dr. Kelleher had no relevant disclosures.

An updated Cochrane Review on infant skincare interventions for preventing atopic dermatitis (AD) and food allergy has reaffirmed previous study findings indicating a lack of benefit, and strengthened the suggestion of harm associated with early use of emollients.

The document, published in November 2022, updates a February 2021 version, said Robert Boyle, MD, PhD, senior author of the Cochrane Review and a pediatric allergist at Imperial College London. “The differences were slight,” he told this news organization. “Mainly, we had a little more data about food allergy outcomes, which slightly strengthened the concern about a possible increase in food allergy with emollients; and we had some new genetic information, which allowed us to add some further interaction analyses and confirm that chromosome 11 intergenic variant rs2212434 doesn’t seem to impact the effect – or lack of effect – of emollient on eczema development.”

The updated Cochrane Review concludes that, “based on low‐ to moderate-certainty evidence, skin care interventions such as emollients during the first year of life in healthy infants are probably not effective for preventing eczema; may increase risk of food allergy; and probably increase risk of skin infection.”

The latest publication should strengthen clinicians’ confidence in not recommending emollient use for preventing AD in at-risk infants – however, that message is being diluted by a stream of contradictory conclusions from poor-quality systematic reviews, say Dr. Boyle and two coauthors. “It’s a systematic problem of people churning out endless systematic reviews without much rigor,” explained the lead author Maeve Kelleher, MD, from Children’s Health Ireland, Crumlin. There have been “misleading systematic reviews published, often in high-ranking journals,” agreed Dr. Boyle.

“I have been an advocate of systematic reviews for the last 20 years, but they have gone completely out of control,” added Hywel Williams, MD, PhD, another of the Cochrane Review coauthors, who is professor of dermato-epidemiology and codirector of the Centre of Evidence Based Dermatology, at Nottingham (England) University Hospitals NHS Trust. In an editorial, published last year, Dr. Williams even posed the question: “Are Dermatology Systematic Reviews Spinning Out of Control?” in which he blamed “the misrepresentation of study results” – which he calls “the sin of spin” – for degrading the quality of science in dermatology.

“The field has become a ‘sausage machine’ industry that undermines the value of systematic reviews in providing a summary of the best evidence to inform patient care,” he wrote. “Fewer systematic reviews are needed in dermatology,” but “better ones” are needed, he continued, calling for all systematic reviews to be registered prospectively, and reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.

Earlier this year, in a letter to the editor, Dr. Kelleher, Dr. Boyle, Dr. Williams, and several others outlined their concerns after a systemic review and meta-analysis was published, “which came to very different conclusions” than their Cochrane Review.

“It is quite common to see non-Cochrane reviews published in leading specialty journals, which interpret data in a more positive light than Cochrane reviews, which have assessed a similar dataset/topic,” Dr. Boyle said in the interview.

Such concerns also apply to the publication of another systematic review that was recently published. “Overall, early application of emollients is an effective strategy for preventing AD development in high-risk infants,” reported senior author Xiaojing Kang, MD, PhD, from People’s Hospital of Xinjiang Uygur Autonomous Region, Urumchi, China, and coauthors, who could not be reached for comment. In their discussion, the authors cite several criticisms of the Cochrane Review: that it included two meeting abstracts and two “ineligible” studies; did not do subgroup analysis of high-risk infants; did not look at different types of emollients; and did not examine the risk of food sensitization.

“A Cochrane Review can be quite a large and complex document to negotiate for those who are not very familiar with Cochrane’s methodology,” said Dr. Boyle. He dismissed the criticism, saying “we did do subgroup analysis of high risk infants, we did look at different types of emollient, and we did look at food sensitization and food allergy risk. We only included eligible studies. … Certainly we would include abstracts of trials, which are not reported in any other form, in order to capture as complete a picture.”

Ultimately, Dr. Boyle said, the discrepancy in conclusions between such systematic reviews and the Cochrane Review relates to quality of methodology. “Our Cochrane review was an individual participant data (IPD) meta-analysis, meaning that authors of the main trials in this area shared their original datasets with us,” he said in the interview. “This is the ‘gold standard’ in systematic reviews, and allowed us to check data/ query inconsistencies and to apply a single-analysis methodology across all studies. It also allowed us to undertake some analyses, which are just not possible in aggregate data analysis based on published work without IPD.”

The most recently published systematic review had no registered protocol, “so, there is no transparency about the methods used,” he noted. “It is free and simple to register a protocol – multiple websites such as PROSPERO, open science framework, and zenodo allow this,” he said “In the journal I edit, we use availability of a registered protocol as a marker of quality. We find that systematic reviews with no registered protocol are almost universally poor quality.”

Dr. Williams is a founding member and coordinating editor of the Cochrane Skin Group 1998 to 2017. Dr. Boyle was paid by Cochrane for senior editor work, until recently, and had no other relevant disclosures. Dr. Kelleher had no relevant disclosures.

An updated Cochrane Review on infant skincare interventions for preventing atopic dermatitis (AD) and food allergy has reaffirmed previous study findings indicating a lack of benefit, and strengthened the suggestion of harm associated with early use of emollients.

The document, published in November 2022, updates a February 2021 version, said Robert Boyle, MD, PhD, senior author of the Cochrane Review and a pediatric allergist at Imperial College London. “The differences were slight,” he told this news organization. “Mainly, we had a little more data about food allergy outcomes, which slightly strengthened the concern about a possible increase in food allergy with emollients; and we had some new genetic information, which allowed us to add some further interaction analyses and confirm that chromosome 11 intergenic variant rs2212434 doesn’t seem to impact the effect – or lack of effect – of emollient on eczema development.”

The updated Cochrane Review concludes that, “based on low‐ to moderate-certainty evidence, skin care interventions such as emollients during the first year of life in healthy infants are probably not effective for preventing eczema; may increase risk of food allergy; and probably increase risk of skin infection.”

The latest publication should strengthen clinicians’ confidence in not recommending emollient use for preventing AD in at-risk infants – however, that message is being diluted by a stream of contradictory conclusions from poor-quality systematic reviews, say Dr. Boyle and two coauthors. “It’s a systematic problem of people churning out endless systematic reviews without much rigor,” explained the lead author Maeve Kelleher, MD, from Children’s Health Ireland, Crumlin. There have been “misleading systematic reviews published, often in high-ranking journals,” agreed Dr. Boyle.

“I have been an advocate of systematic reviews for the last 20 years, but they have gone completely out of control,” added Hywel Williams, MD, PhD, another of the Cochrane Review coauthors, who is professor of dermato-epidemiology and codirector of the Centre of Evidence Based Dermatology, at Nottingham (England) University Hospitals NHS Trust. In an editorial, published last year, Dr. Williams even posed the question: “Are Dermatology Systematic Reviews Spinning Out of Control?” in which he blamed “the misrepresentation of study results” – which he calls “the sin of spin” – for degrading the quality of science in dermatology.

“The field has become a ‘sausage machine’ industry that undermines the value of systematic reviews in providing a summary of the best evidence to inform patient care,” he wrote. “Fewer systematic reviews are needed in dermatology,” but “better ones” are needed, he continued, calling for all systematic reviews to be registered prospectively, and reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.

Earlier this year, in a letter to the editor, Dr. Kelleher, Dr. Boyle, Dr. Williams, and several others outlined their concerns after a systemic review and meta-analysis was published, “which came to very different conclusions” than their Cochrane Review.

