Summary Background The Global Burden of Disease (GBD) Study provides an annually updated resource to study disease‐related morbidity and mortality worldwide. Objectives Here we present the burden estimates for atopic dermatitis (AD), including data from inception of the GBD project in 1990 until 2017. Methods Data on the burden of AD were obtained from the GBD Study. Results Atopic dermatitis (AD) ranks 15th among all nonfatal diseases and has the highest disease burden among skin diseases as measured by disability‐adjusted life‐years (DALYs). Overall, the global DALY rate for AD in 1990 was 121 [95% uncertainty interval (UI) 65·4–201] and remained similar in 2017 at 123 (95% UI 66·8–205). The three countries with the highest DALY rates of AD were Sweden (327, 95% UI 178–547), the UK (284, 95% UI 155–478) and Iceland (277, 95% UI 149–465), whereas Uzbekistan (85·1, 95% UI 45·2–144), Armenia (85·1, 95% UI 45·8–143) and Tajikistan (85·1, 95% UI 46·1–143) ranked lowest. Conclusions The global prevalence rate of AD has remained stable from 1990 to 2017. However, the distribution of AD by age groups shows a bimodal curve with the highest peak in early childhood, decreasing in prevalence among young adults, and a second peak in middle‐aged and older populations. We also found a moderate positive correlation between a country’s gross domestic product and disease burden. GBD data confirm the substantial worldwide burden of AD, which has remained stable since 1990 but shows significant geographical variation. Lifestyle factors, partially linked to affluence, are likely important disease drivers. However, the GBD methodology needs to be developed further to incorporate environmental risk factors, such as ultraviolet exposure, to understand better the geographical and age‐related variations in disease burden.

IMPORTANCE Most clinical trials assessing systemic immunomodulatory treatments for patients with atopic dermatitis are placebo-controlled. OBJECTIVE To compare the effectiveness and safety of systemic immunomodulatory treatments for patients with atopic dermatitis in a systematic review and network meta-analysis. DATA SOURCES The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Latin American and Caribbean Health Science Information database, Global Resource of Eczema Trials database, and clinical trial registries were searched from inception to October 28, 2019. STUDY SELECTION English-language randomized clinical trials of 8 weeks or more of treatment with systemic immunomodulatory medications for moderate to severe atopic dermatitis were included. Titles, abstracts, and articles were screened in duplicate. Of 10 324 citations, 39 trials were included. DATA EXTRACTION AND SYNTHESIS Data were extracted in duplicate, and the review adhered to Preferred Reporting Items for Systematic Reviews and Meta-analyses for Network Meta-Analyses guidelines. Random-effects bayesian network meta-analyses were performed and certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. MAIN OUTCOMES AND MEASURES Prespecified outcomes were change in signs of disease, symptoms, quality of life, itch, withdrawals, and serious adverse events. RESULTS A total of 39 trials with 6360 patients examining 20 medications and placebo were included. Most trials were conducted for adults receiving up to 16 weeks of therapy. Dupilumab, 300 mg every 2 weeks, was associated with improvement in the Eczema Area and Severity Index score vs placebo (mean difference, 11.3-point reduction; 95% credible interval [CrI], 9.7-13.1 [high certainty]). Cyclosporine (standardized mean difference, −1.1; 95% CrI, −1.7 to −0.5 [low certainty]) and dupilumab (standardized mean difference, −0.9; 95% CrI, −1.0 to −0.8 [high certainty]) were similarly effective vs placebo in clearing clinical signs of atopic dermatitis and may be superior to methotrexate (standardized mean difference, −0.6; 95% CrI, −1.1 to 0.0 [low certainty]) and azathioprine (standardized mean difference, −0.4; 95% CrI, −0.8 to −0.1 [low certainty]). Several investigational medications for atopic dermatitis are promising, but data to date are limited to small early-phase trials. Safety analyses were limited by low event rates. CONCLUSIONS AND RELEVANCE Dupilumab and cyclosporine may be more effective for up to 16 weeks of treatment than methotrexate and azathioprine for treating adult patients with atopic dermatitis. More studies directly comparing established and novel treatments beyond 16 weeks are needed and will be incorporated into future updates of this review.

Although issues around validity of surrogate markers and clinical end points have complicated trial data in the field, currently available evidence is not persuasive as regards the clinical application of these agents. There remains a clear and growing need for emerging therapeutics to be used in combination with RAAS blocking agents.

Lichen sclerosus is one of the dermatoses that specifically affects the anogenital skin. It has peaks of incidence in prepubertal girls and postmenopausal women. The objective of this critical appraisal was to review systematically the evidence for efficacy and safety of different treatments. There are no randomized controlled studies of treatment in prepubertal girls and most studies are small case series or case reports. There is little focus on quality of life.