Summary

Polistes (P.) dominula, also called “European paper wasp”, is a social wasp of clinical relevance for Southern Europe and the Mediterranean areas. This species has recently spread from its native Eurasia to all continents except Antarctica.

The prevalence of Hymenoptera-induced anaphylaxis is estimated at 3% in adults and 1% in children, with 40 to 100 Hymenoptera sting-induced fatalities being documented annually in the United States. The risk of repeated anaphylaxis is 30% to 70%. An estimated 9 to 42% of the general population is sensitized to Hymenoptera venom.

Hunters, greenhouse workers, and rural populations are at higher risk of developing Hymenoptera venom allergy (HVA). Mast cell disorders including hereditary α-tryptasemia and elevated baseline serum tryptase are associated with an increased risk of occurrence and severity of Hymenoptera sting-induced reactions. A history of Hymenoptera-induced anaphylaxis is a red flag for an underlying clonal mast cell disorder.

Five molecular allergens belonging to the molecular families of phospholipase A1 (PLA1), hyaluronidase, dipeptidyl peptidase IV, antigen 5, and serine protease have been characterized so far from P. dominula venom (PDV). Pol d 5 is the only one widely currently available for routine in vitro diagnosis. PDV, like venom from other Polistes spp, is devoid of cross-reacting carbohydrate determinants (CCD).

Allergen

Nature

PDV consists of a complex mixture of allergenic and non-allergenic molecules contained in the venom sac at the distal extremity of the insect’s abdomen [1]. Similar to most Hymenoptera, P. dominula can extract its stinger from the victim and is thus able to sting multiple times during its lifetime.

Taxonomy

Domain: Eukaryota

Kingdom: Metazoa (Animalia)

Phylum Arthropoda

Subphylum: Hexapoda

Class: Insecta

Order: Hymenoptera

Suborder: Apocrita

Family: Polistinae

Genus: Polistes

Species: P. dominula

The order Hymenoptera comprises the families Vespids (wasps and hornets), Apids (bees and bumblebees) and Formicids (stinging ants). The two Vespid subfamilies are Vespinae, with genera Vespula, Dolichovespula, and Vespa, and Polistinae, with Polistes and Polybia [1].

Tissue

Vespid venoms contain three major constituents: proteins, including allergens; small peptides, e.g. neurotoxic and antimicrobial peptides; and substances of low molecular weight such as bioactive amines [2]. PDV contains multiple allergens, with five currently included in the IUIS/WHO Allergen Nomenclature [3]. Of these, phospholipase A1 (PLA1) Pol d 1 and CAP (cystein-rich, antigen 5 and pathogenesis-related proteins) member Pol d 5 represent a significant portion of dry PDV weight [1].

Epidemiology

Worldwide distribution

In Southern Europe, PDV allergy is frequent, either as monosensitization or in association with Vespula (yellow jacket) venom (YJV). Its prevalence could be underestimated in other regions, where PDV is not included in Vespid allergy investigation [4]. Primary PDV sensitization was demonstrated in 34-56% of the double PDV/YJV sensitized patients in Southern Europe [4-8].

Double sensitization, whether resulting from genuine double sensitization or cross-reactivity, may be clinically relevant and puts the patients, especially those with underlying mast cell disorders, at risk of severe reactions to stings from various Hymenoptera species [1, 9].

Indeed, Hymenoptera stings cause 48% of severe anaphylactic reactions occurring in European adults, and 20% of those occurring in children [1].

It is estimated that the worldwide annual incidence of immunologic reactions to Hymenoptera stings, ranging from local wheal-and-flare reactions to fatal anaphylaxis, is comprised between 0.3 and 3.0%, which equates to almost 100 million cases per year [10]. An estimation for the USA suggests that Hymenoptera-induced systemic reactions occur in 3% of adults and 1% of children, leading to approximately 40 to 100 fatalities each year, a figure likely to be higher [11]. Among people being stung by a Hymenoptera, it is estimated that 0.5 to 3.3% in the USA and 0.3 to 7.5% in Europe will develop a systemic reaction [12, 13].

Fatal insect venom anaphylaxis occurs at an approximate rate of 0.1 cases per million population, a consistent finding across studies in Australia, Canada, the UK and the USA [14].

Risk factors

Identifying patients at risk for severe reactions to Hymenoptera venom requires a careful record of clinical history and a stepwise procedure in the use of diagnostic tests [1, 9, 13]. The severity of past reactions to Hymenoptera stings is the best predictor of the severity of recurrent reactions, while the most significant risk factor for severe reactions is an underlying mast cell disorder [5, 9].

The prevalence and severity of Hymenoptera (including Polistes) venom reactions are increased in patients with mast cell disorders including hereditary α-tryptasemia, with or without an elevated baseline serum tryptase concentration [12, 15]. In a European study, HVA was reported in 50% of patients with systemic mastocytosis without hereditary α-tryptasemia and in 82% of those with concurrent hereditary α-tryptasemia [15]. In a 1-year US survey for 2018 using a health database, mastocytosis was 9.7 times more prevalent among HVA patients (odds-ratio 2.4 in children and 14.3 in adults) than in general population [12].

Cardiovascular risk factors, male gender and older age have also been associated with an increased risk of severe reactions to Hymenoptera venom [16]. Lifestyle, including outdoor leisure activities or occupational exposure, may result in an increased prevalence of Hymenoptera stings, sensitization and systemic reactions [1]. On the other hand, sensitization to Hymenoptera venom is frequent, estimated at 9.2% to 42% of the adult population, and comprises a majority of asymptomatic individuals [1].

Pediatric issues

The prevalence of systemic reactions to Hymenoptera venoms is estimated at 3.4% in children [13]. In children younger than 16 years experiencing a cutaneous reaction to Hymenoptera venom, the chance of anaphylaxis if re-stung is lower than 3% [11].

Cross-Reactivity

As a rule, high cross-reactivity is observed within European Polistes venoms on one hand and American Polistes venoms on the other hand, while incomplete cross-reactivity is observed between the two groups, American and European Polistes [1]. Incomplete PDV/YJV cross-reactivity is also observed [1].

Explained Results

Allergen Information

PDV contains a complex mixture of biologically active molecules relevant for European Polistes species and is devoid of cross-reactive carbohydrate determinants.

Clinical information

PDV allergy may manifest as life-threatening systemic reactions, which require clinical and in vitro investigation including assessment of concurrent mast cell disorders and hereditary α-tryptasemia and are eligible for VIT. The prevalence of systemic reactions to Hymenoptera stings in adults ranges from 0.3% to 7.5%. Conversely, asymptomatic sensitization to Hymenoptera venoms is found in a substantial proportion of the general population, precluding its use for Hymenoptera venom allergy screening.

Cross-reactivity

PDV displays cross-reactivity with other Vespid venoms, including YJV and American Polistes. The marker allergens Pol d 1 and Pol d 5 are currently available for the identification of genuine sensitization to Vespid venom, especially in areas of high P. dominula exposure.

Author: Dr. Joana Vitte

Reviewed: Dr. Michael Spangfort

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