Skin Deep: A Case Report of Erythema Nodosum Induced by Dupilumab Therapy.

Dupilumab is a fully human monoclonal antibody that inhibits interleukin (IL)-4 and IL-13 signaling, thereby attenuating type 2 inflammatory pathways. It is currently approved for the treatment of severe eosinophilic asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, and other allergic conditions. Erythema nodosum (EN) is the most common form of panniculitis, characterized by tender, erythematous subcutaneous nodules typically distributed over the extensor surfaces of the lower extremities. Drug-induced EN represents a minority of all EN cases and has been rarely described in association with biologic therapies including anti-IL-4/13 and anti-IL-5 agents. Notably, dupilumab-associated EN is exceedingly rare, and this report describes a case of clinically suspected dupilumab-associated EN occurring in a patient with severe eosinophilic asthma in the setting of suppressed peripheral blood eosinophils following a treatment interruption. We present the case of a 68-year-old woman with severe eosinophilic asthma who developed clinically suspected EN shortly after initiation of dupilumab therapy and a subsequent two-month treatment interruption. She presented with painful bilateral lower extremity and upper arm nodules following her fifth injection. Notably, her peripheral blood eosinophil count, which had been persistently elevated for more than one year before dupilumab initiation, transiently rebounded during the treatment gap but was adequately suppressed (0.2 × 103/μL) at the time of presentation, reflecting the combined immunomodulatory effects of dupilumab and recent short-term systemic corticosteroid therapy. The diagnosis of clinically suspected dupilumab-associated EN was supported by characteristic clinical findings, a suggestive temporal association with drug reinitiation, and the systematic exclusion of alternative etiologies. Symptoms resolved following discontinuation of dupilumab and initiation of supportive management. This case demonstrates that clinically suspected dupilumab-associated EN may occur in the absence of peripheral blood eosinophilia. Clinicians should maintain awareness that normal or suppressed peripheral eosinophil counts do not preclude the development of paradoxical immune-mediated cutaneous reactions during biologic therapy.