Q:

3/11/2013
We examined a 67 year old male for severe allergic reaction to bee venom sting. Within minutes of his sting he started developing total body hives, eye, ear and lip swelling. He was seen by paramedics and administered epinephrine immediately. Within a few minutes of receiving epinephrine he experienced a heart attack which was triggered by the epinephrine. When we tested this patient he was negative for honey bee, yellow hornet , yellow jacket, wasp and white faced horned. We then did IGE rast and results as follows:

honey bee <0.10

yellow hornet 1.95

yellow jacket 0.24

paper wasp <0.10

white faced hornet <0.10

All of these findings are very low. Our question to the academy is if this patient is a candidate for venom immunotherapy. We realize his rast testing is basically normal, however the fact that this gentleman is unable to receive epinephrine is concerning. What is the recommendation? Thank You.

A:

Thank you for your inquiry.

Before I begin the response to your inquiry, I want to clarify an issue. The Academy has no position in regards to your inquiry. The opinion that is expressed herein will be based on my own clinical judgment and does not represent an official opinion of the Academy. The reason for this, in part, is because there is no definitive published guideline on how one might manage this patient. The management strategy is in great part dependent upon general principles of managing anaphylaxis, and venom anaphylaxis in particular.

I think the most important principle to mention is that there is no absolute contraindication to the administration of epinephrine in a true case of anaphylaxis. Since anaphylaxis is potentially life-threatening, and since the only drug which is recognized to prevent a fatal reaction is epinephrine, it has to be administered if the event is truly threatening regardless of any preexisting condition. At least, this is the general consensus opinion. Thus, should your patient experience another episode of anaphylaxis that is life-threatening, epinephrine would still be the drug of choice.

Secondly, it is very important to note that although certainly epinephrine could have been responsible for his infarction, and such cases have been reported, it may not have been the culprit since myocardial infarction can occur during an anaphylactic event even when epinephrine has not been administered. Some mast cell mediators are coronary artery vasoconstrictors, and one could just as readily surmise that his infarction was related to release of these mediators rather than to the epinephrine.

These two principles underlie the opinion that I will express. That is, I think that your patient should be treated the same as if he had not experienced an infarction during the recent event. That is, I would treat him like any patient who had experienced a life-threatening anaphylactic event after a hymenoptera sting.I would employ the same criteria to decide whether or not venom immunotherapy is indicated and whether or not an automatic epinephrine injector should be prescribed.

Thus, I would certainly give him an automatic epinephrine injector. The most perplexing issue is whether or not to start venom immunotherapy because, by history, he was stung by a bee, and yet does not show specific IgE against bee venom.

This observation would prompt me to obtain a serum tryptase, and if it was 11.4 mcg or higher, I would investigate this patient for mastocytosis or mast cell activating syndrome by doing a bone marrow, and also would empirically initiate venom immunotherapy at least to bee venom (1, 2). In fact, even if the serum tryptase was less than that, I might still consider a bone marrow in this patient.

The other issue is, could a repeat skin test and/or in vitro test be of help? I think we can gain some insight into this issue from the most recent insect sting parameter (3) . The parameter notes that a negative test for venom-specific IgE obtained within the first few weeks after a sting reaction needs to be interpreted cautiously. In addition, it states that a negative in vitro test in addition to a negative skin test does not fully exclude the possibility of an anaphylactic reaction to a subsequent sting. Furthermore, when one looks at the allergen immunotherapy parameters (4), it is recommended that if both skin tests and in vitro tests are negative,repeat skin tests, in vitro tests, or both should be repeated in three to six months.

In summary, there is no definitive guideline-endorsed answer to your inquiry, but in my opinion, based on the best information we have available, I would suggest the following:

1.That this patient be treated like any patient who has experienced an anaphylactic reaction to an insect sting regardless of the fact that he had a myocardial infarction because the infarction could have been due to the anaphylactic episode itself rather than the epinephrine (there is no way to tell for sure), and because there is no treatment for a potentially fatal anaphylactic event other than epinephrine. Therefore he should be given an automatic epinephrine injector and instructed in its use.

2. As is recommended in our insect sting and immunotherapy parameters, as well as several articles in the literature, a baseline serum tryptase should be performed, and if the value is 11.4 or higher, a bone marrow should be done. And, in my opinion, it should be strongly considered even if the baseline serum tryptase level is lower. If there is any evidence based upon a bone marrow of mast cell activating disorder, then he should be empirically treated with all venoms because he is at risk for a sting reaction regardless of the venom involved and test results.
3.I would also strongly consider repeating, if his bone marrow is negative and you do not empirically place him on venom immunotherapy, his skin tests and in vitro tests in three to six months.

Thank you again for your inquiry and we hope this response is helpful to you.

References:
1. Bonadonna, et al. Systemic reactions after hymenoptera sting and raised serum tryptase strongly suggest clonal mast cell disorders. J Allergy Clin Immunol 2009 (February); 123(2): Supplement, Page S242.
2. Bonadonna, et al. Venom immunotherapy in patients with clonal mast CELL disorders: efficacy, safety and practical considerations. J Allergy Clin Immunol 2013 (February); 131(2):Supplement, Page AB25.
3. Golden DBK, et al. Stinging insect hypersensitivity: a practice parameter update 2011. J Allergy Clin Immunol 2011; 127:852-854.
4. Cox L, Nelson H, Lockey R, et al. Allergen immunotherapy: a practice parameter, third update. Journal of Allergy and Clinical Immunology, January 2011; Volume 127 (1), Supplement, page S1-S55.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology