Azathioprine-Induced Hypersensitivity Syndrome Presenting as Sepsis-Like Syndrome in a Patient With Mucous Membrane Pemphigoid: A Report of a Rare Case

Azathioprine hypersensitivity syndrome (AHS) is a unique, idiosyncratic drug reaction with typical occurrence within the first 2-4 weeks of azathioprine initiation. It features low-grade fever, gastrointestinal symptoms, malaise, and sometimes life-threatening hemodynamic instability. It commonly masquerades as septic shock with an unknown source of infection or an underlying autoimmune pathology flare-up. We present a case of a woman in her late 60s who was started on azathioprine for a new diagnosis of mucous membrane pemphigoid. The patient presented on two occasions with circulatory shock, lactic acidosis, and acute kidney injury occurring approximately two weeks after azathioprine exposure, including after inadvertent rechallenge. An extensive infectious and endoscopic workup was negative. The diagnosis of AHS was established, given the temporal association of azathioprine exposure and symptom occurrence and a negative alternative etiological workup. The resolution of the patient's symptoms within a few days of drug discontinuation further strengthened the diagnosis. The patient was subsequently transitioned to mycophenolate mofetil for her mucous membrane pemphigoid with no symptom recurrence and appropriate disease control. This case highlights the importance of recognizing AHS as a unique cause of unexplained septic shock-like presentations in patients with recent exposure to azathioprine, and the danger of inadvertent rechallenge of azathioprine. This case also highlights the rare presentation of AHS with significant circulatory collapse, lactic acidosis, and no cutaneous involvement.