Evaluation of Skin Reactivity during (Immuno-) Therapy. Validation of Methods for Estimation of Changes in Skin Reactivity and Correlation to Shock Organ Sensitivity

Abstract

Background: Parallel line bioassay (PLBA) has been acknowledged to be the gold standard for estimation of changes in reactivity, e.g., in RAST and ELISA inhibition tests. Objective: To study correlations between two simple methods for evaluation of changes in skin prick test (δSPT), using the slope of the allergen dose response (drr a) in relation to PLBA. Methods: Skin prick test data from two published immunotherapy trials were used. In a D. farinae trial we used duplicate tests with three fixed tenfold concentrations and in a P. judaica trial three tenfold individually chosen allergen concentrations causing wheals of similar size to that of histamine dihydrochloride 10 mg/mL, tenfold lower and tenfold higher concentration. Evaluation of the δSPT by PLBA, and two simple methods were correlated. In the D. farinae trial δSPT was compared to the change of conjunctival threshold concentration. Results: The δSPT as measured by both the simple methods gave similar results to that of PLBA (p<0.001). The δSPT was around 30-fold, i.e., about 3% of the pre-treatment reactivity. The δSPT correlated with the δCPT threshold concentration. Conclusions: Estimation of the δSPT during therapy expressed as change in concentration using simple methods based on the slope of the drr a correlated well to changes by PLBA and CPT and should therefore be used both in clinical research and in practice.

Evaluation of Skin Reactivity: The concept of Histamine Equivalent Allergen Threshold Concentration (Cha)

“…Such data are not available for the longest diameter. However, changes in conjunctival sensitivity correlate well with changes of wheal area and mean wheal diameter [12].…”

“…The C ha is much more useful than the wheal diameter or area and can be used for estimation of changes in skin sensitivity during therapy, e.g. with antihistamines or by immunotherapy [12]. However, when using the results of skin prick tests for this purpose, the technique must be optimal with a c.v. less than 20% (or optimally <10%) using the wheal diameter.…”

“…from before to after therapy or between samples of patients. However, the difference can also be expressed as a ratio providing the fold-increase or decrease in skin sensitivity [12].…”

“…Then the endpoint, a concentration of allergen, was used as a measure of skin sensitivity and was often used to determine the starting dose for immunotherapy. The end point concentration as determined by SPT correlates with the threshold concentration using the gold standard for estimation of the histamine equivalent allergen concentration, Cha, the parallel line bio-assay [20,21], and with shock organ sensitivity as expressed by CPT [12,22].…”

“…The forth method does not correct for differences in SPT technique [6] or for changes in histamine sensitivity due to changes in allergen sensitivity over time or due to therapy [12].…”