“It is quite common to see non-Cochrane reviews published in leading specialty journals, which interpret data in a more positive light than Cochrane reviews, which have assessed a similar dataset/topic,” Dr. Boyle said in the interview.

Such concerns also apply to the publication of another systematic review that was recently published. “Overall, early application of emollients is an effective strategy for preventing AD development in high-risk infants,” reported senior author Xiaojing Kang, MD, PhD, from People’s Hospital of Xinjiang Uygur Autonomous Region, Urumchi, China, and coauthors, who could not be reached for comment. In their discussion, the authors cite several criticisms of the Cochrane Review: that it included two meeting abstracts and two “ineligible” studies; did not do subgroup analysis of high-risk infants; did not look at different types of emollients; and did not examine the risk of food sensitization.

“A Cochrane Review can be quite a large and complex document to negotiate for those who are not very familiar with Cochrane’s methodology,” said Dr. Boyle. He dismissed the criticism, saying “we did do subgroup analysis of high risk infants, we did look at different types of emollient, and we did look at food sensitization and food allergy risk. We only included eligible studies. … Certainly we would include abstracts of trials, which are not reported in any other form, in order to capture as complete a picture.”

Ultimately, Dr. Boyle said, the discrepancy in conclusions between such systematic reviews and the Cochrane Review relates to quality of methodology. “Our Cochrane review was an individual participant data (IPD) meta-analysis, meaning that authors of the main trials in this area shared their original datasets with us,” he said in the interview. “This is the ‘gold standard’ in systematic reviews, and allowed us to check data/ query inconsistencies and to apply a single-analysis methodology across all studies. It also allowed us to undertake some analyses, which are just not possible in aggregate data analysis based on published work without IPD.”

The most recently published systematic review had no registered protocol, “so, there is no transparency about the methods used,” he noted. “It is free and simple to register a protocol – multiple websites such as PROSPERO, open science framework, and zenodo allow this,” he said “In the journal I edit, we use availability of a registered protocol as a marker of quality. We find that systematic reviews with no registered protocol are almost universally poor quality.”

Dr. Williams is a founding member and coordinating editor of the Cochrane Skin Group 1998 to 2017. Dr. Boyle was paid by Cochrane for senior editor work, until recently, and had no other relevant disclosures. Dr. Kelleher had no relevant disclosures.

The patient is diagnosed with atopic dermatitis (AD) complicated by skin infection. 

AD is the most common chronic pruritic inflammatory skin disorder that affects both children and adults. In the United States, up to 18% of children and 7% of adults are affected. Atopic dermatitis is associated with diminished quality of life, including disruption in activities of daily living, sleep disturbance, depression, and anxiety. Moreover, patients with AD have an increased risk for infections. A significantly higher prevalence of cutaneous and systemic infections is seen in patients with AD compared with individuals without AD.

Bacterial infections are common in AD and are usually caused by Staphylococcus aureus. Examples include impetigo, which typically presents with oozing serum that dries, resulting in a honey-crusted appearance surrounded by an erythematous base. Fluid-filled blisters (bullous impetigo) may also be present, which can be mistaken for eczema herpeticum (EH).

Nonpurulent skin and soft tissue infections (SSTIs) include erysipelas and cellulitis. In most cases, these infections begin in a focal skin area but spread rapidly across the affected sites such as the arms, legs, trunk, or face. Signs typically include focal erythema, swelling, warmth, and tenderness; fever and bacteremia may also be present. 

Purulent SSTIs present as skin abscesses, involving fluctuant or nonfluctuant nodules or pustules surrounded by an erythematous swelling; the lesions may also be tender and warm. Methicillin-resistant S aureus (MRSA) is a common cause of purulent SSTIs. 

Systemic complications of SSTI in AD may include bacteremia, osteomyelitis, septic arthritis, or bursitis; less often, endocarditis and staphylococcal scalded skin syndrome may occur. Clinicians should maintain a high index of suspicion for these complications in patients who present with an ill-looking appearance, lethargy, focal point tenderness of the bone, joint swelling, heart murmur, and widespread desquamation. Persistent elevated inflammatory markers (eg, C-reactive protein or erythrocyte sedimentation rate) should increase the level of suspicion.

Nonbacterial infections can occur concurrently with bacterial skin infections and the two can be difficult to distinguish. For example, EH results from the local spread of herpes simplex virus, which has a predilection for AD lesions. Early during EH, skin lesions appear as superficial clusters of dome‐shaped vesicles and/or small, round, punched‐out erosions. With progression, the lesions may become superficially infected with S aureus and may develop the characteristic honey-colored scale of impetigo.

Factors that contribute to the increased prevalence of infections in AD include skin barrier defects, suppression of cutaneous innate immunity by type 2 inflammation, S aureus colonization, allergen sensitivity, filaggrin loss-of-function mutation, and cutaneous dysbiosis. 

Daily skin hydration and moisturization is a fundamental component of treatment for any patient with AD, both to treat the AD and prevent infection. Patients with AD should bathe daily, followed by gentle drying and application of a moisturizer or a prescribed topical medication. Standard topical anti-inflammatory medications, including topical corticosteroids and topical calcineurin inhibitors, improve skin barrier functions and have been reported to decrease S aureus colonization in AD lesions. Similarly, the monoclonal antibody dupilumab has been shown to decrease S aureus colonization and increase microbial diversity.
 
In the presence of an uncomplicated, nonpurulent skin infection, a beta-lactam antibiotic that covers both S aureus and beta-hemolytic streptococci (eg, cefazolin or cephalexin) may be sufficient, depending on clinical response or culture and in consideration of local epidemiology and resistance patterns. For patients with AD who present with a skin abscess, history of MRSA colonization, close contacts with a history of skin infections, or recent hospitalization, coverage for MRSA should be considered. Acceptable oral options for MRSA skin infections include clindamycin, doxycycline, trimethoprim-sulfamethoxazole, and linezolid, assuming that the isolate is susceptible in vitro. Topical mupirocin ointment can be used for patients with minor, localized skin infections (eg, impetigo). 

William D. James, MD, Professor, Department of Dermatology, University of Pennsylvania, Philadelphia.

Disclosure: William D. James, MD, has disclosed the following relevant financial relationships:
Received income in an amount equal to or greater than $250 from: Elsevier.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The patient is diagnosed with atopic dermatitis (AD) complicated by skin infection. 

AD is the most common chronic pruritic inflammatory skin disorder that affects both children and adults. In the United States, up to 18% of children and 7% of adults are affected. Atopic dermatitis is associated with diminished quality of life, including disruption in activities of daily living, sleep disturbance, depression, and anxiety. Moreover, patients with AD have an increased risk for infections. A significantly higher prevalence of cutaneous and systemic infections is seen in patients with AD compared with individuals without AD.

Bacterial infections are common in AD and are usually caused by Staphylococcus aureus. Examples include impetigo, which typically presents with oozing serum that dries, resulting in a honey-crusted appearance surrounded by an erythematous base. Fluid-filled blisters (bullous impetigo) may also be present, which can be mistaken for eczema herpeticum (EH).

Nonpurulent skin and soft tissue infections (SSTIs) include erysipelas and cellulitis. In most cases, these infections begin in a focal skin area but spread rapidly across the affected sites such as the arms, legs, trunk, or face. Signs typically include focal erythema, swelling, warmth, and tenderness; fever and bacteremia may also be present. 

