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Cardiology›Condition·Updated Apr 16, 2026·v1

Kounis Syndrome

Kounis syndrome is a hypersensitivity-induced acute coronary syndrome involving mast cell degranulation. It requires a high index of suspicion when chest pain accompanies allergic reactions. Management focuses on stabilizing both the allergic response and the myocardium, often requiring cautious use of epinephrine and vasodilators.

Moderate Evidence16 references·942 words·4 min read·v1
cardiologyallergyemergency_medicineacute_coronary_syndrome

Quick Reference

RxDrug of choiceH1/H2 blockers (Diphenhydramine/Famotidine) plus Corticosteroids
AltAlternativesNicorandil (for vasospasm with borderline hypotension)
⊘AvoidBeta-blockers (acute phase); High-dose bolus Epinephrine (relative)
DxTest of choiceCoronary Angiography (for classification) and Serum Tryptase (for diagnosis)
ScKey scoreKounis Classification (Type I, II, III)
→When to referRefer all patients to Cardiology for ischemic workup and Allergy/Immunology for trigger identification.
Kounis syndrome is an allergic-mediated ACS requiring simultaneous management of hypersensitivity and myocardial ischemia while avoiding treatments that exacerbate either condition.
Kounis syndrome, also known as allergic myocardial infarction, is the concurrent occurrence of acute coronary syndrome (ACS) and hypersensitivity reactions. It is characterized by the release of inflammatory mediators (histamine, tryptase, leukotrienes) from mast cell activation, which triggers coronary vasospasm, plaque rupture, or stent thrombosis. The syndrome is classified into three types: Type I (normal coronary arteries with vasospasm), Type II (pre-existing coronary disease with plaque rupture), and Type III (stent thrombosis). Clinical presentation typically involves chest pain and anaphylaxis symptoms within 20 minutes of exposure to a trigger, such as medications (e.g., NSAIDs, antibiotics) or insect stings. Management is uniquely challenging as standard anaphylaxis treatments (like epinephrine) may exacerbate myocardial ischemia, while standard ACS treatments (like beta-blockers) may worsen anaphylaxis.

Overview and Recommendations

Background

  • •Define as the co-occurrence of an allergic reaction and an acute coronary syndrome.
  • •Recognize the three variants: Type I (vasospastic, normal arteries), Type II (plaque rupture, diseased arteries), and Type III (stent thrombosis).
  • •Identify common triggers including insect stings, medications (e.g., , antibiotics), and environmental allergens.
  • •Note the male predominance (68.5%) and a median age of presentation around 57 years.

Evaluation

  • •Obtain an immediate 12-lead (ECG) for any patient presenting with chest pain and allergic symptoms.
  • •Monitor for ST-segment elevation, which occurs in over 70% of cases triggered by insect bites.
  • •Measure serum tryptase levels 1–2 hours after the onset of symptoms to confirm mast cell activation.
  • •Check serial levels to quantify myocardial injury.
  • •Perform to assess for regional wall motion abnormalities.
  • •Order urgent to classify the syndrome variant and determine the need for intervention.
  • •Rule out the ATAK complex (Adrenaline, Takotsubo, Anaphylaxis, and Kounis) in patients with grade 4 anaphylaxis.

Management

  • •Administer H1 and H2 receptor antagonists (e.g., Diphenhydramine 25-50 mg IV and Famotidine 20 mg IV) to block histamine effects.
  • •Give IV corticosteroids (e.g., Hydrocortisone 100-200 mg or Methylprednisolone 40-125 mg) to suppress the inflammatory cascade.
  • •Use Epinephrine with extreme caution; prefer low-dose continuous IV titration over bolus administration to avoid worsening coronary vasospasm.
  • •Administer Nitrates for coronary vasospasm if the patient is normotensive; avoid if systolic BP <90 mmHg.
  • •Consider Nicorandil as an alternative vasodilator due to its limited effect on systemic blood pressure.
  • •Initiate standard ACS protocols (e.g., , heparin) for Type II and Type III variants.
  • •Perform urgent percutaneous coronary intervention (PCI) for Type III (stent thrombosis) or Type II (plaque rupture) presentations.
  • •Avoid beta-blockers during the acute phase as they may cause unopposed alpha-adrenergic activity and worsen vasospasm.
  • •Refer to an allergist for identification of the inciting trigger and future avoidance strategies.

Board Review — High Yield

  • •Type I Variant — Coronary vasospasm in patients with normal or nearly normal coronary arteries (most common type).
  • •Type II Variant — Allergic reaction causing plaque rupture or erosion in patients with pre-existing coronary artery disease.
  • •Type III Variant — Stent thrombosis where histological analysis shows mast cells and eosinophils in the thrombus.
  • •Serum Tryptase — The most reliable marker for mast cell activation; levels peak 1–2 hours after the reaction.
  • •Epinephrine Dilemma — Necessary for anaphylaxis but can worsen Kounis syndrome by inducing coronary vasospasm and increasing oxygen demand.
  • •ATAK Complex — A clinical constellation involving Adrenaline, Takotsubo, Anaphylaxis, and Kounis syndrome.
  • •Common Trigger — Diclofenac is a frequently cited pharmacological trigger for Kounis syndrome.
  • •ECG Findings — ST-segment elevation is the most common ischemic finding, present in >70% of insect-sting-induced cases.

