Case Report: Bullous erythema multiforme induced by omalizumab

Bullous erythema multiforme (BEM) is an acute immune-mediated mucocutaneous disease, with drug induction being one of its common causes. Omalizumab, a recombinant humanized IgG1 monoclonal antibody targeting free IgE, is widely used in chronic spontaneous urticaria and asthma due to its favorable safety profile, while severe cutaneous bullous adverse reactions induced by it are extremely rare. We report a 36-year-old female patient with a history of bronchial asthma, allergic rhinitis, allergic conjunctivitis, and chronic spontaneous urticaria who developed generalized wheals. After the first subcutaneous injection of omalizumab 300 mg, multiple raised, edematous erythematous papules and plaques, vesicles, and bullae appeared on the trunk, limbs, palms, soles, and oral mucosa 17 days later, accompanied by fever, chills, and fatigue. Laboratory examinations showed elevated eosinophil count and IgE level, and skin biopsy from the left upper limb revealed focal epidermal necrotic keratinocytes, intraepidermal and subepidermal blister formation, and massive eosinophilic infiltration. The patient was diagnosed with omalizumab-induced BEM. Initial treatment with methylprednisolone combined with intravenous immunoglobulin (IVIG) was ineffective. The condition was successfully controlled after increasing the dose of methylprednisolone and adding oral upadacitinib. This case suggests that omalizumab may induce BEM, and combination therapy with high-dose glucocorticoids and JAK inhibitors may be an effective strategy for refractory cases. Clinicians should be alert to such rare adverse reactions when using omalizumab.