Kounis Syndrome is first described by Nicholas Kounis M.D. as a coincidental occurence of chest pain and allergic reaction, accompanied by clinical and laboratory findings of classical angina pectoris. Observed signs of allergic reaction are hypotension, diaphoresis, pallor and bradycardia, and electrocardiographic findings may show myocardial ischemia, arrythmias and conduction defects (1). Historically, medical reports about cardiovascular symptoms associated with allergic backgrounds are first published more than 80 years ago (3).
In later years, definition of Kounis Syndrome was expanded as: “the concurrence of acute coronary syndromes including coronary spasm, acute myocardial infarction, and stent thrombosis, with conditions associated with mast-cell and platelet activation and involving interrelated and interacting inflammatory cells, such as macrophages and T-lymphocytes, in the setting of allergic or hypersensitivity and anaphylactic or anaphylactoid insults” (4). Additionally, recent researches showed that Kounis Syndrome can also affect the mesenteric (5) and cerebral arteries (6).
Three main types of Kounis Syndrome. Type I variant is the most common form caused by coronary vasospasm, includes patients without underlying coronary artery disease. Inflammatory mediators released from allergic or hypersensitivity reaction causes coronary artery spasm and may have results ranging from mild clinical syndrome without increase of cardiac enzymes and troponins, to acute myocardial infarction with increased levels of those markers. Type II variant includes patients with underlying stable pre-existing atherosclerotic disease in coronary arteries, leading to outcomes ranging from coronary vasospasm and normal levels of cardiac enzymes and troponins, to vasospasm accompanied with plaque erosion or rupture manifesting as acute myocardial infarction. Type III variant includes patients with coronary artery stent thrombosis, in which thrombus material shows presence of eosinophils and mast cells (7).
Main reason of coronary thrombosis is the mast-cell degranulation triggered by allergic or hypersensitivity reactions which results in activating low and high affinity IgE receptors upon the surface of the platelets (8), which in turn trigger the activation, adhesion and aggregation of the platelets. Previous researches upon this subject shows that, even without the setting of allergic or hypersensitivity reaction, mast cells are present in both ruptured coronary plaque sites and also in plaques which are susceptible to both erosion and rupture, thus leading to the conclusion of mast cell presentation at plaque sites ready to degranulate just before the acute coronary event. Same study showed that the ratio of degranulated mast cell infiltrates between the site of the coronary atheromatous erosion or rupture and nearby normal endothelial segments were found in a ratio of 200 to 1 (9). Thus, the patients with coronary artery atheromatous lesions susceptible to erosion or rupture, already contain increased ratio of mast cell infiltration and the setting of allergic or hypersensitivity reaction triggers this mast cell degranulation and platelet activation cascade, leading to coronary thrombus formation.
Main diagnostic workup in suspected Kounis Syndrome includes complete blood count (CBC) with attention to eosinophil levels, cardiac enzymes and troponin I or T, C-reactive protein (CRP), total and spesific (IgE), histamine, chymase, tryptase levels. In differential diagnosis, Takotsubo syndrome or stress-induced cardiomyopathy and hypersensitivity myocarditis should be considered, along with other causes of inflammatory cardiac diseases.
Therapeutic approach is divided in 2; myocardial revascularization and treatment of allergic reaction. Current guidelines don’t have specific treatment algorithm for Kounis Syndrome. Approach on acute coronary syndromes should be based upon ACS guidelines. In this case report; resolution of ST segment changes and chest pain, combined with low probability of underlying coronary artery disease, has led us to perform non-invazive coronary artery imaging, which showed no coronary artery obstruction and/or significant coronary vasospasm. Follow-up therapy was designed according to these findings.
Allergic reactions have three phases; early-phase reaction develops within minutes of exposure to allergen, resulting with releasing of early-phase mediators. Late-phase typically develops after 2–6 hours and peaks 6–9 hours after exposure. Chronic phase is caused by repetitive or prolonged exposure to the allergen. Patient’s initial therapy and follow-up plan should be designed according to these phases of allergic reactions. In this case, we have added selective H-1 anti-histaminic drug oral therapy, and referred the patient to Allergy & Immunology specialist after discharge.
Pericarditis epistenocardica is described as pericarditis occuring within days after myocardial infarction. If the pericarditis develops with delay after the initial infarction, it is described as Dressler Syndrome. Acute pericarditis may develop from different causes. The most common form is idiopathic pericarditis. Other causes include infections (e.g. viral (most commonly), bacterial, parasitic or fungal), cardiac damage (e.g. myocardial infarction, cardiac trauma, pulmonary thromboembolism), infiltrative or inflammatory cardiac diseases, metabolic diseases (e.g. uremic pericarditis), drugs, radiotherapy etc.
Diagnosis of acute pericarditis requires at least 2 of the 4 following criteria: pericarditic chest pain, pericardial rubs, new widespread ST-elevation or PR depression on ECG, and pericardial effusion (new or worsening). Additional supporting findings are elevation of markers of inflammation and evidence of pericardial inflammation by an imaging technique (e.g. CT, CMR). Major predictors of poor prognosis include fever > 38°C, subacute onset, large pericardial effusion, cardiac tamponade and lack of response to aspirin or non steroidal antiinflammatory drugs (NSAID) after at least 1 week of therapy. Minor predictors include myopericarditis, immunosuppression, trauma and oral anticoagulant therapy. Main management of pericarditis include anti-inflammatory therapy with aspirin/ibuprofen with dose decrease every 1–2 weeks, and adjunct therapy with colchicine which is continued for 3 months. Low dose of corticosteroids should be considered if there is a contra-indication or failure of therapy with aspirin/NSAID, with the exclusion of infectious cause or there is a spesific indication (e.g. auto-immune disease). Exercise restriction should be considered until symptom resolution and normalization of CRP, ECG and echocardiography.
Both the Kounis Syndrome and pericarditis are based on inflammatory and/or immunologic mechanisms. Considering this, concommitance of both clinical settings may exist more than previously reported. In this situation, treatment regime should be patient-based, due to the potential involvement of myocardial necrosis, which may be exaggerated with the use of NSAIDs/corticosteroids.