The atopic diseases were originally defined as sensitization based on hereditary predisposition (thus differentiating affected persons from nonaffected persons exposed to the same commonly found antigens) and characterized by immediate urticarial skin reaction to offending antigen and by the Prausnitz-Kьstner reaction. Prausnitz and Kьstner demonstrated in 1921 that serum from a sensitized person, when injected into the skin of a nonsensitized person, would produce a cutaneous reaction on challenge with appropriate antigen (cutaneous passive transfer). The serum factor responsible was known as reagin (skin-sensitizing antibody). In 1966, reagin was found to be IgE, which has subsequently been shown to trigger immediate local hypersensitivity reactions by causing release of histamines and vasoactive substances from mast cells, which, in turn, produce local anaphylaxis in skin or mucous membranes. The IgE system thus mediates atopic dermatitis, allergic rhinitis, and many cases of asthma. In patients with rhinitis, nasal itching is the most suggestive symptom of IgE-associated allergy. Allergens may come from the environment (pollens, foods, allergenic dust, molds), certain chronic infections (fungus, parasites), medications (penicillin), or industrial sources (cosmetics, chemicals). Sometimes there is a strong hereditary component; sometimes none is discernible. Discovery that IgE is the key substance in these reactions has led to measurement of serum IgE levels as a test for presence of atopic allergy sensitization.

Total immunoglobulin E levels

Serum total IgE levels are currently measured by some type of immunoassay technique. The most common method is a paper-based radioimmunosorbent test procedure. Values are age dependent until adulthood. Considerably elevated values are characteristically found in persons with allergic disorders, such a atopic dermatitis and allergic asthma, and also in certain parasitic infections and Aspergillus-associated asthma. Values above reference range, however, may be found in some clinically nonallergic persons and therefore are not specific for allergy. On the other hand, many patients with allergy have total IgE levels within normal population range. It has been reported, however, that total IgE values less than 20 international units/ml suggest small probability of detectable specific IgE. Besides IgE, there is some evidence that IgG4 antibodies may have some role in atopic disorders.

Specific immunoglobulin E levels

Specific serum IgE (IgE directed against specific antigens) can be measured rather than total IgE. This is being employed to investigate etiology of asthma and atopic dermatitis. The current system is called the radioallergosorbent test (RAST). Specific antigen is bound to a carrier substance and allowed to react with specific IgE antibody. The amount of IgE antibody bound is estimated by adding radioactive anti-IgE antibody and quantitating the amount of labeled anti-IgE attached to the IgE-antigen complex. The type of antigen, the degree and duration of stimulation, and current exposure to antigen all influence IgE levels to any particular antigen at any point in time. Studies thus far indicate that RAST has an 80%-85% correlation with results of skin testing using the subcutaneous injection method (range, 35%-100%, depending on the investigator and the antigen used). It seems a little less sensitive than the intradermal skin test method, but some claim that it predicts the results of therapy better (in other words, it is possibly more specific). Since only a limited number of antigens are available for use in the RAST system, each antigen to be tested for must be listed by the physician. Some advise obtaining a serum total IgE assay in addition to RAST; if results of the RAST panel are negative and the serum IgE level is high, this raises the question of allergy to antigens not included in the RAST panel. Total serum IgE values can be normal, however, even if the findings of one or more antigens on the RAST panel are positive. There is some cross-reaction between certain antigens in the RAST system. The RAST profile is more expensive than skin testing with the same antigens. However, the skin test is uncomfortable, and in a few hyperallergic patients it may even produce anaphylactic shock. Modifications of the RAST technique that are more simple and easy to perform are being introduced, and a dipstick method with a limited number of selected antigens is now commercially available.


Peripheral blood eosinophilia is frequently present in persons with active allergic disorders, although a rather large minority of these patients do not display abnormal skin tests. Correlation is said to be better in persons less than 50 years old. Unfortunately, there are many possible causes for peripheral blood eosinophilia (see Chapter 6), which makes interpretation more difficult. Presence of more than occasional eosinophil in sputum suggests an allergic pulmonary condition.

In some patients with nasopharyngeal symptoms, a nasal smear for eosinophils may be helpful. The specimen can be collected with a calcium alginate swab and thin smears prepared on glass slides, which are air-dried and stained (preferably) with Hansel’s stain or Wright’s stain. If more than a few eosinophils are present but not neutrophils, this suggests allergy without infection. If neutrophils outnumber eosinophils, this is considered nondiagnostic (neither confirming nor excluding allergy).