I have two questions regarding venom immunotherapy in high risk patients (Grade IV reactions). The first has to do with dosing intervals. Although the package specifies that maintenance doses should be given at four week intervals, it is common practice to increase the interval to six or even eight weeks after a year or two of maintenance. Is there data to suggest that Grade IV reactors are at higher risk of systemic reactions if their interval is increased to six or eight weeks? Or do they have the same excellent long term protection that individuals have with less severe histories?

The second question has to do with IgG testing. An adult patient of mine with a history of a Grade IV reaction read about the availability of IgG testing for venom. He asked to have this sent. He has completed two years of maintenance and I would assume his levels are protective (>3 ug/ml). If we go ahead and test and his levels are low, is there sufficient experience/data to support an increase in his maintenance dose?


Thank you for your inquiries.

I am forwarding your questions to Dr. David Golden who, as you know, is an international expert in venom allergy. As soon as we hear from Dr. Golden, we will forward his response to you.

Thank you again for your inquiry.

Phil Lieberman, M.D.

We have received a response from Dr. David Golden. Thank you again for your inquiry.
Warm regards,
Phil Lieberman, M.D.
Response from Dr. David Golden:
As with so many questions in insect allergy, there has not been a specific study designed to address the first question. In fact, there is almost no published evidence to support the extended interval of 6 - 8 weeks in any patients, despite the fact that it is common practice and is supported by the Practice Parameters. However, there is growing and convincing evidence that a 12 week interval is safe and effective in patients treated for 3 years or longer, including patients with very severe sting reactions. However, over the past 30 years, thousands of patients have been treated at extended intervals (6-8 weeks), with no reported problems of severe reactions to shots or stings. It is hard to answer the last part of that question (long term protection) because such patients are considered high risk for stopping VIT and are recommended to continue treatment for an extended and possibly indefinite period of years. That is to say, "long-term protection" is not reliable in these patients even with treatment at 4 week intervals.

The utility of venom-IgG measurements has been debated. We published one of the largest studies on this issue using sting challenge as the outcome measure (Golden DBK, Lawrence ID, Kagey-Sobotka A, Valentine MD, Lichtenstein LM. Clinical correlation of the venom-specific IgG antibody level during maintenance venom immunotherapy. J Allergy Clin Immunol 1992;90:386-93.) During the first 3 years of VIT, and specifically for YJ allergy, the venom-IgG was highly correlated with protection (1.6% sting reaction if IgG >3, but 30% reaction rate for IgG <3 mcg/ml). There were only a few cases in which we increased the dose and repeated a sting challenge, but in those patients there was only one who still had a reaction. Although IgG was not assessed, Rueff et al (2001) showed that patients who have reactions to stings while on VIT (ie, treatment failures) were protected when the dose was doubled. The editorial critique argued that VIT is so reliably effective that measuring IgG is not necessary.(Reisman RE. Should routine measurements of serum venom-specific IgG be a standard of practice in patients receiving venom immunotherapy? J Allergy Clin Immunol 1992;90:282-4.) However, VIT gives full protection in only 85-90% of patients on single vespid venoms (eg YJ or wasp), and in only 75-85% of HB-treated patients (mostly beekeepers). It is these sub-groups in whom the IgG level might be most useful to detect those who have incomplete protection, so their dose can be increased before they become a "treatment failure". I should also point out that venom-IgG is not a useful marker of protection in untreated patients or in those treated longer than 3 years. It is therefore not useful in the decision about discontinuing VIT.

David Golden, M.D.

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