Safety of 1 mcg/mL as the starting dose in cluster protocol for hymenoptera immunotherapy
Main Article Content
Keywords
cluster protocol, hymenoptera stings, hymenoptera venom allergy, safety, venom immunotherapy
Abstract
Background: Hymenoptera venom allergy is a potentially severe allergic reaction in the general population. The only preventative approach in these cases is venom immunotherapy (VIT), which follows different protocols. The recommended initial dose is 0.001–0.1 mcg of venom extract. However, few reports have declared the safety of 1 mcg venom as the starting dose.
Methods: The study was conducted on Iranian patients with a history of anaphylaxis to venom. Skin tests confirmed hypersensitivity to honeybee, yellow jacket, and/or paper wasp from subfamily Polistes using Apis melifera, Vespula spp, and Polistes spp venom extracts, respectively. Subsequently, the patients were treated with the cluster protocol.
Results: Twenty-two patients (17 males and 5 females, aged 28.3±11.8 years) were enrolled in the study. Skin prick tests and intradermal tests showed positive results for yellow jacket in 17 (77.3%) and 21 (95.4%) patients, honeybee in 14 (63.6%) and 17 (77.3%) patients, and wasp in 14 (63.6%) and 17 (77.3%) patients, respectively. Upon administering the initial dose of 1 mcg/mL, 40.9% (9 cases) of patients presented mild local reactions, including 7 with yellow jacket allergy, 5 with honeybee allergy, and 3 with wasp allergy. One patient with yellow jacket allergy had a mild systemic reaction. Patients with a positive skin test for wasp had significantly lower rate of reactions after the first dose of venom (p=0.026). Throughout the entire build-up phase, more than 90% (20 of 22) of patients experienced mild local reactions, followed by large local reactions (3 cases, 13.6%), mild systemic reactions (1 case at 1 mcg/mL dose), and moderate-to-severe systemic reactions (3 cases, 13.6%). Large local and moderate-to-severe systemic reactions were detected after injecting 50 mcg (each one case) and 100 mcg (each 2 cases) of venom extracts.
Conclusion: This study recommends 1 mcg/mL of the venom extract as a safe starting dose for VIT. This accelerated protocol could successfully reduce the time and costs of therapy for patients undergoing out-patient cluster VIT.
References
2 Antonicelli L, Bilò MB, Bonifazi F. Epidemiology of Hymenoptera allergy. Curr Opin Allergy Clin Immunol. 2002;2(4):341-6. 10.1097/00130832-200208000-00006
3 Bilò BM, Bonifazi F. Epidemiology of insect-venom anaphylaxis. Curr Opin Allergy Clin Immunol. 2008;8(4):330-7. 10.1097/ACI.0b013e32830d9ff4
4 Kołaczek A, Skorupa D, Antczak-Marczak M, Kuna P, Kupczyk M. Safety and efficacy of venom immunotherapy: a real life study. Postepy Dermatol Alergol. 2017;34(2):159-67. 10.5114/pdia.2017.66680
5 Demšar Luzar A, Korošec P, Košnik M, Zidarn M, Rijavec M. Hymenoptera Venom Immunotherapy: Immune Mechanisms of Induced Protection and Tolerance. Cells. 2021;10(7). 10.3390/cells10071830
6 Ruëff F, Przybilla B, Biló MB, Müller U, Scheipl F, Aberer W, et al. Predictors of side effects during the buildup phase of venom immunotherapy for Hymenoptera venom allergy: the importance of baseline serum tryptase. J Allergy Clin Immunol. 2010;126(1):105-11.e5. 10.1016/j.jaci.2010.03.037
7 David F Graft M. Hymenoptera venom immunotherapy: Technical issues, protocols, adverse effects, and monitoring. 2022. In: Uptodate [Internet]. Available from: https://www.uptodate.com/contents/hymenoptera-venom-immunotherapy-technical-issues-protocols-adverse-effects-and-monitoring.
8 Roumana A, Pitsios C, Vartholomaios S, Kompoti E, Kontou-Fili K. The safety of initiating Hymenoptera immunotherapy at 1 microg of venom extract. J Allergy Clin Immunol. 2009;124(2):379-81. 10.1016/j.jaci.2009.05.022
9 Kontou-Fili K PD, Palaiologos G. Hymenoptera immunotherapy: lack of correlation between the initial venom concentration and severity of observed reactions. Schweiz Med. 1991.
10 Cadavid-Moreno S, González-Fernández T, Méndez-Brea P, Armisén M, Vidal C. A Clustered Schedule for Venom Immunotherapy With a Depot Extract: Reaching the Target in 7 Days. J Investig Allergol Clin Immunol. 2023;33(5):395-7. 10.18176/jiaci.0970
11 Mosbech H, Müller U. Side-effects of insect venom immunotherapy: results from an EAACI multicenter study. European Academy of Allergology and Clinical Immunology. Allergy. 2000;55(11):1005-10. 10.1034/j.1398-9995.2000.00544.x
12 Ruëff F, Kroth J, Przybilla B. Risk factors in Hymenoptera venom allergy. Allergol Select. 2017;1(1):53-8. 10.5414/ALX01759
13 Tarhini H, Knani J, Michel FB, Bousquet J. Safety of venom immunotherapy administered by a cluster schedule. J Allergy Clin Immunol. 1992;89(6):1198-9. 10.1016/0091-6749(92)90213-Y
