Diagnosis of insect sting/venom allergy

History is essential for diagnosis

Venom-specific IgE antibodies are present in clinically non-reactive individuals, i.e. people without symptoms. The diagnosis of insect sting allergy relies on the history of allergic reaction.

The identity of the insect that caused the sting is a notoriously unreliable part of the history. However, the location and timing of the sting or the location of the nest may help to determine the type of insect.

Concurrent medications such as beta-blockers can contribute to anaphylactic reaction. It is important to check serum tryptase in all patients undergoing workup for venom allergy to rule out indolent mastocytosis.


Figure 1. Mind map of insect venom allergy (click to enlarge the image).

Reaction to Wasp Reaction to Bee
More common Rarer
After a single sting After many stings
Typical narrow waist and little hair Hairy "fuzzy" bee
Table 1. Comparison of allergic reactions to wasp and bee venom.


Figure 2. A yellow jacket wasp with a typical narrow waist (left) and a honey bee with a fat hairy "fuzzy" body (right). Image source: Wikipedia 1, 2, GNU Free Documentation License.

Skin tests - intradermal

The standard method of skin testing is with the intradermal technique, using the 5 Hymenoptera venom protein extracts. Whole body extracts are not used, with the exception of fire ant.

For Hymenoptera venom testing, intradermal tests are performed with venom concentrations in the range of 0.001–1.0 μg/mL to find the minimum concentration giving a positive result. Epicutaneous tests at 1 μg/mL concentration is typically used initially, before the intradermal tests. 25% of patients are skin test positive only at the 1.0 μg/mL concentration (top dose).

The patient may be sensitized to multiple venoms even when there has only been a reaction to only a single insect. Therefore, skin testing should be performed with:

- complete set of the 5 Hymenoptera venoms
- negative diluent (human serum albumin-saline) control
- positive histamine control

Some patients have negative skin tests for 6 weeks after a sting reaction attributed to a refractory period of ‘anergy’.

Negative skin tests in a history-positive patient may represent the loss of sensitivity, especially if the sting was in the remote past.

ImmunoCAP is positive in 10% of patients with negative skin tests. Patients with negative skin tests and a convincing history of anaphylaxis should be further investigated with serologic testing, and if still negative, the skin tests should be repeated after 3–6 months.

In vitro tests, specific IgE

High levels of venom-specific IgE are typically diagnostic. The problem lies with the low levels that are more difficult to detect.

There is no exact correlation between venom skin tests (intradermal) and venom-specific IgE assays (ImmunoCAP).

Specific IgEs are negative in up to 20% of skin-test positive subjects. Venom skin tests are negative in 10% of persons with elevated IgE antibodies.

Neither test alone can detect all cases of insect sting allergy. Each test is useful as a supplement to the other - if the other test is negative.

Only 70% of patients with stinging insect allergy fill their epinephrine prescriptions (Rudders, Annals 2013).

References:

Chapter 57 – Insect Allergy, David B.K. Golden, Adkinson: Middleton's Allergy: Principles and Practice, 7th ed., 2008.
Insect Venom Allergy: Brief Review
Bee Aware Allergy - Insect allergy educational website by Hollister-Stier Laboratories.

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