D3.383 - Delayed T-cell–mediated hypersensitivity to dimethyl fumarate: clinical presentation and diagnostic considerations

Dimethyl fumarate (DMF) is widely used as an oral disease-modifying therapy for relapsing–remitting multiple sclerosis. Published hypersensitivity reactions to DMF are uncommon and, when reported, most correspond to delayed T-cell–mediated eruptions confirmed through patch testing (PT) or lymphocyte transformation tests (LTT). We present a case of a delayed reaction with negative skin test, PT and positive LTT.

Clinical data, chronology and differential diagnosis were reviewed, and the case was compared with previously published reports of DMF hypersensitivity.

Allergy study: skin prick tests, patch test with DMF 0.01&0.1%, and LTT.

A 49-year-old man with a past medical history of hypertension, diabetes, and cervical myelopathy, receiving enalapril, empagliflozin, linagliptin, and clonazepam, with no previous drug allergies, and diagnosed with multiple sclerosis initiated DMF following a weekly ascending schedule. Four hours after the first 250-mg dose, he developed generalized pruritic erythematous lesions, throat itching and a sensation of pharyngeal blockage. He required emergency evaluation, where symptoms resolved after treatment with antihistamines and corticosteroids. DMF was discontinued, with no further reactions. Although the clinical pattern, timing, and complete resolution after drug withdrawal initially suggested an immediate hypersensitivity reaction, the allergological evaluation supported a delayed-type hypersensitivity mechanism. In contrast to previously reported delayed maculopapular or urticarial eruptions attributed to DMF through patch testing or lymphocyte transformation test positivity, this case presented with a rapid-onset systemic reaction.

No alternative trigger was identified. Controlled challenge test (CCT) was not realiced due to LTT positivity and clinical severity.

This case highlights that dimethyl fumarate hypersensitivity may present with an immediate-onset clinical picture despite an underlying delayed-type immune mechanism. A positive lymphocyte transformation test with negative skin and patch tests supports the role of T-cell–mediated reactions even in rapidly developing systemic presentations. Awareness of this atypical phenotype is essential to avoid misclassification of the reaction mechanism and to guide appropriate diagnostic and management strategies in patients receiving DMF.