Severe distributive shock, neutrophilic dermatosis, and Kounis syndrome in the setting of azathioprine hypersensitivity syndrome

Abstract Background: Azathioprine is a purine synthesis inhibitor used as an immunosuppressive therapy for many immune-mediated diseases. Azathioprine hypersensitivity reaction is a rare, life-threatening adverse reaction characterized by a range of multisystem manifestations including fever, abdominal pain, arthralgias, erythematous cutaneous eruption, acute renal failure, neutrophilia, and more rarely, distributive shock. Furthermore, allergic coronary vasospasm (Kounis syndrome) has been described as a reaction to several allergens, but has previously never been associated with azathioprine or its hypersensitivity syndrome. Case Presentation: We describe a case of a 59-year-old male with Crohn’s disease who developed severe azathioprine hypersensitivity syndrome that included distributive shock, cutaneous eruption of neutrophilic dermatosis, and ST-elevation acute coronary syndrome consistent with Kounis syndrome. Clinical improvement was seen after cessation of azathioprine and administration of glucocorticoid therapy. This case report is the first of its kind to describe such a severe reaction to azathioprine, especially with the occurrence of Kounis syndrome. Conclusion: In patients receiving azathioprine, hypersensitivity syndrome, distributive shock, neutrophilic dermatosis, and Kounis syndrome should be recognized as potential adverse events.