In the very important paper published recently in this Journal (Omalu, Hammers, DiAngelo, & Luckasevic, 2011) the authors described two patients who died suddenly due to isolated eosinophilic coronary arteritis. The first patient had a past history of hypertension, multiple sclerosis, depression, and thyroid dysfunction attributed to Hashimoto's thyroiditis. During the following postmortem examination the anterior descending coronary artery was found without any thrombus formation but the adventitia and media were infiltrated by numerous eosinophils. The second patient had also a past history of hypertension and depression. Microscopic postmortem examination revealed an acute dissection of the proximal left anterior descending coronary artery with eosinophilic infiltration of media and adventitia. The authors of this report postulated that sudden death was due to cardiac arrhythmia induced by atraumatic coronary artery dissection or due to inflammatory coronary vasospasm.
However, they did not search for mast cells in the post-mortem biopsy and they did not refer to the Kounis hypersensitivity acute coronary syndrome (Kounis, Mazarakis, Tsigkas, Giannopoulos, & Goudevenos, 2011).
Kounis syndrome combines acute coronary syndromes with conditions associated with mast cell activation, involving interrelated and interacting inflammatory cells, and includes anaphylactic or anaphylactoid and allergic or hypersensitivity insults. It is caused by preformed and newly synthesized inflammatory mediators released during the anaphylactic process. A subset of platelets bearing FCεRI and FCεRII receptors are also involved in the activation cascade.
Three variants of Kounis syndrome have been described so far. In type I variant coronary spasm, in normal or nearly normal coronary arteries, associated with anaphylactic reaction can progress to myocardial infarction. In type II variant culprit but quiescent pre-existing atheromatous disease combined with anaphylactic reaction can result in acute myocardial infarction. In type III variant, hypersensitivity to any implanted intracoronary stent components can result in devastating intrastent thrombosis.
Kounis syndrome is a hypersensitivity-induced coronary syndrome that shares nearly similar etiology, symptomatology, cardiac manifestations, and laboratory findings with two other hypersensitivity cardiac diseases including eosinophilic arteritis and hypersensitivity myocarditis (Kounis, Zavras, Soufras, & Kitrou, 1989).
Kounis syndrome can rarely complicate the Churg-Strauss syndrome or allergic granulomatous angiitis (bronchial asthma, eosinophilia, vasculitis affecting medium and small-sized arteries and veins in a variety of organs). Churg-Strauss syndrome is sometimes associated with coronary artery spasm (Buhaescu, Williams, & Yood, 2009) or with acute myocardial injury and repeated angina pectoris-like attacks (Suzuki et al., 1991).
Isolated eosinophilic arteritis is a cryptogenic form of coronary arteritis leading to vasospastic angina, myocardial infarction, coronary artery dissection, and sudden death. This entity can also complicate Churg-Strauss syndrome and seems to share the same pathophysiology with type I variant of Kounis syndrome. It is characterized by eosinophilic infiltration of adventitia, media, and intimal subendthelium together with diffusely distributed mast cells (Arena et al., 2010). Eosinophils are bone marrow-derived granulocytic leukocytes, which normally reside in tissues and express H4 histamine receptors and play an important role in the pathophysiology of coronary spasm. Eosiniphilic receptors facilitate eosinophil chemotaxis toward mast cells, which are the major producers of an array of inflammatory soluble mediators, which can induce Kounis syndrome. Soluble mediators secreted by mast cells and eosinophils also modulate reciprocal interactions between these two cells in the so called "allergic effector unit" (Minai-Fleminger, & Levi-Schaffer, 2009). Eosinophilic coronary arteritis has been reported in association with hypersensitivity myocarditis in a patient suffering from bronchial asthma (Rupani, Amonkar, & Deshpande, 2010). The first report of eosinophilic coronary arteritis manifesting as angina pectoris culminated in fatal unstable angina (Kajihara et al., 1988).
