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Venom immunotherapy with shortage of venom vaccine

Question:

7/7/2017
We are facing what I assume is not an uncommon problem as the venom shortage seems to be lessening. We have several patients that have not received their immunotherapy in several months (Two of our most recent patient's gaps were 175 days, 208 days respectively). I looked through the archive and found a 2013 thread that recommended either restarting from the beginning of buildup or retesting and treating as appropriate. I was wondering if more data has come about or if there was any new evidence/studies to support decreasing the dose, but not restarting at the beginning since that question was asked?

Answer:

There is no completely acceptable answer to the lack of availability of purified venoms for immunotherapy. Fortunately, the AAAAI and ACAAI formed a task force to address this problem. There is a document here summarizing the recommendations.

The recommendations are voluntary and temporary and do not replace physician judgement. The suggested strategies are:
1. Extend the maintenance interval
2. Decrease the maintenance dose
3. Suspend or restrict treatment for those at lowest risk
4. Develop strategies to minimize wastage.

The factors identified in the 2016 practice parameters that place a patient at greater risk are history of a life-threatening reaction, a systemic reaction during immunotherapy either to a sting or the immunotherapy, underlying cardiovascular disease (I would add persistent asthma), beta blocker therapy and possibly ACE inhibitor, beekeeper with honeybee allergy or high risk of stings due to unavoidable work activities, and an elevated baseline tryptase. These subjects would be granted highest priority for continuation of treatment.

For both adults and children who were started on venom therapy with a systemic cutaneous reaction or large local reaction, I would discontinue treatment since they are at very low risk. Since there is no universally accepted position on the absolute duration of venom immunotherapy, I would consider discontinuing patients who have received treatment for more than 3 years without a reaction during treatment and without a history of a life-threatening reaction to field sting. You certainly could repeat allergy testing and discontinue anyone who has a negative test if they have not experienced a life-threatening reaction to a sting. The 2016 practice parameter recommends indefinite therapy with a history of life-threatening reaction. The practice parameter states that 3 years may be sufficient for children but 5 years is better than 3 years for adults (Table 1). You could extend the duration between maintenance doses to 6-8 weeks after 12-24 months of maintenance and up to 12-16 weeks after 36 months of maintenance. Finally, for patients not allergic to honey bee, you may wish to reduce the maintenance dose to one-half the typical maintenance dose (50 mcg for a single venom) for children and one-half to three-fourths (50-75 mcg for individual venoms) for adults (1,2,3).

Other additional strategies include discontinuation of treatment with multiple venoms if the culprit insect is strongly suspected, use of multidose vials since single dose vials are associated with greater overall wastage and rely more on in vitro testing, although very little venom is used for testing reagents.

All of these options will need to be discussed with affected patients and the decision documented in the record. It may be helpful to have a practice policy in your clinic along a rationale for the policy in case any questions are raised as to why you made changes.

1. Houliston L, Nolan R, Noble V, Pascoe E, Hobday J, Loh R, et al. Honeybee venom immunotherapy in children using a 50-mcg maintenance dose. J Allergy Clin Immunol 2011;127:98-9.
2. Konstantinou GN, Manoussakis E, Douladiris N, Hatziioannou A, Giavi S, Saxoni-Papageorgiou P, et al. A 5-year venom immunotherapy protocol with 50 mcg maintenance dose: safety and efficacy in school children. Pediatr Allergy Immunol 2011;22:393-7.
3. Reisman RE, Livingston A. Venom immunotherapy: 10 years of experience with administration of single venoms and 50 micrograms maintenance dose. J Allergy Clin Immunol 1992;89:1189-95.

I hope this information is of help to you and your practice.

All my best.
Dennis K. Ledford, MD, FAAAAI