Rare Infection Induced Recurrent Erythema Multiforme

Erythema multiforme (EM) is an immune-mediated mucocutaneous disorder, most commonly associated with herpes simplex virus (HSV). Diagnosis relies on characteristic targetoid skin lesions, yet becomes challenging when lesions are confined to oral mucosa, often mimicking recurrent aphthous ulcers (RAU). A 14-year-old girl presented with an 8-year history of recurrent oral ulcers, initially misdiagnosed as RAU. Despite topical therapy (compounded chamomile-lidocaine gel), symptoms persisted. Until developing pathognomonic skin lesions, serological testing revealed acute Toxoplasma gondii infection (IgM+). Comprehensive laboratory evaluations excluded alternative etiologies, including humoral immunity, cellular immunity, autoimmune antibody profile, autoimmune bullous disease antibodies, allergen testing (including cat hair, common foods, dust mites, etc.) and so on. The patient, a cat owner, received anti-toxoplasma therapy (compounded sulfamethoxazole tablets, 0.48 g twice daily) alongside antihistamines (cetirizine) and topical corticosteroids (budesonide suspension). Complete lesion resolution occurred within two weeks, with no recurrence over 24 months. This case establishes Toxoplasma gondii as a novel trigger for EM, broadening its etiological spectrum beyond viral and drug-related causes. Globally, 30-50% of individuals exhibit toxoplasmosis seropositivity, with elevated prevalence among cat owners. We propose toxoplasmosis screening (IgM/IgG) in recurrent EM cases refractory to HSV-targeted therapies, particularly in patients with feline exposure. Toxoplasmosis screening (IgM/IgG) is critical in recurrent EM unresponsive to HSV therapy, particularly with cat exposure. Pathogen-directed treatment achieved sustained remission, emphasizing etiology-driven management. Clinicians should prioritize zoonotic testing in atypical mucocutaneous cases.