Purulent SSTIs present as skin abscesses, involving fluctuant or nonfluctuant nodules or pustules surrounded by an erythematous swelling; the lesions may also be tender and warm. Methicillin-resistant S aureus (MRSA) is a common cause of purulent SSTIs. 

Systemic complications of SSTI in AD may include bacteremia, osteomyelitis, septic arthritis, or bursitis; less often, endocarditis and staphylococcal scalded skin syndrome may occur. Clinicians should maintain a high index of suspicion for these complications in patients who present with an ill-looking appearance, lethargy, focal point tenderness of the bone, joint swelling, heart murmur, and widespread desquamation. Persistent elevated inflammatory markers (eg, C-reactive protein or erythrocyte sedimentation rate) should increase the level of suspicion.

Nonbacterial infections can occur concurrently with bacterial skin infections and the two can be difficult to distinguish. For example, EH results from the local spread of herpes simplex virus, which has a predilection for AD lesions. Early during EH, skin lesions appear as superficial clusters of dome‐shaped vesicles and/or small, round, punched‐out erosions. With progression, the lesions may become superficially infected with S aureus and may develop the characteristic honey-colored scale of impetigo.

Factors that contribute to the increased prevalence of infections in AD include skin barrier defects, suppression of cutaneous innate immunity by type 2 inflammation, S aureus colonization, allergen sensitivity, filaggrin loss-of-function mutation, and cutaneous dysbiosis. 

Daily skin hydration and moisturization is a fundamental component of treatment for any patient with AD, both to treat the AD and prevent infection. Patients with AD should bathe daily, followed by gentle drying and application of a moisturizer or a prescribed topical medication. Standard topical anti-inflammatory medications, including topical corticosteroids and topical calcineurin inhibitors, improve skin barrier functions and have been reported to decrease S aureus colonization in AD lesions. Similarly, the monoclonal antibody dupilumab has been shown to decrease S aureus colonization and increase microbial diversity.
 
In the presence of an uncomplicated, nonpurulent skin infection, a beta-lactam antibiotic that covers both S aureus and beta-hemolytic streptococci (eg, cefazolin or cephalexin) may be sufficient, depending on clinical response or culture and in consideration of local epidemiology and resistance patterns. For patients with AD who present with a skin abscess, history of MRSA colonization, close contacts with a history of skin infections, or recent hospitalization, coverage for MRSA should be considered. Acceptable oral options for MRSA skin infections include clindamycin, doxycycline, trimethoprim-sulfamethoxazole, and linezolid, assuming that the isolate is susceptible in vitro. Topical mupirocin ointment can be used for patients with minor, localized skin infections (eg, impetigo). 

William D. James, MD, Professor, Department of Dermatology, University of Pennsylvania, Philadelphia.

Disclosure: William D. James, MD, has disclosed the following relevant financial relationships:
Received income in an amount equal to or greater than $250 from: Elsevier.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The patient is diagnosed with atopic dermatitis (AD) complicated by skin infection. 

AD is the most common chronic pruritic inflammatory skin disorder that affects both children and adults. In the United States, up to 18% of children and 7% of adults are affected. Atopic dermatitis is associated with diminished quality of life, including disruption in activities of daily living, sleep disturbance, depression, and anxiety. Moreover, patients with AD have an increased risk for infections. A significantly higher prevalence of cutaneous and systemic infections is seen in patients with AD compared with individuals without AD.

Bacterial infections are common in AD and are usually caused by Staphylococcus aureus. Examples include impetigo, which typically presents with oozing serum that dries, resulting in a honey-crusted appearance surrounded by an erythematous base. Fluid-filled blisters (bullous impetigo) may also be present, which can be mistaken for eczema herpeticum (EH).

Nonpurulent skin and soft tissue infections (SSTIs) include erysipelas and cellulitis. In most cases, these infections begin in a focal skin area but spread rapidly across the affected sites such as the arms, legs, trunk, or face. Signs typically include focal erythema, swelling, warmth, and tenderness; fever and bacteremia may also be present. 

Purulent SSTIs present as skin abscesses, involving fluctuant or nonfluctuant nodules or pustules surrounded by an erythematous swelling; the lesions may also be tender and warm. Methicillin-resistant S aureus (MRSA) is a common cause of purulent SSTIs. 

Systemic complications of SSTI in AD may include bacteremia, osteomyelitis, septic arthritis, or bursitis; less often, endocarditis and staphylococcal scalded skin syndrome may occur. Clinicians should maintain a high index of suspicion for these complications in patients who present with an ill-looking appearance, lethargy, focal point tenderness of the bone, joint swelling, heart murmur, and widespread desquamation. Persistent elevated inflammatory markers (eg, C-reactive protein or erythrocyte sedimentation rate) should increase the level of suspicion.

Nonbacterial infections can occur concurrently with bacterial skin infections and the two can be difficult to distinguish. For example, EH results from the local spread of herpes simplex virus, which has a predilection for AD lesions. Early during EH, skin lesions appear as superficial clusters of dome‐shaped vesicles and/or small, round, punched‐out erosions. With progression, the lesions may become superficially infected with S aureus and may develop the characteristic honey-colored scale of impetigo.

Factors that contribute to the increased prevalence of infections in AD include skin barrier defects, suppression of cutaneous innate immunity by type 2 inflammation, S aureus colonization, allergen sensitivity, filaggrin loss-of-function mutation, and cutaneous dysbiosis. 

Daily skin hydration and moisturization is a fundamental component of treatment for any patient with AD, both to treat the AD and prevent infection. Patients with AD should bathe daily, followed by gentle drying and application of a moisturizer or a prescribed topical medication. Standard topical anti-inflammatory medications, including topical corticosteroids and topical calcineurin inhibitors, improve skin barrier functions and have been reported to decrease S aureus colonization in AD lesions. Similarly, the monoclonal antibody dupilumab has been shown to decrease S aureus colonization and increase microbial diversity.
 
In the presence of an uncomplicated, nonpurulent skin infection, a beta-lactam antibiotic that covers both S aureus and beta-hemolytic streptococci (eg, cefazolin or cephalexin) may be sufficient, depending on clinical response or culture and in consideration of local epidemiology and resistance patterns. For patients with AD who present with a skin abscess, history of MRSA colonization, close contacts with a history of skin infections, or recent hospitalization, coverage for MRSA should be considered. Acceptable oral options for MRSA skin infections include clindamycin, doxycycline, trimethoprim-sulfamethoxazole, and linezolid, assuming that the isolate is susceptible in vitro. Topical mupirocin ointment can be used for patients with minor, localized skin infections (eg, impetigo). 

William D. James, MD, Professor, Department of Dermatology, University of Pennsylvania, Philadelphia.

Disclosure: William D. James, MD, has disclosed the following relevant financial relationships:
Received income in an amount equal to or greater than $250 from: Elsevier.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Phototherapy—particularly UVB phototherapy, which utilizes UVB rays of specific wavelengths within the UV spectrum—is indicated for a wide variety of dermatoses. In-office and at-home UVB treatments commonly are used, as are salon tanning and sunbathing. When selecting a form of phototherapy, patients are likely to consider safety, cost, effectiveness, insurance issues, and convenience. Research on patient preferences; the reasons for these preferences; and which options patients perceive to be the safest, most cost-effective, efficacious, and convenient is lacking. We aimed to assess the forms of phototherapy that patients would most consider using; the factors influencing patient preferences; and the forms patients perceived as the safest and most cost-effective, efficacious, and convenient.

