Kounis Syndrome

Kounis syndrome, also known as allergic angina or allergic myocardial infarction, is when patients suffer severe chest pain or heart attack due to allergic reactions.  Kounis syndrome is caused by mast cell activation causing vasospasm of the coronary artery. About 0.002% of acute heart attacks are due to Kounis syndrome.  There are, to date, over 300 cases described in literature.

There are two well defined variants of Kounis Syndrome.  Type I is defined by coronary spasm (spasm of one of the major blood vessels of the heart.)  This may be endothelial dysfunction or microvascular angina.  These patients often have normal coronary arteries with no predisposing factors.  Release of mast cell mediators can induce coronary spasm without the increase of cardiac enzymes and troponins , or it can progress to myocardial infarction (heart attack) with raised cardiac enzymes and troponins.  Type II is defined by coronary thrombosis (blood clot formation inside one of the major blood vessels of the heart.)  These patients sometimes have preexisting coronary disease.  Mast cell mediators can cause spasm with normal cardiac enzymes and troponins, but lead to rupture of the vessel resulting in heart attack.

A third type of Kounis Syndrome has been proposed pertaining to stent thrombosis.  In these patients, biopsies of the thrombosis show high eosinophils and mast cells.  Chest pain occurs during an allergic reaction and shows ischemic changes on the ECG.  Enzymes and troponins are negative and coronary angiogram is normal.  Tryptase and histamine are elevated. 

Symptoms of Kounis Syndrome include chest pain, faintness, nausea, malaise, shortness of breath, difficulty in swallowing, abdominal pain, numbness, vomiting, fainting, itching, urticaria, sweating, paleness, low blood pressure and cardiorespiratory arrest.  ST elevations in anterior and inferior leads are sometimes seen, but the ECG can show nonspecific ST-t wave changes, or can show nothing.  When it progresses, it usually leads to inferior wall myocardial ischemia/infarction, still with a normal angiogram.  The right coronary artery is usually the one vasospasming.

A very similar syndrome is hypersensitivity myocarditis.  They are differentiated by the presence of eosinophils, atypical lymphocytes and giant cells in the myocardial biopsy.  They are treated the same way.

Treatment is two-pronged, requiring intervention for both the cardiac events and for the anaphylaxis.  The former is treated with oxygen, nitrates and calcium channel blockers.  Diuretics and inotropics may be used in some patients.  Anaphylaxis should be treated with H1 and H2 antihistamines administered intravenously.  Use of steroids is not well described in Kounis Syndrome, but is thought to be safe and appropriate. 

Fluid support is extremely important.  The increased vascular permability (leaky blood vessels) in anaphylaxis can force 50% of the fluid in the vessels into the spaces outside of the vessels where the body can’t it in only 10 minutes.  In adults, 1-2L of normal saline should be administered at a rate of 5-10 mg/kg in the first five minutes of treatment.  Children can receive up to 30 ml/kg in the first hour.  Despite the necessity of fluids, care must be taken not to fluid overload. 

In Kounis Syndrome, use of epinephrine to treat anaphylaxis may not provide enough benefit to outweigh the risks.  Epinephrine can cause coronary vasospasm, cardiac ischemia and arrhythmia.  The accompanying increase in blood pressure in Kounis Syndrome patients given epinephrine can cause brain bleeding.  It is more likely to cause coronary vasospasm in patients who previously received beta blockers.  In these patients, glucagon or methoxamine can be considered. 

References:

Biteker M.  Current understanding of Kounis Syndrome.  Expert Rev Clin Immunol 2010 Sep;6(5):777-88.