Delayed reactions to stings

The recent update on Stinging Insect Hypersensitivity addresses immediate dermal reactions to stings and suggests that large local reactions to a sting can be monitored clinically. "Most patients with large local reactions need only symptomatic care and are not candidates for testing for venom specific IgE or venom immunotherapy (VIT). There is, however, increasing evidence that VIT significantly reduces the size and duration of large local reactions and thus might be useful in affected individuals with a history of frequent un- avoidable large local reactions and detectable venom specific IgE. The decision to give VIT for patients with large local reactions must be weighed against the added cost and potential inconvenience." In patients with more local symptoms then "However, immunotherapy is usually not required for patients who have experienced only cutaneous systemic reactions after an insect sting. In a prospective field-sting study of children, there was a 10% chance of having a systemic reaction if re-stung (usually milder than their previous sting reactions), and a 3% or less chance of a more severe reaction. Prospective sting challenge studies in adults found a less than 3% chance of a more severe reaction in such people. VIT is still an acceptable option if there are special circumstances, such as frequent exposure, or lifestyle considerations (potential impairment in quality of life) and must be weighed against added cost and potential inconvenience. There is evidence that VIT improves the quality of the patient’s life in patients with cutaneous systemic reactions."

There is not a lot of data on "delayed reactions" from sting reactions. The articles I could find were for the late 1980's and may provide some guidance for the treatment of your patient.

Lichtenstein LM, Golden DB. Postscript to bee stings: delayed “serum sickness.” Hosp Pract 1983;18:36. (III).
Sakhuja V, Bhalla A, Pereira BJG, Kapoor MM, Bhusnurmath SR, Chugh KS. Acute renal failure following multiple hornet stings. Nephron 1988;49:319-21. (III).
Reisman RE, Livingston A. Late-onset allergic reactions, including serum sick-
ness, after insect stings. J Allergy Clin Immunol 1989;84:331-7. (III).

VIT could be consider for this clinical scenario but there is a paucity of data on this patient population.

Below is answer to a previous Ask the Expert question similar to yours: 8/20/2014
A 34 yo pool maintenance worker with no atopic history was seen after a bee sting in my office. After he was stung he developed a local reaction that swelled mildly and became itchy and irritated. This continued for ~ 4 days then subsided. 3 days later (1 week after the initial sting), he developed urticaria and angioedema of his lips, face and hands unresponsive to antihistamines. Symptoms eventually subsided with a 1 week course of Prednisone. ~ 3 weeks after stopping the Prednisone, pt was stung again by what he thinks was a wasp (black). He developed a local reaction but nothing further. Immunocap testing revealed class 3 to yellow hornet, paper wasp and honey bee as well as class 4 to yellow jacket.

1) It seems unlikely that an IgE mediated reaction could occur after 1 week but could the history as represented here indicate a delayed IgE-mediated reaction or a T-cell mediated reaction manifesting as urticaria and angioedema?

2) Should immunotherapy be offered/recommended given this patient's outdoor occupation and risk for more severe reactions?

3) Pt was rechallenged soon after above events and experienced no untoward effect. Is that reassuring in any way?

A: The reaction, delayed urticaria and angioedema after an insect sting, that you described has been reported in the literature (see abstract copied below), and the author of this report, Dr. Robert Reisman, a nationally recognized authority in hymenoptera allergy, did choose to treat the patients described with venom immunotherapy. Thus there is precedence in the literature to do so. However, the numbers are exceedingly small, but they are all that we have to my knowledge.

Also serum sickness-like reactions have been reported to hymenoptera venom as reported in the same article mentioned above, and the urticaria could have been a component of such reaction. Thus, there is no definitive answer to your question as to whether or not to administer immunotherapy, but my own opinion would be not to treat at this time. Nevertheless, as mentioned, you do have at least some evidence in the literature that this treatment could be effective (see abstract copied below). Unfortunately, in my opinion, the re-sting without reaction does not give you any assurance that he would not react upon further stings.

In summary, I do not believe you could be criticized either way - that is, should you choose to treat or withhold treatment with immunotherapy based upon the above observations. But my best guess is that his urticaria and angioedema, if at all related to the sting, would more than likely be a serum sickness-like response and thus not require immunotherapy. And unfortunately, I do not think that the fact that he was stung again will give you any solace as to whether or not he might react in the future.

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

J Allergy Clin Immunol. 1989 Sep;84(3):331-7.
Late-onset allergic reactions, including serum sickness, after insect stings.
Reisman RE1, Livingston A.
Author information
1Buffalo General Hospital, Department of Medicine, State University of New York 14203.
Abstract
Allergic reactions after insect stings may have a delayed onset, differing from the usual immediate anaphylactic pattern. Ten patients, aged 6 to 78 years, had allergic reactions 1 to 2 weeks after an insect sting. Six patients had had multiple stings preceding the reaction. In two instances, immediate anaphylaxis also occurred. Four of the 10 patients had serum sickness-type reactions; two other patients had more severe anaphylactic symptoms, including throat edema. All patients in this group had venom-specific IgE; four of the 10 patients had serum venom-specific IgG. Eight patients subsequently received venom immunotherapy (VIT). There have been no reactions from seven re-stings. Five patients had generalized hives starting 6 to 24 hours after an insect sting. All patients in this group had venom-specific IgE; three patients have received VIT. Two other patients developed hives, one with throat edema 3 days after an insect sting. Both patients had high titers of serum venom-specific IgE; neither patient has received VIT, one patient because of extreme sensitivity. These observations suggest that after an insect sting, patients may develop delayed-onset allergic symptoms that range from typical anaphylaxis to serum sickness and are mediated by venom-specific IgE. VIT is recommended for patients with these reactions.

Sincerely,
Phil Lieberman, M.D.

I hope all this information has been helpful.
Andrew Murphy MD FAAAAI