Dupilumab-Associated Mycosis Fungoides: Unmasked, Direct Effect, or a Lymphoid Reaction?

Dupilumab, an interleukin (IL)-4 and IL-13 antagonist, is a biological agent approved in 2017 for the treatment of moderate-to-severe atopic dermatitis (AD). While dupilumab has proven revolutionary in managing AD, recent reports have emerged linking its use with the subsequent development of cutaneous T-cell lymphomas (CTCLs), including mycosis fungoides (MF) and Sézary syndrome. Between 2017 and 2023, a total of 178 cases of CTCLs were reportedly associated with dupilumab therapy for AD. The most common theory for this association is "unmasking," where patients were initially misdiagnosed with AD, failed first-line treatments and dupilumab, and later were correctly diagnosed with CTCLs. Another possibility is dupilumab might exacerbate or cause progression of preexisting CTCLs in a patient with concomitant AD. However, conversely, there is also the confounder of a false-positive diagnosis of MF after dupilumab that may overinflate the association data. It has also been reported that dupilumab can cause a reversible benign cutaneous lymphoid reaction that mimics early-stage MF both clinically and histologically, though data are sparse. As CTCL has been exclusively diagnosed in patients who received dupilumab for AD and not in patients who received dupilumab for other conditions such as asthma and since no increased incidence of noncutaneous lymphoma has been reported with dupilumab therapy, it appears unlikely that dupilumab causes or has an actual oncopathogenic effect in developing CTCL or transforming AD into lymphoma. However, this alarming observation emphasizes the need for further biological investigation in determining the mechanism by which dupilumab is associated with CTCL.