Patients with negative skin tests

Abstract

The aim of this article is to present and discuss the clinical problem of systemic anaphylaxis to Hymenoptera venoms in patients without detectable immunoglobulin E, as it appears in recent literature. Reported at variable frequency in large series of patients undergoing evaluation, systemic anaphylaxis was previously considered to reflect lost sensitization or to involve non-immunoglobulin E mediated mechanisms. Sporadic case-reports drew attention to the fact that severe or even fatal reactions may occur in patients with negative skin tests. A breakthrough article by Golden et al., who performed deliberate stings on skin test negative venom anaphylaxis patients, demonstrated that clinical sensitivity was still present in a subset of these subjects and pointed out to the limitations of present diagnostic methods or reagents. New immunobiochemical methods and highly specific recombinant allergens--when all clinically relevant Hymenoptera venom allergens have been identified, cloned, sequenced and expressed in the proper system--are anticipated to increase the diagnostic yield. Non-specific mechanisms causing anaphylactoid reactions will probably explain some enigmatic, skin test negative radioallergosorbent test negative cases in the future. Occult mastocytosis, predisposing patients to anaphylactoid reactions, has been reported with increasing frequency among skin test negative patients. Lastly, other causes mimicking venom anaphylaxis may on rare occasions contribute to the problem. With the present understanding of venom allergy, the practising clinician is not infrequently faced with the dilemma of the skin test negative patient. Once other identifiable causes have been carefully ruled out, referral to a specialized center for deliberate sting-challenges appears in selected cases to be a medically appropriate and ethically justified management approach.