In vitro diagnostics in hymenoptera venom allergy: Current concepts and perspectives

Hymenoptera venom allergy (HVA) is a leading cause of anaphylaxis in adults and requires precise diagnostic work-up to guide venom immunotherapy (VIT). However, the high prevalence of asymptomatic sensitization and frequent double sensitization complicate the identification of clinically relevant allergens.

This narrative review summarizes current concepts and recent advances in in vitro diagnostics of HVA, including conventional IgE testing, component-resolved diagnostics (CRD), IgE ratio analysis, and cellular assays and biomarkers for risk stratification. Emphasis is placed on their diagnostic performance, limitations, and clinical applicability.

Measurement of venom-specific IgE remains the cornerstone of HVA diagnosis, offering high sensitivity for clinically relevant HVA. CRD using recombinant, CCD-free allergens improves discrimination between primary sensitization and cross-reactivity, particularly in patients with double sensitization to honeybee and yellow jacket venoms. However, incomplete allergen panels, especially in honeybee venom allergy, limit sensitivity. IgE ratio analysis has emerged as a complementary tool to identify the most likely culprit venom, although it may be influenced by recent sting exposure. Cellular assays such as the basophil activation test provide functional information and may support diagnosis in complex cases but are restricted to specialized centers. In addition, biomarkers such as basal serum tryptase and KIT p.D816V mutation are important for risk stratification.

Modern in vitro diagnostics substantially enhance the precision of HVA diagnosis but cannot replace clinical history. An integrated approach combining serology, molecular diagnostics, ratio analysis and, where appropriate, functional assays, is essential for accurate identification of the relevant venom and optimal patient management.