Atopic Dermatitis and Cutaneous T-Cell Lymphoma

Key highlights

Reports, systemic reviews, and cross-sectional studies have reported dupilumab administration in CTCL misdiagnosed as AD or eczema, CTCL itself, AD followed by CTCL, concomitant CTCL and AD. Based on the ongoing safety surveillance, the available evidence does not support a causal association between dupilumab and CTCL.

Article of interest:

Ariel Park BS, et al. Cutaneous T-cell lymphoma following dupilumab use: a systematic review. Int J Dermatol . 2023 Jul;62(7):862-876

CTCL & CTCL Subtypes

CTCL is a group of non-Hodgkin’s lymphomas arising from the malignant proliferation of skin-homing T-cells. CTCL subtypes include Mycosis fungoides (MF), Lymphomatoid papulosis, and Sezary syndrome (SS), as well as 11 more rare subtypes. MF is the most common, accounting for 39-53% of CTCLs, and along with SS, it is considered a prototype of CTCL^2,3.

Differential Diagnosis of CTCL and AD

Early-stage MF can be difficult to distinguish from AD. Clinically, MF mimics eczema and other benign inflammatory dermatoses, presenting as well-defined itchy patches and plaques in a swimming suit distribution³. Furthermore, histological findings may overlap, as neoplastic cells constitute only a minority of the infiltrate².

The median age of diagnosis of MF and SS is lower in individuals presenting with early stages of the disease (57 years) compared to those presenting with advanced stages (63 years)².

Management of CTCL

The prognosis of early-stage MF is generally indolent with normal life expectancy. Treatment options include "wait-and-see," topical skin-directed therapies, and phototherapy.

AD as a Risk Factor for Cutaneous Lymphoma

There is a modest increase in the risk of lymphoma in patients with AD compared to the general population, with a relative risk (RR) of 1.43. However, the severity of AD is a significant risk factor, which can also be due to the confusion between severe AD and CTCL⁵.

Dupilumab and CTCL

A systematic review, published in the International Journal of Dermatology, investigated the association between dupilumab use and the development of CTCL. The study synthesizes data from 12 studies involving 27 patients who developed CTCL after starting dupilumab⁷.

Key findings include⁷:

• 23 out of 27 patients were initially diagnosed with presumed AD, however, these cases were later reclassified as mycosis fungoides (MF) after further evaluation.
• 3 out of 27 patients were initially diagnosed with MF from the start.
• 1 out of 27 patients was initially diagnosed with psoriasiform dermatitis, which was later reclassified as MF.
• CTCL was diagnosed on average 7.8 months after initiating dupilumab.
• Mean age of diagnosis was 57 years – much like MF independent of dupilumab.

This suggests that MF can often be misdiagnosed as AD or other skin conditions due to overlapping clinical features. The reclassification typically occurs after additional diagnostic procedures, such as skin biopsies, reveal the true nature of the disease. This underscores the importance of considering MF in patients with atypical or treatment-resistant dermatitis and highlights the need for thorough and ongoing evaluation in such cases⁷.

The study suggests that earlier biopsies, around three to four months after starting dupilumab, may help in the early recognition of CTCL in patients who are not improving or showing new symptom. Furthermore, dupilumab discontinuation upon CTCL diagnosis is recommended⁷.

The question of dupilumab association with CTCL has also been raised by some papers^4,8-9. While some authors ponder whether pre-existing CTCL is unmasked by dupilumab or whether cases were early-stage CTCL that resembled AD clinically and pathologically⁸. Other articles suggest that dupilumab therapy for atopic dermatitis is associated with increased risk of cutaneous T cell lymphoma, while presenting several limitations⁹. For example, the methodology does not justify the outcomes and could have unintended negative effects on patient care. Because of the complexity and heterogeneity of AD, a more detailed, carefully stratified, and comprehensive approach is required to address such important issues.

Based on prior evaluations and ongoing safety surveillance, the available evidence does not support a causal association between dupilumab and CTCL.

Conclusion