What is Kounis syndrome?

Kounis Syndrome: Allergic Acute Coronary Syndrome

Kounis syndrome is an acute coronary syndrome triggered by allergic or anaphylactic reactions, manifesting as coronary artery vasospasm, acute myocardial infarction, or coronary stent thrombosis resulting from inflammatory mediator release and inappropriate activation of mast cells and platelets. 1

Definition and Classification

Kounis syndrome has three established variants:

1. Type I (Vasospastic allergic angina): Occurs in patients without pre-existing coronary artery disease, where allergic mediators induce coronary vasospasm with or without myocardial injury 2

2. Type II (Allergic myocardial infarction): Occurs in patients with pre-existing atheromatous disease, where allergic reactions trigger plaque erosion or rupture leading to acute myocardial infarction 2, 3

3. Type III (Stent thrombosis): Occurs in patients with drug-eluting stent thrombosis with eosinophil and/or mast cell infiltration 2

Pathophysiology

The syndrome results from:

• Mast cell degranulation during allergic reactions
• Release of inflammatory mediators (histamine, leukotrienes, thromboxane)
• Platelet activation
• Subsequent coronary vasospasm and/or plaque rupture 1, 2

Triggers

Kounis syndrome can be triggered by numerous agents:

• Medications: Antibiotics, NSAIDs, anesthetics, infliximab 1
• Environmental exposures: Insect stings, latex
• Foods: Various allergens 4
• Traditional medicines: Including Chinese herbal medicines 5
• Conditions: Post-abortion status, stress combined with environmental factors 5

Clinical Presentation

Patients typically present with:

• Symptoms of allergic reaction (urticaria, angioedema, wheezing)
• Concurrent chest pain or discomfort
• ECG changes (ST-segment elevation or depression)
• Elevated cardiac biomarkers in some cases
• Potential hemodynamic instability 4

Diagnosis

Diagnosis requires high clinical suspicion, particularly in patients presenting with acute coronary syndrome without previous history of coronary artery disease coinciding with allergic symptoms 4. Diagnostic workup includes:

• Laboratory tests:

  • Cardiac biomarkers (troponin, CK-MB)
  • Inflammatory markers
  • Mast cell activation markers (tryptase, histamine)
  • Eosinophil count (may be elevated) 5

• ECG: May show ST-segment changes, arrhythmias

• Coronary angiography: To evaluate coronary anatomy and identify vasospasm or occlusion

Management

Treatment should address both the allergic and cardiac components:

1. Allergic reaction management:

   • Epinephrine for anaphylaxis (caution in patients with acute coronary syndrome)
   • H1 and H2 antihistamines
   • Corticosteroids
   • Mast cell stabilizers if needed

2. Cardiac management (based on type):

   • Type I: Calcium channel blockers, nitrates
   • Type II: Standard acute coronary syndrome management including antiplatelet therapy, anticoagulation, and consideration for coronary intervention
   • Type III: Specialized management of stent thrombosis 3

3. Long-term management:

   • Identification and avoidance of triggers
   • Consideration of prophylactic anti-allergic medications
   • Management of underlying coronary artery disease if present 5

Prognosis

Prognosis varies based on:

• Severity of the allergic reaction
• Extent of myocardial damage
• Pre-existing coronary disease
• Prompt recognition and treatment

Follow-up for 1-4 years has shown that avoiding triggers can successfully prevent recurrence 5.

Clinical Pearls and Pitfalls

• Underdiagnosis: Kounis syndrome is "not a rare disease but an infrequently diagnosed clinical entity" 2
• Diagnostic challenge: Overlapping symptoms of allergic reaction and myocardial ischemia can delay diagnosis 1
• Recurrent episodes: May occur with repeated exposure to allergens 5
• Special populations: Can affect young patients without traditional cardiovascular risk factors 4
• Treatment dilemma: Some medications used for acute coronary syndrome may worsen allergic reactions and vice versa

Conclusion

Maintaining a high index of suspicion for Kounis syndrome is crucial, particularly in patients presenting with acute coronary syndrome without traditional risk factors or in the context of potential allergic triggers. Prompt recognition and appropriate management addressing both allergic and cardiac components are essential for optimal outcomes.