The diagnosis of inhalant allergic disorders such as allergic rhinitis and asthma requires two components, and both need to be positive to make such a diagnosis.

First, there needs to be a positive allergic history. That occurs when an exposure to a suspected allergen (a protein capable of causing an allergy) results in signs and symptoms that are typical for allergic disease (itching, sneezing, runny or stuffy nose, red itchy eyes, cough, wheeze, or shortness of breath). For example, a positive history for cat allergy occurs when a patient reports any of the above typical allergic symptoms upon entry to a space that contains cats but does not have such symptoms away from that space. Pollen allergy involves seasonality because specific pollens are airborne only at certain times of the year. Classic mold allergy, which is not that common, is typically an outdoor problem since molds are saprophytes growing in soil and outdoor vegetation.

Second, the antibody, called immunoglobulin E or IgE, responsible for causing allergy must be detected. Most IgE is bound to allergic mediator-containing cells in the respiratory mucosa, gut, and skin. When IgE is exposed to the specific protein antigen it recognizes, these mediator cells release histamine and other molecules which, in turn, cause allergic symptoms listed above. It is the production of IgE in allergic individuals that differentiates them from nonallergic individuals as all humans are routinely exposed to a wide array of allergens. The production of IgE is called sensitization. The demonstration of preexisting IgE antibody in the sensitized host is required to make a diagnosis of an allergy.

Specific IgE (IgE directed toward one allergen) can be detected in two ways: 1) by in vitro blood assay called a RAST (radioallergosorbent test); or, 2) by in vivo skin testing. Skin tests involve challenging the potential allergy mediator-containing cells (in the skin to which IgE is bound) to the suspected allergen being tested. The process starts with the introduction of an allergen on the surface of the skin to determine if it will interact with the IgE-coated cells. Epicutaneous and RASTs are the most specific tests for detection of specific IgE and are considered equivalent due to their excellent specificity with low false positive results.

When epicutaneous tests and/or RASTs are negative to an allergen, a less specific but somewhat more sensitive intradermal (ID) test can be performed. The ID test involves injecting dilute allergen just beneath the epidermis. ID testing is necessary to rule out allergy to drugs and bee venom. Many allergists have avoided the ID test to inhalant allergens due to false positive reactivity caused by irritants when allergens are injected directly into the skin. In other words, when an epicutaneous test or RAST to an allergen is negative, that patient has either no allergy or a low or insignificant level of allergy sensitization.

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