Accumulation of eosinophils, mast cells, and basophils in the spleen and the coronary arteries in anaphylactic deaths: is the Kounis hypersensitivity associated syndrome present?

In a very interesting study published in Forensic Science,Medicine, and Pathology [1] it was found that measure-ment of eosinophils and mast cells in the spleen combinedwith serum tryptase measurement could diagnose anaphy-laxis and anaphylactic death with a high degree of cer-tainty. The authors stated that anaphylactic death cannot bediagnosed by autopsy alone or by counting mast cells in thelung and airways because these methods have failed to giveconsistent results. The search for other tissues infiltrated byallergic inflammatory cells could prove of paramountimportance in diagnosing anaphylactic sudden death. Theyrecommended that splenic tissue should be sampled forimmunohistochemical examination in all cases of unwit-nessed sudden death.Eosinophils, mast cells, and basophils are importanteffector cells in the allergic response and they have beenimplicated in the pathogenesis of anaphylaxis. Whilediagnosing the cause of sudden death is a challenging taskfor both physicians and forensic pathologists, anaphylacticetiology is rarely suspected. Frequently, sudden death casesare attributed to myocardial involvement, but unrecognizedanaphylaxis may accompany up to 13 % of sudden unex-pected deaths in adults [2]. There is experimental andclinical evidence that anaphylaxis is frequently associatedwith myocardial involvement due to coronary artery spasmand thrombosis manifesting as Kounis type I and Kounistype II variant [3]. Some experiments have shown thatanaphylactic cardiac damage is not due to peripheralvasodilation but is the result of the action of anaphylacticmediators on the coronary vasculature [4]. Clinically, thereare patients with anaphylactic cardiac shock who do notrespond to fluid replacement but need anti-allergic andcurrent myocardial infarction protocol treatment, thusdenoting that the heart and especially the coronary arteriesare primarily affected [5, 6]. However, differentiatingglobal myocardial hypoperfusion from a primary cardiacmyocardial suppression due to mast cell mediator action isclearly challenging and combined myocardial suppressionand peripheral vasodilatation might occur simultaneously.There are reports of sudden death due to coronary arteryspasm in which the coronary arteries are involved. In apatient with repeated episodes of coronary spasm, who diedsuddenly following cessation of his treatment, the numberof adventitial mast cells was found to be increased [7]. Inthis patient, histologic sections in all three major coronaryarteries, including the area of spasm, were stained withtoluidine blue and showed increased mast cells. In the samereport, two additional subjects with sudden cardiac deathalso had increased mast cells in their coronary arteries withthe highest counts in atherosclerotic and hemorrhagic pla-ques. Furthermore, coronary arteries of cardiac patients arehyper-reactive and contain stores of amines deriving frominflammatory cells that are the main culprits in inducingcoronary spasm [8]. Type I and type II variants of theKounis syndrome have led to coronary artery spasm andsudden death in two patients with drug-eluting stents. It is