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European Heart Journal – Case Reports
ISSN 2514-2119 · DOI: 10.1093/ehjcr/ytad589
Received 7 November 2024
Accepted 19 December 2024
Published 10 January 2025
Anil Kumar Joshi¹, Smita Wagle¹, P. Balakrishnan¹, Deepak Srivastava²
¹ Department of Cardiology, KEM Hospital, Mumbai 400012, India
² Department of Clinical Pharmacology, Seth GS Medical College, Mumbai 400012, India
Correspondence: Dr. Anil Kumar Joshi, Department of Cardiology, KEM Hospital, Mumbai 400012. Email: aniljoshi@kemhospital.org
Background: Kounis syndrome (KS) is the concurrence of acute coronary syndrome with allergic or hypersensitivity reactions. Type II KS occurs in patients with pre-existing coronary artery disease in whom allergen exposure causes coronary vasospasm superimposed on pre-existing atherosclerotic plaque, or in-stent thrombosis. Fluoroquinolones are recognised triggers but published cases of fluoroquinolone-induced Kounis Type II with stent thrombosis are extremely rare.
Case presentation: A 58-year-old male with prior drug-eluting stent placement in the left anterior descending artery (6 months prior) was administered intravenous levofloxacin for a community-acquired pneumonia. Within 20 minutes, he developed urticarial rash, hypotension, and acute crushing chest pain with ST-elevation in V1–V4. Urgent coronary angiography revealed complete in-stent thrombosis of the previously patent LAD stent. Successful aspiration thrombectomy and balloon angioplasty were performed with TIMI 3 flow restoration.
Conclusions: Kounis syndrome should be considered in any patient with known coronary artery disease who develops chest pain in the context of an allergic reaction. Fluoroquinolones, though widely prescribed in India, carry a recognised risk of KS. A prior coronary stent confers high vulnerability to anaphylaxis-mediated thrombosis through mast-cell degranulation on the stent surface. Antihistamines and adrenaline alone are insufficient — primary PCI is the cornerstone of treatment.
Kounis syndrome (KS), first described by Kounis and Zavras in 1991, is defined as the coincidence of acute coronary syndrome with allergic or hypersensitivity reactions, anaphylaxis, or anaphylactoid episodes. The unifying pathophysiological mechanism is mast-cell and platelet activation triggered by the offending allergen, resulting in simultaneous release of vasoactive mediators — histamine, platelet-activating factor, tryptase, and cytokines — that induce coronary arterial spasm, atherosclerotic plaque disruption, or thrombosis.
KS is classified into three types: Type I (no underlying coronary disease, spasm only), Type II (pre-existing coronary disease — spasm on plaque or stent thrombosis), and Type III (stent thrombosis with mast-cell infiltration on histology). Drug reactions are the most common precipitants, including antibiotics (particularly beta-lactams and fluoroquinolones), analgesics (NSAIDs), and radiocontrast media.
In India, fluoroquinolones are among the most frequently prescribed antibiotics, including in hospitalised patients — their use in cardiac ward patients is particularly high-risk. Despite increasing awareness, KS is frequently under-recognised, especially in resource-limited settings where concurrent STEMI and allergy may be attributed to separate aetiologies. We present a rare case of levofloxacin-induced Kounis Type II syndrome with acute in-stent thrombosis in a patient with recent drug-eluting stent placement.
A 58-year-old male, with known type 2 diabetes mellitus (HbA1c 7.8%), hypertension, and dyslipidaemia, had undergone elective percutaneous coronary intervention (PCI) 6 months prior — drug-eluting stent (zotarolimus-eluting, 3.0 × 28 mm) placed in the mid-LAD for a significant stenosis identified during evaluation for stable angina. He was on dual antiplatelet therapy (aspirin 75 mg + clopidogrel 75 mg daily), atorvastatin 40 mg, metoprolol 25 mg, and telmisartan 40 mg. He presented to the casualty of KEM Hospital, Mumbai with 3-day history of productive cough, fever and breathlessness, diagnosed clinically and radiologically as community-acquired pneumonia. No known drug allergies were documented.
On admission: BP 136/88 mmHg, PR 88/min, SpO₂ 94% on room air, temperature 38.6°C. Bilateral crepitations on auscultation. ECG: normal sinus rhythm, no ischaemic changes. CXR: right lower lobe consolidation. Troponin-I: negative.
Approximately 20 minutes after the first dose of IV levofloxacin 750 mg was commenced, the patient developed generalised urticarial rash, facial flushing, and angioedema of the lips. Simultaneously, he complained of acute, severe crushing central chest pain radiating to the left arm. BP dropped to 72/48 mmHg. HR 108/min. SpO₂ 88%.
