{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:00:59Z","timestamp":1790280059602,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Hymenoptera venom allergy is a cause of anaphylaxis, which significantly affects patients\u2019 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.<\/jats:p>","DOI":"10.3390\/toxins18040187","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T12:25:30Z","timestamp":1776255930000},"page":"187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Five-Year Real-World Outcomes of Hymenoptera Venom Immunotherapy: Clinical Effectiveness and Immunological Modifications"],"prefix":"10.3390","volume":"18","author":[{"given":"Claudia","family":"Panzera","sequence":"first","affiliation":[{"name":"Allergy and Clinical Immunology Unit of G. Martino Hospital, Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiano","family":"Gangemi","sequence":"additional","affiliation":[{"name":"Allergy and Clinical Immunology Unit of G. Martino Hospital, Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3105-8347","authenticated-orcid":false,"given":"Luisa","family":"Ricciardi","sequence":"additional","affiliation":[{"name":"Allergy and Clinical Immunology Unit of G. Martino Hospital, Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1111\/all.13262","article-title":"EAACI Guidelines on Allergen Immunotherapy: Hymenoptera Venom Allergy","volume":"73","author":"Sturm","year":"2018","journal-title":"Allergy"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.iac.2007.03.008","article-title":"Insect Sting Anaphylaxis","volume":"27","author":"Golden","year":"2007","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1046\/j.1365-2222.1999.00614.x","article-title":"Epidemiological study of the prevalence of allergic reactions to Hymenoptera in a rural population in the Mediterranean area","volume":"29","author":"Fernandez","year":"1999","journal-title":"Clin. Exp. Allergy"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1080\/21645515.2017.1264748","article-title":"Hymenoptera venom allergy in outdoor workers: Occupational exposure, clinical features and effects of allergen immunotherapy","volume":"13","author":"Toletone","year":"2017","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"58","DOI":"10.15586\/aei.v50i2.523","article-title":"Social wasps in Spain: The who and where","volume":"50","author":"Vega","year":"2022","journal-title":"Allergol. Immunopathol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ricciardi, L., Silvestro, O., Martino, G., Catalano, A., Vicario, C.M., Lund-Jacobsen, T., Schwarz, P., Sapienza, D., Gangemi, S., and Pioggia, G. (2024). Health-related quality of life in severe hypersensitivity reactions: Focus on severe allergic asthma and hymenoptera venom anaphylaxis-a cross-sectional study. Front. Psychol., 15.","DOI":"10.3389\/fpsyg.2024.1394954"},{"key":"ref_7","first-page":"134","article-title":"Epidemiological factors on hymenoptera venom allergy in a Spanish adult population","volume":"14","author":"Navarro","year":"2004","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_8","first-page":"244","article-title":"Clinical aspects of hymenoptera venom allergy and venom immunotherapy","volume":"51","author":"Tontini","year":"2019","journal-title":"Eur. Ann. Allergy Clin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jaci.2014.11.035","article-title":"Clonal mast cell disorders in patients with severe Hymenoptera venom allergy and normal serum tryptase levels","volume":"136","author":"Zanotti","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1097\/ACI.0b013e32832d2bc7","article-title":"Stinging Hymenoptera and mastocytosis","volume":"9","author":"Przybilla","year":"2009","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1111\/all.13817","article-title":"Medical Algorithms: Diagnosis and treatment of Hymenoptera venom allergy","volume":"74","author":"Sturm","year":"2019","journal-title":"Allergy"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1111\/j.1398-9995.2005.00963.x","article-title":"Diagnosis of Hymenoptera venom allergy","volume":"60","author":"Rueff","year":"2005","journal-title":"Allergy"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"154","DOI":"10.5414\/ALX02430E","article-title":"Diagnosis and treatment of Hymenoptera venom allergy: S2k Guideline of the German Society of Allergology and Clinical Immunology (DGAKI) in collaboration with the Arbeitsgemeinschaft f\u00fcr Berufs- und Umweltdermatologie e.V. (ABD), the Medical Association of German Allergologists (AeDA), the German Society of Dermatology (DDG), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNOKC), the German Society of Pediatrics and Adolescent Medicine (DGKJ), the Society for Pediatric Allergy and Environmental Medicine (GPA), German Respiratory Society (DGP), and the Austrian Society for Allergy and Immunology (\u00d6GAI)","volume":"7","author":"Bauer","year":"2023","journal-title":"Allergol. Select"},{"key":"ref_14","first-page":"17","article-title":"Mechanisms of Allergen Immunotherapy","volume":"8","author":"Akdis","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100472","DOI":"10.1016\/j.waojou.2020.100472","article-title":"World allergy organization anaphylaxis guidance 2020","volume":"13","author":"Cardona","year":"2020","journal-title":"World Allergy Organ. