Kounis syndrome (KS), or allergic angina, is the occurrence of acute coronary syndrome (ACS) triggered by a hypersensitivity event.1 In KS, inflammatory mediators activate platelets and immune cells, induce coronary vasospasm, and erode existing atherosclerotic plaques, causing myocardial ischemia and infarction.2 Family and emergency physicians have a high suspicion of ACS when evaluating chest pain, even though ischemic cardiac disease comprises a minority of final diagnoses3-5 and most chest pain is undiagnosed.6 Kounis syndrome is much less considered in differential diagnoses despite being diagnosed in 2% of patients with anaphylactic reactions,7 and accounting for 3.4% of allergy-related admissions.7,8 This diagnosed prevalence is likely lower than the true prevalence of KS and suggests that physicians treating chest pain should have a higher index of suspicion for it.
Physicians should be particularly suspicious of KS in patients who present with chest pain and typical allergic symptoms including rash, urticaria, or wheezing.9 Kounis syndrome most commonly affects 40- to 70-year-olds and is most often triggered by medications, animal bites, or stings.9,10 The most important risk factor for KS is a history of allergies, which is present in up to 25% of patients; other risk factors include hypertension, smoking, diabetes, and dyslipidemia.9,10
We report a case of KS in a 23-year-old man. We highlight the similar presentations of ACS and KS and review the process for effective diagnosis and treatment.
Case
A 23-year-old man with a known peanut allergy presented to the emergency department (ED) 30 minutes after having consumed peanuts. The patient had no prior history of anaphylaxis, had never used an epinephrine autoinjector, and had no major risk factors for atherosclerosis. The patient developed throat irritability that progressed to difficulty speaking; midsternal, nonradiating chest pain; headache; maculopapular rash; and had 1 episode of vomiting. Vital signs included a heart rate of 87 beats per minute (BPM), a respiratory rate of 18 breaths/min, a blood pressure (BP) of 104/74 mm Hg, an oxygen saturation of 100%, and a temperature of 35.7°C. On physical examination, the patient had a rash across his axilla and neck, a muffled voice, and his chest was clear to auscultation. Physical examination results were otherwise unremarkable and there was no mucosal involvement. Cardiac monitoring was initiated, showing normal sinus rhythm (Figure 1), and epinephrine was administered within 15 minutes of presentation due to the involvement of multiple systems and worsening airway compromise.
ECG rhythm strip showing normal sinus rhythm at patient intake
Approximately 5 minutes after epinephrine administration, the patient vomited again and became dizzy and diaphoretic, and had clammy skin. During this episode, his heart rate dropped to 35 BPM before recovering to 74 BPM and becoming irregular. His BP rose to 191/125 mm Hg. Shortly after, morphine was administered for the patient’s chest pain. A newly-acquired 12-lead electrocardiogram (ECG) showed sinus bradycardia with worsening ST depression in lead II and bigeminal premature ventricular contractions (Figure 2). At 20 minutes following epinephrine administration, a subsequent ECG showed a return to sinus rhythm, but with a severe ST depression (Figure 3). However, the patient’s BP began to trend downward, chest pain began to subside, and no respiratory distress was noted.
ECG taken after administration of epinephrine: The ECG demonstrates sinus bradycardia 224 with worsening inferolateral ST depressions, elevation in lead V, and bigeminal PVC.
ECG taken 20 minutes after administration of epinephrine: The ECG demonstrates return to sinus 229 rhythm with severe ST depression.
Laboratory test results revealed a troponin level of 405 ng/L. Treatment for presumed myocardial infarction was initiated, and the patient was given 162 mg of acetylsalicylic acid (ASA). The patient’s chest pain subsided over the subsequent hours and vital signs normalized. Troponin levels peaked at 2938 ng/L 7.5 hours after presentation to the ED and declined over the following 2 days. An echocardiogram showed normal left ventricular function with no wall motion abnormalities. Cardiology was consulted and recommended no angiography given the patient’s low-risk status. The patient was discharged with outpatient cardiology follow-up.
