Delayed Hypersensitivity Reaction to Oral Dimethyl Fumarate

Abstract

Dimethyl fumarate (DMF) is a molecule derived from fumaric acid that is administered orally for the treatment of relapsing-remitting multiple sclerosis (MS). The mechanism of action of DMF comprises suppression of allergen-induced T-cell proliferation and modulation of the cytokine balance by suppressing only IFN- and not IL-5 [1-2], thus restoring the T H 1/T H 2 balance. It is also involved in interference with the intracellular redox balance and activation of nuclear (erythroidderived 2)-like 2 related factor-mediated antioxidative response pathways leading to additional cytoprotective effects, and it seems to exert a marked effect on mitochondria [1][2][3].We present the case of a 46-year-old woman with relapsing-remitting MS who had received several treatment options. However, given that she was a frequent traveller, she switched to DMF, which is a convenient, practical, efficacious first-line treatment for MS. Several hours after intake of the first dose of 240 mg, she developed generalized confluent and intensely pruritic wheals without angioedema or other systemic symptoms. These were treated at the emergency department with intramuscular methylprednisolone (60 mg) and dexchlorpheniramine (5 mg). She denied having taken NSAIDs, infection, or other possible causes of urticaria and had never experienced urticaria during her lifetime. Following recently published indications [1], we performed a skin prick test (SPT) with DMF at 7 µg/mL and intradermal tests with DMF at 0.7 µg/mL and 0.07 µg/mL. The results were negative. We also carried out a lymphocyte transformation test (LTT) using several concentrations: 70 µg/mL, 35 µg/mL, 15 µg/mL, 7 µg/mL, 5 µg/mL, 3.5 µg/mL, 1 µg/mL, 0.5 µg/ mL, 0.1 µg/mL, and 0.05 µg/mL. The results were positive. Phytohemagglutinin A (PHA) as a control mitogen LTT is considered weakly positive or doubtful if the stimulation index (SI) is between 2 and 3 and definitely positive if the SI is >3

Clinical use of dimethyl fumarate in multiple sclerosis treatment: an update to include China, using a modified Delphi method

“…There have been few reports of hypersensitivity in the literature, despite large numbers of patients treated with DMF. 161,162,163,164,165 Where they have occurred, management has shown a response to steroid and antihistamine treatment.…”