The phenomenon we now called Kounis Syndrome has previously been called by names like morphologic cardiac reactions, acute carditis and lesions with basic characteristics of rheumatic carditis. It is sometimes still referred to as allergic angina or allergic myocardial infarction/heart attack depending upon the presentation. Allergic angina, which affected patients as microvascular angina, was first noted to progress to allergic heart attack in 1991.
In a small study done at a hospital, 31 patients with anaphylaxis or non-anaphylactic severe allergic reactions had higher serum troponin I than healthy control patients. Among those 31 patients, those that experienced anaphylaxis had the highest troponin I overall. This report, and similar findings, indicates that cardiovascular damage may be a frequent component of anaphylaxis, well beyond what is reported.
Mast cell patients often struggle to identify which is the chicken and which is the egg in the many instances of comorbid conditions. There is no such confusion here – mast cell activation causes Kounis Syndrome. Tryptase increases in peripheral blood during a spontaneous heart attack. However, when coronary spasm is induced with medications, there is no such increase in tryptase. In instances where Kounis Syndrome was caused by disruption of an atherosclerotic plaque, mast cells entered the lesion and released mediators prior to the initiation of the coronary event.
Stress is well known to induce mast cell degranulation. It has been documented in dozens of papers from various disciplines in the last twenty years. Corticotropin releasing hormone (CRH) is a stress hormone that can bind to the CRHR-1 receptor on mast cells, inducing the manufacture of VEGF. At the same time as CRH is released, neurotensin can also be released. Experimental work has shown that stress induced mast cell degranulation can be compromised if the neurotensin receptor is blocked.
Reactive oxygen species can activate mast cells and induce sensory nerves to release substance P. Substance P is a potent mast cell degranulator, inducing secretion of histamine and release of VEGF and other inflammatory mediators. These multiple activation pathways triggered by stress result in mast cell mediator release, which can induce coronary hypersensitivity syndromes such as Kounis Syndrome.
References:
Kounis NG, et al. Kounis Syndrome (allergic angina and allergic myocardial infarction). In: Angina Pectoris: Etiology, Pathogenesis and Treatment 2008.
Lippi G, et al. Cardiac troponin I is increased in patients admitted to the emergency department with severe allergic reactions. A case-control study. International Journal of Cardiology 2015, 194: 68-69.
Kounis NG, et al. The heart and coronary arteries as primary target in severe allergic reactions: Cardiac troponins and the Kounis hypersensitivity-associated acute coronary syndrome. International Journal of Cardiology 2015, 198: 83-84.
Fassio F, et al. Kounis syndrome: a concise review with focus on management. European Journal of Internal Medicine 2016; 30:7-10.
Kounis Syndrome: Aspects on pathophysiology and management. European Journal of Internal Medicine 2016.
Kounis NG. Kounis syndrome: an update on epidemiology, pathogenesis, diagnosis and therapeutic management. Clin Chem Lab Med 2016
Kounis NG. Coronary hypersensitivity disorder: the Kounis Syndrome. Clinical Therapeutics 2013, 35 (5): 563-571.
Alevizos M, et al. Stress triggers coronary mast cells leading to cardiac events. Ann Allergy Asthma Immunol 2014; 112 (4): 309-315.