Methods

Study Participants—We recruited 500 Amazon Mechanical Turk users who were 18 years or older to complete our REDCap-generated survey. The study was approved by the Wake Forest University institutional review board (Winston-Salem, North Carolina).

Evaluation—Participants were asked, “If you were diagnosed with a skin disease that benefited from UV therapy, which of the following forms of UV therapy would you consider choosing?” Participants were instructed to choose all of the forms they would consider using. Available options included in-office UV, at-home UV, home tanning, salon tanning, sunbathing, and other. Participants were asked to select which factors—from safety, cost, effectiveness, issues with insurance, convenience, and other—influenced their decision-making; which form of phototherapy they would most consider along with the factors that influenced their preference for this specific form of phototherapy; and which options they considered to be safest and most cost-effective, efficacious, and convenient. Participants were asked to provide basic sociodemographic information, level of education, income, insurance status (private, Medicare, Medicaid, Veterans Affairs, and uninsured), and distance from the nearest dermatologist.

Statistical Analysis—Descriptive and inferential statistics (χ² test) were used to analyze the data with a significance set at P<.05.

Results

Five hundred participants completed the survey (Table 1).

Factors Influencing Patient Preferences—When asked to select all forms of phototherapy they would consider, 186 (37.2%) participants selected in-office UVB, 263 (52.6%) selected at-home UV, 141 (28.2%) selected home tanning, 117 (23.4%) selected salon tanning, 191 (38.2%) selected sunbathing, and 3 (0.6%) selected other. Participants who selected in-office UVB as an option were more likely to also select salon tanning (P<.012). No other relationship was found between the UVB options and the tanning options. When asked which factors influenced their phototherapy preferences, 295 (59%) selected convenience, 266 (53.2%) selected effectiveness, 220 (44%) selected safety, 218 (43.6%) selected cost, 72 (14.4%) selected issues with insurance, and 4 (0.8%) selected other. Forms of Phototherapy Patients Consider Using—When asked which form of phototherapy they would most consider using, 179 (35.8%) participants selected at-home UVB, 108 (21.6%) selected sunbathing, 92 (18.4%) selected in-office UVB, 62 (12.4%) selected home-tanning, 57 (11.4%) selected salon tanning, 1 (0.2%) selected other, and 1 participant provided no response (P<.001).

Reasons for Using Phototherapy—Of the 179 who selected at-home UVB, 125 (70%) cited convenience as a reason. Of the 108 who selected salon tanning as their top choice, 62 (57%) cited cost as a reason. Convenience (P<.001), cost (P<.001), and safety (P=.023) were related to top preference. Issues with insurance did not have a statistically significant relationship with the top preference. However, participant insurance type was related to top phototherapy preference (P=.021), with privately insured patients more likely to select in-office UVB, whereas those with Medicaid and Medicare were more likely to select home or salon tanning. Efficacy was not related to top preference. Furthermore, age, gender, education, income, and distance from nearest dermatologist were not related to top preference.

In-office UVB was perceived to be safest (P<.001) and most efficacious (P<.001). Meanwhile, at-home UVB was selected as most convenient (P<.001). Lastly, sunbathing was determined to be most cost-effective (P<.001)(Table 2). Cost-effectiveness had a relationship (P<.001) with the participant’s insurance, as those with private insurance were more likely to select at-home UVB, whereas those with Medicare or Medicaid were more likely to select the tanning options. Additionally, of the54 uninsured participants in the survey, 29 selected sunbathing as the most cost-effective option.

Comment

Phototherapy Treatment—UVB phototherapy at a wavelength of 290 to 320 nm (311–313 nm for narrowband UVB) is used to treat various dermatoses, including psoriasis and atopic dermatitis. UVB alters skin cytokines, induces apoptosis, promotes immunosuppression, causes DNA damage, and decreases the proliferation of dendritic cells and other cells of the innate immune system.¹ In-office and at-home UV therapies make use of UVB wavelengths for treatment, while tanning and sunbathing contain not only UVB but also potentially harmful UVA rays. The wavelengths for indoor tanning devices include UVB at 280 to 315 nm and UVA at 315 to 400 nm, which are similar to those of the sun but with a different ratio of UVB to UVA and more intense total UV.² When in-office and at-home UVB options are not available, various forms of tanning such as salon tanning and sunbathing may be alternatives that are widely used.³ One of the main reasons patients consider alternative phototherapy options is cost, as 1 in-office UVB treatment may cost $140, but a month of unlimited tanning may cost $30 or perhaps nothing if a patient has a gym membership with access to a tanning bed. Lack of insurance benefits covering phototherapy can exacerbate cost burden.⁴ However, tanning beds are associated with an increased risk for melanoma and nonmelanoma cancers.^5,6 Additionally, all forms of phototherapy are associated with photoaging, but it is more intense with tanning and heliotherapy because of the presence of UVA, which penetrates deeper into the dermis.⁷ Meanwhile, for those who choose UVB therapy, deciding between an in-office and at-home UVB treatment could be a matter of convenience, as patients must consider long trips to the physician’s office; insurance status, as some insurances may not cover at-home UVB; or efficacy, which might be influenced by the presence of a physician or other medical staff. In many cases, patients may not be informed that at-home UVB is an option.

Patient Preferences—At-home UVB therapy was the most popular option in our study population, with most participants (52.6%) considering using it, and 35.9% choosing it as their top choice over all other phototherapy options. Safety, cost, and convenience were all found to be related to the option participants would most consider using. Prior analysis between at-home UVB and in-office UVB for the treatment of psoriasis determined that at-home UVB is as safe and cost-effective as in-office UVB without the inconvenience of the patient having to take time out of the week to visit the physician’s office,^8,9 making at-home UVB an option dermatologists may strongly consider for patients who value safety, cost, and convenience. Oddly, efficacy was not related to the top preference, despite being the second highest–cited factor (53.2%) for which forms of phototherapy participants would consider using. For insurance coverage, those with Medicaid and Medicare selected the cheaper tanning options with higher-than-expected frequencies. Although problems with insurance were not related to the top preference, insurance status was related, suggesting that preferences are tied to cost. Of note, while the number of dermatologists that accept Medicare has increased in the last few years, there still remains an uneven distribution of phototherapy clinics. As of 2015, there were 19 million individuals who qualified for Medicare without a clinic within driving distance.¹⁰ This problem likely also exists for many Medicaid patients who may not qualify for at-home UVB. In this scenario, tanning or heliotherapy may be effective alternatives.

In-Office vs At-Home Options—Although in-office UVB was the option considered safest (26.2%) and most efficacious (26.8%), it was followed closely by at-home UVB in both categories (safest, 23.8%; most efficacious, 24.2%). Meanwhile, at-home UVB (40.2%) was chosen as the most convenient. Some patients consider tanning options over in-office UVB because of the inconvenience of traveling to an appointment.¹¹ Therefore, at-home tanning may be a convenient alternative for these patients.

