Non-steroidal anti-inflammatory drugs (NSAID)-induced allergic myocardial infarction (Kounis syndrome)

INTRODUCTION

Kounis syndrome (KS) or allergic myocardial infarction is a rare life-threatening condition characterized by the acute onset of chest pain with symptoms of coronary artery spasm following an allergic reaction.¹ The syndrome is named after Dr Nicholas Kounis, who first described it in 1991. The syndrome is caused by the release of inflammatory mediators due to an inflammatory response to an allergen, which can result in the constriction of coronary arteries, leading to myocardial infarction or even cardiac arrest. Prompt recognition and treatment are crucial to managing KS, including discontinuation of the offending drug or allergen, administration of antihistamines or corticosteroids, and, in severe cases, interventions to restore coronary blood flow.² In our case report, we underscore drug-induced KS due to non-steroidal anti-inflammatory drugs (NSAID). Healthcare professionals and patients should be aware of this potential complication of NSAID use, especially in individuals with a history of allergies.

THE CASE

A 40-year-old female with no co-morbid conditions presented to the medical emergency following administration of injection diclofenac for muscular pain. She developed a rash after 60 minutes of receiving the drug and experienced angina-type chest pain after 20 minutes of the rash. She also developed an acute onset of shortness of breath with palpitations. The patient had no similar episodes and had no allergy to diclofenac in the past. She had no family history of heart disease or substance abuse. On examination, the patient was anxious and tachypnoeic. Skin examination showed erythema at the site of diclofenac injection and generalized maculopapular rash with involvement of both upper limbs, trunk, abdomen, and lower limbs. Her blood pressure was 90/60 mmHg, respiratory rate was 28/minute, pulse rate of 102/minute, SpO2 96% with 4 litres of oxygen/minute. On auscultation, bilateral inspiratory crepitations were present.

Electrocardiogram (ECG) showed diffuse ST depression and ST elevation in aVR (Fig. 1), suggestive of left main coronary occlusion. The cardiac enzymes (Troponin T and CK-MB) were elevated. The metabolic panel and haemogram were normal. The tryptase levels were elevated, suggesting the involvement of basophils in the background of anaphyl-axis. The echocardiography revealed global hypokinesia of the left ventricle with no regional wall motion abnormality and an ejection fraction (EF) of 40%.

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FIG 1.

(a) Shows diffuse ST (segment) depression with ST elevation in lead aVR (augmented Vector Right) with left bundle branch block (LBBB); (b) shows resolution of ST depression and LBBB after epinephrine

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ECG changes, along with raised cardiac biomarkers and depressed cardiac function, made us consider the diagnosis of KS. Diagnostic coronary angiogram revealed normal coronary arteries (Fig. 2). She was treated with intramuscular adrenaline 0.5 ml (1:1000), antihistamines, and steroids. Pulmonary oedema was managed with the cautious use of intravenous (IV) fluids.

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FIG 2.

Coronary angiography: (a) demonstrates the left coronary artery with normal left main coronary artery (LMCA) left anterior descending (LAD) artery, and left circumflex (LCX) artery; (b) shows the coronary angiogram of the right coronary artery (RCA) with no obstruction

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After 2 hours, ECG changes started regressing with the ST-segment returning to baseline and disappearance of left bundle branch block. On day 2, the ECG had further regression of ST changes and returned to normal on day 3. She improved clinically with a decline in oxygen requirement.

The patient recovered completely and was advised to avoid NSAIDs. On the follow-up visit after 2 weeks, she was asymptomatic and had a normal ejection fraction.

DISCUSSION

Myocardial injury occurring in the context of anaphylaxis can occur due to anaphylaxis itself causing coronary vasospasm, called KS.^3,4 There are three variants of KS; Type 1–KS with no underlying coronary artery disease (CAD); can be treated with adrenaline, antihistamines, steroids, vasodilators, and mast cell stabilizers, and no antiplatelet therapy is indicated. Type 2–KS in patients with underlying CAD but inactive pre-existing atheromatous disease, in whom the allergic insult leads to plaque erosion or rupture, leading to acute myocardial infarction or coronary vasospasm; can be treated with the same drugs as Type 1 plus standard acute coronary syndrome protocol (i.e. antiplatelet therapy is indicated). Type 3–KS occurs as post-procedure stent thrombosis; it can be treated as Type 2.⁵ Most cases of KS are associated with coronary vasospasm, causing ST-elevation myocardial infarction (STEMI), and in our case, there was a NSTEMI and no evidence of coronary spasm.

The main pathophysiology of KS is mast cell activation by triggers like drugs, environmental exposure to allergens, food, insect bites, and inherited allergic conditions. Mast cells release histamine, platelet activation factor, arachidonic acid, chymase, and tryptase, which mediate the systemic symptoms (vasodilation, hypotension, decreased venous return) and coronary effects (coronary vasospasm, plaque erosion, thrombus formation).⁶ It may or may not have concomitant obstructive coronary arteries.⁴ The management of KS involves withholding the potential triggers and administering steroids, antihistamines, epinephrine, and IV fluids. In severe cases of KS, nitrates and calcium channel blockers are used in the recovery period.⁷ Although morphine is used routinely in acute coronary syndrome, morphine administered in KS aggravates coronary pathology by releasing histamine in an acute episode. Beta-blockers are also avoided when the suspicion of KS is likely due to unopposed action of alpha-adrenergic activity.

As observed in our patient, the serum tryptase was elevated, which highlights the allergic pathology due to mast cell activation. Vigorito et al. previously reported a paradoxical vasoconstriction mediated by histamine-1 receptors.⁸ Although the ergotamine maleate provocation test can reproduce symptoms of KS, it is harmful to use in clinical practice. KS due to peanut, bee sting, and ceftriaxone was reported in a series by Memon et al.⁹

In KS, it is difficult to differentiate primary myocardial damage due to mast cell activation from hypoperfusion myocardial injury due to vasodilation in anaphylaxis. KS remains a diagnostic and therapeutic challenge, and some authors argue against vasospasm as an underlying patho-physiology.⁵ Rare cases of epinephrine-induced worsening have been reported, probably related to coronary vasospasm with higher doses of epinephrine. Jayamali et al. reported a case of STEMI in a 21-year-old healthy male with no risk factors for coronary disease after using epinephrine in anaphylaxis.¹⁰ The mechanism postulated would be due to alpha-1-mediated vasoconstriction. Epinephrine at low doses stimulates beta 1 and beta 2 receptors, causing an increase in heart rate and vasodilation. At higher doses, it stimulates the alpha 1 receptor and causes vasoconstriction. Our report highlights the importance of KS as a differential diagnosis in a myocardial infarction occurring in the background of anaphylaxis.