Skin tests for epidemiologic studies

All over the world, allergists have found an increase in the number of patients suffering from symptoms caused by immediate or type I allergic reactions during the last 10 years. This has created a need for epidemiologic studies of the prevalence, incidence, and cumulative incidence of these diseases. It is important that epidemiologic studies of type I allergy or atopy be done in a way that gives results which can be compared with studies from different geographic regions. Before an epidemiologic study can be considered to be reliable and comparable with other studies, it has to give a clear definition of the IgE-mediated conditions studied and the populations concerned (3, 5, 6, 9). Additional information about the population studied includes age, sex, and race. Moreover, information about concomitant treatment with antihistamines and long-acting antihistammes is also important (1, 8, 12, 14). Other factors such as circadian rhythm, site of the body on which tests are applied, and the time of year when the tests are done may also influence the results. If possible, these factors should be taken into account when an epidemiologic study is planned (1, 6, 12). It is important for the reliability of an epidemiologic study on atopy that the allergen extracts used be well controlled and of good quality. The production of allergen preparation starts with collection of the source material. Collection of pollen should be supervised by a person with botanic expertise. The pollen content from other species should be limited to 1 "o of mixed pollens and 0.5 "„ of the single pollen, as determined by a microscopic particle count. Other contamination, including particles other than pollen, should not exceed a total of 10 % by microscopic count (13). Accepted methods should be used to extract the allergen. Furthermore, the intermediate product should then be used as an inhouse reference for characterization, calibration, and biologic standardization of the extract. Characterization means that the extract is analyzed for protein and carbohydrate content by biochemical methods. Immunochemical methods determine the allergenic content, verifying that all possible major intermediate and minor allergenic components oi" the extract are present in proper proportions. It is also important that the extract be calibrated. This means that the diagnostic capacity of the skin testing is studied by determining an optimum allergen concentration and a cutoff value of the skin test (1-4, 10, 11, 13). These requirements should also be fulfilled by locally made extracts when possible. It is also important how the extract has been stored and how its stability has been determined (1, 2, 13). When one plans an epidemiologic study using skin tests, special attention should be given to the material used for skin tests, the site of the skin to be tested, the testing method, and the reading and recording of the results. If possible, the standardized method of skin prick testing described in the Nordic Guidelines for allergen preparations should be followed (13). A prick test lancet with a 1-mm tip and shoulders preventing further penetration of the skin should be used. The drop of allergen applied to the skin should have a controlled size. A negative control by the dilution fluid used for the allergen preparation and a positive control containing a histamine solution of 54.3 mmol/1 should be used as controls for the patients' skin reactivity. The reading of the test results should be done 15 min after application, and the result recorded either as area (mm-^), or as the largest diameter (D) o^ the wheal added to the diameter (d) at a right angle to it and the sum divided by 2 (D -id/2). Skin tests are considered to be positive when the size of the wheal is at least half the size of the positive control with histamine. A wheal size o[ 1 m\xr corresponding to a diameter of 3 mm may also be considered to be a cutoff for a positive reaction to skin prick. The persons doing the testing should be trained. The reproducibility of their testing method should be assessed before the study starts. A practical way of doing this is to use two histamine skin tests in 20 volunteers. With this kind of test, a good technician has a variation coeflicient of around 0.15 (1, 5, 6, 8 9, 10-13). In summary, I list below the recommendations for epidemiologic studies using skin tests from the position paper of the European Academy of Allergology and Clinical Immunology on "Allergen standardization and skin tests" (1). According to this paper, skin tests should: