Hymenoptera Venom Immunotherapy

Beatrice M Bilò; Floriano Bonifazi


Immunotherapy. 2011;3(2):229-246. 

In This Article

How can VIT Safety be Improved?

Pretreatment with a H1 antihistamine has been demonstrated to reduce the number and severity of LLRs and mild SRs to VIT, such as urticaria and angioedema.[10] Antihistamine pretreatment medication during the dose-increase phase could increase the long-term efficacy of VIT through enhancement of Treg cell actions by activation of histamine receptor-2-dependent events,[12] as suggested by one study demonstrating that antihistamine premedication with terfenadine improved the clinical efficacy of ultrarush honeybee VIT.[94] However, this finding was not confirmed by another recent study, although levocetirizine was able to affect the expression of histamine receptors and cytokine production by allergen-specific T cells.[95] Further studies are needed in order to elucidate this topic.

Pretreatment with a combination of H1 antihistamine and a corticosteroid have not yet been performed in honeybee and vespid VIT, except in patients with mast-cell diseases.[52] In a prospective, double-blind, randomized, placebo-controlled pilot study the occurrence of local reactions following VIT was significantly delayed by pretreatment with the leukotriene antagonist montelukast.[96]

Pretreatment with anti-IgE monoclonal antibodies may permit more rapid and higher doses of allergen immunotherapy while improving its safety. Moreover, this pretreatment could play an important role in insect-venom allergic patients who are intolerant to VIT. There are several case reports of bee venom allergic patients,[97] including those suffering from indolent systemic mastocytosis,[98] who experienced SRs to VIT but were able to tolerate VIT following pretreatment with omalizumab. However, Soriano Gomis et al. did report a case of systemic allergic reaction with bee VIT despite pretreatment with omalizumab and antihistamines.[99]

Until now, the optimal time for its administration during VIT (should it be administered 6 months, 2 weeks, 1 week or 1 h before VIT?), the appropriate dosage (should we use the the recommended dose of 150 or 300 mg?), the long-term effects (should omalizumab be discontinued after first administration or administered before each shot?) and the best incremental protocol of VIT (should the protocol be conventional or rush/ultrarush?) to be used are still unknown. It is important to underline that omalizumab is not approved for the prevention of anaphylaxis and it must be prescribed as off-label. In addition, taking into account its high cost, omalizumab should be limited to patients with repeated severe SAR to VIT injections preventing reaching the maintenance dose.

Although the object of a certain amount of criticism,[100] sublingual immunotherapy (SLIT) is increasingly being used in European countries thanks to its good safety profile.[101] Even though LLRs are not an indication for VIT, in a placebo-controlled, double-blind study on bee venom SLIT in patients with a history of LLRs, the diameter of LLR to a bee sting challenge was reduced by more than 50% in 57% of active-treated patients.[102] However, on the basis of these findings alone (a partial or complete treatment failure in 43% of patients with LLRs) and without experimental data on the pharmacokinetics of venom SLIT, caution should be exercised when considering SLIT as a therapeutic option for patients with severe SRs.[103]

There is a sound theoretical basis for believing that PA and PAHA extracts, whose efficacy is comparable to that of NPA preparations, have the potential to reduce the incidence of VITs side effects. A recent study compared the safety and tolerability of VIT with purified extracts and nonpurified products in yellow jacket and honeybee allergic patients. The induction phase was carried out using a 2–7-day ultrarush protocol and results showed that VIT with purified extracts resulted in a significantly lower number of severe LLRs compared with VIT using nonpurified preparations.[104] At present, compared with the therapy with an aqueous extract (both purified and nonpurified), VIT with a depot extract is superior with respect to the frequency of occurrence of LLRs and SRs, and purified extracts appear to be safer than nonpurified, especially with respect to the frequency of LLRs.[77] Hence, if protection through VIT is to be achieved rapidly, the use of purified preparations is preferable for rush treatment with the use of depot preparations for maintenance therapy.[77]


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