Fact checked byKristen Dowd

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August 11, 2023
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Testing options for insect venom allergies depend on patient evaluations

Fact checked byKristen Dowd
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Key takeaways:

  • Patients with suspected or known systemic allergic reactions to stings should be tested.
  • Patients with cutaneous systemic reactions or who do not have a sting history should not be tested.

PARK CITY, Utah — Patients who have had systemic reactions to insect stings should be evaluated, including education and testing, according to a presentation here.

“We all try to avoid stinging insects,” Melinda M. Rathkopf, MD, MBA, allergist and immunologist with Children’s Healthcare of Atlanta, said during her presentation at the Association of PAs in Allergy, Asthma and Immunology Annual Allergy, Asthma & Immunology CME Conference. “But we’ll talk a little more.”

Honeybee sting
The most common insect stings in the United States include honeybee, yellowjacket, yellow hornet, white-faced hornet and wasp. Image: Adobe Stock

Education should include avoidance, according to Rathkopf, who also is a provisional associate professor of pediatrics in the division of allergy and immunology at Emory University School of Medicine, and patients should be considered for venom immunotherapy when testing is positive.

Insect avoidance

Patients with systemic reactions to insect stings should be instructed to avoid preparing, grilling or eating food outdoors, Rathkopf said. They also should avoid flowering plants and drinking from straws, cans or bottles outdoors.

Melinda M. Rathkopf

“[If] you’re going to have a can at a picnic, have something over it,” she said, adding that she has taught her children to hold any cans that they are drinking out of up to their ear to listen for any insects that may have flown or crawled inside.

Fallen fruit and pet feces should be removed from yards as well, she continued. Plus, trashcans should be covered. When mowing the lawn, patients should watch out for nests in the bushes or in the ground. Patients should avoid going barefoot outdoors as well.

Insect repellants are not effective, Rothkopf said, and neither is avoiding fragrances or brightly colored or floral clothing.

“We used to say, ‘Don’t look like a flower. Don’t smell like a flower,’” she said. “That really doesn’t seem to change it.”

Patient evaluations

Venom-induced anaphylaxis may include skin symptoms such as generalized urticaria, flushing and angioedema.

“In most children, this can be the sole manifestation. About 60% of those will just have these skin symptoms,” Rathkopf said. “But only about 15% of adults with systemic reactions develop cutaneous isolation.”

Adults are more likely to have respiratory symptoms such as a hoarse voice, upper airway obstruction, shortness of breath and wheezing or cardiovascular symptoms such as lightheadedness to hypotension, shock and circulatory collapse.

“You want to test patients with suspected or known systemic allergic reaction to sting,” Rathkopf said, adding that patients with a history suggestive of or convincing for a past systemic allergic reaction to a sting that involved organs other than the skin should be tested as well.

However, she continued, patients with cutaneous systemic reactions should not be tested.

“The chance of a future systemic reaction has been estimated to be about 7% to 10% per sting,” Rathkopf said. “Most of these reactions are limited to the skin, and less than 3% will have severe anaphylaxis.”

Testing and immunotherapy are not indicated in most of these cases, Rothkopf advised.

Patients who do not have a sting history should not be tested either, she continued. These patients may be concerned about the possibility of a severe reaction to a sting because someone in their family has a venom allergy, Rathkopf explained, but that does not mean that they should be tested, nor should they be recommended for immunotherapy.

Additionally, most patients who have large local reactions should not be tested. These reactions come with a 5% to 10% risk for a future systemic reaction, with less than a 3% risk for anaphylaxis. Testing and immunotherapy, Rathkopf said, are not indicated.

Testing options

Skin testing and in vitro testing are options for venom-specific IgE, Rathkopf said, but skin testing is preferred for initial testing in most patients because it is more sensitive and less expensive in most health care systems.

“Skin testing is positive in 66% to 90% of patients with a history suggestive of venom,” Rathkopf said. “Fifteen percent to 20% of those with positive skin tests will have negative in vitro blood tests.”

When skin testing is positive and results support the clinical history, she said, in vitro testing is not necessary.

Also, 5% to 10% of patients with negative skin tests may have in vitro results that are positive. In vitro testing is indicated when skin testing is negative with a suggestive clinical history or when it cannot be performed. It also is helpful when the skin testing results and clinical history are not consistent or when they leave unanswered questions, according to Rathkopf.

“The combination of skin testing and in vitro together, though, should detect 95% of patients who will have a systemic reaction to a subsequent sting,” she said.

Rathkopf recommended testing occur at least 4 to 6 weeks after the sting because tests that are administered immediately after the sting can be negative.

“You can test, but if it’s negative, you have to retest,” Rathkopf said, adding that retesting is expensive and invasive.

Testing also should include venoms from all the potentially relevant insects that inhabit the area.

“In the U.S., that pretty much means honeybee, yellowjacket, yellow hornet, white-faced hornet and wasp,” Rathkopf said.

Typically, testing is intracutaneous or intradermal. It is not necessary to use skin prick testing first, Rathkopf said, unless the patient has had severe anaphylaxis and may be highly sensitive to venom at concentrations of 100 µg/mL.

“If I had someone very high risk, I would probably start with specific IgE testing in the blood first,” Rathkopf said.

Honeybee, yellowjacket, white-faced hornet, yellow hornet and wasp venom extracts all are available for skin testing and venom immunotherapy. Whole body extract (WBE) is effective and available for suspected fire ant hypersensitivity as well, Rathkopf said.

“You just throw a bunch of fire ants into a blender and use that to do the venom,” Rathkopf said.

Injections use 0.02 mL to 0.03 mL of venom extract to produce a 3 mm bleb. Wheals that are 3 mm to 5 mm greater than the negative control with surrounding erythema at a concentration of 1 mg/mL or less indicate a positive test with sIgE antibodies.

Nonspecific responses at concentrations of 1 mg/mL or greater may cause false positives, Rathkopf said.

“Your test goes up to 1 milligram per milliliter. That’s usually the final step for most of us,” she said. “That’s when you’re going to start getting some false positives.”

When the history is positive but the skin test is negative, Rathkopf recommended sIgE testing and basal serum tryptase.

“And you may need to repeat the skin test in 3 to 6 months,” she continued.

When the history is positive but the tests are a mix of positive and negative results, Rathkopf said, further evaluation for negative venoms based on serum IgE and/or repeat skin tests may be needed to identify potentially relevant sensitivities before venom immunotherapy begins.

“Even repeat negative in vitro skin test results do not fully exclude the possibility of anaphylactic reactions,” Rathkopf said.

In vitro testing is indicated for patients who have a convincing clinical history of systemic symptoms following a sting and negative skin testing. It also is indicated for patients who cannot participate in skin testing because of a dermatographism or severe or active skin diseases.

Additionally, some patients cannot get skin tests because they cannot discontinue medications that can render the skin unreactive such as high-dose tricyclic antidepressants.

In vitro testing is indicated when evaluation is needed in the initial weeks following a systemic event and there is concern that skin reactivity may be suppressed.

“Or, again, when the results of skin testing are not fully consistent with the clinical history and you still have some questions,” Rathkopf said.