Coronary hypersensitivity disorder: the Kounis syndrome

Background: When allergy or hypersensitivity and anaphylactic or anaphylactoid insults lead to cardiovascular symptoms and signs, including acute coronary events, the result might be the recently defined nosologic entity Kounis syndrome. Vasospastic allergic angina, allergic myocardial infarction, and stent thrombosis with occluding thrombus infiltrated by eosinophils and/or mast cells are the 3 reported variants of this syndrome.

Objective: The purpose of this review was to highlight and consolidate the recent literature on allergic angina and allergic myocardial infarction and to propose new therapeutic modalities for stabilizing mast cells.

Methods: A search for current literature on the pathophysiology, causality, clinical appearance, variance, prevention, and treatment of Kounis syndrome was conducted.

Results: Kounis syndrome is caused by inflammatory mediators such as histamine; neutral proteases, including tryptase, chymase, and cathepsin-D; arachidonic acid products; platelet-activating factor; and a variety of cytokines and chemokines released during the mast-cell activation. Platelets with Fc γ receptor (FcγR) Ι, FcγRII, FcεRI, and FcεRII also have a role in the activation cascade. The same mediators released from the similar inflammatory cells are involved in acute coronary events of nonallergic etiology. These cells are not only present in the involved region before plaque erosion or rupture but also release their contents just before an acute coronary event. Pro-inflammatory mediators similar to those found in Kounis syndrome are found in some cases with nonallergic etiology, suggesting that this is a more general problem. The acute coronary and cerebrovascular events in Kounis syndrome may be prevented by the inhibition of mast-cell degranulation. Substances and natural molecules that protect the mast-cell surface and stabilize the mast-cell membrane are emerging as novel agents in the prevention of acute coronary and other arterial events.

Conclusions: The 3 reported variants of Kounis syndrome-vasospastic allergic angina, allergic myocardial infarction, and stent thrombosis with occluding thrombus-are caused by inflammatory mediators. Agents that inhibit mast-cell degranulation may be efficacious in preventing the acute coronary and cerebrovascular events of Kounis syndrome.