Specific-IgE for multiple stinging insects

The issue of cross-reactions or false positive skin or in vitro testing for insect allergy is a vexing issue. I think this is similar to the situation with food allergy testing, in which false positive results are common. If the physician performs the test, then the physician better be prepared to deal with the results. A direct approach is to use sting challenge, as we use food challenge, to define the culprit insect, but logistical challenges and risk limit the applicability of this approach. However, in some countries this is utilized procedure. In the case of stinging insects, there are carbohydrate determinants which result in non-specific, false-positive allergy test results. Component testing, in vitro inhibition of specific-IgE and basophil activation tests may help identify the primary sensitizer versus the cross-reactive insect, particularly between honey bee and vespids; but these tests are not currently available commercially. The latest practice parameter offers the following statements (1):

“Include in VIT all venoms for which the patient has demonstrated specific IgE (Recommendation; C evidence) Treatment with some venoms may not be needed if cross-reactivity can be demonstrated by a radioallergosorbent inhibition test. (Recommendation C evidence)”

“Venoms contain some shared antigenic components. Cross- sensitization and immunologic cross-reactivity are extensive between hornet and yellow jacket venoms, somewhat less extensive for yellow jacket and hornet with wasp venoms, and less common between honeybee and the other venoms. It is therefore common for skin or serum tests for venom IgE to test positive for multiple vespid venoms, and many patients test positive to both honeybee and vespid venoms.”

“Selection of Venoms for Immunotherapy
Identification of the stinging insect responsible for a reaction can be aided by the geographic locality, the circumstances of the sting, and the appearance and location of the insect and nest. On the other hand, patient identification of stinging insects is notoriously unreliable. Consensus data on which venoms to include for immunotherapy are not available. In the opinion of some authors, applying a knowledge of venom cross-reactivity and insect identification, the extract used for VIT need only contain a single venom if the culprit is definitively known, despite positive skin or in vitro test results for other stinging insects. Other authors recommend that the treatment include venoms from all insects for which positive test results were obtained because of the potential for reaction to any venoms to which the patient is sensitized. Both these approaches are valid, and they are not mutually exclusive. In vitro radioallergosorbent inhibition tests (where available) can distinguish those yellow jacket allergic patients who are cross-sensitized to Polistes wasp venom from those with true dual sensitivity, which would inform the choice of venoms for VIT. This approach has also been used for honeybee and yellow jacket double positivity. More recently, the use of recombinant venom allergens has resolved dual sensitivity to honeybee and yellow jacket from cross-reactivity that may be due to crossreacting venom allergens or their cross-reacting carbohydrate determinants.”

I think the parameter document summarizes the controversy with some experts suggesting the inclusion of all positive insects whereas others suggest utilizing additional information based upon situation of sting, insect characteristics and knowledge of cross-reactivity. One could argue that you should not test for insects that you are confident are not responsible, as you then must deal with the results.

A review article in 2017 summarized the testing methods and reagents for evaluating cross-reactivity. The article is very informative, but all of the listed laboratories that offer component testing were from outside the US (2). I searched some of the national reference laboratories in the US and could not find any listings for inhibition assays, component testing or basophil activation.

In summary, clinical judgement, documentation of a discussion and shared decision making are essential in making these decisions. In light of the uncertainty, the associated anxiety with insect stings in natural settings, and the fixed costs of travel and time while undergoing insect immunotherapy, usually results in my including all venoms with a positive test. In Florida and other areas of the Southern US, imported fire ant stings are identified with a characteristic sterile pustule, and I do not test for other stinging insects when I am evaluating insect allergy with a high probability of imported fire ant sensitivity. I do not want to explain a potentially positive result for which I do not recommend treatment.

1. Golden DBK, Demain J, Freeman T et al. Stinging insect hypersensitivity: A practice parameter update 2016. Ann Allergy Asthma Immunol 2017;118:28-54.
2. Jakob T, Muller U, Heibling A, Spillner E. Component resolved testing for hymenoptera venom allergy. Curr Opinion Allergy Clin Immunol 2017;17:363-72.

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

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