Considerations—Although our study was limited to an adult population, issues with convenience exist for the pediatric population as well, as children may need to miss multiple days of school each week to be treated in the office. For these pediatric patients, an at-home unit is preferable; however; issues with insurance coverage remain a challenge.¹² Increasing insurance coverage of at-home units for the pediatric population therefore would be most prudent. However, when other options have been exhausted, including in-office UVB, tanning and sunbathing may be viable alternatives because of cost and convenience. In our study, sunbathing (33.2%) was considered the most cost-effective, likely because it does not require expensive equipment or a visit to a salon or physician’s office. Sunbathing has been effective in treating some dermatologic conditions, such as atopic dermatitis.¹³ However, it may only be effective during certain months and at different latitudes—conditions that make UVB sun rays more accessible—particularly when treating psoriasis.¹⁴ Furthermore, sunbathing may not be as cost-effective in patients with average-severity psoriasis compared with conventional psoriasis therapy because of the costs of travel to areas with sufficient UVB rays for treatment.¹⁵ Additionally, insurance status was related to which option was selected as the most cost-effective, as 29 (53.7%) of 54 uninsured participants chose sunbathing as the most cost-effective option, while only 92 (34.2%) of 269 privately insured patients selected sunbathing. Therefore, insurance status may be a factor for dermatologists to consider if a patient prefers a treatment that is cost-effective. Overall, dermatologists could perhaps consider guiding patients and optimizing their treatment plans based on the factors most important to the patients while understanding that costs and insurance status may ultimately determine the treatment option.

Limitations—Survey participants were recruited on Amazon Mechanical Turk, which could create sampling bias. Furthermore, these participants were representative of the general public and not exclusively patients on phototherapy, therefore representing the opinions of the general public and not those who may require phototherapy. Furthermore, given the nature of the survey, the study was limited to the adult population.

Phototherapy—particularly UVB phototherapy, which utilizes UVB rays of specific wavelengths within the UV spectrum—is indicated for a wide variety of dermatoses. In-office and at-home UVB treatments commonly are used, as are salon tanning and sunbathing. When selecting a form of phototherapy, patients are likely to consider safety, cost, effectiveness, insurance issues, and convenience. Research on patient preferences; the reasons for these preferences; and which options patients perceive to be the safest, most cost-effective, efficacious, and convenient is lacking. We aimed to assess the forms of phototherapy that patients would most consider using; the factors influencing patient preferences; and the forms patients perceived as the safest and most cost-effective, efficacious, and convenient.

Methods

Study Participants—We recruited 500 Amazon Mechanical Turk users who were 18 years or older to complete our REDCap-generated survey. The study was approved by the Wake Forest University institutional review board (Winston-Salem, North Carolina).

Evaluation—Participants were asked, “If you were diagnosed with a skin disease that benefited from UV therapy, which of the following forms of UV therapy would you consider choosing?” Participants were instructed to choose all of the forms they would consider using. Available options included in-office UV, at-home UV, home tanning, salon tanning, sunbathing, and other. Participants were asked to select which factors—from safety, cost, effectiveness, issues with insurance, convenience, and other—influenced their decision-making; which form of phototherapy they would most consider along with the factors that influenced their preference for this specific form of phototherapy; and which options they considered to be safest and most cost-effective, efficacious, and convenient. Participants were asked to provide basic sociodemographic information, level of education, income, insurance status (private, Medicare, Medicaid, Veterans Affairs, and uninsured), and distance from the nearest dermatologist.

Statistical Analysis—Descriptive and inferential statistics (χ² test) were used to analyze the data with a significance set at P<.05.

Results

Five hundred participants completed the survey (Table 1).

Factors Influencing Patient Preferences—When asked to select all forms of phototherapy they would consider, 186 (37.2%) participants selected in-office UVB, 263 (52.6%) selected at-home UV, 141 (28.2%) selected home tanning, 117 (23.4%) selected salon tanning, 191 (38.2%) selected sunbathing, and 3 (0.6%) selected other. Participants who selected in-office UVB as an option were more likely to also select salon tanning (P<.012). No other relationship was found between the UVB options and the tanning options. When asked which factors influenced their phototherapy preferences, 295 (59%) selected convenience, 266 (53.2%) selected effectiveness, 220 (44%) selected safety, 218 (43.6%) selected cost, 72 (14.4%) selected issues with insurance, and 4 (0.8%) selected other. Forms of Phototherapy Patients Consider Using—When asked which form of phototherapy they would most consider using, 179 (35.8%) participants selected at-home UVB, 108 (21.6%) selected sunbathing, 92 (18.4%) selected in-office UVB, 62 (12.4%) selected home-tanning, 57 (11.4%) selected salon tanning, 1 (0.2%) selected other, and 1 participant provided no response (P<.001).

Reasons for Using Phototherapy—Of the 179 who selected at-home UVB, 125 (70%) cited convenience as a reason. Of the 108 who selected salon tanning as their top choice, 62 (57%) cited cost as a reason. Convenience (P<.001), cost (P<.001), and safety (P=.023) were related to top preference. Issues with insurance did not have a statistically significant relationship with the top preference. However, participant insurance type was related to top phototherapy preference (P=.021), with privately insured patients more likely to select in-office UVB, whereas those with Medicaid and Medicare were more likely to select home or salon tanning. Efficacy was not related to top preference. Furthermore, age, gender, education, income, and distance from nearest dermatologist were not related to top preference.

In-office UVB was perceived to be safest (P<.001) and most efficacious (P<.001). Meanwhile, at-home UVB was selected as most convenient (P<.001). Lastly, sunbathing was determined to be most cost-effective (P<.001)(Table 2). Cost-effectiveness had a relationship (P<.001) with the participant’s insurance, as those with private insurance were more likely to select at-home UVB, whereas those with Medicare or Medicaid were more likely to select the tanning options. Additionally, of the54 uninsured participants in the survey, 29 selected sunbathing as the most cost-effective option.

Comment

Phototherapy Treatment—UVB phototherapy at a wavelength of 290 to 320 nm (311–313 nm for narrowband UVB) is used to treat various dermatoses, including psoriasis and atopic dermatitis. UVB alters skin cytokines, induces apoptosis, promotes immunosuppression, causes DNA damage, and decreases the proliferation of dendritic cells and other cells of the innate immune system.¹ In-office and at-home UV therapies make use of UVB wavelengths for treatment, while tanning and sunbathing contain not only UVB but also potentially harmful UVA rays. The wavelengths for indoor tanning devices include UVB at 280 to 315 nm and UVA at 315 to 400 nm, which are similar to those of the sun but with a different ratio of UVB to UVA and more intense total UV.² When in-office and at-home UVB options are not available, various forms of tanning such as salon tanning and sunbathing may be alternatives that are widely used.³ One of the main reasons patients consider alternative phototherapy options is cost, as 1 in-office UVB treatment may cost $140, but a month of unlimited tanning may cost $30 or perhaps nothing if a patient has a gym membership with access to a tanning bed. Lack of insurance benefits covering phototherapy can exacerbate cost burden.⁴ However, tanning beds are associated with an increased risk for melanoma and nonmelanoma cancers.^5,6 Additionally, all forms of phototherapy are associated with photoaging, but it is more intense with tanning and heliotherapy because of the presence of UVA, which penetrates deeper into the dermis.⁷ Meanwhile, for those who choose UVB therapy, deciding between an in-office and at-home UVB treatment could be a matter of convenience, as patients must consider long trips to the physician’s office; insurance status, as some insurances may not cover at-home UVB; or efficacy, which might be influenced by the presence of a physician or other medical staff. In many cases, patients may not be informed that at-home UVB is an option.

