The diagnostic workup in patients with a history of anaphylactic reaction to an insect sting involves multiple levels of exploration, including the presence of systemic mastocytosis (SM), according to findings from a review published in The Journal of Allergy and Clinical Immunology: In Practice.

A patient’s evaluation typically involves a number of steps, known as decision points, to identify any high-risk issues that signal the need for a more comprehensive workup. Possible reactions can vary and may include the following:    

  • Localized skin swelling,
  • Cutaneous systemic reaction, including urticaria,     
  • Prominent airway symptoms, including severe anaphylaxis, and/or   
  • Cardiovascular symptoms, including hypotension.

A detailed clinical history will help determine whether a skin or serum venom immunoglobulin E (IgE) assessment and preventive therapy for venom allergy are needed. An initial decision to be made is whether a particular patient is a candidate for Hymenoptera venom allergy (HVA) testing.

Read more about experimental therapies for SM

Patients with severe HVA warrant referral to an allergist or immunologist, who will evaluate them for potential genetic, immunologic, and environmental causes that might indicate any current or future risk factors. In addition, demographic data, medication use, and the time interval from the sting to the onset of a reaction may be helpful as well.

Older age also may be relevant, as it is likely indicative of the presence of comorbidities and decreased cardiovascular reserves. All of these considerations will aid the clinician in rendering a decision regarding the use of venom immunotherapy.

Diagnostic testing involves the use of stepwise skin testing with Hymenoptera venoms, as well as possible serum analysis for the presence of venom-specific IgE. Intradermal skin tests for HVA are typically conducted in a stepwise fashion, with 15- to 20-minute intervals between the venom injections. Commercially available venom extracts available include yellowjacket, honey bee, yellow and bald-faced hornets, and common Polistes wasps.

Individuals who present with strong histories but negative skin test or blood test results should undergo repeat
testing with the other modality. If all results of initial testing are negative, repeat testing should be performed in 1 to
2 months.

Read more about comorbidities in SM

The use of basophil activation tests, which can improve the detection of venom allergy, as well as predict the efficacy of venom immunotherapy and severity of allergic reactions, is a promising biomarker. The severity of any prior sting reactions, along with the presence or absence of hypotension or urticaria, are predictive of the occurrence of severe sting reactions in the future and any underlying mast cell disorders, including SM. In fact, elevations in basal serum tryptase levels can predict the presence of a mast cell disorder.

The key reason for using component-resolved diagnosis in HVA testing is that the culprit insect, rather than the severity of an allergic reactions to bee and vespid venom, can be established with molecular diagnosis.

Bone marrow biopsy is the definitive tool for characterizing mast cell disorders that are related to the most severe outcomes among patients who experience an allergic reaction to an insect sting.

“We have reviewed the decision points and options for evaluation of the patient with insect sting allergy,” the researchers noted. “There remain knowledge gaps that require future research,” they concluded.


Bonadonna P, Korosec P, Nalin F, Golden DB. Venom anaphylaxis: decision points for a more aggressive workup. J Allergy Clin Immunol Pract. Published online April 27, 2023. doi:10.1016/j.jaip.2023.04.016