Discussion
Kounis syndrome can be divided into type I, involving hypersensitivity-induced vasospasm of the coronary arteries; type II, where pre-existing silent atheromatous disease is aggravated by a hypersensitivity reaction; and type III, where a reaction causes stent thrombosis in patients with stents in situ.1 Type I KS is the most common subtype and should be highly suspected in patients with ACS findings who do not have risk factors for atherosclerosis.2,9,10 Other common findings in type I KS include normal cardiac enzymes and ECG changes that are non-specific or transient.2
In cases where there is a reasonable probability of underlying atheromatous disease or the patient has cardiac stents, emergency angiography should be completed to distinguish type I from type II and III KS. Patient observation is reasonable in low-risk cases where type I KS is most likely. Types II and III involve the presence of a thrombus and require treatment similar to classic ACS but with modifications.1
Nitrates and calcium channel blockers can ameliorate coronary vasospasm and decrease myocardial oxygen demand and are therefore generally recommended.1,11 However, nitroglycerin can exacerbate cardiovascular collapse caused by anaphylaxis.12 Caution should be used when administering nitroglycerin to patients with KS, particularly if they are hypotensive. Sublingual or intravenous administration is preferable because transdermal administration is associated with allergic reactions.12 While ASA is indicated in ACS, it upregulates leukotriene production, which can worsen coronary vasospasm.12,13 Acetylsalicylic acid administration in type II or III KS is reasonable, but patients should be carefully monitored for signs of worsening anaphylaxis. If there is a history of ASA allergy, alternatives such as P2Y12 inhibitors should be considered. Morphine is typically the analgesic of choice in ACS, but it can stimulate mast cell degranulation, further aggravating anaphylaxis.14 Administering fentanyl results in much less degranulation and is preferred in KS management.12
While β-blockers are a mainstay of ACS treatment, they are not recommended in KS because they can worsen coronary vasospasm and inhibit the antianaphylactic effect of epinephrine.11,15 If β-blockers have already been administered and hemodynamic stability is compromised, glucagon, which has positive chronotropic and inotropic effects, may be an effective addition or alternative to epinephrine.16
While KS types II and III require treatments used for classic ACS, type I resolves with treatment of the hypersensitivity event.1 This primarily involves intravenous corticosteroids and H1 or H2 antihistamines.1 Importantly, many of the treatment options for both ACS and anaphylaxis can complicate the management of KS, and timely recognition is required to avoid exacerbating myocardial ischemia. Nitrates, ASA, β-blockers, and morphine all have potential adverse effects, and these medications are likely unnecessary to treat type I KS. The use of epinephrine, the criterion standard of anaphylaxis treatment, is complicated in KS. Epinephrine may worsen vasospasm, causing ischemia and provoking arrhythmias.12,17 Exogenous epinephrine also increases thromboxane A2 production, platelet sensitivity to adenosine diphosphate,18 and thrombin-mediated platelet aggregation.19 While there are no official guidelines for epinephrine use in KS, practice suggests its use be reserved for cases involving airway compromise, refractory shock, or hypotension.
Conclusion
Kounis syndrome is an underdiagnosed presentation to the ED that often masquerades as ACS. The treatment for KS differs substantially due to the complex and often antagonistic relationships between the traditional treatments for hypersensitivity and ACS. A high level of suspicion is necessary for individuals presenting to the ED with chest pain and either a history of allergies or current anaphylactic symptoms.
Acknowledgment
Calvin Armstrong and Anil Esleben made equal contributions to this report and are co–first authors.
Notes
Editor’s key points
▸ Kounis syndrome (KS) frequently masquerades as acute coronary syndrome and should especially be suspected in individuals with classic allergic symptoms or a history of anaphylaxis.
▸ If there is a reasonable probability of atherosclerotic disease, urgent angiography is highly recommended. This allows for the differentiation of type I from type II or III KS, which in turn informs treatment.
▸ The treatments of acute coronary syndrome and KS can be antagonistic. Quick recognition of anaphylactic involvement is essential to resolving rather than exacerbating myocardial ischemia.
Points de repère du rédacteur
▸ Le syndrome de Kounis (SK) ressemble souvent à s’y méprendre à un syndrome coronarien aigu et devrait surtout être soupçonné chez des personnes ayant des symptômes allergiques classiques ou des antécédents de choc anaphylactique.
▸ S’il existe une probabilité raisonnable d’athérosclérose, une angiographie urgente est fortement recommandée pour permettre de faire une distinction entre un SK de type I et ceux de types II ou III, ce qui guide alors le traitement.
▸ Les traitements d’un syndrome coronarien aigu et ceux d’un SK peuvent s’opposer les uns aux autres. Une reconnaissance rapide d’une causalité anaphylactique est essentielle pour corriger plutôt qu’exacerber l’ischémie myocardique.
Footnotes
Competing interests
None declared
This article has been peer reviewed.
Cet article a fait l’objet d’une révision par des pairs.
- Copyright © 2025 the College of Family Physicians of Canada
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