Dear Editor,
Snakebites remain a public health concern, especially in the tropics, but the clinical focus is generally on the toxic effects of the venomous species. Bites from nonvenomous snakes, such as Ptyas mucosa (Indian rat snake), are often considered benign; however, they can occasionally elicit severe systemic responses, including anaphylaxis.
Allergic myocardial infarction or Kounis syndrome is an increasingly accepted but little-emphasized clinical entity characterized by hypersensitivity reactions triggering acute coronary symptoms. Kounis syndrome, first described in 1991 [
1], is the co-occurrence of acute coronary syndromes, such as coronary spasm, acute myocardial infarction, and stent thrombosis, with conditions linked to platelet and mast-cell activation; this results in the release of interconnected and interacting inflammatory cells, such as T-lymphocytes and macrophages, in the context of allergic or hypersensitivity reactions and anaphylactic or anaphylactoid insults [
2]. While many of the typical suspects including drugs, insect stings, food, and environmental exposures have been implicated (
Table 1) [
3], cases describing Kounis syndrome secondary to snake bites are exceedingly rare.
Here we present the rare and complex case of a middle-aged man bitten by a nonvenomous snake called P. mucosa, followed by inferior wall myocardial infarction with a diagnosis of Kounis syndrome. This case highlights the need for adequate history taking and emphasizes the risk of potentially fatal complications from what is typically considered an innocuous interaction with a nonvenomous snake, a novel precipitant of Kounis syndrome.
CASE PRESENTATION
A 65-year-old male snake rescue operator presented to the emergency department with complaints of acute retrosternal chest pain associated with an episode of syncope at home. On arrival, he was conscious and oriented with a blood pressure of 110/70 mmHg, pulse rate 92 beats per minute, respiratory rate 18 breaths per minute, and oxygen saturation 96% on room air. A comprehensive systemic examination, including cardiovascular, respiratory, abdominal, and neurological systems, revealed no abnormal findings. However, his electrocardiography showed ST-segment elevations in the inferior leads (
Fig. 1) and his point-of-care echocardiography showed inferior wall hypokinesia with an ejection fraction of 50%. A detailed head-to-toe examination revealed significant localized swelling of the right leg extending to the groin region. On further questioning, he attributed the swelling to the snake bite by a nonvenomous snake,
P. mucosa, which he had identified himself. No signs of neuroparalysis were found in the patient and the results of a 20-minute whole-blood clotting test were normal, suggesting a nonvenomous exposure.
The patient was given dual antiplatelets and statins per the institutional ST-elevation myocardial infarction protocol. Primary coronary angiography was performed after an emergent cardiology consultation and revealed no abnormalities in the coronary vessels. Provocative tests for coronary spasm, considered the gold standard for diagnosis of vasospastic anginas, were not done due to the risk of complications. Laboratory investigations revealed a total leukocyte count of 12,000 cells/mm3 with differential counts of neutrophils 70%, lymphocytes 15%, eosinophils 11%, and monocytes 4%. Serum tryptase was elevated at 14.1 μg/L, troponin I was markedly raised at greater than 50,000 pg/mL, and creatine kinase-MB was 64 ng/mL. The differential diagnosis included type 1 myocardial infarction, Prinzmetal angina, Takotsubo cardiomyopathy, and Kounis syndrome. The coexistence of myocardial infarction with anaphylaxis and normal coronary angiography supported the diagnosis of type I Kounis syndrome. No recent exposure to known allergens or pharmacologic agents was identified prior to symptom onset, strengthening the attribution of the snakebite as the primary trigger. Once Kounis syndrome was confirmed, the patient was given antihistamines, hydrocortisone, nitrates, and supportive care. He was moved to the critical care unit for further management.
DISCUSSION
Kounis syndrome or allergic myocardial infarction is a rare intersection of hypersensitivity reactions and acute coronary syndromes. In 1991, Kounis and Zavras [
1] first described the provocation of cardiac events like myocardial infarction or angina by common allergic and anaphylactic reactions. Given the increasing frequency of allergic disorders worldwide, this currently underdiagnosed and often disregarded entity may have growing clinical relevance.
The syndrome has three types, depending upon the pathophysiologic cause and coronary artery status [
4]: type I is mainly caused by coronary artery spasm due to mast cell degranulation and is present in patients with angiographically normal coronary arteries; type II occurs in patients with preexisting atheromatous coronary artery disease, in whom an acute allergic reaction triggers plaque rupture or erosion, leading to acute coronary syndrome, reflecting the combination of significant underlying coronary artery disease and superimposed allergy-mediated coronary events rather than allergy alone in structurally normal arteries; and type III is connected to stent thrombosis, which might have been induced by allergic reactions to clopidogrel or other stent components.
Mast cells play an essential role in the pathophysiology of Kounis syndrome. They release several inflammatory mediators like histamine, leukotrienes, tryptase, and platelet-activating factor when activated. These mediators eventually play a role in thrombotic activities, elevated vascular permeability, and vasoconstriction [
2]. Through the activation of platelets and induction of coronary vasospasm and thrombosis, these mediators might directly relate allergic reaction to acute myocardial ischemia [
5]. Clinical presentations of Kounis syndrome are highly variable, ranging from mild chest pain to myocardial infarction. The usual biomarkers of myocardial injury (troponin) and allergic response (tryptase, histamine) are not always elevated at the same time; therefore, the diagnosis often relies primarily on clinical assessment in the emergency department.