Patient Preferences—At-home UVB therapy was the most popular option in our study population, with most participants (52.6%) considering using it, and 35.9% choosing it as their top choice over all other phototherapy options. Safety, cost, and convenience were all found to be related to the option participants would most consider using. Prior analysis between at-home UVB and in-office UVB for the treatment of psoriasis determined that at-home UVB is as safe and cost-effective as in-office UVB without the inconvenience of the patient having to take time out of the week to visit the physician’s office,^8,9 making at-home UVB an option dermatologists may strongly consider for patients who value safety, cost, and convenience. Oddly, efficacy was not related to the top preference, despite being the second highest–cited factor (53.2%) for which forms of phototherapy participants would consider using. For insurance coverage, those with Medicaid and Medicare selected the cheaper tanning options with higher-than-expected frequencies. Although problems with insurance were not related to the top preference, insurance status was related, suggesting that preferences are tied to cost. Of note, while the number of dermatologists that accept Medicare has increased in the last few years, there still remains an uneven distribution of phototherapy clinics. As of 2015, there were 19 million individuals who qualified for Medicare without a clinic within driving distance.¹⁰ This problem likely also exists for many Medicaid patients who may not qualify for at-home UVB. In this scenario, tanning or heliotherapy may be effective alternatives.

In-Office vs At-Home Options—Although in-office UVB was the option considered safest (26.2%) and most efficacious (26.8%), it was followed closely by at-home UVB in both categories (safest, 23.8%; most efficacious, 24.2%). Meanwhile, at-home UVB (40.2%) was chosen as the most convenient. Some patients consider tanning options over in-office UVB because of the inconvenience of traveling to an appointment.¹¹ Therefore, at-home tanning may be a convenient alternative for these patients.

Considerations—Although our study was limited to an adult population, issues with convenience exist for the pediatric population as well, as children may need to miss multiple days of school each week to be treated in the office. For these pediatric patients, an at-home unit is preferable; however; issues with insurance coverage remain a challenge.¹² Increasing insurance coverage of at-home units for the pediatric population therefore would be most prudent. However, when other options have been exhausted, including in-office UVB, tanning and sunbathing may be viable alternatives because of cost and convenience. In our study, sunbathing (33.2%) was considered the most cost-effective, likely because it does not require expensive equipment or a visit to a salon or physician’s office. Sunbathing has been effective in treating some dermatologic conditions, such as atopic dermatitis.¹³ However, it may only be effective during certain months and at different latitudes—conditions that make UVB sun rays more accessible—particularly when treating psoriasis.¹⁴ Furthermore, sunbathing may not be as cost-effective in patients with average-severity psoriasis compared with conventional psoriasis therapy because of the costs of travel to areas with sufficient UVB rays for treatment.¹⁵ Additionally, insurance status was related to which option was selected as the most cost-effective, as 29 (53.7%) of 54 uninsured participants chose sunbathing as the most cost-effective option, while only 92 (34.2%) of 269 privately insured patients selected sunbathing. Therefore, insurance status may be a factor for dermatologists to consider if a patient prefers a treatment that is cost-effective. Overall, dermatologists could perhaps consider guiding patients and optimizing their treatment plans based on the factors most important to the patients while understanding that costs and insurance status may ultimately determine the treatment option.

Limitations—Survey participants were recruited on Amazon Mechanical Turk, which could create sampling bias. Furthermore, these participants were representative of the general public and not exclusively patients on phototherapy, therefore representing the opinions of the general public and not those who may require phototherapy. Furthermore, given the nature of the survey, the study was limited to the adult population.

Phototherapy—particularly UVB phototherapy, which utilizes UVB rays of specific wavelengths within the UV spectrum—is indicated for a wide variety of dermatoses. In-office and at-home UVB treatments commonly are used, as are salon tanning and sunbathing. When selecting a form of phototherapy, patients are likely to consider safety, cost, effectiveness, insurance issues, and convenience. Research on patient preferences; the reasons for these preferences; and which options patients perceive to be the safest, most cost-effective, efficacious, and convenient is lacking. We aimed to assess the forms of phototherapy that patients would most consider using; the factors influencing patient preferences; and the forms patients perceived as the safest and most cost-effective, efficacious, and convenient.

Methods

Study Participants—We recruited 500 Amazon Mechanical Turk users who were 18 years or older to complete our REDCap-generated survey. The study was approved by the Wake Forest University institutional review board (Winston-Salem, North Carolina).

Evaluation—Participants were asked, “If you were diagnosed with a skin disease that benefited from UV therapy, which of the following forms of UV therapy would you consider choosing?” Participants were instructed to choose all of the forms they would consider using. Available options included in-office UV, at-home UV, home tanning, salon tanning, sunbathing, and other. Participants were asked to select which factors—from safety, cost, effectiveness, issues with insurance, convenience, and other—influenced their decision-making; which form of phototherapy they would most consider along with the factors that influenced their preference for this specific form of phototherapy; and which options they considered to be safest and most cost-effective, efficacious, and convenient. Participants were asked to provide basic sociodemographic information, level of education, income, insurance status (private, Medicare, Medicaid, Veterans Affairs, and uninsured), and distance from the nearest dermatologist.

Statistical Analysis—Descriptive and inferential statistics (χ² test) were used to analyze the data with a significance set at P<.05.

Results

Five hundred participants completed the survey (Table 1).

Factors Influencing Patient Preferences—When asked to select all forms of phototherapy they would consider, 186 (37.2%) participants selected in-office UVB, 263 (52.6%) selected at-home UV, 141 (28.2%) selected home tanning, 117 (23.4%) selected salon tanning, 191 (38.2%) selected sunbathing, and 3 (0.6%) selected other. Participants who selected in-office UVB as an option were more likely to also select salon tanning (P<.012). No other relationship was found between the UVB options and the tanning options. When asked which factors influenced their phototherapy preferences, 295 (59%) selected convenience, 266 (53.2%) selected effectiveness, 220 (44%) selected safety, 218 (43.6%) selected cost, 72 (14.4%) selected issues with insurance, and 4 (0.8%) selected other. Forms of Phototherapy Patients Consider Using—When asked which form of phototherapy they would most consider using, 179 (35.8%) participants selected at-home UVB, 108 (21.6%) selected sunbathing, 92 (18.4%) selected in-office UVB, 62 (12.4%) selected home-tanning, 57 (11.4%) selected salon tanning, 1 (0.2%) selected other, and 1 participant provided no response (P<.001).

Reasons for Using Phototherapy—Of the 179 who selected at-home UVB, 125 (70%) cited convenience as a reason. Of the 108 who selected salon tanning as their top choice, 62 (57%) cited cost as a reason. Convenience (P<.001), cost (P<.001), and safety (P=.023) were related to top preference. Issues with insurance did not have a statistically significant relationship with the top preference. However, participant insurance type was related to top phototherapy preference (P=.021), with privately insured patients more likely to select in-office UVB, whereas those with Medicaid and Medicare were more likely to select home or salon tanning. Efficacy was not related to top preference. Furthermore, age, gender, education, income, and distance from nearest dermatologist were not related to top preference.

In-office UVB was perceived to be safest (P<.001) and most efficacious (P<.001). Meanwhile, at-home UVB was selected as most convenient (P<.001). Lastly, sunbathing was determined to be most cost-effective (P<.001)(Table 2). Cost-effectiveness had a relationship (P<.001) with the participant’s insurance, as those with private insurance were more likely to select at-home UVB, whereas those with Medicare or Medicaid were more likely to select the tanning options. Additionally, of the54 uninsured participants in the survey, 29 selected sunbathing as the most cost-effective option.

