2/11/2013
I have an unusual case of insect venom anaphylaxis that I was hoping you would be willing to comment on. The patient is a 35 year old female physician’s wife with a history of two anaphylactic reactions occurring 12 to 18 hours after insect stings. Symptoms include shortness of breath, subjective throat swelling, lightheadedness and hives. She was hospitalized for one of these reactions.

Allergy skin tests for insect venoms were negative at 20 minutes. These were performed within 6 months of her most recent sting reaction. The patient called back the following day to indicate that she had reacted 12 to 18 hours later to both the 1 mcg/ml skin tests and the 0.1mcg/ml skin tests. She sent pictures – her strongest reactions were to yellow jacket and hornet with lesser reactivity to wasp and negative for honey bee, and with lesser reactivity to the 0.1 mcg/ml tests. Interestingly, she had a recurrent systemic reaction, milder though similar to her prior reactions, at the same time her skin tests reacted. She was treated by her husband at home who is a physician.

Serologic tests for specific IgE performed at Hopkins were equivocal for wasp only, but negative for others.

I have a couple of questions:
Should I repeat the skin tests per the guidelines? Would that be useful? I am concerned about repeating skin tests given the history of delayed anaphylaxis to the first tests, which could recur.

Is she a candidate for immunotherapy? Would it be effective with this presentation and unclear mechanism? I would also be concerned about delayed systemic reactions to her immunotherapy injections. Your help is greatly appreciated.

Thank you for your inquiry.

I am going to ask Dr. David Golden for a response regarding your patient. As you know, Dr. Golden is a nationally known expert in hymenoptera allergy. As soon as we receive Dr. Golden’s response, we will forward it to you.

Thank you again for your inquiry.

Sincerely,
Phil Lieberman, M.D.

We received a response from Dr. David Golden regarding your Ask the Expert inquiry. Thank you again for your inquiry and we hope this response is helpful to you.

Sincerely,
Phil Lieberman, M.D.

Response from Dr. David Golden:
It is exceedingly rare, but not unheard of, to have delayed anaphylaxis to a sting, and the mechanism, of course, is unexplainable (theoretically, perhaps, T-cell mediated anaphylaxis to peptide components). I would have been skeptical about just subjective symptoms, but if there were hives, then there is objective evidence of reaction. If the skin tests wee convincingly positive at 12-18 hours, then it supports the diagnosis of delayed anaphylaxis (especially with the actual systemic symptoms after the skin test - did this include hives?). It sounds like repeating skin tests will not change anything. The Europeans would do a basophil activation test, and this might be available in the US (eg IBT labs) but it may not be covered by insurance.
 
Regardless, the practical question remains about VIT. I think I would have to recommend VIT to mixed vespid venom, although you could start with just yellow jacket. We could consider adding wasp venom later. I agree that there is an obvious chance of delayed reaction to VIT. I do not believe that starting at extremely low doses and building up exceedingly slowly will make any difference. In fact, repeated low doses may simply increase the sensitivity long before it would result in any beneficial immune response. That leads to the option of rush VIT using an in-patient desensitization protocol over 2-3 days with pre-medication (there are several references, especially Bernstein J et al, JACI 1994, and Goldberg A et al, JACI). There is one report of a patient who had anaphylaxis 4 hours after a sting, and 4 hours after skin tests and/or VIT, but had uneventful rush VIT and did well on maintenance VIT (Ghaffari et al. AAAAI abstract. JACI) Of course, you should consider trying a routine approach first because some patients do surprisingly well (perhaps due to less reaction to subcutaneous doses than to intradermal doses). If even rush VIT fails, Xolair would be worth a try prior to rush VIT (several reports of success).
 
I would be interested in a follow-up report on whatever course of action you take. Good luck.

Sincerely,
David Golden