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"268","DOI":"10.2500\/aap.2024.45.240035","article-title":"Efficacy and safety of hymenoptera venom immunotherapy","volume":"45","author":"Kayikci","year":"2024","journal-title":"Allergy Asthma Proc."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Dem\u0161ar Luzar, A., Koro\u0161ec, P., Ko\u0161nik, M., Zidarn, M., and Rijavec, M. (2021). Hymenoptera Venom Immunotherapy: Immune Mechanisms of Induced Protection and Tolerance. Cells, 10.","DOI":"10.3390\/cells10071575"},{"key":"ref_18","first-page":"75","article-title":"Stinging insect allergy: Current perspectives on venom immunotherapy","volume":"8","author":"Ludman","year":"2015","journal-title":"J. Asthma Allergy"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"180","DOI":"10.18176\/jiaci.0310","article-title":"Hymenoptera Venom Allergy: Management of Children and Adults in Clinical Practice","volume":"29","author":"Pravettoni","year":"2019","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/0091-6749(91)90095-6","article-title":"Clinical and immunologic follow-up of patients who stop venom immunotherapy","volume":"88","author":"Keating","year":"1991","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_21","first-page":"151","article-title":"Efficacy, safety, and modulation of immunologic markers by immunotherapy with honeybee venom: Comparison of standardized quality depot versus aqueous extract","volume":"27","author":"Quercia","year":"2006","journal-title":"Allergy Asthma Proc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"331","DOI":"10.3109\/02770906609106941","article-title":"Diagnosis and treatment of insect sensitivity","volume":"3","author":"Mueller","year":"1966","journal-title":"J. Asthma Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.anai.2014.05.029","article-title":"The HIT study: Hymenoptera Identification Test--how accurate are people at identifying stinging insects?","volume":"113","author":"Baker","year":"2014","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100884","DOI":"10.1016\/j.waojou.2024.100884","article-title":"Diagnosis and treatment of Hymenoptera venom allergy in adults: A single-center experience in Lithuania","volume":"17","author":"Cerniauskas","year":"2024","journal-title":"World Allergy Organ. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1097\/01.all.0000136760.43571.f2","article-title":"Distribution of vespid species in Europe","volume":"4","year":"2004","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1097\/ACI.0b013e32833bcf91","article-title":"Diagnosis and treatment of allergy to hymenoptera venoms","volume":"10","author":"Hamilton","year":"2010","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12948-018-0087-6","article-title":"Hymenoptera sting reactions in southern Italy forestry workers: Our experience compared to reported data","volume":"16","author":"Ricciardi","year":"2018","journal-title":"Clin. Mol. Allergy"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1111\/all.15769","article-title":"Allergy to stings and bites from rare or locally important arthropods: Worldwide distribution, available diagnostics and treatment","volume":"78","author":"Sturm","year":"2023","journal-title":"Allergy"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1111\/j.1398-9995.2005.00960.x","article-title":"Prevention and Treatment of hymenoptera venom allergy: Guidelines for clinical practice","volume":"60","author":"Bonifazi","year":"2005","journal-title":"Allergy"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1159\/000542248","article-title":"Characteristics of Patients with Anaphylaxis to European Hornet (Vespa crabro) Venom Compared to Anaphylaxis to Wasp (Vespula spp.) Venom in Southern Germany","volume":"186","author":"Bertlich","year":"2025","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"407","DOI":"10.5414\/ALX02543E","article-title":"Occupational anaphylaxis: A Position Paper of the German Society of Allergology and Clinical Immunology (DGAKI)","volume":"8","author":"Treudler","year":"2024","journal-title":"Allergol. Select"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Grosch, J., Hilger, C., Bil\u00f2, M.B., Kler, S., Schiener, M., Dittmar, G., Bernardin, F., Lesur, A., Ollert, M., and Schmidt-Weber, C.B. (2020). Shedding Light on the Venom Proteomes of the Allergy-Relevant Hymenoptera Polistes dominula (European Paper Wasp) and Vespula spp. (Yellow Jacket). Toxins, 12.","DOI":"10.3390\/toxins12050323"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ruiz-Leon, B., Serrano, P., Vidal, C., and Moreno-Aguilar, C. (2022). Management of Double Sensitization to Vespids in Europe. Toxins, 14.","DOI":"10.3390\/toxins14020126"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"165","DOI":"10.2174\/1381612828666220817091039","article-title":"Hymenoptera Venom Allergy and Anaphylaxis","volume":"29","author":"Danieli","year":"2023","journal-title":"Curr. Pharm. Des."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1097\/ACI.0000000000001011","article-title":"Evidence-based data support strategies for the prevention of Hymenoptera venom anaphylaxis","volume":"24","author":"Kamga","year":"2024","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.jaip.2013.06.014","article-title":"Venom immunotherapy in patients with clonal mast cell disorders: Efficacy, safety, and practical considerations","volume":"1","author":"Bonadonna","year":"2013","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.anai.2023.09.015","article-title":"Anaphylaxis: A 2023 practice parameter update","volume":"132","author":"Golden","year":"2024","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1016\/j.jaci.2013.10.060","article-title":"Component resolution reveals additional major allergens in patients with honeybee venom allergy","volume":"133","author":"Blank","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1080\/1744666X.2018.1413350","article-title":"Venom immunotherapy in patients with allergic reactions to insect stings","volume":"14","author":"Incorvaia","year":"2018","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Blank, S., and Hilger, C. (2021). Editorial: Novel Advances in Allergy Diagnosis and Treatment. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.662699"},{"key":"ref_41","first-page":"199","article-title":"European hornet (Vespa crabro) sting: A new risk factor for life-threatening reaction in hymenoptera allergic patients?","volume":"35","author":"Antonicelli","year":"2003","journal-title":"Eur. Ann. Allergy Clin. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40413-018-0183-6","article-title":"Vespa crabro immunotherapy versus Vespula-venom immunotherapy in Vespa crabro allergy: A comparison study in field re-stings","volume":"11","author":"Macchia","year":"2018","journal-title":"World Allergy Organ. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/all.13980","article-title":"Venom immunotherapy in patients with clonal mast cell disorders: IgG4 correlates with protection","volume":"75","author":"Jarkvist","year":"2020","journal-title":"Allergy"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.2217\/imt.11.91","article-title":"Laboratory markers of mast cell and basophil activation in monitoring rush immunotherapy in bee venom-allergic children","volume":"3","author":"Dorynska","year":"2011","journal-title":"Immunotherapy"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1159\/000368925","article-title":"Increased osteopontin levels in children undergoing venom immunotherapy may serve as a marker of clinical efficacy","volume":"165","author":"Yavuz","year":"2014","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Zissler, U.M., and Schmidt-Weber, C.B. (2020). Predicting Success of Allergen-Specific Immunotherapy. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01826"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1067\/mai.2002.125827","article-title":"Venom immunotherapy improves health-related quality of life in patients allergic to yellow jacket venom","volume":"110","author":"Guyatt","year":"2002","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/S1081-1206(10)61376-2","article-title":"Flexible approaches in the design of subcutaneous immunotherapy protocols for Hymenoptera venom allergy","volume":"97","author":"Alessandrini","year":"2006","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.anai.2025.07.020","article-title":"Ultrarush protocol safety and efficacy in Hymenoptera venom immunotherapy","volume":"135","author":"Biagi","year":"2025","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"195","DOI":"10.2500\/aap.2024.45.240011","article-title":"Hymenoptera venom immunotherapy: Safety and efficacy of an accelerated induction regimen with depot aluminum adsorbed extracts","volume":"45","author":"Brunetto","year":"2024","journal-title":"Allergy Asthma Proc."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/4\/187\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T12:29:05Z","timestamp":1776256145000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/4\/187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,15]]},"references-count":50,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["toxins18040187"],"URL":"https:\/\/doi.org\/10.3390\/toxins18040187","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,15]]}}}