Dupilumab-associated atypical T-cell infiltrates: A report of two additional cases

Summary: Dupilumab, a monoclonal antibody that inhibits interleukin (IL)4/13 signaling, is the approved treatment for moderate to severe atopic dermatitis (AD).Reports linking dupilumab use with both unmasking/ progression of cutaneous T-cell lymphoma (CTCL) and more recently an atypical lymphoid reaction mimicking CTCL exist. While a postulated pathogenesis of these atypical lymphoid infiltrates may involve increased free IL-13 and cyclin D1;there remains a paucity of literature describing the evolution of clinical and histopathological features characterizing this phenomenon.Herein,we report two further cases of patients treated with dupilumab for AD and eczematous dermatitis respectively, who developed progression and worsening of symptoms within one year of starting treatment.Pre-dupilumab biopsy of one patient showed spongiotic dermatitis while their post -dupilumab biopsies showed increased atypical epidermotropic lymphocytes comprised of CD3 (+) T-cells with CD4 greatly predominating over CD8.A diagnosis of an evolving T-cell dyscrasia was suspected. Both patients responded well to discontinuation of dupilumab and treatment with bexarotene.Improvement of symptoms was noted within two months; faster than the usual response time.A high index of suspicion must therefore be maintained for such cases of recalcitrant eczema or AD that do not respond or worsen with dupilumab;and a skin biopsy alongwith further work-up and close clinical follow-up is warranted.