Dupilumab and T-Cell Lymphoma in Atopic Dermatitis: Current Evidence and Considerations
There is emerging evidence suggesting an association between dupilumab treatment for atopic dermatitis and an increased risk of cutaneous T-cell lymphoma (CTCL), particularly mycosis fungoides. Recent research indicates that patients with atopic dermatitis treated with dupilumab may have up to 4 times higher risk of developing CTCL compared to those not treated with dupilumab 1.
Current Evidence on Dupilumab and CTCL
Risk Association
- A 2024 retrospective cohort study found an odds ratio of 4.1 (95% CI 2.055-8.192) for CTCL in atopic dermatitis patients treated with dupilumab compared to those who weren't 1
- A 2025 population-based cohort study of asthma patients showed dupilumab was associated with higher risk of lymphoma (HR=1.79), with particularly elevated risk for T and NK cell lymphomas (HR=4.58) 2
- Most CTCL cases (27/41) were diagnosed more than 1 year after dupilumab initiation 1
Potential Mechanisms and Confounding Factors
Several important considerations must be evaluated when interpreting this association:
Pre-existing undiagnosed CTCL: Atopic dermatitis and early-stage CTCL share clinical features, making differential diagnosis challenging 3
Benign lymphoid reactions: A 2023 study identified dupilumab-associated lymphoid reactions in atopic dermatitis patients that mimic CTCL but have distinctive histopathologic features and are reversible upon treatment discontinuation 4
Unmasking effect: Some cases suggest dupilumab may unmask previously undiagnosed mycosis fungoides rather than causing it 5
Clinical Implications and Management
For Patients Starting Dupilumab
- Thorough skin examination before initiating therapy to identify suspicious lesions
- Consider skin biopsy for persistent, atypical lesions that don't respond to conventional therapy
- Document baseline skin condition with photographs when possible
For Patients on Dupilumab
- Regular monitoring for new or changing skin lesions
- Biopsy suspicious lesions that develop during treatment, particularly those with:
- Persistent patches/plaques despite treatment
- Asymmetric distribution
- Atypical morphology
- Poor response to standard therapy
Histopathologic Evaluation
When evaluating biopsies from patients on dupilumab with suspected CTCL:
- Look for distinctive features of true CTCL vs. benign lymphoid reactions:
- CTCL: Epidermotropism with atypical lymphocytes, Pautrier microabscesses
- Benign lymphoid reactions: Sprinkled distribution of small hyperchromatic lymphocytes, dysregulated CD4:CD8 ratio, CD30 overexpression without loss of CD2/CD3/CD5 4
Risk-Benefit Assessment
Despite the potential increased risk of CTCL, the overall benefit-risk profile of dupilumab remains favorable for most patients with moderate-to-severe atopic dermatitis:
- Dupilumab has strong evidence for efficacy in moderate-to-severe atopic dermatitis 6
- The American Academy of Dermatology strongly recommends dupilumab as a first-line systemic agent for adults with moderate-to-severe atopic dermatitis 7
- The absolute risk of CTCL remains low despite the relative risk increase
- In asthma patients, dupilumab was associated with lower all-cause mortality despite the increased lymphoma risk 2
Conclusion
While there appears to be an association between dupilumab treatment and increased risk of CTCL in atopic dermatitis patients, causality has not been established. Clinicians should maintain vigilance with regular skin examinations and low threshold for biopsy of suspicious lesions in patients receiving dupilumab. The benefits of dupilumab in controlling moderate-to-severe atopic dermatitis generally outweigh this risk for most patients, but individualized risk assessment is essential.
For patients with a history of CTCL or strong risk factors, alternative therapies may be considered, though some case reports suggest dupilumab may actually improve both atopic dermatitis and CTCL in certain patients 3.