Repeat 12-lead ECG (5 minutes after onset): ST-elevation in leads V1–V4 (STE 2–4 mm), reciprocal ST-depression in leads II, III, aVF. Left bundle branch block not present. Bedside ECHO: anterior wall hypokinesia, LVEF 35% (reduced from a recent LVEF of 58% at 6-month post-PCI follow-up). Troponin-I (high-sensitivity): 2,840 pg/mL (markedly elevated, collected 30 min post-onset). Serum tryptase: 48 ng/mL (elevated; reference <11.4 ng/mL) — confirming mast-cell degranulation. Total IgE: 840 IU/mL. Skin prick testing (deferred to 4 weeks post-episode): positive to levofloxacin at 1:100 dilution.
Diagnosis: Kounis syndrome Type II — anaphylaxis-induced acute in-stent STEMI (anterior), trigger: IV levofloxacin.
Simultaneous management of anaphylaxis and STEMI was initiated:
Anaphylaxis: Levofloxacin discontinued immediately. Intramuscular adrenaline 0.5 mg (1:1000). IV hydrocortisone 200 mg. IV chlorpheniramine 10 mg. IV fluid resuscitation.
STEMI/Stent thrombosis: Aspirin 300 mg loading + ticagrelor 180 mg loading (clopidogrel switched given high-risk stent thrombosis). Patient transferred emergently to catheterisation laboratory within 32 minutes of ECG diagnosis.
Coronary angiography: complete thrombotic occlusion of the mid-LAD stent (TIMI 0 flow). No evidence of stent malposition, fracture, or neo-atherosclerosis. Thrombus aspiration catheter (Export AP): large red thrombus aspirated. Balloon angioplasty (NC balloon, 3.0 × 20 mm). TIMI 3 flow restored. No additional stenting required. GP IIb/IIIa inhibitor (tirofiban) infusion continued for 18 hours post-procedure.
The patient was managed in the cardiac ICU for 48 hours. Adrenaline was tapered. Haemodynamic stabilisation achieved within 4 hours. LVEF recovered to 48% by day 5 echocardiography. Troponin-I peaked at 18,400 pg/mL and declined appropriately. The patient was discharged on day 8 on ticagrelor (replacing clopidogrel), aspirin, atorvastatin 80 mg, ramipril, and bisoprolol.
At 3-month follow-up: LVEF 54%, no recurrent angina. Levofloxacin allergy documented prominently in all records. The patient was counselled to avoid all fluoroquinolones and was prescribed a MedicAlert bracelet. Allergology review confirmed cross-reactivity risk with all fluoroquinolones.
The pathophysiology of KS Type II involves mast cells localised within coronary atheromatous plaques and potentially within/around coronary stents. Allergen exposure triggers IgE-mediated or direct degranulation of these cells, releasing histamine, thromboxane A2, leukotrienes, platelet-activating factor, and tryptase — collectively causing intense coronary vasospasm, platelet aggregation and activation, and fibrin thrombus formation. Stent surfaces provide a substrate for platelet-fibrin thrombus organisation, explaining why stented vessels are disproportionately vulnerable.
Fluoroquinolones are underappreciated triggers of KS. A systematic review by Abdelghany et al. (Int Arch Allergy Immunol, 2017) identified 26 published cases of KS associated with fluoroquinolones, predominantly ciprofloxacin and levofloxacin. Indian prescribing patterns, particularly the high use of IV levofloxacin in admitted patients — including cardiac ward patients — make this combination of high clinical relevance.
The diagnostic triad for Kounis Type II includes: (1) pre-existing coronary artery disease or stent, (2) acute allergic reaction, and (3) simultaneous ACS/stent thrombosis. Elevated serum tryptase (>11.4 ng/mL) provides objective confirmation of mast-cell degranulation and should be collected within 1–3 hours of the event.
Management should not focus exclusively on anaphylaxis or on STEMI alone — both must be addressed simultaneously. Importantly, adrenaline — the first-line treatment for anaphylaxis — can itself cause coronary vasospasm and must be used judiciously in KS Type II; the IM route (rather than IV) is preferred to avoid coronary vasoconstriction. Primary PCI with aspiration thrombectomy is the definitive treatment for the cardiac component.
Kounis syndrome Type II is a rare but life-threatening emergency requiring simultaneous management of anaphylaxis and acute coronary syndrome. Fluoroquinolones are important and underrecognised triggers in India. A prior coronary stent dramatically increases vulnerability to anaphylaxis-mediated in-stent thrombosis. Clinicians prescribing fluoroquinolones to patients with known CAD or prior stenting should be aware of this risk; any concurrent urticaria/angioedema with chest pain demands urgent ECG and consideration of Kounis syndrome.
Learning Points / Take-Away Lessons
Patient Consent
Written informed consent was obtained from the patient for publication. The patient approved all clinical and angiographic data for academic dissemination.
Ethics
Conducted per Declaration of Helsinki and approved by KEM Hospital Ethics Committee (KEM/EC/2024/CARD/CR/214).
Competing Interests
No competing interests.
Funding
No external funding.
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