Cutaneous T-cell lymphomas and dupilumab for atopic dermatitis: A systematic review and expert consensus

Abstract

Introduction: Dupilumab, a standard treatment for atopic dermatitis (AD), has been associated with cutaneous T-cell lymphomas (CTCL), particularly mycosis fungoides (MF) and Sézary syndrome (SS). Nevertheless, the available data remain heterogeneous. Objectives: To characterize the clinical features, timeline and outcomes of dupilumab-related CTCL emergence in order to develop consensus-based recommendations for dupilumab use in CTCL-related settings. Methods: A systematic review was conducted involving 51 studies reporting cases of CTCL in patients treated with dupilumab, followed by a modified delphi process to generate expert consensus recommendations. Results: Data were obtained from 547 patients (mean age: 58 years; SD: 11.5; range: 10–85). New or worsening skin lesions were reported after dupilumab initiation, occurring at a mean of 8.9 months (SD 5.1; range 0.5–27 months). These were diagnosed as MF in 72% of cases, SS in 11% and other CTCL subtypes in 19%, of which 53% were at an early stage (stage ≤IIA). Dupilumab was discontinued in 75% of cases, and 62% received CTCL-directed treatment. Clinical remission was achieved in 44 of the 63 patients with available follow-up. The expert panel reached broad consensus, agreeing that dupilumab may unmask or exacerbate pre-existing CTCL and should be avoided in cases of MF/SS and mogamulizumab-induced rashes. They emphasized the importance of diagnostic vigilance, providing recommendations for skin biopsy, histology and clonality testing before and during treatment, particularly for patients with AD onset after the age of 40 or with atypical features. Dupilumab should be discontinued once CTCL confirmed, and methotrexate or phototherapy considered as alternatives. Cyclosporine and JAK inhibitors are considered unsuitable, and switching to other Th2-targeting biologics is discouraged due to insufficient data. Conclusions: Dupilumab may unmask or exacerbate CTCL, particularly MF and SS. The consensus-based recommendations offer practical guidance for the safe management of patients.