What is the diagnosis and treatment for a patient with suspected Kounis syndrome, a condition characterized by an allergic reaction with symptoms such as chest pain, shortness of breath, and skin rashes?

Kounis Syndrome: Diagnosis and Management

What is Kounis Syndrome?

Kounis syndrome is an acute coronary syndrome triggered by an allergic, hypersensitivity, or anaphylactic reaction, where mast cell degranulation and inflammatory mediator release cause coronary vasospasm, plaque rupture, or stent thrombosis. 1, 2 This condition represents a critical diagnostic challenge because it simultaneously presents with both allergic manifestations (rash, pruritus, shortness of breath) and cardiac ischemia (chest pain, ST-segment changes) 1, 3.

The syndrome occurs when inflammatory mediators released during allergic reactions—including histamine, leukotrienes, and tryptase—directly affect coronary arteries, making them susceptible to acute cardiac events 1, 2.

Clinical Variants

Three distinct types have been defined 4:

• Type I (No pre-existing coronary disease): Allergic reaction induces coronary vasospasm in patients without atherosclerotic disease, causing chest pain with ECG changes 4
• Type II (Pre-existing coronary disease): Hypersensitivity reaction causes plaque erosion or rupture in patients with known atherosclerotic disease, culminating in acute myocardial infarction 4
• Type III (Coronary stent thrombosis): Occurs in patients with drug-eluting stents where allergic reaction triggers acute stent thrombosis 4

Diagnostic Approach

Key Clinical Features to Identify

Look for the simultaneous occurrence of:

Allergic manifestations 5, 1:

• Cutaneous: Diffuse pruritic rash, urticaria, flushing, angioedema
• Respiratory: Dyspnea, wheezing, bronchospasm, laryngeal edema, stridor
• Gastrointestinal: Nausea, vomiting, crampy abdominal pain
• Systemic: Hypotension, tachycardia (or bradycardia in vasovagal-like presentations)

Cardiac manifestations 1, 3:

• Chest pain with characteristics of acute coronary syndrome
• ECG changes: ST-elevation or depression, T-wave inversions, new arrhythmias
• Elevated cardiac biomarkers (troponin)

Laboratory Confirmation

Obtain serum tryptase levels optimally between 15 minutes to 3 hours after symptom onset, with a baseline level after recovery for comparison 5. Elevated tryptase (>11.4 µg/L) supports mast cell degranulation 3. However, normal tryptase does not exclude the diagnosis, as these tests are not universally available and lack specificity for anaphylaxis 5.

Cardiac workup includes 1:

• Serial ECGs
• Cardiac troponin measurements
• Urgent coronary angiography if ST-elevation or hemodynamic instability present

Critical Differential Diagnosis

Distinguish Kounis syndrome from 5:

• Vasovagal reaction: Bradycardia without skin manifestations (urticaria, angioedema, pruritus)
• Primary acute coronary syndrome: Absence of allergic triggers or cutaneous/respiratory symptoms
• Panic attack: No significant vital sign changes or objective findings
• Asthma exacerbation alone: History of asthma without cardiac symptoms

Management Strategy

Immediate Treatment Algorithm

The management of Kounis syndrome differs critically from standard acute coronary syndrome and anaphylaxis protocols due to potential medication interactions. 1, 6

Step 1: Simultaneous Stabilization

Stop the allergen exposure immediately if ongoing (e.g., drug infusion) 5.

Administer epinephrine with extreme caution 7, 6:

• Epinephrine 0.2-0.5 mg (1 mg/mL) intramuscularly for anaphylaxis, repeated every 5-15 minutes as needed 5
• Critical caveat: Epinephrine can paradoxically worsen coronary vasospasm and myocardial ischemia in Kounis syndrome 6. One case report documented severe myocardial ischemia provoked by epinephrine administration for laryngeal edema 6
• Despite this risk, epinephrine remains first-line for life-threatening anaphylaxis with no absolute contraindications, including in patients with cardiac disease 5, 7
• Use the lowest effective dose and monitor cardiac status continuously

Step 2: Cardiovascular Support

Fluid resuscitation 5:

• Normal saline 1-2 L IV at 5-10 mL/kg in first 5 minutes
• Crystalloids or colloids in 20 mL/kg boluses for hypotension

Vasopressor support if needed 5:

• Dopamine 400 mg in 500 mL at 2-20 µg/kg/min, OR
• Vasopressin 0.01-0.04 U/min

For bradycardia: Atropine 600 µg IV 5

For patients on beta-blockers: Glucagon 1-5 mg IV infusion over 5 minutes 5

Step 3: Antiallergic Therapy

H1/H2 antagonists 5:

• Diphenhydramine 50 mg IV plus ranitidine 50 mg IV

Corticosteroids 5:

• Methylprednisolone 1-2 mg/kg IV every 6 hours (or equivalent dose)

Step 4: Cardiac-Specific Management

Oxygen supplementation for respiratory compromise or hypoxemia 5

Urgent cardiology consultation for 1:

• ST-elevation myocardial infarction: Consider emergent coronary angiography
• Hemodynamic instability
• Ongoing chest pain despite initial management

Critical Medications to AVOID or Use with Extreme Caution

Beta-blockers: May worsen bronchospasm and are relatively contraindicated in acute anaphylaxis; can also mask compensatory tachycardia 1

Morphine: Can trigger further mast cell degranulation and histamine release, potentially worsening the allergic reaction 1

Vasodilators (nitrates): May cause profound hypotension in the setting of anaphylaxis-related vasodilation 1

Aspirin and NSAIDs: Use with caution as they can trigger or worsen allergic reactions in susceptible patients 1

Post-Acute Management

Document the allergen trigger in the medical record allergy field with detailed description of symptoms, timing, and treatment 5.

Prescribe epinephrine autoinjector for future allergic reactions, with comprehensive counseling on recognition of anaphylaxis and proper use 5, 7.

Allergy/immunology referral for identification of specific allergens and consideration of desensitization protocols if the culprit medication is essential 2.

Cardiology follow-up for risk stratification, optimization of coronary disease management, and assessment for need of coronary intervention 1, 4.

Key Clinical Pitfalls

Underrecognition: Kounis syndrome is frequently underdiagnosed because emergency providers may not consider acute coronary syndrome in the context of allergic reactions 1, 2.

Epinephrine paradox: While epinephrine is life-saving for anaphylaxis, it can worsen coronary ischemia in Kounis syndrome—yet withholding it risks death from anaphylaxis 6. The solution is to use epinephrine when indicated for severe anaphylaxis but with heightened cardiac monitoring and lowest effective dosing.

Medication selection errors: Standard ACS medications (beta-blockers, morphine, nitrates) can be harmful in this context 1.

Tryptase timing: Obtaining tryptase too early (<15 minutes) or too late (>3 hours) reduces diagnostic yield 5.