Detecting T-cell receptor clonality in patients with severe atopic dermatitis refractory to dupilumab

J Eur Acad Dermatol Venereol. 2024 Oct;38(10):1939-1946. doi: 10.1111/jdv.20053. Epub 2024 Apr 30.

Abstract

Background: Trials and real-life studies demonstrated clinically meaningful improvements of disease activity in the majority of patients with moderate to severe atopic dermatitis (AD) treated with the anti-IL-4RA-antibody dupilumab. However, misdiagnosis or confounding skin diseases in particular cutaneous T-cell lymphoma (CTCL) may lead to inadequate response.

Objective: To investigate the clinical and pathological features of patients with AD who showed insufficient response to dupilumab.

Methods: We reviewed the medical records of 371 patients treated with dupilumab for severe AD. Insufficient response was defined as failure to achieve an improvement of the eczema area severity index (EASI) of at least 50% (EASI-50) at Week 16 and of 75% (EASI-75) at Week 52. Among 46 patients with insufficient response, 35 patients consented to a re-evaluation including a full physical exam, biopsies and laboratory assessments including immunohistochemistry and T-cell receptor gene rearrangement analysis to differentiate CTCL.

Results: Of the 371 patients treated with dupilumab, 46 (12.3%) patients showed insufficient response to dupilumab. Of these, 35 underwent further evaluation, and 19 (54.2% of inadequate responders) were finally diagnosed with mycosis fungoides (MF). In these patients, transition to or addition of conventional MF treatment led to clinical improvements.

Conclusions: Insufficient response to dupilumab treatment may help uncover early MF on an existing AD background.

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Dermatitis, Atopic* / drug therapy
  • Female
  • Humans
  • Lymphoma, T-Cell, Cutaneous / drug therapy
  • Male
  • Middle Aged
  • Mycosis Fungoides / drug therapy
  • Mycosis Fungoides / genetics
  • Receptors, Antigen, T-Cell / genetics
  • Retrospective Studies
  • Severity of Illness Index
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology
  • Treatment Failure

Substances

  • dupilumab
  • Antibodies, Monoclonal, Humanized
  • Receptors, Antigen, T-Cell