Consensus Helps Dermatologists Spot CTCL Mimicking Atopic Dermatitis on Dupilumab

Atopic dermatitis and early-stage cutaneous T-cell lymphoma (CTCL) can look identical on the skin, and dupilumab (Dupixent; Sanofi and Regeneron), the biologic most used to treat the former, may be unmasking the latter. A new expert consensus gives dermatologists and payers a playbook for telling the 2 apart before and after that prescription is written.¹

Why Atopic Dermatitis Can Mimic Early CTCL

Dupilumab is one of the most widely prescribed systemic therapies for moderate to severe atopic dermatitis (AD), blocking interleukin 4 (IL-4) and IL-13 signaling to calm inflammation and itch. Case reports of CTCL, particularly mycosis fungoides (MF) and Sézary syndrome (SS), emerging or worsening during dupilumab treatment have accumulated since approval, and some retrospective cohorts have linked dupilumab exposure to a higher CTCL incidence than in untreated patients with AD.

The 2 conditions are not easy to tell apart histologically. A definitive MF diagnosis requires a band-like dermal infiltrate and epidermal involvement with Pautrier abscesses, and early-stage disease often needs several biopsies from an experienced pathologist, per the National Cancer Institute.² That overlap is why the French Cutaneous Lymphoma Group (GFELC) and the French Study Group on Atopic Eczema (GREAT) catalogued every published case of CTCL following dupilumab exposure and translated the pattern into guidance.¹

The review searched PubMed, Web of Science, and the Cochrane Library through January 2, 2025, pulling in 51 studies and 547 patients: mostly case reports and series, plus 6 retrospective cohorts and 2 pharmacovigilance studies. None of the included studies were randomized trials; most were single-center, conducted mainly in the US, Europe, and Asia.

Findings went to 37 experts, mostly hospital-based dermatologists plus 2 pathologists, from 26 institutions in France and Belgium. The panel voted on statements across 2 Delphi rounds on a 9-point scale, with consensus defined as at least 75% agreement and a median score of 7 or higher.

Dupilumab-Associated CTCL by the Numbers

Patients were a mean of 58 years old (range, 10-85), and 47% were women. New or worsening lesions appeared a mean of 8.9 months after dupilumab initiation. MF accounted for 72% of diagnosed cases, SS for 11%, and other subtypes for 19%; just over half (53%) were caught at an early stage.

Dupilumab was stopped in 75% of cases with data, and 62% received CTCL-directed treatment, most often bexarotene or phototherapy. Among the 63 patients with follow-up data, 44 (70%) reached remission, 11 (17%) had stable disease, and 8 (13%) died.

The panel agreed, with 94% to 100% support, that CTCL should be considered before starting dupilumab for newly diagnosed AD in adults older than 40, those with no personal atopy history, or those with atypical features such as erythroderma or enlarged peripheral nodes. It recommended at least one skin biopsy with clonality testing in those cases, expanding to blood flow cytometry if erythroderma or widespread lesions are present. The same workup applies if lesions worsen atypically once dupilumab is underway.

Once CTCL is confirmed, the message is unambiguous: discontinue dupilumab immediately, with 97% agreement. Clinicians can consider brief monitoring if the disease looks non-aggressive but should otherwise move to CTCL-directed treatment and report the case to pharmacovigilance authorities.

“Dupilumab may unmask or exacerbate CTCL, particularly MF and SS,” the authors wrote. “The consensus-based recommendations offer practical guidance for the safe management of patients.”

When a biopsy is inconclusive, the panel calls for close monitoring and repeat testing within 3 months, or sooner if lesions flare. For a treatment swap in that gray zone, methotrexate and phototherapy drew strong support, while cyclosporine and JAK inhibitors were explicitly discouraged. Switching to tralokinumab or lebrikizumab failed to reach consensus, with most panelists voting against it for lack of safety data.

No randomized trial has studied this question, and much of the evidence is weak. Most case reports and series were rated poor quality, and the 2 pharmacovigilance studies, covering 287 of the 547 patients, reported no individual-level data, with remaining cases skewing toward more severe presentations than the full data set. Pooled phase 3 dupilumab trials, with over 7000 patient-years of exposure, logged one cutaneous lymphoma case, while a real-world cohort of 14,900 dupilumab users treated for asthma found a hazard ratio above 5 for CTCL, though low case counts limited power.

For health plans setting dupilumab utilization criteria, the consensus offers something concrete. A documented biopsy and clonality workup for late-onset or atypical AD, not a blanket checklist.

References
1. Amatore F, Neildez M, de Masson A, et al. Cutaneous T-cell lymphomas and dupilumab for atopic dermatitis: a systematic review and expert consensus. J Eur Acad Dermatol Venereol. 2026;40(8):1344-1358. doi:10.1111/jdv.70407

2. Mycosis fungoides (including Sézary syndrome) treatment (PDQ)–health professional version. National Cancer Institute. Accessed October 8, 2026. https://www.cancer.gov/types/lymphoma/hp/mycosis-fungoides-treatment-pdq