Tolerability, course and follow-up of specific immunotherapy using a modified ultra-rush procedure in children and adolescents with insect venom allergy

Summary Background Specific immunotherapy with insect venom (hymenoptera venom (HG)-AIT) is an effective and the only causal treatment for patients with systemic reactions due to IgE-mediated insect venom allergy. The present study investigated the quality of care after bee and wasp venom allergy, the tolerability of modified ultra-rush immunotherapy and the course after the conclusion of maintenance therapy in children and adolescents. Studies on the quality of life of children with insect venom allergy are scarce. Methods The efficacy, safety and tolerability of an ultra-rush protocol was analysed in 114 patients aged 4–17 years with insect venom allergy. After the end of HG-AIT, patients were contacted by questionnaire and asked to report on the quality of care as well as the course of insect venom allergy, including accidental stinging events. Quality of life was validated using the established questionnaire VQLQ‑d (Vespid Quality of Life Questionnaire), which is also used for bee venom allergy patients. Results Discontinuation of the initial therapy was not necessary in any patient. Side effects were mostly mild and did not require treatment. In 16 patients, a new sting reaction occurred during maintenance therapy, in another 15 patients a sting event was documented after cessation of HG-AIT. The intensity of the reaction to the accidental insect bite according to the severity classification after Ring and Messmer decreased from an average of 2.3 to 0.9 in these patients. This corresponds to a decrease of 61%. An emergency kit was carried by 70% of the patients, the expiry date of which, however, had already passed in almost 40% of the respondents. After the end of the therapy, most patients were not under any medical care or had never been to a check-up (92%). The evaluation of the VQLQ‑d showed a medium to low level of stress during or after therapy. Discussion Ultra-rush AIT in childhood and adolescence is safe, tolerable and effective. HG-AIT has a lasting positive effect on the health-related quality of life of patients. However, after the end of HG-AIT, there are deficits in the follow-up and care of the patients.

Risk factors in bee and Vespula venom allergy: state of the art

Summary Background Correct recognition of risk factors enables individualized management and treatment of venom allergic patients. Methods Systematic research and review of current literature regarding the risk of (1) severe sting-induced anaphylaxis, (2) anaphylactic adverse event during venom immunotherapy (VIT), and (3) treatment failure. Results and discussion (1) Mastocytosis is the most important risk factor for severe sting-induced anaphylaxis. Hereditary α‑tryptasemia was recently identified as a genetic predictor of severe reactions. Older age is clearly associated with an increased risk; the respective impact of defined cardiovascular comorbidities has yet to be determined. Recent data do not support an aggravation of venom-induced anaphylaxis by intake of β‑blockers or angiotensin-converting enzyme (ACE) inhibitors. A higher risk in men can be attributed to more intensive exposure to stinging insects. (2) Anaphylactic side effects of VIT are most common during the buildup phase, particularly in the course of (ultra-)rush protocols involving a high number of injections and high cumulative daily doses. They are significantly more frequent during honeybee compared to Vespula VIT. Data supporting a negative effect of mastocytosis on the tolerability of VIT are scarce. Older age and cardiovascular medication are not associated with a higher incidence of VIT-induced anaphylaxis. (3) Relapsing anaphylactic reactions to both field and challenge stings are significantly more common during and after honeybee compared to Vespula VIT. Reports of severe field-sting reactions in mastocytosis patients suggest an increased risk of treatment failure which may be overcome by higher maintenance doses and longer duration of VIT.

