KOUNIS SYNDROME

ANKIT GURJAR
 INTRODUCTION
• kounis syndrome discovered by kounis and zavras in 1991.
• in 1998 an editorial published by Braun Wald that describe that vasospastic
angina could be triggered by allergic reactions with mediator like histamine and
leukotrienes acting upon the smooth muscles of coronary artery.
• kounis syndrome is coincidental occurring of acute coronary syndrome with
allergic reaction anaphylactic or anaphylactoid.
• Today, allergic angina and allergic myocardial infraction indicates to Kounis
syndrome.
• serious allergic reactions can be the cause of acute coronary syndrome in patient
with health or altered coronary arteries without involvement of cardiovascular
risk factor
INTRODUCTION
• Mast cells differentiate and mature in tissues, that takes several days or up
to weeks. while the basophils mature in bone marrow from granulocyte
precursors and enter the circulation as mature cells; they do not
immediately go into tissues, they will go late stage of an allergic reaction.
• mast cell are abundant in cardiac tissues so its prudentially locate at the site
of coronary plaque. The areas of plaque erosion or rupture infiltrate by
activated mast cells act on smooth muscles of coronary arteries.
• Although mast cells can go to brain tissue, but due the blood-brain barrier
because IgE antibodies cannot pass through it so the brain is not affected by
allergic reactions.
Types
Epidemiology
• recent reports have shawn that kounis syndrome is found in every race starting from as
group 2- 90 years old and geographic locations.
• kounis syndrome mostly found in southern Europe specially Spain, Italy, Greece, Turkey.
• in the only retrospective study published so far of annual incidence of kounis syndrome
at the emergency department in one year among all the admissions and patient with
allergy was 19.4 per 100,000 and 3.4%(27 of 793).
• “the overall prevalence of Kounis syndrome among the patients hospitalized for allergy,
hypersensitivity, and anaphylactic reactions was 1.1% (unstable angina, 0.2%; ST
elevation myocardial infarction, 0.2%; and nonST elevation myocardial infarction, 0.7%);
a subsequent inpatient mortality rate of 7.0% was noted.
• the Numazu city hospital emergency department japan the annual incidence of kounis
syndrome in patient with anaphylaxis was 2% (2 of 100), one of these patient survived
but other died.at the shizoku hospital of Juntendo university it was 2.2%(3 of 138).
• the incidence of anaphylaxis with circulatory symptoms is estimated at 7.9-9.6/100,00
per year with mortality rate of 0.0001%.
pathophysiology
• the pathophysiology of kounis syndrome coronary artery spasm and atheromatous
plaque erosion or rupture during an anaphylactic reaction.
• the mast cells interact with microphases and T-lymphocytes.
• The areas of plaque erosion or rupture infiltrate by activated mast cells act on smooth
muscles of coronary arteries.
• antigen and antibodies reaction occurs on the surface of mast and basophilic cells that
triggered degranulation of the mast cell and release of inflammatory mediators or
activation of compliment system(C3a,C5a).
• Histamine, neutral protases chymase, heparin, tryptase and cathepsin-D with increase
production of leukotrienes tolboxane , peptides, proteoglycans, cytokines, growth
factors, prostacyclin, platelet-activating factor (PAF) and tumor necrosis factor-α (TNF-
α) all these together plays role of inflammatory mediators in this reaction.
pathophysiology
• Histamine induced increase intimal thicking platelets activation decreased the
diastolic blood pressure and coronary vasoconstriction, tissue factor expiration
and platelets activation.
• the anticoagulatory effect of heparin and tryptase triggered degradation of
fibrinogen which leads to destabilization and maturation of thrombi.
Clinical presentation
• Routine cardiac examination for myocardial injury, biomarkers such as cardiac enzymes
including CPK-MB and troponins.
• histamine and try.tase levels should be undertaken in any patient with any grading of
allergic reaction.
• Cardiac symptoms- chest pain, dyspnea, faintness, nausea, Vomiting, syncope,urticaria,
angina pectoris, coronary vasospasm, acute cardiac failure, myocardial infarction and
sudden cardiac death associated.
• sighn- diaphoresis, hypotension, pallor, palpitation, bradycardia and tachycardia.
• there are so many variety of ECG changes seen in this disease like ST segment elevation,
depression, arrythmia, T wave flattering , T wave inversion, QRS complex prolongation, QT
segment prolongation, sinus tachycardia, sinus bradycardia, nodal rhythm, atrial fibrillation,
ventricular ectopic, bigeminal rhythm any degree of heart block , and can also be seen
resembling with digitalis intoxication.
Clinical presentation
Differential Diagnosis:
• This disease is frequently misdiagnosing with MI, Acute coronary
syndrome and Takayasu myocarditis that’s why literature about
differential diagnosis is still not available on international research
articles. Which we can say the major drawback for this disease. With
that this is syndrome consist of many diseases so its always in
misdiagnose.
DIAGNOSIS
• patients with systemic allergic reactions associated with clinical,
electrocardiographic and laboratory findings of acute myocardial ischemia should
be suspected as having Kounis syndrome.
• modern techniques like cardiac magnetic resonance imaging and myocardial
scintigraphy have helped to confirm the diagnosis.
• Cardiac enzymes such as CK and in particular CK-MB values in diagnosing cardiac
damage associated with allergic or anaphylactic insults.
