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. 2023 Nov 1;159(11):1240-1247.
doi: 10.1001/jamadermatol.2023.3849.

Dupilumab-Associated Lymphoid Reactions in Patients With Atopic Dermatitis

Celeste M Boesjes  1 , Lian F van der Gang  1 , Daphne S Bakker  1 , Tess A Ten Cate  1 , Lotte S Spekhorst  1 , Marlies de Graaf  1 , Marijke R van Dijk  2 , Marjolein S de Bruin-Weller  1
Affiliations

Dupilumab-Associated Lymphoid Reactions in Patients With Atopic Dermatitis

Celeste M Boesjes et al. JAMA Dermatol. .

Abstract

Importance: Since the increased use of dupilumab for atopic dermatitis (AD) in daily practice, several cases have been reported on the development of cutaneous T-cell lymphomas (CTCL) and lymphoid infiltrates.

Objective: To provide insight in the clinical and histopathologic features of patients with AD clinically suspected for CTCL during dupilumab treatment.

Design, setting, and participants: This retrospective observational case series included adult (≥18 years) patients with AD treated with dupilumab between October 2017 and July 2022 at the University Medical Center Utrecht in the Netherlands.

Main outcomes and measures: Relevant patient, disease, and treatment characteristics were evaluated. Skin biopsies before, during, and after treatment were collected and reassessed.

Results: Fourteen patients (54.5% male) with a median (IQR) age of 56 (36-66) years suspected for CTCL with deterioration of symptoms during dupilumab treatment were included. Of 14 patients, 3 were retrospectively diagnosed with preexistent mycosis fungoides (MF). Eleven patients with AD were eventually diagnosed with a lymphoid reaction (LR). These patients showed MF-like symptoms; however, histopathologic findings were different, and included sprinkled distribution of small hyperchromatic lymphocytes in the upper epidermal section, a dysregulated CD4:CD8 ratio, and CD30 overexpression, without loss of CD2/CD3/CD5. The median time to clinical worsening was 4.0 months (IQR, 1.4-10.0). Posttreatment biopsies showed complete clearance of the LR in all patients.

Conclusions and relevance: This study found that dupilumab treatment can cause a reversible and benign LR, which mimics a CTCL, though has distinctive histopathologic features.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Boesjes reported personal fees from AbbVie and personal fees from Lilly and Company outside the submitted work. Dr Bakker reported personal fees from Sanofi Genzym, Janssen, LEO pharma, and Novartis outside the submitted work. Dr Ten Cate reported contributions to this research as a result of an academic internship at the dermatology department at UMCU during medical education (master’s degree in medicine). She received no payments or other compensation in context of this research. Dr Spekhorst reported personal fees from Abbvie outside the submitted work. Dr de Graaf reported personal fees from AbbVie (fee for advisory board and lectures, paid to institution), Eli Lilly (fee for advisory board, paid to institution), LEO Pharma (fee for advisory board and lectures, paid to institution), Novartis (fee for lectures, paid to institution), Pfizer (fee for lectures, paid to my institution); grants from Regeneron Pharmaceuticals and Sanofi, personal fees from Sanofi (fee for advisory board and lectures, paid to institution), and Almiral (fee for advisory board, paid to institution) outside the submitted work. Dr de Bruin-Weller reported grants from Abbvie paid to the insitution, personal speaker and consultant fees from Abbvie, grants from Pfizer paid to the insitution, personal speaker and consultant fees from Pfizer, grants from Lilly paid to the insitution, personal speaker and consultant fees from Lilly, Galderma, and Almirall , grants from Leo Pharma paid to the insitution, personal speaker and consultant fees from Leo Pharma, Aslan, Janssen, and Arena, grants from sanofi-Genzyme paid to the institution, personal fees from sanofi-Genzyme, grants from Regeneron paid to the institution, and personal fees from Regeneron outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Flowchart and Clinical Presentation of Dupilumab-Associated Lymphoid Reactions
A, Flowchart of number of biopsies performed before, during, and after dupilumab treatment. B, Images of the clinical presentation of dupilumab-associated lymphoid reactions. LR indicates lymphoid reaction; MF, mycosis fungoides.
Figure 2.
Figure 2.. Histopathologic Images of Dupilumab-Associated Lymphoid Reactions (LRs) From Different Patients
Figure 3.
Figure 3.. Images of Posttreatment Biopsies After the Development of a Dupilumab-Associated Lymphoid Reaction and Summary of Histopathologic Features
A, Overview slide with complete clearance of the lymphoid infiltrate. B, Complete clearance of the lymphoid reaction and negative CD30 staining results. C, Overlapping and differences in histopathologic features of atopic dermatitis, lymphoid reactions, and mycosis fungoides.
See this image and copyright information in PMC

Comment in

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