143 - KOUNIS SYNDROME (ALLERGIC CORONARY VASOSPASM) IN THE SETTING OF AZATHIOPRINE HYPERSENSITIVITY SYNDROME

Case background: Kounis syndrome, which was first described in 1991 by Nicholas Kounis and George Zavras, and has also been referred to as “allergic angina”, is defined as acute coronary syndrome associated with mast-cell and platelet activation in the setting of an allergic reaction. Kounis syndrome can occur from coronary artery spasm and/or atheromatous plaque erosion or rupture during an allergic or anaphylactic insult. Kounis syndrome seems to be caused by mast cell interaction with macrophages and T-lymphocytes in areas of coronary plaque which can lead to plaque rupture and/or coronary vasoconstriction. Several allergens have been reported (including various drugs, traditional Chinese medicines, insect bites, food allergens, and IV contrast. Recently, COVID-19 has also been proposed as a cause of Kounis syndrome. However, azathioprine has never previously been described as a causative agent.

We describe a case of azathioprine hypersensitivity syndrome in which a patient with Crohn’s disease was prescribed azathioprine developed severe distributive shock, a diffuse rash with biopsy consistent with neutrophilic dermatosis, and allergic coronary vasospasm (Kounis syndrome) with elevated cardiac enzymes, transient ST elevation MI, but a lack of obstructive coronary disease at time of coronary angiography.

Management Challenges: Azathioprine hypersensitivity syndrome and Kounis syndrome are both under-recognized adverse reactions of azathioprine. Given the presentation of Kounis syndrome in the setting of severe azathioprine hypersensitivity syndrome demonstrated in this case, azathioprine hypersensitivity should be considered in the differential diagnosis of patients recently started on the medication presenting with a distributive shock and acute coronary syndrome picture. As in this case, cessation of azathioprine appears to be effective in resolving both reactions. Avoidance of azathioprine should be strongly recommended in patients who develop this severe reaction, especially given the availability of alternate immune-mediating therapies.