A 60-year-old woman with known allergy to honeybee venom was stung on her right hand by a “wasp” while gardening. She suffered a syncopal spell and was transported by emergency medical services to the closest hospital. The patient had no other allergies and gave a medical history of osteoarthritis and mild hypertension managed with nonsteroidal anti-inflammatory agents and hydrochlorothiazide, respectively. On arrival in the emergency department, the patient was hypotensive (systolic blood pressure <100 mmHg) with inverted T-waves on her electrocardiogram. The patient was treated with intravenous fluids (500 mL of normal saline), intravenous boluses of diphenhydramine (25 mg), and dexamethasone (2 mg), and a single intramuscular injection of 0.3 mL of a 1:1000 dilution of epinephrine (0.3 mg). Despite initial positive response to rehydration and medication, the patient developed hemolysis and acute oliguric renal failure requiring hemodialysis 12 hours after admission. Recovering from renal failure 10 days later, the patient became tachycardic (heart rate >120 bpm) and hypotensive (systolic blood pressure <100 mmHg), and an apical balloon configuration of the left ventricle was found during cardiac catheterization performed to rule out acute myocardial infarction (Figure 1). 1 Cardiac damage biomarkers, including troponin, were not significantly elevated. Coronary angiography did not find evidence of coronary artery disease or vasospasm. Within 5 days, the patient recovered completely from both renal and cardiovascular toxicity and was discharged. A consulting allergist/immunologist recommended Hymenoptera venom immunotherapy as an outpatient.
Left ventriculography during cardiac catheterization at systole that demonstrates apical ballooning akinesis with basal hyperkinesis. This was not the left ventriculogram during the cardiac catheterization of the case reported. Photograph by Steven Fruitsmaak (public domain).
DIAGNOSES Kounis syndrome with acute renal failure and takotsubo cardiomyopathy (“octopus pot heart”) due to Hymenoptera venom allergy.
Discussion
Most people are stung by bees, wasps, or hornets (order Hymenoptera) during their lifetimes and experience only local, short-lived symptoms. 2 Significant allergic reactions with regional edema and urticaria will, however, develop in less than 10% of individuals stung by Hymenoptera. Potentially fatal systemic allergic reactions, such as anaphylactic shock, may occur in less than 10% of individuals who are stung. 2 The most unusual manifestations of hymenoptera venom allergy include Kounis syndrome with or without takotsubo or octopus pot heart cardiomyopathy.2,3
The risk factors for significant allergic reactions to Hymenoptera venom have been identified as multiple prior stings in predisposed beekeepers and gardeners, previous allergic reactions to Hymenoptera stings, elevated baseline serum tryptase levels (>10 ng/mL), mastocytosis, and antihypertensive therapy with angiotensin-converting enzyme inhibitors and possibly β-blockers. 2 In the case presented, the patient exhibited 2 of these risk factors for Hymenoptera venom allergy: prior Hymenoptera stings as an outdoor gardener, and known allergy to honeybee (order Hymenoptera, family Apidae) venom.
