A 'Difficult' Insect Allergy Patient

Reliable History of a Sting, but All Testing Negative

James M. Tracy; Jonathan A. Olsen; John Carlson


Curr Opin Allergy Clin Immunol. 2015;15(4):358-363. 

In This Article

Abstract and Introduction


Purpose of review Few conditions are as treatable as allergy to stinging insects, with venom immunotherapy (VIT) providing up to 98% protection to subsequent stings. The challenge with VIT is not in the treatment, but in the diagnosis. To offer VIT, one must determine a history of a systemic reaction to a stinging insect in conjunction with the presence venom-specific IgE. Current diagnostic methods, although sensitive and specific, are imperfect, and some newer testing options are not widely available. A conundrum occasionally faced is the patient with a reliable and compelling history of a systemic allergic reaction yet negative venom-specific testing. This diagnostic dilemma presents an opportunity to consider possible causes for this diagnostic challenge.

Recent findings Our evolving understanding of the role of occult mast cell disease may begin to help us understand this situation and develop appropriate management strategies. Venom-specific skin testing has long been the cornerstone of the evaluation of venom sensitivity and is often combined with in-vitro assays to add clarity, but even these occasionally may fall short. Exploring novel venom diagnostic testing methods may help to fill in some of the diagnostic gaps. Do currently available venom vaccines contain all the key venom species? Are there enough differences between insect species that we may simply be missing the relevant allergens? What is the significance of the antigenicity of carbohydrate moieties in venoms? What is the role of recombinant venom extracts?

Summary VIT is the definitive treatment for insect allergic individuals. To utilize VIT, identification of the relevant Hymenoptera is necessary. Unfortunately, this cannot always be accomplished. This deficiency can have several causes: a potential comorbid condition such as occult mast cell disease, limitations of currently available diagnostic resources, or testing vaccines with an insufficient coverage of relevant venom allergens. Exploring these potential causes may help to provide important insight into this important diagnostic conundrum. The use of a case report may help clarify this challenge.


Venom immunotherapy is the definitive treatment Hymenoptera sensitivity and should be offered and initiated, provided the necessary criteria of a reliable history of anaphylaxis and the presence of venom-specific IgE are met. What does one do, however, if the later criterion is not fulfilled? This diagnostic dilemma has been the source of discussion for some time and how best to address this important issue remains an important clinical challenge for the allergist.[1,2] Currently available diagnostic tools including conventional skin testing and new in-vitro methods are complimentary and appear to detect venom-specific IgE in 95–98% of individuals with a reliable history of sting-related anaphylaxis.[3,4]

It is the remaining 2–5% that fall into this diagnostic hole and will be the focus of this review. We will explore several possible sources of this diagnostic conundrum worthy of consideration. First, is this primarily a problem of the diagnostic sensitivity of currently available methods? Second, is this situation one complicated by other comorbid conditions, such as indolent mast cell disease? Is it caused by a non-IgE, but immunologic mechanism? Finally, commercially available extracts are available for only a small fraction of relevant Hymenoptera species, by the use of species representative available commercially, in which some may lack unique antigens that available testing extracts may not identify. Invasive species of Hymenoptera have become established across the world, and standard testing with endemic species may fail to identify venom-allergic patients in particular. This case may help to illustrate this practical situation.