Hypersensitivity myocarditis, on the other hand, is an inflammatory disease affecting the cardiac conduction system and the myocardial tissue manifesting mainly as a complication of drug therapy. The only differences between this disease and the Kounis syndrome are that in hypersensitivity myocarditis there is presence of eosinophils, atypical lymphocytes and giant cells in myocardial biopsy, whereas biopsy in Kounis syndrome is typically normal. Furthermore, the coronary angiogram in hypersensitivity myocarditis is normal, whereas angiograms in Kounis syndrome, especially in type II variant, show the presence of coronary artery disease. Mildly elevated cardiac enzymes and mild chest pain are characteristics of drug-induced myocarditis while eosinophilia may be absent in both conditions. Hypersensitivity myocarditis can affect individuals of any age, but cases of Kounis syndrome have been reported in juveniles (Parent, Wearden, Kounis, & Chrysostomou, 2011). Hypersensitivity myocarditis can also complicate Churg-Strauss syndrome (Shanks, Ignaszewski, Chan, & Allard, 2003).
Therefore, all these three pathologic entities seem to share a common pathophysiologic basis. A common pathway between eosinophils, allergy and angina pectoris seems to exist. Forensic nurses should be aware of the existence of these three associated and interrelated clinical entities namely isolated eosinophilic coronary arteritis, hypersensitivity myocarditis, and Kounis syndrome, because they seem to be not rare diseases, but are very rarely diagnosed and very difficult differentiated diseases. In any sudden death, forensic nurses should always search for bronchial asthma and eosinophilia since these manifestations characterize the Churg-Strauss syndrome complications to which are all three above described clinical entities. The failure to recognize them clinically is confirmed at necropsy!
Arena V., Valerio L., Arena E., De-Giorgio F., Stigliano E., Monego G., Capelli A. (2010). Isolated eosinophilic coronary arteritis. Clinical. Pathology, 63
Buhaescu I., Williams A., & Yood R. (2009). Rare manifestations of Churg-Strauss syndrome: Coronary artery vasospasm, temporal artery vasculitis, and reversible monocular blindness-a case report. Clinical Rheumatoly, 28
Kajihara H, Kato Y, Takanashi A, Nakagawa H, Tahara E, Otsuki T, Tsuchioka Y, Amioka H, Okamoto M, & Matsuura H. (1988). Periarteritis of coronary arteries with severe eosinophilic infiltration. A new pathologic entity (eosinophilic periarteritis)? Pathology, Research & Practice, 1988 184
Kounis N.G., Mazarakis A., Tsigkas G., Giannopoulos S., & Goudevenos J. (2011). Kounis syndrome: A new twist on an old disease. Future Cardiology, 7
Kounis N.G., Zavras G.M., Soufras G.D., & Kitrou M.P. (1989). Hypersensitivity myocarditis. Annals of Allergy, 62
Minai-Fleminger Y., & Levi-Schaffer F. (2009). Mast cells and eosinophils: The two key effector cells in allergic inflammation. Inflammation Research, 58
Omalu B., Hammers J., DiAngelo S., & Luckasevic T. (2011). Autopsy features of sudden death due to isolated eosinophilic coronary arteritis: Report of two cases. Journal of Forensic Nursing, 7
Parent B., Wearden P., Kounis N.G., & Chrysostomou C. (2011). Kounis syndrome or allergic coronary vasospasm in a two-year-old. Congenital Heart Disease, 6
Rupani A., Amonkar G., & Deshpande J. (2010). Eosinophillic myocarditis and coronary arteritis in a fatal case of asthma. Indian Journal of Pathology and Microbioly, 53
Shanks M., Ignaszewski A.P., Chan S.Y., & Allard M.F. (2003) Churg-Strauss syndrome with myocarditis manifesting as acute myocardial infarction with cardiogenic shock: Case report and review of the literature. Canadian Journal of Cardiology, 19
Suzuki N., Arai Y., Miyamoto Y., Isokane N., Fukushima N., & Sano Y. (1991). Acute myocardial injury and repeated angina pectoris-like attacks in a young patient with Churg-Strauss syndrome. Nihon Kyobu Shikkan Gakkai Zasshi, 29