Erythema multiforme (EM) is an uncommon acute mucocutaneous illness with target lesions primarily on the face and limbs. Slow-onset hypersensitivity reactions to infections (including herpes simplex virus and mycoplasma pneumonia) and medicines (including antibiotics, anticonvulsants, and nonsteroidal anti-inflammatory drugs) cause EM. A 4-year-old male with EM after taking metamizole, ampicillin, cloxacillin, and an unknown puffer, the major developed lip sores and blisters on various places of his body. Dermatological examination revealed haemorrhagic crusts on the lips. On both hands and feet, typical target lesions with central blisters, purplish red in color, well-defined boundaries, round to oval in form, and variable size were seen. There were erythematous macules and genital oedema. A blood test revealed higher levels of leucocytes and CRP. Serological testing revealed no IgG, IgM, or anti-HSV1&2 antibodies. The X-ray of the chest was normal. Clinical improvement occurred after elimination of suspected drugs and intravenous dexamethasone, gentamicin, and paracetamol, oral cetirizine, fusidic acid 2% cream, 0.9% NaCl compress, and sterile gauze. The diagnosis of EM was established based on the presence of multiple typical target lesions with central blisters, symmetrical distribution on the extremities (dorsal surfaces of hands and feet), and involvement of lip and genital mucosal lesions after taking drugs. Negative IgG and IgM Anti HSV 1&2 test results lead to the diagnosis of drug allergy-related Erythema Multiforme Major.
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