Kounis syndrome induced by oral intake of aspirin: case report and literature review
Abdelkader Jalil El Hangouche1,2,3,&, Ouiame Lamliki1, Latifa Oukerraj1, Taoufiq Dakka2, Nawal Doghmi1, Jamila Zarzur1, Mohammed Cherti1
1Department of Cardiology B, Ibn Sina Hospital, Mohammed V University, Rabat, Morocco, 2Exercise Physiology and Autonomic Nervous System Team "EPE-SNA", Faculty of Medicine and Pharmacy of Rabat, Mohammed V University, Rabat, Morocco, 3Laboratory of Physiology, Faculty of Medicine and Pharmacy of Tangier, Abdelmalek Essaâdi University, Tangier, Morocco
Abdelkader Jalil El Hangouche, Department of Cardiology B, Ibn Sina Hospital, Mohammed V University, Rabat, Morocco
The Kounis-Zavras syndrome is defined as the coincidental occurrence of acute coronary events and hypersensitivity reactions following an allergic reaction including a mast-cell degranulation of vasospastic mediators. This report describes a case of Kounis-Zavras syndrome in the setting of aspirin-induced asthma also known as Samter-Beer triad combining nasal polyps, asthma, and aspirin allergy leading to vasospasm and myocardial infarction. All physicians should be aware of The Kounis syndrome and always keep that unique clinical entity in mind to recognize it promptly and direct the therapy at suppressing the allergic reaction.
Kounis syndrome is currently the term used for allergic angina pectoris or allergic myocardial infarction involving release of inflammatory cytokines through mast cell activation, which leads to coronary artery vasospasm and/or atheromatous plaque erosion or rupture [1, 2]. This syndrome includes the whole clinical spectrum of acute myocardial ischemia, from angina pectoris, the more frequent clinical presentation, to acute myocardial infarction (MI), which is relatively rare . There are three variants of Kounis syndrome have been defined. Several causes have been described ables to induce this syndrome such as drugs, insect stings, foods, environmental exposures and medical conditions . We report a case of Kounis-Zavras syndrome caused by taking aspirin in a woman With Samter's Triad.
Patient and observation
A 49-year-old woman with no past medical history or cardiovascular risk factors presents to the emergency department with severe chest pain and shortness of breath. Review of system revealed left hip pain for which patient took aspirin 1 g couple of hours prior to her current presentation. Further history reveals that she experiences similar symptoms of chest pain and shorness of breath after taking aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs). On arrival, the heart rate was 100 bpm, blood pressure: 120/70 mmHg. Physical exam reveals bilateral expiratory lung wheezing. Chest X ray was unremarkable, ECG showed ST segment elevation in the inferior leads. Transthoracic echocardiography showed a kinetic abnormalities of anterolateral and inferior walls with a left ventricule ejection fraction of 35%.
The initial troponin I us was makeredly increased with concentration of 50 ng/ml (147 times the normal laboratory value). Coronary angiogram revealed a severe stenosis in the ostium of Right coronary artery (RCA) and a discrete stenosis in the distal left anterior descending artery (LAD). A percutaneous angioplasty was performed on RCA lesion. Repeated echocardiogram showed an improvement of the left ventricule ejection fraction to 50%. Patient was discharged on standard medical therapy including aspirin and clopidogrel.
In the subsequent month, patient had multiple recurrences of chest pain asthma attacks and was admitted with a NSTEMI a month later. Repeat coronary angiography showed a patent LAD stent and severe diffuse stenosis affecting all coronary arteries. This time patient was treated with intracoronary nitroglycerin with relieve of symptoms (Figure 1). The new occurrence of asthma attacks associated with asprin consumption was finalty related to Samter's syndrome.
Sinus tomography and a nasal endoscopy revealed the presence of bilateral nasal polyposis confirming the diagnosis of the aspirin-exacerbated respiratory disease (AERD) diagnosed as the coexistence of asthma, nasal polyps and aspirin allergy (Figure 2). Aspirin was discontinued and patient discharged on Clopidogrel. Patient remained free of asthma attack and chest pain during two year follow-up.
The association of nasal polyps, asthma and hypersensitivity to aspirin
was first described by Widal et al in 1922 and thereafter popularized by
Samter and Beers in 1968 referring to this clinical triad .
This syndrome has been termed "Syndrome de Widal" or "Samter's Triad." and
it affects 5-10% of patients with asthma. In patients with cardiovascular
diseases the incidence is unknown .
The pathophysiology of Samter's triad is not fully understood. It's believed
that hypersensitivity to aspirin is non-IgE-mediated and results of shunting
of the arachidonic pathway by cyclooxygenase-1 inhibition with overproduction
of cysteinyl leukotrienes and release of inflammatory mediators, such as
tryptase and histamine, from mast cells and eosinophils. It was observed
that in these patients cysteinyl leukotrienes and their receptors are elevated
at baseline, which considerably increase after NSAIDs ingestion. Since the
chronic airway inflammation persists even with strict avoidance of aspirin
and other NSAIDs, the ingestion of aspirin simply exacerbates the asthma
but does not cause the asthma .