Characterization of New Allergens from the Venom of the European Paper Wasp Polistes dominula

Discriminating Polistes dominula and Vespula spp. venom allergy is of growing importance worldwide, as systemic reactions to either species’ sting can lead to severe outcomes. Administering the correct allergen-specific immunotherapy is therefore a prerequisite to ensure the safety and health of venom-allergic patients. Component-resolved diagnostics of Hymenoptera venom allergy might be improved by adding additional allergens to the diagnostic allergen panel. Therefore, three potential new allergens from P. dominula venom—immune responsive protein 30 (IRP30), vascular endothelial growth factor C (VEGF C) and phospholipase A2 (PLA2)—were cloned, recombinantly produced and biochemically characterized. Sera sIgE titers of Hymenoptera venom-allergic patients were measured in vitro to assess the allergenicity and potential cross-reactivity of the venom proteins. IRP30 and VEGF C were classified as minor allergens, as sensitization rates lay around 20–40%. About 50% of P. dominula venom-allergic patients had measurable sIgE titers directed against PLA2 from P. dominula venom. Interestingly, PLA2 was unable to activate basophils of allergic patients, questioning its role in the context of clinically relevant sensitization. Although the obtained results hint to a questionable benefit of the characterized P. dominula venom proteins for improved diagnosis of venom-allergic patients, they can contribute to a deeper understanding of the molecular mechanisms of Hymenoptera venoms and to the identification of factors that determine the allergenic potential of proteins.

A Review of Honeybee Venom Allergens and Allergenicity

Honeybee venom is a source of proteins with allergenic properties which can result in in various symptoms, ranging from local reactions through to systematic life-threatening anaphylaxis, or even death. According to the World Allergy Organization (WAO), honeybee venom allergy is one of the most common causes of anaphylaxis. Among the proteins present in honeybee venom, 12 protein fractions were registered by the World Health Organization’s Allergen Nomenclature Sub-Committee (WHO/IUIS) as allergenic. Most of them are highly immunogenic glycoproteins that cross-react with IgE and, as a consequence, may give false positive results in allergy diagnosis. Allergenic fractions are different in terms of molecular weight and biological activity. Eight of these allergenic fractions have also been identified in honey. This explains frequent adverse reactions after consuming honey in people allergic to venom and sheds new light on the causes of allergic symptoms in some individuals after honey consumption. At the same time, it also indicates the possibility of using honey as a natural source of allergen in specific immunotherapy.

The role of component-resolved diagnosis in Hymenoptera venom allergy in clinical practice

Background: Hymenoptera venom allergy is an immunoglobulin (Ig) E mediated hypersensitivity reaction to Hymenoptera venoms. Obvious identification of the culprit insect that causes the clinical symptoms and, hence, the accurate selection of venom for curative treatment, is of great importance for the effectiveness and safety of venom immunotherapy. Objective: In this study, the contribution of component-resolved diagnostics (CRD) is evaluated in the diagnosis of Hymenoptera venom allergy. Method: Ninety-three patients from four different centers in Turkey were included in the study. Conventional tests, including prick and intradermal skin tests, with commercial venom extracts and serum specific IgE (sIgE) levels for whole venoms were performed. An sIgE analysis for venom allergen components, including rApi m 1, rApi m 2, rApi m 10, rVes v 1, rVes v 5, were evaluated by immunoblotting. Results: In conventional test results, 17 of 35 patients with bee venom allergy were positive to honey bee venom, whereas 18 patients were positive to bee and wasp venoms. In 28 of 35 patients with bee venom allergy, the diagnosis was confirmed with CRD. CRD revealed a sensitivity of 80% in patients with bee venom allergy. According to conventional tests, 7 of 24 patients with vespid venom allergy demonstrated sensitivity only to Vespula species, whereas 17 patients revealed double positivity. The total diagnostic sensitivity of Ves v 1 and Ves v 5 was calculated as 87.5%. Ten of 23 patients with a history of hypersensitivity to both venoms showed double sensitivity with CRD; one patient had cross-reactivity, one patient was found to be sensitive only to bee venom, and, eight patients were sensitive only to Vespula species. Eleven patients had an uncertain history in terms of the culprit insect type and six of them had double sensitivity in CRD. Conclusion: CRD seemed to be more helpful in diagnosing vespid venom allergy than bee venom allergy. It can also discriminate clinically significant sensitizations from irrelevant ones.