For millions of people living with moderate to severe atopic dermatitis, the arrival of dupilumab was transformative. Chronic itch was eased, inflamed skin was calmed, and the quality of life improved for patients who had often cycled through topical steroids, immunosuppressants, and phototherapy with limited success. Approved in 2017, dupilumab rapidly became one of the most prescribed biologic therapies in dermatology.
Yet over the past several years, dermatologists and oncologists have been confronted with a puzzling pattern. A small number of patients treated with dupilumab for presumed atopic dermatitis were later diagnosed with cutaneous T cell lymphoma, a rare form of skin cancer that can closely mimic eczema in its early stages. The association is uncommon, complex, and frequently misunderstood. It has also triggered an important scientific conversation about diagnosis, not drug safety.
A growing body of research led by Shamir Geller at Memorial Sloan Kettering Cancer Center and collaborators has begun to clarify what is happening. Across retrospective cohort studies, matched analyses, and pharmacovigilance datasets published in leading dermatology journals, the evidence suggests a subtle yet critical insight. Dupilumab does not appear to cause lymphoma. Instead, it may unmask an underlying disease that was already present but difficult to detect.
A breakthrough drug with a complex clinical backdrop
Dupilumab is a monoclonal antibody that targets the interleukin-4 receptor alpha subunit, thereby blocking signaling from both interleukin-4 and interleukin-13. These cytokines are central drivers of type 2 inflammation, the immunological hallmark of atopic dermatitis. By suppressing this pathway, dupilumab reduces inflammation, itch, and barrier dysfunction in the skin.
The clinical success of dupilumab has been well-documented in large Phase 3 trials and real-world registries. Its safety profile has also been reassuring, with no signal of malignancy emerging during pre-approval studies. However, clinical trials rarely capture rare events, particularly those that depend on long diagnostic timelines or disease misclassification. Patients enrolled in clinical trials typically present with classical disease features and well-defined diagnoses, as study protocols often exclude individuals with diagnostic uncertainty or significant comorbidities. In contrast, in real-world clinical practice, dupilumab is frequently prescribed to patients who do not meet textbook diagnostic criteria and who have greater medical complexity.
Cutaneous T-cell lymphoma, particularly its most common subtype, mycosis fungoides, often presents as chronic, scaly, itchy patches that are clinically indistinguishable from eczema. Histological findings can overlap, biopsies may be non-diagnostic, and multiple samples over several years are often required before a definitive diagnosis is made. This diagnostic ambiguity forms the backdrop against which the dupilumab story unfolds.
The first warning signs from specialist clinics
Dermatologists at tertiary cancer centres began noticing a pattern shortly after dupilumab entered widespread use. Patients referred for evaluation of persistent or worsening dermatitis despite biologic therapy were sometimes found to have cutaneous T cell lymphoma on repeat biopsy.
In a retrospective cohort study published in the Journal of the American Academy of Dermatology, Shamir Geller and colleagues examined cases seen at Memorial Sloan Kettering Cancer Center between 2017 and 2024. They identified 30 patients who had been treated with dupilumab for atopic dermatitis or eczematous rash before receiving a clinicopathologically confirmed diagnosis of cutaneous T cell lymphoma.
Importantly, the majority of these patients had been diagnosed with eczema prior to starting dupilumab, often supported by a skin biopsy. The median time from dupilumab initiation to lymphoma diagnosis was approximately one year. Furthermore, the development of mycosis fungoides (MF) was attributed to the severe, chronic course of atopic dermatitis (AD) rather than to dupilumab treatment itself. The study also showed that similar patients with long-standing AD who did not receive dupilumab, but were treated with other immunological therapies, did not demonstrate an increased risk of a later diagnosis of MF.
Comparing outcomes to separate signal from fear
A central concern for clinicians and patients alike is whether dupilumab alters the natural history of cutaneous T cell lymphoma. Does it accelerate disease progression or worsen outcomes once lymphoma emerges?
To address this, a matched cohort study published in the Journal of the European Academy of Dermatology and Venereology compared patients diagnosed with mycosis fungoides or Sézary syndrome after exposure to dupilumab with stage-matched controls who had no prior biologic therapy.