Comment

Phototherapy Treatment—UVB phototherapy at a wavelength of 290 to 320 nm (311–313 nm for narrowband UVB) is used to treat various dermatoses, including psoriasis and atopic dermatitis. UVB alters skin cytokines, induces apoptosis, promotes immunosuppression, causes DNA damage, and decreases the proliferation of dendritic cells and other cells of the innate immune system.¹ In-office and at-home UV therapies make use of UVB wavelengths for treatment, while tanning and sunbathing contain not only UVB but also potentially harmful UVA rays. The wavelengths for indoor tanning devices include UVB at 280 to 315 nm and UVA at 315 to 400 nm, which are similar to those of the sun but with a different ratio of UVB to UVA and more intense total UV.² When in-office and at-home UVB options are not available, various forms of tanning such as salon tanning and sunbathing may be alternatives that are widely used.³ One of the main reasons patients consider alternative phototherapy options is cost, as 1 in-office UVB treatment may cost $140, but a month of unlimited tanning may cost $30 or perhaps nothing if a patient has a gym membership with access to a tanning bed. Lack of insurance benefits covering phototherapy can exacerbate cost burden.⁴ However, tanning beds are associated with an increased risk for melanoma and nonmelanoma cancers.^5,6 Additionally, all forms of phototherapy are associated with photoaging, but it is more intense with tanning and heliotherapy because of the presence of UVA, which penetrates deeper into the dermis.⁷ Meanwhile, for those who choose UVB therapy, deciding between an in-office and at-home UVB treatment could be a matter of convenience, as patients must consider long trips to the physician’s office; insurance status, as some insurances may not cover at-home UVB; or efficacy, which might be influenced by the presence of a physician or other medical staff. In many cases, patients may not be informed that at-home UVB is an option.

Patient Preferences—At-home UVB therapy was the most popular option in our study population, with most participants (52.6%) considering using it, and 35.9% choosing it as their top choice over all other phototherapy options. Safety, cost, and convenience were all found to be related to the option participants would most consider using. Prior analysis between at-home UVB and in-office UVB for the treatment of psoriasis determined that at-home UVB is as safe and cost-effective as in-office UVB without the inconvenience of the patient having to take time out of the week to visit the physician’s office,^8,9 making at-home UVB an option dermatologists may strongly consider for patients who value safety, cost, and convenience. Oddly, efficacy was not related to the top preference, despite being the second highest–cited factor (53.2%) for which forms of phototherapy participants would consider using. For insurance coverage, those with Medicaid and Medicare selected the cheaper tanning options with higher-than-expected frequencies. Although problems with insurance were not related to the top preference, insurance status was related, suggesting that preferences are tied to cost. Of note, while the number of dermatologists that accept Medicare has increased in the last few years, there still remains an uneven distribution of phototherapy clinics. As of 2015, there were 19 million individuals who qualified for Medicare without a clinic within driving distance.¹⁰ This problem likely also exists for many Medicaid patients who may not qualify for at-home UVB. In this scenario, tanning or heliotherapy may be effective alternatives.

In-Office vs At-Home Options—Although in-office UVB was the option considered safest (26.2%) and most efficacious (26.8%), it was followed closely by at-home UVB in both categories (safest, 23.8%; most efficacious, 24.2%). Meanwhile, at-home UVB (40.2%) was chosen as the most convenient. Some patients consider tanning options over in-office UVB because of the inconvenience of traveling to an appointment.¹¹ Therefore, at-home tanning may be a convenient alternative for these patients.

Considerations—Although our study was limited to an adult population, issues with convenience exist for the pediatric population as well, as children may need to miss multiple days of school each week to be treated in the office. For these pediatric patients, an at-home unit is preferable; however; issues with insurance coverage remain a challenge.¹² Increasing insurance coverage of at-home units for the pediatric population therefore would be most prudent. However, when other options have been exhausted, including in-office UVB, tanning and sunbathing may be viable alternatives because of cost and convenience. In our study, sunbathing (33.2%) was considered the most cost-effective, likely because it does not require expensive equipment or a visit to a salon or physician’s office. Sunbathing has been effective in treating some dermatologic conditions, such as atopic dermatitis.¹³ However, it may only be effective during certain months and at different latitudes—conditions that make UVB sun rays more accessible—particularly when treating psoriasis.¹⁴ Furthermore, sunbathing may not be as cost-effective in patients with average-severity psoriasis compared with conventional psoriasis therapy because of the costs of travel to areas with sufficient UVB rays for treatment.¹⁵ Additionally, insurance status was related to which option was selected as the most cost-effective, as 29 (53.7%) of 54 uninsured participants chose sunbathing as the most cost-effective option, while only 92 (34.2%) of 269 privately insured patients selected sunbathing. Therefore, insurance status may be a factor for dermatologists to consider if a patient prefers a treatment that is cost-effective. Overall, dermatologists could perhaps consider guiding patients and optimizing their treatment plans based on the factors most important to the patients while understanding that costs and insurance status may ultimately determine the treatment option.

Limitations—Survey participants were recruited on Amazon Mechanical Turk, which could create sampling bias. Furthermore, these participants were representative of the general public and not exclusively patients on phototherapy, therefore representing the opinions of the general public and not those who may require phototherapy. Furthermore, given the nature of the survey, the study was limited to the adult population.

Key clinical point: Patients with moderate-to-severe atopic dermatitis (AD) had the highest incidence rate (IR) per 1000 person-years for major adverse cardiovascular events (MACE), followed by venous thrombotic events (VTE), deep vein thrombosis (DVT), and pulmonary embolism (PE).

Major finding: The IR per 1000 person-years for MACE, VTE, DVT, and PE were 2.6 (95% CI 2.1-3.2), 2.0 (95% CI 1.5-2.5), 1.6 (95% CI 1.2-2.1), and 0.7 (95% CI 0.5-1.0), respectively.

Study details: This retrospective cohort study included 8197 patients aged ≥12 years with moderate-to-severe AD.

Disclosures: This study was funded by Pfizer, Inc. Some authors declared receiving grant funding from Pfizer. Two authors declared being current or former employees and shareholders of Pfizer.

Source: Hedderson MM et al. Rates of cardiovascular events among patients with moderate-to-severe atopic dermatitis in an integrated health care system: A retrospective cohort study. PLoS One. 2022;17(11):e0277469 (Nov 17). Doi: 10.1371/journal.pone.0277469

Key clinical point: Patients with moderate-to-severe atopic dermatitis (AD) had the highest incidence rate (IR) per 1000 person-years for major adverse cardiovascular events (MACE), followed by venous thrombotic events (VTE), deep vein thrombosis (DVT), and pulmonary embolism (PE).

Major finding: The IR per 1000 person-years for MACE, VTE, DVT, and PE were 2.6 (95% CI 2.1-3.2), 2.0 (95% CI 1.5-2.5), 1.6 (95% CI 1.2-2.1), and 0.7 (95% CI 0.5-1.0), respectively.

Study details: This retrospective cohort study included 8197 patients aged ≥12 years with moderate-to-severe AD.

Disclosures: This study was funded by Pfizer, Inc. Some authors declared receiving grant funding from Pfizer. Two authors declared being current or former employees and shareholders of Pfizer.

