Thank you for your inquiry.
The question you posed is a good one and is clearly salient. Unfortunately, there is no good, definitive answer. A positive skin test does not necessarily indicate clinical sensitivity (only sensitization) and a negative skin test does not completely rule out clinical sensitivity. The same is true with in vitro tests for specific IgE, but the difference is in vitro tests are less sensitive. In vitro tests can be negative in up to 20% of skin test-positive subjects, and skin tests can be negative in approximately 10% of patients who exhibit positive in vitro tests. In addition, it should be remembered that the presence of IgE antibodies to hymenoptera venom in general is common, with over 30% of adults stung in the previous few months showing venom-specific IgE by skin test or immunoassay, and 10 to 20% of all adults demonstrate positive skin test or blood test to yellow jacket or honeybee venom (1).
And, unfortunately, sting challenge tests can also be fraught with inconsistency. Sting challenge of untreated patients who have had a history of a previous reaction and who exhibit positive skin tests causes a reaction in varying percentages of patients ranging between 21% and 73%. And the lack of a reaction to a single challenge sting has been demonstrated to be of limited clinical significance, because a subsequent sting can cause a reaction even when such a challenge has been negative (1, 2, 3).
These facts make it quite clear that the diagnosis of an insect sting reaction is made on the basis of the clinical manifestations of the reaction, and testing, even via a sting challenge, is used as evidence to support or refute the clinical diagnosis. In your patient, the history is not characteristic of an anaphylactic event in that the only clinical manifestations were tingling in his face and the observation that there was left-sided facial angioedema and a small welt on his arms. Also the rather delayed occurrence (only appearing perhaps 30 to 45 minutes after the sting) also puts an anaphylactic event in question. But once again, in the final analysis, you are simply going to have to make a clinical decision as to whether or not you judge these manifestations to have been an anaphylactic event.
In direct answer to your question therefore, there is at least to my knowledge nothing else that you can do to make a definite diagnosis. I know of no studies which would resolve the discrepancy between your testing, and as far as the fire ant is concerned, I do not see a large discrepancy due to the fact that your in vitro test is considered less sensitive than the skin tests, and I would not be surprised that a person with a positive skin test had a negative in vitro test.
None of this, however, will give you a final answer as to whether or not this individual experienced an anaphylactic event. As noted, this is a clinical decision. I can only give you an opinion as to whether or not, based on the history you described, he had a true anaphylactic episode. In my opinion, it is unlikely that he did, but there is no way to prove the validity of this opinion. In the end analysis, one is forced, if you do make a judgment in this instance, to it make mainly based on your interpretation of the history.
Thank you again for your inquiry and we hope this response is helpful to you.
1. Golden DBK. Insect Allergy. In: Middleton's Allergy: Principles and Practice 2009; 7th edition. Chapter 57.
2. Franken HH, et al. Lack of reproducibility of a single negative sting challenge response in the assessment of anaphylactic risks in patients with repeated yellow jacket hypersensitivity. J Allergy Clin Immunol 1994; 93:431-436.
3. Golden DBK, et al. Clinical and entomological factors influence the outcome of sting challenge studies. J Allergy Clin Immunol 2006; 117:670-675.
Phil Lieberman, M.D.