The association between atopic dermatitis and hand eczema: a systematic review and meta-analysis Samine M.D. Ruff1; Kristiane A. Engebretsen 1,2 MD; Claus Zachariae1 MD, DMSc; Jeanne D. Johansen2 MD, DMSc; Jonathan I. Silverberg3 MD, PhD; Alexander Egeberg1 MD, PhD; Jacob P. Thyssen1,2 MD, PhD, DMSc   1Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark 2National Allergy Research Centre, Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark 3Feinberg School of Medicine at Northwestern University, Departments of Dermatology, Preventive Medicine, and Medical Social Sciences, Chicago, Illinois, USA

Introduction What’s already known? Atopic dermatitis (AD) and hand eczema (HE) are common chronic and relapsing skin conditions that often co-occur Several studies have shown that AD increases the risk of HE, however, the exact risk estimate is unknown

Objective The aim of this study was to review published articles on the relationship between AD and HE to identify the strength of an association

Methods 1 A systematic literature search was performed in PubMed, Embase and Web of Science The following search terms were used: (atopic dermatitis OR atopic eczema) AND (hand dermatitis OR hand eczema) The search was limited to articles published after 1960 written in English The prevalence of HE was divided into point-, one- year- and lifetime prevalence of HE

Methods 2 Separate meta-analyses were performed on the association between: AD and HE (all studies) AD and occupational HE (only occupational studies) AD and HE in the general population (only general population studies) Study quality was assessed using the Newcastle- Ottawa Scale For each meta-analysis, sensitivity analyses were performed where the study with the largest sample size was excluded

Results 35 studies were included in the qualitative synthesis and 26 studies in the quantitative synthesis AD was positively associated with HE: Present HE: OR 2.35 (95% CI: 1.47-3.76) (p=0.0003) HE within past year: OR 4.29 (95% CI: 3.13-5.88) (p<0.0001) HE ever: OR 4.06 (95% CI: 2.72-6.06) (p<0.0001) AD was positively associated with occupational HE: Occupational HE within past year: OR 4.31 (95% CI: 2.08- 8.91) (p<0.0001) Occupational HE ever: OR 2.81 (95% CI: 2.08-3.79) (p<0.0001)

Similar positive associations between AD and HE were found in the general population studies: HE within past year: OR 4.19 (95% CI: 3.46-5.08) (p<0.0001) HE ever: OR 5.69 (95% CI: 4.41-7.36) (p<0.0001) Meta-analyses based on study quality (NOS) showed no difference in effect estimate: Good quality: OR 4.33 (95% CI: 2.99-6.27) (p<0.0001) Fair quality: OR 3.68 (95% CI: 1.69-8.03) (p=0.0011) Sensitivity analysis showed similar associations for each meta-analysis

Present HE

HE within past year

HE ever

Discussion What does this study add? Individuals with present or past AD have a 3-4 fold increased risk of having experienced HE Similar estimates were found when making sub- analysis on occupational HE and HE in the general population Both atopic, irritant and allergic HE play a role in the increased association of HE in patients with AD, but their relative contribution is unknown

Conclusions AD was significantly associated with an increased prevalence of HE when measuring point-, one-year- and lifetime prevalence Future studies should determine the association between AD and different types of HE Individuals with AD should steer away from professions that include wet work and prolonged exposure to irritants and allergens

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