The real incidence of the Kounis Zavras syndrome is not well known and most of
the data in the literature comes from isolated clinical cases (almost 300)
[1-6]. Three variants have been described. Type I variant
refers to patients with normal or near normal coronary arteries without
predisposing factors for coronary artery disease, in whom the acute allergic
attacks can induce coronary artery spasm leading to either coronary spasm
without raised cardiac enzymes and troponins or acute myocardial infarction
[7, 8]. Type II variant refers to
patients with quiescent preexisting atheromatous coronary plaque susceptible
to erosion or rupture, while an acute allergic insult, leading to acute
myocardial infarction . Type III variant includes
patients with late or very late pharmacoactive stent thrombosis. It's thought,
in those patients, the hypersensitivity to the compound of nickel alloys,
eluted drugs and polymers present in the stent trigger an inflammatory reaction
developing over a few days or weeks after the implementation of the stent
. This hypothesis is supported by some cases of acute
pharmacoactive stent thrombosis occuring in predisposed patients with history
of atopy, asthma or other related conditions [7, 10, 11].
Our case had a combined variant of Kounis syndrome (Type I and Type II).
Several chemical substances seems to be implicated in Kounis syndrome (tryptase,
chymase, histamine) that are massively released in cardiac tissue, coronary
arteries and plaques by mast cells during immunological reaction [1-12].
Histamine is the most important one, and has strong vasoconstrictive effects
mediated by H1- receptors . Also mast cells are found
extensively in and around thrombi, and could contribute to the destabilization
and maturation of thrombi by the anticoagulant effect of heparin and tryptase-induced
degradation of fibrinogen .
Many etiologies of Kounis syndrome have been reported as drugs (antibiotic, analgesic,
nonsteroidal antiinflammatory, anticoagulant, corticosteroid, heparin, Intravenous
anesthetic, skin disinfectant, Thrombolytic ..) or environmental exposure (ant
sting, bee sting, viper venom, wasp sting, jellyfish sting, latex contact, Shellfish
]. To our knowledge, there is a few cases, reported
in the literature, of kounis syndrome occurred in the setting of allergy to acetylsalicylic
acid (aspirin), this is the fourth case [2-14
]. The sharp
rise in cysteinyl leukotrienes after aspirin ingestion in Samter's triad is responsible
of myocardial ischemia in patients with normal coronary artery, presumably due
to coronary vasospasm [15
Management of Kounis syndrome consists in treating both allergic and cardiac
symptoms, in the same time, which may have contradictory effects; indeed, some
administered drugs may aggravate the heart function or worsen the allergic reaction
]. Guidelines for the treatment of allergic angina pectoris
are lacking; therefore, the efficacy of the treatment is based on individuals
cases report [1
]. In patients with the type I variant, treatment
of the allergic event alone may abolish symptoms by using intravenous hydrocortisone
and antihistamines. The administration of vasodilators like calcium channel blockers
and nitrates may be considered to reduce hypersensitivity-induced vasospasm.
In patients with the type II variant, treatment should be started with an acute
coronary event protocol, associated with corticosteroids and antihistamines.
Whereas, in patients with the type III variant an acute myocardial infarction
protocol should be realized with urgent aspiration of intra-stent thrombus [17
However, administration of the usual dose of epinephrine (the drug of choice
used in anaphylaxis) in patients under the effect of beta-blockers may exaggerate
coronary spasm due to unopposed activity of alpha-adrenergic receptors [17
Furthermore, beta blockers may enhance the generation and release of anaphylaxis
mediators and their effects on end organs [20
Treatment of aspirin-exacerbated respiratory disease includes the substitution
of another category of antiplatelet agents, such as thienopyridines, or a desensibilization
as an alternative for patients who are allergic to aspirin and need long-term
therapy of aspirin for cardiovascular diseases [5
]. We tried
a desensibilisation for our patient without much success. Considering the persistence
of symptoms and especially considering the frequency, and the risk of recurrence
of angina pectoris if spaced taking aspirin; The aspirin intake was stopped and
since then, the patient has taken only clopidogrel as antiplatelet agent.
In recent years, our understanding of Kounis syndrome has improved. In this article, we are reporting a rare clinical entity of coronary spasm caused by taking non-steroidal anti-inflammatory resulting in acute myocardial infarction, and in which case the only eviction of the allergen has led to the cessation of symptoms.
The authors declare no competing interest.
All the authors have read and agreed to the final manuscript.
Figure 1: coronary angiograms before and after intracoronary nitroglycerin; (A) left coronary angiogram with a tubular severe stenosis in the distal LAD and a subtotal occlusion of the first diagonal; (B) left coronary angiogram after intracoronary nitroglycerin injection; the spasm in the distal LAD is completely relieved, the subtotal occlusion of the diagonal is partially improved; (C) right coronary artery (RCA) with patent stent in the proximal segment and diffuse severe stenosis in the mid to distal vessel; (D) RCA after intracoronary nitroglycerin injection with complete relief of the spasm
Figure 2: sinus tomography revealing the presence of bilateral nasal polyposis
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