G Plus Heart Hospital, Kalyan, Maharashtra 421301, India.

Kounis syndrome, first described by Nicholas Kounis and Zavras in 1991, refers to the concurrent occurrence of acute coronary syndrome and hypersensitivity reactions following an allergenic event [1]. Common triggers include antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs), as well as environmental exposures and insect stings [2]. The three variants of the condition are: Type I refers to coronary artery spasm in patients with angiographically normal coronary arteries; Type II involves acute plaque rupture or erosion in those with pre-existing atherosclerosis; and Type III refers to coronary stent thrombosis or restenosis precipitated by allergic reactions [3]. 

A 28-year-old previously healthy male with no family history of cardiovascular or allergic disorders underwent double-J (DJ) stent exchange with retrograde intrarenal surgery (RIRS) for renal calculi. Post-procedure, he developed a fever and was started on ceftriaxone. Due to persistent fever, antibiotics were escalated to intravenous piperacillin-tazobactam. Within minutes of drug administration (4.45g), he experienced severe anaphylaxis with hypotension (systolic BP <80 mmHg), generalised erythematous rash, and respiratory distress and acute retrosternal chest pain with diaphoresis.

The patient was evaluated through laboratory biomarkers, imaging, and cardiac function tests to establish the diagnosis and assess organ function. All reports are summarised in Table 1. Initial laboratory results showed leukocytosis with a total WBC of 15,400/µL and marked neutrophilia (91%), along with relative lymphopenia (3%), indicating an acute systemic inflammatory and allergic response. Hemoglobin (15.7 g/dL), platelet count (464,000/µL), and red cell indices were normal. Follow-up counts normalised, though mild eosinophilia persisted, further supporting an allergic cause. Cardiac enzymes revealed a slight increase in CK-MB (27 U/L) and a minimally elevated troponin I level, suggestive of myocardial infarction. Biochemistry demonstrated a mild rise in transaminases (AST 108 U/L, ALT 62 U/L), with normalised bilirubin and protein levels, consistent with a short hepatocellular stress likely secondary to anaphylaxis. Renal function was unchanged. The lipid profile showed total cholesterol at 178 mg/dL, LDL at 113.7 mg/dL, triglycerides at 111 mg/dL, and HDL at 41 mg/dL, which suggests borderline dyslipidemia. Fasting blood sugar was 195 mg/dL, consistent with diabetes. Vitamin D was low at 12 ng/mL, pointing to further metabolic issues. Urine examination demonstrated gross haematuria (>200 RBCs/HPF) and proteinuria (++ albumin), findings attributed to the patient’s underlying renal calculi and recent stent exchange rather than the acute cardiac event. Serial echocardiograms gave useful diagnostic details. The initial test showed severe global hypokinesia of the left ventricle, with an ejection fraction between 15 and 20%. On follow-up after four days, the repeat echocardiogram showed partial improvement, with ejection fraction rising to 40 to 45%. The heart valves appeared normal, with no signs of diastolic dysfunction, pulmonary hypertension, or pericardial effusion. Electrocardiographic changes were consistent with acute coronary involvement. Fig.1a represents the ECG at presentation with marked ST-segment elevation in anterior precordial leads, consistent with acute myocardial injury during anaphylaxis. A subsequent ECG [Fig.1b] demonstrated evolving changes with attenuation of ST-segment elevation, in line with clinical recovery. Fig.2 represents the abdominal ultrasound performed during hospitalisation. A coronary angiogram was performed to exclude structural coronary disease. Fig.3 represents the angiogram revealed completely normal epicardial coronaries with TIMI-III flow, confirming the diagnosis of Type I KS (vasospastic mechanism without atherosclerotic obstruction).

KS was described as an allergic angina, which is a rare but fatal condition due to the co-incidental occurrence of an acute coronary syndrome with hypersensitivity reactions [8]. The management of the syndrome depends on the types, such as Type I, which usually requires conservative management with antiallergic and vasodilator therapy, whereas Types II and III often necessitate standard acute coronary syndrome protocols, including antiplatelets, anticoagulation, and, in some cases, revascularisation [2,9]. The first immediate action is discontinuation of the offending allergen, followed by corticosteroids, antihistamines, and intravenous fluids. Although epinephrine remains the first-line therapy, it is advised to use it cautiously and preferably intramuscularly, as intravenous administration may aggravate coronary vasospasm [9,10]. 

This case highlights the necessity of considering Type I KS as a cause of acute cardiac involvement in anaphylaxis, even in patients with no cardiac risk factors and angiographically normal coronaries. Early recognition can prevent misdiagnosis and inadequate management, needing a careful consideration of life-saving anaphylaxis therapy compared with interventions to mitigate the effects of coronary vasospasm. Physician awareness is necessary for the successful treatment of this rare but potentially fatal condition.

Contributors: CJS was responsible for conceptualisation, methodology, and manuscript writing. SHV and AGC contributed to drafting of the original manuscript. Data curation, investigation, methodology, and visualisation were performed by all authors. CJS will act as a study guarantor.  All authors participated in the review and editing of the manuscript and approved the final version for publication.

Funding: None; Competing interests: None stated.