Source: Hedderson MM et al. Rates of cardiovascular events among patients with moderate-to-severe atopic dermatitis in an integrated health care system: A retrospective cohort study. PLoS One. 2022;17(11):e0277469 (Nov 17). Doi: 10.1371/journal.pone.0277469

Key clinical point: Patients with moderate-to-severe atopic dermatitis (AD) had the highest incidence rate (IR) per 1000 person-years for major adverse cardiovascular events (MACE), followed by venous thrombotic events (VTE), deep vein thrombosis (DVT), and pulmonary embolism (PE).

Major finding: The IR per 1000 person-years for MACE, VTE, DVT, and PE were 2.6 (95% CI 2.1-3.2), 2.0 (95% CI 1.5-2.5), 1.6 (95% CI 1.2-2.1), and 0.7 (95% CI 0.5-1.0), respectively.

Study details: This retrospective cohort study included 8197 patients aged ≥12 years with moderate-to-severe AD.

Disclosures: This study was funded by Pfizer, Inc. Some authors declared receiving grant funding from Pfizer. Two authors declared being current or former employees and shareholders of Pfizer.

Source: Hedderson MM et al. Rates of cardiovascular events among patients with moderate-to-severe atopic dermatitis in an integrated health care system: A retrospective cohort study. PLoS One. 2022;17(11):e0277469 (Nov 17). Doi: 10.1371/journal.pone.0277469

Key clinical point: Baricitinib could serve as an effective treatment option for patients with difficult-to-treat moderate-to-severe atopic dermatitis (AD), including those unresponsive to dupilumab treatment; however, a high discontinuation rate indicates its rather heterogenous efficacy.

Major finding: At week 16, the mean Eczema Area and Severity Index score and numerical rating scale-pruritis significantly decreased from 18.3 to 11.1 (P < .0001) and from 6.6 to 5.3 (P < .0001), respectively. The most frequent adverse events (AE) were nausea (11.8%), urinary tract infection (9.8%), and herpes simplex infections (7.8%). Baricitinib treatment was discontinued by 43.2% of patients due to ineffectiveness or AE.

Study details: This multicenter prospective observational study included 51 adult patients with moderate-to-severe AD from the BioDay registry who received baricitinib over 16 weeks.

Disclosures: This study did not report a source of funding. Some authors declared serving as speakers, consultants, advisory board members, or investigators for various organizations.

Source: Boesjes CM et al. Daily practice experience of baricitinib treatment for patients with difficult-to-treat atopic dermatitis: Results from the BioDay registry. Acta Derm Venereol. 2022;102:adv00820 (Nov 24). Doi: 10.2340/actadv.v102.3978

Key clinical point: Baricitinib could serve as an effective treatment option for patients with difficult-to-treat moderate-to-severe atopic dermatitis (AD), including those unresponsive to dupilumab treatment; however, a high discontinuation rate indicates its rather heterogenous efficacy.

Major finding: At week 16, the mean Eczema Area and Severity Index score and numerical rating scale-pruritis significantly decreased from 18.3 to 11.1 (P < .0001) and from 6.6 to 5.3 (P < .0001), respectively. The most frequent adverse events (AE) were nausea (11.8%), urinary tract infection (9.8%), and herpes simplex infections (7.8%). Baricitinib treatment was discontinued by 43.2% of patients due to ineffectiveness or AE.

Study details: This multicenter prospective observational study included 51 adult patients with moderate-to-severe AD from the BioDay registry who received baricitinib over 16 weeks.

Disclosures: This study did not report a source of funding. Some authors declared serving as speakers, consultants, advisory board members, or investigators for various organizations.

Source: Boesjes CM et al. Daily practice experience of baricitinib treatment for patients with difficult-to-treat atopic dermatitis: Results from the BioDay registry. Acta Derm Venereol. 2022;102:adv00820 (Nov 24). Doi: 10.2340/actadv.v102.3978

Key clinical point: Baricitinib could serve as an effective treatment option for patients with difficult-to-treat moderate-to-severe atopic dermatitis (AD), including those unresponsive to dupilumab treatment; however, a high discontinuation rate indicates its rather heterogenous efficacy.

Major finding: At week 16, the mean Eczema Area and Severity Index score and numerical rating scale-pruritis significantly decreased from 18.3 to 11.1 (P < .0001) and from 6.6 to 5.3 (P < .0001), respectively. The most frequent adverse events (AE) were nausea (11.8%), urinary tract infection (9.8%), and herpes simplex infections (7.8%). Baricitinib treatment was discontinued by 43.2% of patients due to ineffectiveness or AE.

Study details: This multicenter prospective observational study included 51 adult patients with moderate-to-severe AD from the BioDay registry who received baricitinib over 16 weeks.

Disclosures: This study did not report a source of funding. Some authors declared serving as speakers, consultants, advisory board members, or investigators for various organizations.

Source: Boesjes CM et al. Daily practice experience of baricitinib treatment for patients with difficult-to-treat atopic dermatitis: Results from the BioDay registry. Acta Derm Venereol. 2022;102:adv00820 (Nov 24). Doi: 10.2340/actadv.v102.3978

Key clinical point: The first exposure of pediatric individuals to general anesthesia (GA) is not associated with an increased or decreased risk of developing atopic dermatitis (AD).

Major finding: Multivariate analysis revealed that individuals who were exposed vs not exposed to GA did not have an increased or decreased risk of developing AD (adjusted hazard ratio 1.03; P  =  .701).

Study details: This retrospective cohort study included pediatric individuals aged ≤18 years who were (n = 7,681) or were not (n = 38,405; control individuals) exposed to GA.

Disclosures: This study was funded by a 2020 Amorepacific (South Korea) grant. The authors declared no  conflicts of interest.

Source: Kim DC et al. No association between first exposure to general anaesthesia and atopic dermatitis in the paediatric population. Acta Derm Venereol. 2022;102:adv00813 (Nov 14). Doi: 10.2340/actadv.v102.2738

Key clinical point: The first exposure of pediatric individuals to general anesthesia (GA) is not associated with an increased or decreased risk of developing atopic dermatitis (AD).

Major finding: Multivariate analysis revealed that individuals who were exposed vs not exposed to GA did not have an increased or decreased risk of developing AD (adjusted hazard ratio 1.03; P  =  .701).

Study details: This retrospective cohort study included pediatric individuals aged ≤18 years who were (n = 7,681) or were not (n = 38,405; control individuals) exposed to GA.

Disclosures: This study was funded by a 2020 Amorepacific (South Korea) grant. The authors declared no  conflicts of interest.

Source: Kim DC et al. No association between first exposure to general anaesthesia and atopic dermatitis in the paediatric population. Acta Derm Venereol. 2022;102:adv00813 (Nov 14). Doi: 10.2340/actadv.v102.2738

Key clinical point: The first exposure of pediatric individuals to general anesthesia (GA) is not associated with an increased or decreased risk of developing atopic dermatitis (AD).

Major finding: Multivariate analysis revealed that individuals who were exposed vs not exposed to GA did not have an increased or decreased risk of developing AD (adjusted hazard ratio 1.03; P  =  .701).

Study details: This retrospective cohort study included pediatric individuals aged ≤18 years who were (n = 7,681) or were not (n = 38,405; control individuals) exposed to GA.

Disclosures: This study was funded by a 2020 Amorepacific (South Korea) grant. The authors declared no  conflicts of interest.

Source: Kim DC et al. No association between first exposure to general anaesthesia and atopic dermatitis in the paediatric population. Acta Derm Venereol. 2022;102:adv00813 (Nov 14). Doi: 10.2340/actadv.v102.2738