ORIGINAL ARTICLE Risk of lymphoma in patients with atopic dermatitis and the role of topical treatment: A systematic review and meta-analysis Laureline Legendre, MD, a Thomas Barnetche, PhD, b Juliette Mazereeuw-Hautier, MD, PhD, a Nicolas Meyer, MD, PhD, a Dedee Murrell, MD, PhD, c and Carle Paul, MD, PhD a Toulouse and Bordeaux, France; and Sydney, Australia Background: There is controversy regarding a potential increased risk of lymphoma in patients with atopic dermatitis (AD). Objective: To assess the risk of lymphoma and the role of topical treatments in patients with AD. Methods: A systematic literature search and a separate meta-analysis were performed on case control and cohort studies. Results: Of the 3979 articles retrieved, 24 references met the inclusion criteria. In cohort studies, the risk of lymphoma was slightly increased, with a relative risk (RR) of 1.43 (95% confidence interval [CI], 1.12-1.81). In case control studies, no significant increased risk of lymphoma was found, with an odds ratio (OR) of 1.18 (95% CI, 0.94-1.47). Severity of AD was a significant risk factor. Highly potent topical steroids were associated with an increased risk of lymphoma. For topical calcineurin inhibitors (TCIs), a significant association between tacrolimus and mostly skin lymphoma was found in 1 study. Limitations: Confusion between severe AD and cutaneous T-cell lymphoma may account for part of the increased risk of lymphoma in patients with AD. Conclusion: This systematic literature review shows a slightly increased risk of lymphoma in patients with AD. Severity of AD appears to be a significant risk factor. The role of topical steroids and TCIs is unlikely to be significant. ( J Am Acad Dermatol http://dx.doi.org/10.1016/j.jaad.2015.02.1116.) Key words: atopic dermatitis; lymphoma; neoplasm; pimecrolimus; systematic review; tacrolimus; topical corticosteroids. A topic dermatitis (AD) is a chronic inflamma- tory skin disease that affects approximately 15% of children in Western countries 1 and 2% to 3% of adults. 2 The risk of lymphoma in patients with AD is debated. Isolated cases of lymphoma in adult patients with AD have been reported in the literature. 3,4 There are multiple confounding factors that make the interpretation of an increased risk of lymphoma From the Department of Dermatology, a Paul Sabatier University, Toulouse; Department of Rheumatology, b Bordeaux University Hospital, Bordeaux; and the Department of Dermatology, c University of New South Wales, Sydney. Funding sources: None. Dr Paul is consultant and investigator for Astellas and Novartis. Dr Meyer is a speaker for and on the advisory board of Roche and BMS, on the advisory board for Amgen, and is a speaker for MSD and AbbVie. None of the grants or honoraria were directly related to this study. Drs Legendre, Barnetche, Mazereeuw-Hautier, and Murrell have no conflicts of interest to declare. Accepted for publication February 9, 2015. Correspondence to: Carle Paul, MD, PhD, Dermatologie, Larrey Hospital, 24 chemin de Pouvourville e TSA 30030-31059 Toulouse cedex 9, France. E-mail: paul.c@chu-toulouse.fr. Published online April 1, 2015. 0190-9622/$36.00 Ó 2015 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2015.02.1116 Abbreviations used: AD: atopic dermatitis CI: confidence interval CTCL: cutaneous T-cell lymphoma OR: odds ratio RR: relative risk SIR: standardized incidence ratio TCI: topical calcineurin inhibitor TCS: topical corticosteroid 1