Exploring the Link Between Dupilumab and Cutaneous T-Cell Lymphomas: A Systematic Review

Abstract: Dupilumab, an IL-4 and IL-13 antagonist, is a biological medication approved for treating moderate-to-severe atopic dermatitis (AD) and other inflammatory conditions. While dupilumab has been effective in managing AD, recent reports suggest a possible link between dupilumab and the unmasking or progression of cutaneous T-cell lymphomas (CTCL), including mycosis fungoides and Sézary syndrome. This systematic review examines 35 studies, including case reports, case series, and retrospective studies, to investigate the association between dupilumab and CTCL development or exacerbation. Findings reveal both cases of symptom relief and worsening pruritus or disease progression in patients treated with dupilumab. Mechanisms proposed include misdiagnosis of early-stage CTCL as AD and potential dupilumab-induced changes in immune signaling pathways that may promote malignant transformation. Key limitations of existing studies include small sample sizes, lack of standardized treatment duration, and limited long-term follow-up, making it challenging to establish causation. While dupilumab remains an important therapy for AD, these findings underscore the need for careful patient evaluation, particularly in those with persistent or atypical presentations. Further large-scale, longitudinal studies are essential to clarify the role of dupilumab in CTCL development and progression and to optimize patient safety in clinical practice.