(4). Inter-individual and intra-individual variability of skin reactivity to histamine at prick testing
Dermatology Online Journal, July 1995
Volume 1, Number 1
Although skin prick tests are a widely used tool, the methodology is not well studied. An examination was therefore performed to assess the variability of skin reactivity of different skin test sites for 40 subjects. Using standard histamine solution in a highly controlled setting, we found a great deal of variation in the the size of the wheal from site to site and from subject to subject. This variation suggests that skin prick tests require careful interpretation and that the results may need verification by more sophisticated and reproducible methods.
The "ideal" diagnostic method for performing prick tests has not been well studied. The classic interpretation of test results is based on comparison of skin response to substances tested to the "standard" histamine wheal/erythema response. This interpretation system is a canon inherited from early allergists. It is based on the assumption that the skin forms some kind of physiological and pharmacological continuum, in other words its reactivity does not depend on the site receiving the stimulus. This supposition may not be true, given the recent revelations in skin pathophysiology.(2)
Given this discrepancy, it was decided to examine the variability of skin reactivity of different skin sites to prick testing. The response to a standard solution of histamine was chosen because histamine is a final common mediator of the immediate hypersensitivity immune response and the histamine response is already the criterion used in the interpretation of prick tests.
The testing procedure was performed in sitting position after 30 minutes adaptation to the testing room. In all patients skin reactivity was tested on left forearm. The prick tests were performed by the same trained and experienced person using Allergopharma lancets. The skin reaction to histamine after 20 minutes was measured using following technique: the contours of the wheal area were marked using a thin-line dermatograph. They were taken using a transparent, self adhesive cellophane tape. Next, the tape was put on a millimeter paper, where the count of the marked areas followed. The intra-individual difference between sizes of the minimal and the maximal wheal areas expressed as alpha ratio computed after following rule: ratio = [(maximal area - minimal area)/maximal area]. The results were analyzed statistically using signs test.
Table I. Wheal response to standard histamine solution in different tests areas
-------------------------------------------- [mm2] A B C -------------------------------------------- mean 34 33 27 median 29 30.5 21 minimum 3 3 3 maximum 126 116 77 lower quartile 14.5 15 12 upper quartile 46 38 38 interquartile range 31.5 23 26 ---------------------------------------------(3) and seasonal variations.(4) Michel and colleagues (5) have shown that a potent source of variability is technique of administration of histamine to the skin. Wise et al. (6) found correlation between cerebral lateralization and skin reactivity asymmetry in humans.
In this study patients were tested between 4 p.m. and 6 p.m. in order to avoid circadian variability and in short, 2-week period in December to avoid the seasonal variability (even though histamine and not pollen allergens were used). All patients tested were right-handed and the test was performed always on the left arm. In all patients the same skin test technique was used, moreover, the tests were performed by the same, trained and routined person.
The results suggest that the intra-individual variation is enough to evoke a skepticism as regarded to reproducibility of skin prick tests. In this aspect, the trials on quantitative skin prick testing(7) are of great interest, although as far to now they are used in research rather than in practice.
The results of our study suggest that even under highly controlled conditions, there is a considerable variability of skin reactions to histamine both between individuals and for the same individual at different skin sites. Furthermore this variation was not a function of the specific site tested and it was not possible to describe the variability using simple mathematical models. Skin prick tests require careful interpretation. The physician should be aware that this method only gives tentative results which need further verification by more sophisticated, but also more specific and reproducible methods.(1). Bousquet J. Diagnostic value of skin tests. In: Middleton E Jr(ed). Allergy. Principles and Practice. C. V. Mosby, St Louis 1988, 430-431.
(3) Lee RE, Smolensky MH, Leach CS, McGovern JP. Circadian rhythms in the cutaneous reactivity to histamine and selected antigens, including phase relationship to urinary cortisol excretion. Ann Allergy. 1969; 38: 231.
Radoslaw Spiewak, M.D
Department of Aerobiology and Allergology Institute
of Agricultural Medicine P. O. Box 185, Jaczewskiego 2, 20-950 Lublin, Poland
All contents copyright (C), 1995. Dermatology Online Journal University of California Davis