In clinical practice, serum tryptase values higher than 11.4 ng/mL are considered indicative of anaphylaxis, and this cutoff has a sensitivity of 73% and a specificity of 98% for diagnosing anaphylaxis. It is used to confirm the allergic/anaphylactic trigger, which then supports the diagnosis of Kounis syndrome when cardiac involvement is also present. Because tryptase has a short half-life of approximately 90 minutes, serial measurements of serum tryptase (typically at least three samples) are recommended. Histamine is rapidly released from mast cells and remains in circulation for approximately 8 minutes after an allergic episode; hence, blood samples should be collected promptly after the onset of chest pain [
6].
Past exposure to the allergen, changing electrocardiographic patterns, and echocardiographic dysfunction can all facilitate diagnosis. The subtype of Kounis syndrome should dictate the therapeutic intervention. Broadly, treatment entails management of the cardiac event and the allergic reaction. Nitrates, calcium channel blockers, and antithrombotic medicines might be needed for the management of cardiac symptoms, while the allergic aspect would require medication such as antihistamines, corticosteroids, and epinephrine. Caution in the use of medications such as epinephrine is advised because they can exacerbate ischemia in patients with coronary artery disease [
3].
This case highlights various manifestations and management challenges of Kounis syndrome, emphasizing the importance of increased clinical suspicion and thorough history taking for hazardous exposures in patients with myocardial infarction. Kounis syndrome should be considered in cases of myocardial infarction with a recent allergen exposure. Allergic biomarkers like tryptase and histamine can be suggestive, as can elevated troponin. Prompt coronary angiography can be diagnostic and can avoid unnecessary thrombolysis. Early detection and a multidisciplinary approach are essential for improving patient outcomes.
NOTES
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Ethics statement
Written informed consent for publication of the research details and clinical images was obtained from the patient.
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Author contributions
Conceptualization: all authors; Investigation: MAAS, JB; Methodology: MAAS, JB; Supervision: SS;
Writing–original draft: MAAS; Writing–review & editing: all authors. All authors read and approved the final manuscript.
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Conflicts of interest
The authors have no conflicts of interest to declare.
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Funding
The authors received no financial support for this study.
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Data availability
Data sharing is not applicable as no new data were created or analyzed in this study.
Fig. 1.Electrocardiography showing ST elevation in leads II, III, aVF, V5, and V6, 15 minutes after arrival with active chest pain.
Table 1.Etiology of Kounis syndrome
Table 1.
|
Category |
Example |
|
Environmental exposure |
Wasp, bee, ant and jellyfish stings |
|
Millet |
|
Poison ivy |
|
Latex |
|
Snake and other venoms |
|
Diesel exhaust |
|
Sarin gas |
|
Mowing the lawn/grass cutting |
|
Foods |
|
Disease and medical condition |
Angioedema |
|
Bronchial asthma |
|
Urticaria |
|
Anaphylaxis related to exercise |
|
Mastocytosis |
|
Churg-Strauss syndrome |
|
Drug-eluting coronary stents |
|
Intracardiac devices |
|
Takotsubo cardiomyopathy |
|
Drug |
|
|
Analgesic |
Dipyrone |
|
Anesthetic |
Etomidate |
|
Antibiotic |
Ampicillin, ampicillin/sulbactam, amoxicillin, amikacin, cefazolin, cefoxitin, cefuroxime, penicillin, vancomycin, ciprofloxacin |
|
Anticholinergic agent |
Trimethaphan |
|
NSAID |
Diclofenac, naproxen, ibuprofen |
|
Antineoplastic |
5-Fluorouracil, carboplatin, cisplatin, cyclophosphamide, interferon |
|
Contrast media |
Indigotin disulfonate, iohexol, ioxaglate |
|
Corticosteroid |
Betamethasone, hydrocortisone |
|
Skin disinfectant |
Chlorhexidine, povidone iodine |
|
Muscle relaxant |
Cisatracurium, rocuronium |
|
Proton pump inhibitor |
Lansoprazole, omeprazole |
|
Thrombolytic agent and anticoagulant |
Heparin, streptokinase, urokinase, lepirudin, hirudin, bivalirudin |
|
Other |
Allopurinol, enalapril, esmolol, insulin, protamine, iodine, nicotine patches |
REFERENCES
- 1. Kounis NG, Zavras GM. Histamine-induced coronary artery spasm: the concept of allergic angina. Br J Clin Pract 1991;45:121-8.
- 2. Kounis NG. Kounis syndrome: an update on epidemiology, pathogenesis, diagnosis and therapeutic management. Clin Chem Lab Med 2016;54:1545-59.
- 3. Rico Cepeda P, Palencia Herrejón E, Rodríguez Aguirregabiria MM. Kounis syndrome. Med Intensiva 2012;36:358-64.
- 4. Benchea LC, Anghel L, Scripcariu DV, et al. Kounis syndrome in clinical practice: insights from clinical case series and mechanistic pathways. J Clin Med 2025;14:768.
- 5. Kounis NG, Giannopoulos S, Tsigkas GG, Goudevenos J. Eosinophilic responses to stent implantation and the risk of Kounis hypersensitivity associated coronary syndrome. Int J Cardiol 2012;156:125-32.
- 6. Forzese E, Pitrone C, Cianci V, et al. An insight into Kounis syndrome: bridging clinical knowledge with forensic perspectives. Life (Basel) 2024;14:91.
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