Q:

7/11/2013
I would really appreciate your advice on this unusual hymenoptera venom patient who is a 13 year old otherwise healthy boy.

In September 2011 and May 2012, the patient had delayed systemic reactions after stings. One sting was thought to be caused by a honey bee; on the other occasion the insect was not seen. On both occasions, he had only a local reaction right after the sting, but the next day (12 to 18 hours later) began with a slowly progressive systemic reaction starting with hives, progressing over a few hours to itching in his throat, sensation of swelling of his throat, swollen tongue, chest tightness, nausea, abdominal cramping, diarrhea and dizziness. The reactions responded to epinephrine and benadryl.

Skin testing was done in July 2012 and was positive for honey bee and white faced hornet, both at 0.1 mcg/mL, and negative for yellow jacket, wasp and yellow hornet. Serum IgEs were negative for all 5 venoms.

He started on venom allergy shots for honey bee and white faced hornet; had 2 episodes of abdominal cramping 2 hours after the injections at 0.4mL of 1 mcg/mL dose, but this did not recur once he started taking Singulair on the day of his injections. He reached the full dose in January and has continued to receive his venom allergy shots at 4 week intervals.

A few weeks ago, "D" was stung again, this time by a yellow and black striped insect, on the ankle. He had a large local reaction and about 30 minutes later had a systemic reaction, with dizziness, chest tightness, swelling of his lips and tongue. He took his EpiPen and benadryl, and recovered.

Repeat skin testing now shows positive reactions to all 5 venoms: honey bee and WF hornet at 0.1mcg/mL and the other 3 at 1 mcg/mL. Immunocaps were positive for WF hornet (0.87) and "indeterminate" (meaning > 0.1 but < 0.35) for the other 4 venoms.

So, we have a boy who previously had late phase systemic reactions, is on IT for honey bee and SF hornet, and now had an immediate reaction to a yellow and black striped insect, probably either yellow jacket or yellow hornet. But he is sensitized to all 5 venoms.

Questions:
1. Are the reactions at 1 mcg/mL ID sometimes just irritant reactions? or representing cross reactivity with the white faced hornet?

2. Are the indeterminate serum IgE levels (which were previously all < 0.1) relevant?

3. Should I treat him with all 5 venoms? I guess the main question is whether to leave out the wasp venom, since he has no history of having a reaction to wasp and only had a + skin test at the highest concentration, and the serum IgE level is only 0.11? or is he at risk for a systemic reaction to a wasp sting in the future?

Thank you for your advice!

A:

Thank you for your inquiry.

I am going to forward your inquiry to Dr. David Golden, who is an internationally known expert in insect sting hypersensitivity and who has helped us answer many previous questions regarding insect sting reactions. As soon as we receive his 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. 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:
This case raises the question of whether there is a de novo sensitivity that led to a sting reaction while on VIT, or whether the YJ sensitivity was present from the beginning but was falsely-negative on the original tests.

1. There are rarely any irritant reactions to venom skin tests at 1.0 mcg/ml concentration, although honeybee venom has slightly more potential for irritation. Cross-reactivity is most common between the vespula venoms (YJ, YH, WH) and almost 50% between vespula and Polistes venoms, but minimal between vespula and HB venoms. The peculiar thing is not that he is positive to all the vespid venoms, but that he did not show these cross-reactivities on his original tests. The most recent results may reflect boosted IgE responses from the most recent sting (presumably YJ). The fact that YJ did not show positive in the past does not ensure a lack of sensitivity. Venom skin tests (and serum IgE tests for venom) are known to vary in intensity such that repeat testing after a month or more can show positive results (at 1 mcg/ml) to venoms that were previously negative. It is unclear whether he has always had a dual sensitization to HB and YJ, or whether these are cross-reactive and attributed to CCDs. Testing with recombinant venom allergens can distinguish this type of cross-reactivity and help to justify excluding HB from VIT treatment in many patients.
 
2. Up to 20% of patients with positive venom skin tests have negative serum IgE tests, so this was not unusual. The serum IgE results can differ from the skin tests, but they do not have any more or less significance (although some studies have shown less chance of reaction when the skin test is negative and serum IgE positive (than when the skin test is positive). I am wondering about details of the lab assays. Was the original test reported as <0.1 or <0.35 kU/L? (until recently most labs were reporting a threshold of 0.35 except for some labs that use a Hycor assay instead of ImmunoCAP and used a 0.1 cutoff despite its questionable accuracy). These are other possible reasons for a false-negative reading on the original lab test.

3. I favor treatment with mixed vespid venom because of the higher total dose of major vespula allergens. The need for wasp venom is uncertain, but should either be included for security, or should be evaluated with a RAST inhibition test (if the serum IgE for wasp venom is sufficiently positive, which his is not). One cannot make assumptions based on the strength of the skin test or serum IgE test, because the strength of the test does not reliably predict the severity of reaction (but correlates with the frequency of reaction).
 
There are other aspects to this situation. If he reacted to a YJ sting because it cross-reacts with WH, then why was he not cross-protected by WH-VIT? We might have to consider him a treatment failure, which would normally lead to doubling of the dose to 200 mcg. However, treatment with 300 mcg of mixed vespid venom is likely to be equivalent. The treatment failure and the severity of the reactions also suggest the need to check baseline serum tryptase, although a mast cell disorder would be unusual in a child unless he has urticaria pigmentosa.

David Golden

AAAAI - American Academy of Allergy Asthma & Immunology