Summary

The European hornet (Vespa crabro) is a large vespid wasp native to most of Europe and Asia. It injects venom for self-defense and to capture prey via a stinging apparatus. In Europe, V. crabro is responsible for only occasional vespid venom allergic reactions, but these reactions are likely to be severe and can induce fatal anaphylaxis. Three allergenic molecules have been characterized in V. crabro venom to date, which cross-react to some degree with homologous proteins in venom from other Hymenoptera insects such as yellow jacket (Vespula spp.) and honeybee (Apis mellifera).

Route Of Exposure

Main

Female Hymenoptera insects have a stinging apparatus at the tail end of their abdominal segment, which is used for self-defense, to repel colony intruders, and to capture prey. A sting can deliver between 100 ng and 50 µg of venom. V. crabro is not particularly aggressive to humans, and usually only stings when provoked or disturbed.

Clinical Relevance

Hymenoptera stings account for 9‒23% of all systemic allergic reactions, and 20‒40% of all types of reported each year, making them a major cause of hypersensitivity responses. An estimated 50% of subjects who experienced fatal reactions had no documented history of a systemic reaction to Hymenoptera sting.

In Europe, V. crabro is responsible for only occasional vespid venom allergic reactions, but these reactions are likely to be severe. A case history analysis of 157 Hymenoptera allergic patients in Portugal estimated that the relative risk of a life-threatening reaction was approximately three times higher with V. crabro versus yellow jacket or honeybee (RR=2.74, CI 95%: 1.93‒3.89; R<0.0001) [ANT03]. In this study, the percentage of life-threatening reactions was 81.2% in the V. crabro allergic patients group (n=35), versus 27.8% in the Vespula spp. allergic group (n=97) and 24% in the Apis mellifera allergic group (n=25).

In general, exposure to venom leads to a type I hypersensitivity reaction, with clinical symptoms that can include local burning, persistent local pain, angioedema, generalized urticaria, decreased blood pressure, bronchospasm, cardiac arrest, and respiratory and anaphylactic shock in sensitized individuals. Interestingly, in a study of 220 patients allergic to bee, wasp, or European hornet venom, total IgE levels of patients with mild symptoms (e.g. grade I, generalized skin symptoms) were higher than those of patients with either moderate reactions (e.g. grade II, moderate pulmonary, cardiovascular, or gastrointestinal symptoms) or severe reactions (e.g. grade III, bronchoconstriction, emesis, anaphylactic shock, or loss of consciousness) (248.0 kU/l vs 75.2 kU/l vs 56.5 kU/l, respectively; p<0.001) [STU07].

A recent review paper identified 55 detailed cases of Vespa spp. hornet sting in 27 papers, with a mortality rate of 36.4% due mainly to multi-organ failure with common complications of renal failure and liver dysfunction.

In a report from Nepal, three subjects developed acute renal failure following multiple hornet stings (species unidentified) and were admitted to hospital; two patients recovered following hemodialysis and treatment and one patient died. A case report from Turkey described a 30-year-old male with no history of cardiovascular or systemic abnormalities who developed atrial fibrillation, shortness of breath, dizziness, and headache following a suspected V. crabro sting and recovered fully after emergency treatment with anti-coagulants and intravenous propafenone. A further case report from Serbia described a healthy 45-year-old male with no history of ischemic heart disease who developed acute myocardial infarction and anaphylaxis following a V. crabro sting and was admitted to ICU. Skin prick tests (SPT) did not confirm sensitivity to bee, wasp, or hornet and total serum IgE levels were normal. The patient was treated with coronary vasodilators, antiarrhythmics, anti-aggregation drugs, and sedatives, and discharged from hospital 20 days following the sting event.

Prevention And Therapy

Allergen immunotherapy

Immunotherapies for wasp venom aim to increase suppressor cytokines such as IL-10 and TNF-β, and decrease IL-4 secretion.

Cross-Reactivity

There is a wide potential for cross-reactivity between different species of Hymenoptera due to high structural and antigenic similarity between primary sequences of allergens. The three major proteins in V. crabro venom (Vesp c 1, Vesp c 2, and Vesp c 5) are structurally and antigenically related to those from other vespid wasps including Vespula yellow jackets.

In Italy, 17 patients with a severe reaction after V. crabro sting showed non discriminative skin/CAP positivity to Vespula spp. In 11/17 of these subjects, Vespula venom completely inhibited IgE binding to V. crabro venom, whereas V. crabro venom only partially (<75%) inhibited IgE binding of Vespula venom.

Cross-inhibition tests in 24 consecutive patients who experienced anaphylaxis after a V. crabro sting in Europe showed that 17/24 were sensitized to wasp (Vespula germanica) venom, 2/24 with completely cross-reactive epitopes, 1/24 with only V. crabro venom, and 4/24 with separate epitopes of both venoms. These authors concluded that at least 70% of the patients who experienced a systemic allergic reaction to V. crabro were actually allergic to wasp venom.

A study in Spain detected IgE antibodies to Polistes dominulus (European paper wasp), Vespula germanica (German wasp), and to a lesser extent V. crabro in a large group of sera from patients sensitized to vespids. As only a minority of subjects in this study had co-existing antibodies to two species, the authors suggested that most of the patients were originally sensitized to just one species with additional positivity to other venoms due to cross-reactivity.

Antigen 5 (Vesp c 5) is found in different social wasp species (e.g., Vespa, Vespula, Polistes, Dolichovespula, and Polybia spp.) and shows sequence homology with a variety of proteins including ant venom, tomato leaf tobacco, mammalian testis protein, and human brain tumor. Vesp c 5 demonstrated sequence identities to Ag5 homologs in venom from Dolichovespula (66.3‒72.1%) and yellow jacket (65.4‒71.6%), but no cross-reactive antigen reactivity with ant venom Ag5.