Are rapid dose increases during venom immunotherapy safe?

Published Online: March 29, 2012

Venom immunotherapy (VIT) protects allergic people from anaphylaxis to accidental insect stings. Treatment starts with very small doses of venom extract injected under the skin. These doses are gradually increased until the individual becomes desensitized so that he/she no longer reacts to a sting. Rapidly increasing the dose over one day (“ultrarush” treatment) is also said to be safe and more convenient, but this has never before been compared directly with a traditional, slower approach.

In a randomized controlled trial published in The Journal of Allergy & Clinical Immunology (JACI), Brown et al directly compared ultrarush VIT with a slower “semirush” approach in patients with a history of anaphylaxis to Australian jack jumper ant (JJA, Myrmecia pilosula) stings. 93 patients were randomized to VIT initiation by either semirush or ultrarush schedules. The primary outcome was the occurrence of one or more objective systemic reactions during VIT initiation. The authors also compared an additional 89 patients who chose which approach they preferred.

Brown et al found that for randomized patients, allergic reactions to VIT were more likely during ultrarush initiation (65% versus 29%). Severe, potentially life-threatening allergic reactions were also more common (12% versus 0%). Similar differences were observed in patients who chose which approach to use, indicating that patient and clinician preference has little impact on risk. Also, whereas the timing of “protective” antibody (IgG4) changes did not differ between treatment approaches, increases in “allergic” antibodies (IgE) occurred earlier and were more intense during ultrarush VIT for the same time period during which the higher reaction risk was observed.

This first randomized, controlled comparison challenges the view that fast methods of VIT are as safe as slower ones. A greater risk of allergic reactions, including severe hypotensive reactions, with ultrarush VIT may be particularly important if there are comorbidities or advanced age, when a severe reaction could be life-threatening.


The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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