Kounis syndrome/allergic coronary spasm
Kounis NG, Zavras GM, Soufras GD, Kitrou MP. Hypersensitivity myocarditis. Ann Allergy 1989;62:71-5.
The Kounis syndrome, named by Professor Nicholas Kounis, is defined as "the concurrence of acute coronary syndromes with conditions associated with mast cell activation, involving interrelated and interacting inflammatory cells, and including allergic or hypersensitivity and anaphylactic or anaphylactoid insults." "It is caused by inflammatory mediators such as histamine, neutral proteases, arachidonic acid products, platelet activating factor and a variety of cytokines and chemokines released during the activation process."{1,2}
1. Kounis NG. Kounis syndrome (Allergic angina and allergic myocardial infarction): A natural paradigm? Int J Cardiol 2006; 110: 7-14. 2. Chen JP, Hou D, Pendyala L, Goudevenos JA, Kounis NG. [...]-eluting stent thrombosis: the Kounis hypersensitivity-associated acute coronary syndrome revisited. JACC Cardiovasc Interv. 2009; 2: 583-93
Kounis syndrome variants
Type I variant: includes patients with normal coronary arteries without predisposing factors for coronary artery disease in whom The Acute release of inflammatory mediators can induce either coronary artery spasm without increase of cardiac enzymes and troponins or coronary artery spasm progressing to acute myocardial infarction with raised cardiac enzymes and troponins
Type II variant: includes patients with culprit but quiescent pre-existing atheromatous disease in whom the acute release of inflammatory mediators can induce either coronary artery spasm with normal cardiac enzymes and troponins or plaque erosion or rupture manifesting as acute myocardial infarction
Clinical implications
It has been shown that the same mediators, released during acute allergic episodes, are increased in blood or urine of patients suffering from acute coronary syndromes of nonallergic etiology. Consequently, the same substances from the same cells are present in both acute allergic episodes and acute coronary syndromes. Does, therefore, Kounis syndrome represent a magnificent natural paradigm and nature’s own experiment in a final trigger pathway implicated in cases of coronary artery spasm and plaque rupture? Drugs and natural molecules which stabilize mast cell membrane and monoclonal antibodies that protect mast cell surface could emerge as novel therapeutic modalities capable to prevent acute coronary and cerebrovascular events.
Causes of Kounis syndrome:
CONDITIONS
Angio-edema
Bronchial asthma
Exercise induced anaphylaxis
Food allergy
Idiopathic anaphylaxis
Mastocytosis
Serum sickness
Urticaria
Churg-Strauss syndrome
DRUGS
Antibiotics
Analgesics
Antineoplastics
Contrast Media
Corticosteroids
Intravenous anaesthetics
Non steroidal
Anti-inflammatory
Drugs (NSAIDs)
Skin disinfectants
Thrombolytics
Anticoagulants
Others
ENVIRONMENTAL EXPOSURES
Ant stings
Bee stings
Wasp stings
Jellyfish sting
Grass [...]
Poison ivy
Latex contact
Limpet ingestion (The kiss of death)
Millet allergy
Shellfish eating (The kiss of death)
Viper venom poisoning
[...]-INDUCED KOUNIS SYNDROME:
ANTIBIOTICS
Ampicillin
Ambicillin/sulfactam
Amoxicillin
Amikacin
Cafazolin
Cefoxitin
Cerufoxime
Cephradine
Cinoxacin
Lincomycin
Penicillin
Sulbactam/cefoperazone
Sulperazon
Vancomycin
CONTRAST MEDIA
Iohexone
Loxagate
Meglumine diatrizoate
Sodium indigotindisulfonate
CORTICOSTEROIDS
Betamethasone
Hydrocortisone
ANALGESICS
Dipyrone
ANTINEOPLASTICS
5-fluoroucacil
Capecitabine
Carboplatin
Denileukin
Interferons
Paclitaxel
Vinca alkaloids
INTRAVENOUS ANESTHETICS
Etomidate
Rocuronium bromide
Suxamethonium
Trimethaphan
NSAIDs
Diclofenac
Naproxen
THROMBOLYTICS AND ANTICOAGULANTS
Heparin
Lepirudin
Streptokinase
Urokinase
SKIN DISINFECTANTS
Chlorhexidine
Povidone-iodine
OTHERS
Allopurinol
Enalapril
Esmolol
Dextran 40
Fructose
Insulin
Iodine
Protamine
Tetanus antitoxin
Glaphenine
TREATMENT OF KOUNIS SYNDROME:
1. Treatment of type I variant: Treatment of allergic event alone can abolish type I variant! a.Give corticosteroids and antiistamines b.Give vasodilators e. g. nitrates and Ca-blockers
2. Treatment of type II variant: a. Apply acute coronary event protocol + corticosteroids and antihistamines b. Give vasodilators e. g. nitrates and Ca-blockers when appropriate
One should bear in mind that:
- Epinephrine is life saving in anaphylaxis but in Kounis syndrome can aggravate ischemia and induce coronary vasospasm. Sulfide free epinephrine is recommended I.M. 0.2-0.5 mg (1:1000) of aqueous solution is preferable.
- In patients on b-blockers epinephrine may be ineffective. It may also promote more vasospasm due to unopposed alpha adrenergic effect. Glucagon may be considered.
- Avoid opiates such as morphine, codeine and meperidine since they can induce massive mast cell degranulation and aggravate allergic reaction.
- Fentanyl and its derivatives show a slight mast cell activation and should be the drugs of choice when narcotic analgesia is necessary
Literature
1950: Pfister CW, et al. Acute myocardial infarction during a prolonged allergic reaction to penicillin. Am Heart J 1950; 40: 945 1965: Zosin P, et al. Allergic myocardial infarction. Romanian Medical Review 1965;19: 26 1991: Kounis NG, et al. Histamine-induced coronary artery spasm: the syndrome of allergic angina. Br J Clin Pract 1991; 45: 121 1995: Constantinides P. “ Allergic reactions can promote plaque disruption” Circulation 1995; 92: 1083 1996: Kounis NG, et al. Allergic angina and allergic myocardial infarction. Circulation 1996; 94: 1789 1998: Braunwald E. “ Allergic reactions with mediators such as histamine or leukotrienes acting on coronary smooth muscle can induce vasospastic angina” Circulation 1998;98: 2219 2003: Zavras GM, et al. Kounis syndrome secondary to allergic reaction. Int J Clin Pract 2003; 57: 62 2006: Kounis NG. Kounis syndrome. Int J Cardiol 2006; 119: 7 2006: Kounis NG, et al. Hypersensitivity to DES: a manifestation of Kounis syndrome? J Am Coll Cardiol 2006; 48: 592 2007: Kounis NG, et al. Coronary stents , Hypersensitivity and the Kounis Syndrome. J Interv Cardiol 2007; 20: 314 2008:Tavil Y, et al. Kounis syndrome secondary to amoxicillin/clavulanic acid use. Int J Cardiol. 2008 20; 124: e4-7 2009: Chen JP, Hou D, Pendyala L, Goudevenos JA, Kounis NG. [...]-eluting stent thrombosis: the Kounis hypersensitivity-associated acute coronary syndrome revisited. JACC Cardiovasc Interv. 2009; 2: 583-93.