• Newer techniques such as thallium-201 single-photon emission computer
tomography (SPECT) and 125I-15-(p_x0002_iodophenyl)-3-(R,S) methyl
pentadecanoic acid (BMIPP) SPECT are also available to diagnosing the diseases
DIAGNOSIS
• Dynamic cardiac magnetic resonance imaging (MRI) is also very useful to find out
cardiac involvement in Kounis syndrome.
• Delayed contrast-enhanced images show normal washout in the subendocardial
lesion area in patients with Kounis syndrome type I variant.
• Histamine release from mast cells has short life that circulates for only about 8
min after an allergic event, therefore blood samples should be collected
immediate after the onset of chest pain and before any analgesic, especially
morphine, administration.
Treatment
• Kounis syndrome is a complex acute coronary syndrome that requires rapid treatment.
a full cardiological work-up, including a 12-lead ECG, echocardiogram and cardiac risk
factor modification, is necessary.
• An allergy work include the assessment of other allergies to food, insect stings, drugs
and other environmental agents. Skin tests and food challenges may be useful in
identifying the culprit agent.
• Treatment of Kounis syndrome is challenging because the drugs given to treat cardiac
symptoms can worsen allergy, and the drugs given for the allergic symptoms can
aggravate the cardiac dysfunction.
• In patients with the type I variant- the allergic event alone may end symptoms.
• The use of hydrocortisone at a dose of 5 mg/kg/day and H1 and H2 antihistamines
such as diphenhydramine (1–2 mg/kg) and ranitidine (1 mg/kg), is adequate.
Treatment
• Vasodilators such as calcium channel blockers and nitrates can treat the vasospasm.
sublingual or Intravenous nitroglycerin seems reasonable and safe in patients with Kounis
syndrome, if the blood pressure is satisfactory.
• In patients with the type II variant- treatment should be started with an acute coronary
event protocol, together with corticosteroids and antihistamines.
• Epinephrine, which is the drug of choice and may save lives in anaphylaxis, but can
aggravate ischemia and worsen coronary artery vasospasm in Kounis syndrome.
• so here we use In severe cases, sulfite-free epinephrine Aqueous solution which is
preferable and given intramuscularly, because it has a faster onset of action and remain
more stable concentration compared with the subcutaneous route (recommended IM
dose, 0.2– 0.5 mg [1:1000]).
• In patients with a history of IHD Epinephrine may be ineffective in patients already on
beta-blockers a potent. an alpha agonist,Methoxamine, can also be considered in patients
who do not respond to epinephrine.
Treatment
• due to massive mast-cell degranulation and aggravate allergic reaction, Opioids
such as morphine, codeine, and meperidine given to relieve acute chest pain
should be given with extreme caution in patients with Kounis syndrome.
• Uncoated aspirin should be given to all patients promptly after presentation,
because of severe hypotension due to reduction in cardiac output ,
Acetaminophen (paracetamol) is not recommended, especially by intravenous
route. Fentanyl and its derivatives are weak mast cell triggers and are preferable.
• In patients with the type III variant- In patients in whom allergic symptoms
appears after stent implantation, the antihistamines together with corticosteroids
and mast-cell stabilizers when together given may relieve the symptoms.
Treatment
• treatment includes the current acute myocardial infarction protocol, urgent
aspiration of intrastent thrombus, and its histological examination with staining
for eosinophils (hematoxylin and eosin) and mast cells (Giemsa).
• Adrenaline is not an innocuous drug in anaphylaxis. It has a narrow therapeutic
index, and should be carefully titrated to effect.
• Anaphylaxis guidelines suggest using 100% O2, but routine oxygen administration
in myocardial infarction may be associated with increased mortality. Oxygen
should thus be titrated to normoxia.
• A dietary supplement containing a combination of mast-cell inhibitors and natural
flavonoids also helps.
CONCLUSION
• Kounis syndrome is ubiquitous disease representing a magnificent natural
paradigm. kounis syndrome also known as allergic angina has been describe as an
the co-occurrents of acute coronary syndrome associated with an anaphylactic
reaction. immediately identify the disease and collecting specimen is necessary
for adequate treatment. the optimal treatment of Kounis syndrome re-main
unanswered. further studies needed to understand this disease. more research
and studies needed in konuis syndrome which will enable appropriate
management and better recognition in the patient.Finally, in the international
literature there is no guide for management of this syndrome, but There is scope
to develop multispecialty guidelines to manage this complex condition.
Reference
• https://www.clinicaltherapeutics.com/article/S0149-2918(13)00078-7/pdf
• https://www.medscape.com/viewarticle/753799_15
• https://www.tandfonline.com/doi/full/10.1080/22201181.2016.1154309?src=recsys
• http://www.balkanmedicaljournal.org/uploads/pdf/pdf_BMJ_2099.pdf
• https://www.researchgate.net/publication/317157582_Management_of_Kounis_syndr
ome_Two_case_reports
• http://www.medintensiva.org/en-kounis-syndrome-articulo-S2173572712000872
• http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0034-70942014000400281
• https://www.degruyter.com/view/j/cclm.2016.54.issue-10/cclm-2016-0010/cclm-
2016-0010.xml
• https://www.ncbi.nlm.nih.gov/m/pubmed/29486712/?i=2&from=/31620259/related
• https://www.pestmagazine.co.uk/media/437994/kounis-syndrome-
epidemiology_x0002_april-2017.pdf