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.