Deep Dive — Evidence Details

References

  1. [1]

    Elmezayen ZW, Zayed A, Sarama A et al.. “Bee sting-induced myocardial infarction: a systematic review with illustrative case.” BMC cardiovascular disorders (2025). PMID: 41299289 ↗

    L2aSR_OBSCited in: Clinical Presentation and Classification, Diagnostic Workup, Prognosis and Complications
  2. [2]

    Dai B, Cavaye J, Judd M et al.. “Perioperative Presentations of Kounis Syndrome: A Systematic Literature Review.” Journal of cardiothoracic and vascular anesthesia (2022). PMID: 35260322 ↗

    L2aSR_OBSCited in: Clinical Presentation and Classification, Diagnostic Workup
  3. [3]

    Monello A, Moderato L, Lazzeroni D et al.. “[Acute coronary syndrome after insect bites: a systematic review of available literature].” Giornale italiano di cardiologia (2006) (2021). PMID: 34709235 ↗

    L2aSR_OBSCited in: Clinical Presentation and Classification, Diagnostic Workup
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    Pejcic AV, Milosavljevic MN, Jankovic S et al.. “Kounis Syndrome Associated With the Use of Diclofenac.” Texas Heart Institute journal (2023). PMID: 36735919 ↗

    L5REVIEW_NARRATIVECited in: Clinical Presentation and Classification, Diagnostic Workup
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    Tan PZ, Chew NWS, Tay SH et al.. “The allergic myocardial infarction dilemma: is it the anaphylaxis or the epinephrine?” Journal of thrombosis and thrombolysis (2021). PMID: 33544285 ↗

    L5REVIEW_NARRATIVECited in: Clinical Presentation and Classification, Diagnostic Workup, Management and Pharmacotherapy
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    Yakushin S, Gurbanova A, Pereverzeva K. “Kounis Syndrome: Review of Clinical Cases.” Cardiovascular & hematological disorders drug targets (2024). PMID: 39021170 ↗

    L5REVIEW_NARRATIVECited in: Clinical Presentation and Classification, Diagnostic Workup
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    Calogiuri G, Savage MP, Congedo M et al.. “Is Adrenaline Always the First Choice Therapy of Anaphylaxis? An Allergist-cardiologist Interdisciplinary Point of View.” Current pharmaceutical design (2023). PMID: 37877509 ↗

    L5REVIEW_NARRATIVECited in: Management and Pharmacotherapy
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    Nallathambi N, Kannan M, Sekar A. “Non-steroidal anti-inflammatory drugs (NSAID)-induced allergic myocardial infarction (Kounis syndrome).” The National medical journal of India (2026). PMID: 41729501 ↗

    L4CASE_REPORTCited in: Management and Pharmacotherapy
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    Sharma V, Parkes A, Diacono J et al.. “Cardiac stress in a child with perioperative anaphylaxis.” BMJ case reports (2025). PMID: 39961677 ↗

    L4CASE_REPORTCited in: Management and Pharmacotherapy
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    Ichinomiya T, Sekino M, Toba M et al.. “Refractory cardiac arrest caused by type I Kounis syndrome treated with adrenaline and nicorandil: A case report.” Medicine (2023). PMID: 37565887 ↗

    L4CASE_REPORTCited in: Management and Pharmacotherapy
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    Shintani R, Sekino M, Egashira T et al.. “Allergen-Related Coronary Vasospasm "Kounis Syndrome" Requiring Administration of Epinephrine and a Coronary Vasodilator.” Journal of cardiothoracic and vascular anesthesia (2021). PMID: 32888803 ↗

    L4CASE_REPORTCited in: Management and Pharmacotherapy
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    Abdelghany M, Subedi R, Shah S et al.. “Kounis syndrome: A review article on epidemiology, diagnostic findings, management and complications of allergic acute coronary syndrome.” International journal of cardiology (2017). PMID: 28153536 ↗

    L5REVIEW_NARRATIVECited in: Prognosis and Complications
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    Ferreira RM, Villela PB, Almeida JCG et al.. “Allergic recurrent coronary stent thrombosis: A mini-review of Kounis syndrome.” Cardiovascular revascularization medicine : including molecular interventions (2018). PMID: 29576520 ↗

    L4CASE_REPORTCited in: Prognosis and Complications
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    Ali M, Helal A, El-Din M et al.. “From Allergy to Angina: A Unique Presentation of Kounis Syndrome.” Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions (2025). PMID: 40148749 ↗

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    Sciatti E, Vizzardi E, Cani DS et al.. “Kounis syndrome, a disease to know: Case report and review of the literature.” Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace (2018). PMID: 29557575 ↗

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    Nanyoshi M, Hayashi T, Sugimoto R et al.. “Type I Kounis syndrome in a young woman without chest pain: a case report.” BMC cardiovascular disorders (2024). PMID: 39218904 ↗

    L4CASE_REPORTCited in: Prognosis and Complications

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