Evolution of Dupilumab-Associated Cutaneous Atypical Lymphoid Infiltrates

Abstract

Background: Observations highlighting the "unmasking" of cutaneous T-cell lymphoma after treatment with dupilumab for atopic dermatitis (AD) have been recently reported. However, there remains a paucity of literature describing the evolution of clinical and histopathological features that characterizes this phenomenon.Objective: To define the clinical and histopathologic evolution of atypical lymphoid infiltrates after the administration of dupilumab for AD. Methods:A cross-sectional study of clinical and histopathologic features in 7 consecutive patients with a diagnosis of "atypical lymphoid infiltrate" or mycosis fungoides (MF) on dupilumab for AD was performed.Results: Seven patients with atypical lymphoid infiltrates or MF in evolution after dupilumab therapy (age range 27-74 years) were reviewed. Average duration of AD before MF diagnosis was 5.7 years, and the average duration on dupilumab treatment was 9.8 months. Notable histopathologic features across predupilumab and postdupilumab biopsies included progressive increase in the densities of the atypical lymphoid infiltrates (7/7), presence of atypical epidermotropic lymphocytes (6/7), and papillary dermal fibrosis (6/7).

Dupilumab unmasking cutaneous T‐cell lymphoma: report of a fatal case

“…The other three patients all had known CTCL and received dupilumab off‐licence for severe pruritus; all three had disease progression following dupilumab, and two of these died due to disease progression. To date, two other cases of a patient dying due to CTCL within months of receiving dupilumab for AD have been reported 3,4 . Questions have previously been raised about the safety of biologics used for psoriasis in patients with CTCL, 5 and ciclosporin has been associated with CTCL progression in case reports 6 …”

Dupilumab-Associated Mycosis Fungoides with a CD8+ Immunophenotype

“…In recent years, several case studies have associated the unmasking or progression of CTCL with dupilumab treatment [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Dupilumab competitively inhibits IL-4 and IL-13 at the IL-4 α1 subunit receptor, preventing the downstream activation of tyrosine kinases promoting gene-transcription and related to both barrier dysfunction and Th2-mediated inflammation [ 15 ].…”

“…A study by Sokumbi et al discussed the evolution of histopathologic and immunophenotypic features of lymphoid infiltrates in seven cases of CTCL after treatment of biopsy-proven AD with dupilumab [ 11 ]. Due to the progressive increase in the density of atypical lymphoid cells, prominent collagen fibrosis in the papillary dermis, and epidermotropic lymphocytes across pre-dupilumab and post-dupilumab biopsies, the authors recommend serial biopsies before and during treatment with dupilumab [ 11 ].…”

“…A study by Sokumbi et al discussed the evolution of histopathologic and immunophenotypic features of lymphoid infiltrates in seven cases of CTCL after treatment of biopsy-proven AD with dupilumab [ 11 ]. Due to the progressive increase in the density of atypical lymphoid cells, prominent collagen fibrosis in the papillary dermis, and epidermotropic lymphocytes across pre-dupilumab and post-dupilumab biopsies, the authors recommend serial biopsies before and during treatment with dupilumab [ 11 ]. In addition, initial biopsy specimens may resemble inflammatory skin-diseases, due to a predominance of reactive lymphocytes and lack of cytologically atypical lymphocytes, leading to low concordance-rates among pathologists for the diagnosis for early MF, further emphasizing the need for serial biopsies from various clinical sites for a definitive diagnosis [ 22 ].…”

“…In 2017, dupilumab was approved by the United States Food and Drug Administration (FDA) for the treatment of moderate-to-severe AD in adults uncontrolled with topical medications, becoming the first biologic agent available to treat AD [ 1 ]. Several case studies in recent years have associated unmasking or progression of cutaneous T-cell lymphomas (CTCL) with dupilumab treatment [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. To date, all cases that have reported a CD4:CD8 ratio have shown a greater proportion of CD4+ cells [ 14 ].…”