Skin reactivity (intracutaneous test) to histamine and allergens was studied cross-sectionally in a Dutch asthmatic patient population from childhood to old age (4-75 years). It was found that the histamine skin reactivity rose significantly (p less than 0.05) during childhood, was significantly higher in the 10-15-year age group, and was constant between 20 and 75 years of age. The mean wheal index (histamine ratio) of all allergens was constant during childhood, and decreased after the age of 25 for grass pollen and house-dust mite and after the age of 15 for the other allergens. The prevalence of a positive skin test decreased with age, except for grass pollen. During childhood the indoor allergens, cat dander and house-dust mite, were the most important, while after the age of 15 sensitivity to an outdoor allergen, grass pollen, increased markedly. At all ages house-dust mite was the most important allergen. After the age of 25 the prevalence of every allergen declines. The prevalence of a positive skin test to Cladosporium was unexpectedly high in childhood (10-40%). It can be concluded that the prevalence of a positive skin test declines with age, except for grass pollen. The degree of sensitization in asthmatics peaked in the age groups between 20 and 40 and sensitivity to indoor allergens developed earlier than sensitivity to outdoor allergens.

In this multicenter study we evaluated the results of a previous study (part I) in a relatively large Dutch patient population, using the two previously tested allergens (house-dust mite and grass pollen) and two other standardized allergens (tree pollen and cat dander). The obtained skin test results were expressed as a histamine ratio and compared with RAST and clinical history (CH). The sensitivity and specificity were calculated at different cutoff values of the skin tests. The optimum cutoff values of 0.7 intracutaneous tests (ICT) and 0.4 skin prick tests (SPT) resulted in a predictive value for the detection of allergic sensitization of 83% (RAST) and 77% (CH), and 91% (RAST) and 86% (CH), for the ICT and SPT, respectively. As the ICT and SPT were performed in different centers, the results of these methods cannot be compared. No systemic side-effects of the skin tests were recorded. These results generally correspond well with the predictions regarding safety and predictive value of part I of this study, in which a limited number of patients was studied. In conclusion, through the use of a limited number of standardized allergens in a small group of patients, it may be possible to predict a safe and efficacious concentration for routine skin testing and to extrapolate from these results to other standardized allergens.

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Standardized extracts of Phleum pratensis (grass) and Dermatophagoides pteronyssinus (house-dust mite) were used as test allergens for multiple regression in order to determine optimum concentrations and cutoff values with regard to diagnostic capacity and safety. If a RAST value of class 1 or more was taken as an indication of sensitization, it was found that the optimum concentrations for the detection of sensitization are in the range 10-100 BU/ml and 1500-10,000 BU/ml for intracutaneous tests (ICT) and skin prick tests (SPT), respectively. The skin test results were expressed as histamine ratios. Using allergen concentrations of 30 and 3,000 BU/ml, we found cutoff values of 0.87 and 0.53 and predictive values of 87.1% and 79.1% for ICT and SPT, respectively. The maximum wheal size (mean wheal size + 2 SD) to be expected in 95% of the population was 26.6 mm (ICT) and 10.9 mm (SPT), sizes regarded as safe by most clinicians. In conclusion, by using this method with a limited number of patients, one can probably improve the diagnostic precision and safety of the skin test. In the second part of this study, these hypotheses were prospectively tested in a multicenter study.

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