The findings revealed no significant differences in progression-free survival, overall survival, treatment intensity, or time to next therapy between the two groups. Patients diagnosed after dupilumab exposure followed a clinical course similar to those diagnosed through conventional pathways. This strongly suggests that dupilumab does not worsen lymphoma behaviour once the disease is recognised.
What large databases reveal and what they cannot
Beyond individual centres, researchers have turned to national and international pharmacovigilance databases to look for broader signals. An analysis of the United States Food and Drug Administration Adverse Event Reporting System, published in the Journal of Investigative Dermatology, found that reports of cutaneous T-cell lymphoma were disproportionately higher among patients receiving dupilumab compared to other dermatologic biologics .
The reporting odds ratio was elevated, indicating an association. However, the absolute numbers were small, accounting for well under one percent of all dupilumab related adverse event reports. Crucially, no increased reporting of non cutaneous lymphomas or other skin cancers was observed.
Pharmacovigilance data are inherently limited. Reports are voluntary, diagnoses cannot be independently verified, and increased awareness can itself drive reporting. These datasets cannot establish causality. What they can do is highlight patterns that warrant closer clinical scrutiny.
In the absence of evidence that interleukin-13/-4-inhibition can transform eczema into lymphoma, dupilumab should not be withheld in patients with confirmed atopic dermatitis out of concern for subsequent lymphoma risk.
A unifying explanation emerges
A comprehensive clinical review published in the American Journal of Clinical Dermatology synthesised decades of literature on atopic dermatitis, cutaneous T-cell lymphoma, and immunomodulatory therapy . The authors, including Shamir Geller, proposed a biologically plausible and clinically consistent explanation.
Rather than inducing malignant transformation, dupilumab appears to unmask pre-existing malignant T cell clones. By suppressing background inflammatory noise in the skin, the therapy may make the underlying lymphoma more clinically apparent. In some cases, the removal of competing inflammatory signals may also allow malignant cells to dominate histological samples, facilitating diagnosis.
This unmasking hypothesis is supported by the observation that cutaneous T-cell lymphoma has not been reported following dupilumab use for non-cutaneous indications such as asthma. It also aligns with the known difficulty of diagnosing early-stage mycosis fungoides and the frequent delays seen even in specialised settings.
Why diagnosis matters more than drug avoidance
The most important clinical message emerging from this research is not to withhold dupilumab from patients who are appropriate candidates. There is no evidence that the drug transforms atopic dermatitis into lymphoma. For many patients, it remains a life-changing therapy.
Instead, the focus shifts to diagnostic vigilance. Adult-onset eczema, atypical lesion distribution, poor response to biologic therapy, or progressive skin changes despite treatment should prompt reconsideration of the diagnosis. This topic actually highlights the need for a precise objective, accessible method to distinguish skin lymphoma from inflammatory dermatoses
These recommendations are now being incorporated into clinical practice guidelines. They reflect a broader shift in medicine toward recognising how powerful targeted therapies can reshape disease presentation without causing the disease itself.
References
- Liao, V., Lavin, L., Pulitzer, M. P., Stuver, R., & Geller, S. (2025). Diagnosis of cutaneous T-cell lymphoma following exposure to biologic agents for atopic dermatitis: A retrospective cohort study from a single tertiary cancer center. Journal of the American Academy of Dermatology. https://doi.org/10.1016/j.jaad.2025.01.088
- Stuver, R., Dusza, S., Epstein‐Peterson, Z. D., Ghione, P., Horwitz, S. M., Johnson, W., … & Geller, S. (2025). Cutaneous T‐cell lymphoma and dupilumab use: A retrospective matched cohort study of clinical characteristics and treatment outcomes. Journal of the European Academy of Dermatology & Venereology, 39(2). https://doi.org/10.1111/jdv.20141
- Lavin, L., Dusza, S., & Geller, S. (2025). Cutaneous T-cell lymphoma after dupilumab use: a real-world pharmacovigilance study of the FDA adverse event reporting system. Journal of Investigative Dermatology, 145(1), 211-214. https://doi.org/10.1016/j.jid.2024.06.1272
- Lavin, L., & Geller, S. (2025). Cutaneous T Cell Lymphoma Following Dupilumab Therapy in Patients with Atopic Dermatitis: Clinical Review and Recommendations: L. Lavin, S. Geller. American Journal of Clinical Dermatology, 1-9.. https://doi.org/10.1007/s40257-025-00955-7
