Abstract
Hymenoptera venom allergy is a cause of anaphylaxis, which significantly affects patients' daily lives due to the constant fear of accidental stings. Venom immunotherapy (VIT) is the only treatment capable of preventing severe systemic reactions (SSRs). Limited long-term real-life data are available, integrating both clinical and immunological outcomes. A five-year prospective observational study was conducted on 35 patients with a history of SSR who underwent VIT at a tertiary allergy center in Southern Italy; two of them had a diagnosis of systemic mastocytosis. Most patients were sensitized to Vespula, but others to Apis, Polistes dominula and Vespa crabro, reflecting the exposure pattern characteristic of Mediterranean regions. Clinical outcomes following accidental re-stings and serological trends, including total IgE, venom-specific IgE, and baseline serum tryptase, were assessed at treatment initiation and after five years of maintenance therapy. During the entire follow-up, all patients tolerated VIT. No SSRs occurred after accidental stings in 17/35 patients, confirming clinical protection achieved with VIT. Vespula serum-specific IgE presented a highly significant decrease; total IgE, tryptase and specific IgE for Apis, Polistes dominula and Vespa crabro showed a statistically significant decrease. Our findings reinforce the role of VIT as a well-tolerated, effective and disease-modifying treatment in a real-world setting.