Abstract
Multiple drug hypersensitivity syndrome (MDHS) is a rare condition characterized by hypersensitivity reactions to at least two chemically unrelated drugs. While non-steroidal anti-inflammatory drugs and antibiotics are the most commonly implicated agents, hypersensitivity to antihistamines is extremely rare. A comprehensive approach, including detailed patient history, skin testing, and drug provocation tests, is essential for the accurate diagnosis and management of MDHS, particularly in patients with multiple drug reactions. When evaluating MDHS, antihistamines should also be considered as potential culprits if suggested by the patient's history. Here, we aimed to present a case of a patient who reported allergic reactions following the administration of diclofenac sodium, paracetamol, COVID-19 mRNA vaccine, clarithromycin, and pheniramine hydrogen maleate. Based on the skin and provocation tests we performed, the patient was diagnosed with multiple drug hypersensitivity along with pheniramine allergy.