In 2006, N.G. Kounis, a cardiologist, described mast cell activation and measured several inflammatory mediators in the serum and urine of patients with acute-onset angina pectoris and acute myocardial infarction. 4 Kounis noted several similarities between acute coronary syndromes associated with chemokine releases and other causes of mast cell activation, such as allergic hypersensitivity reactions and anaphylactoid and anaphylactic reactions to foreign proteins, including Hymenoptera venoms, radiographic contrast agents, chemicals, and medications. 4
Despite the similarities that Kounis described in the chemical inflammatory mediators associated with both cardiac ischemic and acute allergic events, Kounis syndrome remains incompletely understood and may actually represent unusual manifestations of pre-existing cardiac pathology exacerbated by atypical atopic responses to foreign proteins. 5 Future descriptions of similarly documented outcomes following atopic challenges will be required to confirm Kounis’s findings. 5
In 2011, Kounis et al described 3 distinct variants of the Kounis syndrome: Type I. Vasospastic allergic angina; Type II. Allergic myocardial infarction; and Type III. Coronary artery stent thrombosis with the stent-occluding thrombus infiltrated by eosinophils and mast cells. 4 In very rare cases of Kounis syndrome, a distinctive transient cardiomyopathy without myocardial infarction, now known as takotsubo or octopus pot heart cardiomyopathy may occur. 3
Takotsubo cardiomyopathy was first described in Japan in 2008 by Akashi and colleagues and named for the unique apical systolic shape of the left ventricle on angiography which resembled the traditional Japanese fisherman’s octopus trapping pot, the takotsubo (Figure 2). 6 Today, the case definition of takotsubo cardiomyopathy includes 1) a prodromal trigger of severe emotional or physical stressors in most (>85%) cases ranging from severe grief to a sudden illness after Hymenoptera stings; 2) electrocardiographic changes mimicking anterior wall myocardial infarction with moderate elevation of myocardial enzymes and serum tryptase levels; 3) a classic systolic bulging or “ballooning” of the left ventricular apex with a hypercontractile left ventricular base during angiography or echocardiography (Figure 1); 4) absence of any significant coronary artery disease during coronary angiography; and 5) complete recovery of normal left ventricular function and resolution of electrocardiographic cardiac damage biomarker abnormalities within a short period of days to weeks. 6
Traditional Japanese octopus trapping pot or takotsubo. The shape of the octopus pots resembles the characteristic systolic left ventriculogram described in cases of takotsubo or octopus pot cardiomyopathy. Source: National Library of Medicine of the National Institutes of Health (public domain).
The onset of the takotsubo syndrome following severe emotional stressors, such as the death of a spouse or family member gave the transient cardiomyopathy its other name, the “broken heart” syndrome. The mechanism of takotsubo cardiomyopathy is unknown, but is felt to be associated with massive autonomic discharge and coronary artery and microvascular vasospasm after severe stressors. 6 Takotsubo cardiomyopathy is most commonly reported in postmenopausal women and during the winter. 6
Several cases of Kounis syndrome with and, more often, without takotsubo cardiomyopathy have now been described after Hymenoptera stings by bees, wasps, and hornets worldwide (Figures 3 and 4).4,7 In 2010, Jairam and colleagues reported a case of delayed Kounis syndrome with takotsubo cardiomyopathy in India in a 57-year-old man after multiple wasp stings. 4 The patient made a full recovery from both renal and cardiac toxicity with hemodialysis and antiarrhythmic therapy within several days. 4 In 2014, Ralapanawa and Kularatne reported a case of Kounis syndrome without takotsubo cardiomyopathy in Sri Lanka after a lesser banded hornet (Vespa affinis) sting in a patient with known allergy to honeybee venom (Figure 3). 7
The lesser banded hornet, Vespa affinis, is widely distributed throughout Southeast Asia, and is responsible for the highest number of deaths after Hymenoptera stings in Sri Lanka. In addition to fatal anaphylactic shock, its stings have been followed by acute pulmonary edema, acute oliguria renal failure, and Kounis syndrome with and without takotsubo or octopus pot cardiomyopathy. This image was not the implicated Hymenoptera species in the case reported. Public domain image.
The European hornet, Vespa crabro, is the largest hornet in Europe and the only true hornet species in North America, where it is also known as the European hornet. The European hornet was introduced into North America from Europe in the mid-19th century and is now widely distributed throughout North America and some northern areas of Central America. Hornets may be distinguished from yellow jackets and all other wasps by their larger heads and thicker waists and abdomens. Although this image was not the implicated Hymenoptera species in the case reported, this species could indeed have been responsible for the Hymenoptera venom allergic responses described in the case report.
Although the Kounis syndrome and takotsubo cardiomyopathy are among the rarest manifestations of Hymenoptera venom allergy, they are typically transient phenomena not associated with coronary artery disease or any permanent cardiac damage unless allergic myocardial infarction, acute renal failure, or intracranial hemorrhage have co-occurred. 4 -7 In any case, the prognosis for a complete recovery is usually excellent following Kounis syndrome and takotsubo cardiomyopathy.
Footnotes
Acknowledgment
Support for Dr. Diaz was provided by departmental and institutional sources.