12 - Diagnosis of Human Allergic Disease

Abstract

The diagnosis of human allergic disease begins and ends with the patient’s clinical history and physical examination. When the clinical history identifies allergy symptoms that are in temporal relationship to a definable and relevant allergen exposure, immunoglobulin E (IgE) antibody sensitization is then confirmed with in vivo skin tests (puncture/intradermal) or in vitro blood tests (allergen-specific IgE antibody serologic assays). In select cases, such as food allergy, direct provocation tests provide additional diagnostic clarity. Importantly, allergen-specific IgE antibody is simply a marker of allergic sensitization and a risk factor for allergic disease; however, alone it does not make the definitive diagnosis of allergic disease. Confirmation of allergic sensitization with a positive IgE antiallergen analysis increases the likelihood that the patient’s symptoms may be a result of an immediate-type hypersensitivity response. Quantitative IgE antibody levels to selected foods (e.g., milk, egg, fish, and peanut), if above a predefined IgE antibody threshold, may eliminate the need for tedious and expensive double blinded placebo controlled food challenges (DBPCFC). However, caution needs to be exercised in consideration of the predictive threshold levels that vary across clinical studies because of differences in study populations, protocols, and statistical analyses employed. Food antigen–specific IgG and IgG4 antibody levels are not diagnostically useful because they do not correlate with the results of oral food challenges. Clinically successful aeroallergen immunotherapy is almost always accompanied by high (microgram per milliliter) levels of allergen-specific IgG antibody in serum. Mast cell tryptase is a serine esterase used as a marker of mast cell activation during anaphylaxis. Immunoreactive tryptase levels in serum of healthy adults are typically less than 5 μg/L. Elevated mature tryptase levels (>10 μg/L) are detectable 1 to 4 hours after the onset of systemic anaphylaxis with hypotension.