QDoes dupilumab increase the risk of cutaneous T-cell lymphoma (CTCL)?

There has been some controversy around dupilumab’s role in the development, or precipitation, of cutaneous T-cell lymphoma (CTCL). Some atopic dermatitis experts argue that dupilumab use is correlated with disease severity of atopic dermatitis, and that patients with pre-existing atopic dermatitis are more likely to go onto develop CTCL through a variety of proposed mechanisms including chronic antigen stimulation and aberrances with the epidermal flora. These experts may believe that there is a non-causal link between dupilumab and CTCL.

However, a recent retrospective cohort study published in the JAAD examined the exposure history of patients diagnosed with moderate-to-severe atopic dermatitis to biologics and JAK inhibitors and the subsequent risk of developing CTCL. In this study, 30 patients were identified with a positive history of dupilumab exposure, and 2 patients with a history of upadacitinib exposure, demonstrating an increased reporting odds ratio of 8.8 of CTCL following dupilumab use. The study also reviewed the previous biopsies that were diagnostic of atopic dermatitis to confirm that these diagnoses were accurate. This was a small, single-center study, but it corroborates some national data that has demonstrated a similar possible association. 

While the role of dupilumab in the development of CTCL remains unclear, dermatologists should be aware of the possibility and consider it prior to starting moderate to severe atopic dermatitis patients on systemic therapy. Particularly if the patient has some atypical features of their eczema that would indicate a higher likelihood of CTCL development, such as older age of onset, presentation in photoprotected areas, or atypical lymphoid aggregates on dermatopathology, it may be worth considering alternative therapeutic options. 

References:

1. Liao V, Lavin L, Pulitzer MP, Stuver R, Geller S. Diagnosis of cutaneous T-cell lymphoma following exposure to atopic dermatitis: a retrospective cohort study from a single tertiary cancer center. JAAD 2025; epub ahead of print.