Dupilumab-Associated Lymphoid Reactions in Patients With Atopic Dermatitis

Importance Since the increased use of dupilumab for atopic dermatitis (AD) in daily practice, several cases have been reported on the development of cutaneous T-cell lymphomas (CTCL) and lymphoid infiltrates. Objective To provide insight in the clinical and histopathologic features of patients with AD clinically suspected for CTCL during dupilumab treatment. Design, Setting, and Participants This retrospective observational case series included adult (≥18 years) patients with AD treated with dupilumab between October 2017 and July 2022 at the University Medical Center Utrecht in the Netherlands. Main outcomes and measures Relevant patient, disease, and treatment characteristics were evaluated. Skin biopsies before, during, and after treatment were collected and reassessed. Results Fourteen patients (54.5% male) with a median (IQR) age of 56 (36-66) years suspected for CTCL with deterioration of symptoms during dupilumab treatment were included. Of 14 patients, 3 were retrospectively diagnosed with preexistent mycosis fungoides (MF). Eleven patients with AD were eventually diagnosed with a lymphoid reaction (LR). These patients showed MF-like symptoms; however, histopathologic findings were different, and included sprinkled distribution of small hyperchromatic lymphocytes in the upper epidermal section, a dysregulated CD4:CD8 ratio, and CD30 overexpression, without loss of CD2/CD3/CD5. The median time to clinical worsening was 4.0 months (IQR, 1.4-10.0). Posttreatment biopsies showed complete clearance of the LR in all patients. Conclusions and relevance This study found that dupilumab treatment can cause a reversible and benign LR, which mimics a CTCL, though has distinctive histopathologic features.