Hymenoptera Venom Immunotherapy

Beatrice M Bilò; Floriano Bonifazi


Immunotherapy. 2011;3(2):229-246. 

In This Article

Abstract and Introduction


Subcutaneous venom immunotherapy is the only effective treatment for patients who experience severe hymenoptera sting-induced allergic reactions, and the treatment also improves health-related quality of life. This article examines advances in various areas of this treatment, which include the immunological mechanisms of early and long-term efficacy, indications and contraindications, selection of venom, treatment protocols, duration, risk factors for systemic reactions in untreated and treated patients as well as for relapse following cessation of treatment. Current and future strategies for improving safety and efficacy are also examined. However, although progress in the past few years has been fruitful, much remains to be accomplished.


Hymenoptera stings can induce allergic systemic and occasionally fatal reactions. The offending hymenoptera belong to the suborder Aculeate, which are made up of the Apoidea (Apis mellifera and Bombus species) and Vespidae (Vespinae and Polistinae subfamilies) superfamilies,[1,2] although several of the European vespid species differ from those found in the USA where popular names for vespids are different, which may lead to confusion.[3] In the USA, stinging hymenoptera also include the fire ant (Solenopsis invicta), and in Australia, the jack jumper ant (Myrmecia pilosula).[4,5] In Europe, systemic reactions (SRs) from ant stings are extremely rare and are therefore not considered within the scope of this article. Hymenoptera venoms are mixtures of various low-molecular-weight substances, peptides and proteins, which often have enzymatic properties. The major allergens in bee venom are phospholipase A2 (Api m 1), hyaluronidase (Api m 2), and presumably acid phosphatase (Api m 3) and serine protease, while in vespids venoms they are phospholipase A1 (Ves v 1), hyaluronidase (Ves v 2) and antigen 5 (Ves v 5).[1]

Detailed clinical features of insect sting reactions and their pathogenesis are described elsewhere.[1,2] The most frequent clinical patterns of hymenoptera venom allergy (HVA) are large local reactions (LLRs) and SRs; in the latter, the skin, gastrointestinal, respiratory and cardiovascular systems can be involved. Various classifications of the degree of severity of SRs have been proposed, of which the classification of Mueller and Ring are the most frequently used (Box 1). However, Mueller's classification does not take into account the possible absence of cutaneous symptoms and that an isolated cardiovascular shock might be the only allergic sting-induced manifestation, while Ring's system focuses almost entirely on cardiovascular collapse, considering it as more severe than respiratory compromise.[6] A universal definition of anaphylaxis, such as that recently proposed by the National Institute of Allergy and Infectious Disease (NIAID) and the Food Allergy and Anaphylaxis Network (FAAN) symposia,[7] would lead to a more uniform reporting of cases and a more accurate picture of the severity of insect sting reactions after validation by means of prospective multicenter trials.

In the USA, the prevalence of SRs to hymenoptera sting in the general population ranges from 0.5 to 3.3%. European epidemiological studies from the last decade report a prevalence of 0.3–8.9% for SRs, with anaphylaxis reported in 0.3–42.8% of cases.[3,6] The results yielded by a small number of studies indicate that the prevalence rates of SRs are lower in children, ranging from 0.15 to 0.8%, with a recent exception of 4.4% reported in a study from Israel.[8] Although low, mortality rates are not negligible, with the incidence of insect sting mortality due to early anaphylaxis figures ranging from 0.03 to 0.48 fatalities per 1,000,000 individuals per year.[3,6] Underestimates are common worldwide with many sting fatalities going unrecognized and misinterpreted as unexplained.

To date, there is no existing parameter that enables clinicians to predict who will have a future reaction and whether it will be a LLR or generalized anaphylaxis. Several concomitant factors, which include the environment, genetics and individual elements, may account for the occurrence of a SR in any one patient.[6]

An anaphylactic reaction after a hymenoptera sting is an extremely traumatic event for the patient and their family. It has been demonstrated that patients who experience anaphylactic reactions following yellow jacket wasp stings reported impaired quality of life related mainly to the emotional strain of having to remain vigilant while performing everyday routine activities.[9]

Subcutaneous venom immunotherapy (VIT) is a highly effective treatment,[2,4,10] which is designed to reduce the risk of a subsequent SR, prevent morbidity and mortality and also improve health-related quality of life (HRQL), as demonstrated in yellow jacket allergic patients.[11]


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