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Wise et al.

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least 2 mm wider than the glycerin control, this is considered a positive test. 846 While this is a very reproducible test, it is more technically demanding than SPT, is difficult to perform in young children, and carries a higher risk of adverse reactions. 847 Severe adverse events related to intradermal testing are rare. Over a 42-year period, from 1945 to 1987, only 5 fatalities were attributed to intradermal testing without prior prick/puncture testing. 848 Intradermal testing may also be performed using multiple dilutions of the same allergen to more precisely quantify the level of sensitivity to that allergen and suggest a starting point for immunotherapy. 849 A series of dilutions of concentrated allergenic extract (typically supplied as a 1:20 wt/vol solution) can be prepared in either a 1:5 or 1:10 ratio. Intradermal dilutional testing (IDT, previously referred to as skin endpoint titration, or SET) begins with the intradermal placement of a dilute allergen, along with appropriate controls, followed by the placement of progressively more concentrated dilutions of that allergen. The dilution producing the first positive test (defined earlier in this section as a wheal is at least 7 mm and at least 2 mm wider than the glycerin control) followed by progressively larger wheals is called the “endpoint.” To establish progression, a confirmatory wheal, produced by the next higher concentration, must be at least 2 mm wider than the suspected endpoint. IDT endpoint correlates with SPT wheal. 844,850,851 While IDT endpoints have been shown to correlate with biologically relevant measures, such as basophil histamine release, a clear correlation with other measures, such as in vitro sIgE levels, has not yet been established. 852,853 Currently, no studies have demonstrated a clear benefit of quantitative intradermal testing over single intradermal testing with regard to the diagnosis of clinical allergy or the outcome of specific immunotherapy (Table VIII.E.2). As a stand-alone diagnostic test for AR, estimates for sensitivity for intradermal testing range between 60% (95% CI, 31% to 83%) and 79% (95% CI, 63% to 90%), while estimates for specificity range between 68% (95% CI, 49% to 82%) and 69% (95% CI, 52% to 86%). 793,833 This is lower than the pooled estimates of sensitivity (85-88%) and specificity (77%) for SPT, calculated from recent meta-analyses. 830,854 Factors affecting the predictive value of intradermal testing include the comparator used and the concentration of allergen used with the intradermal test. 855 It has been suggested that intradermal testing could potentially increase the sensitivity of SPT by injecting allergenic proteins into deeper tissue layers beneath the keratinized epidermis. 847 However, the literature has not supported a clear benefit of intradermal testing for this purpose. Using intradermal testing in addition to SPT to predict a positive response from nasal challenge with Timothy grass only increased the sensitivity from 87% to 93%. 832 In a similar study, Krouse et al. 831 determined that adding intradermal testing to SPT as a method to predict positive nasal challenge to Alternaria increased the sensitivity from 42% to 58%. These studies suggest marginal increase in sensitivity that may vary based upon the allergen being tested. Nelson et al. 856 studied 28 individuals with a history of SAR. One group had negative SPT to Timothy and Bermuda grass, but positive intradermal testing for Timothy grass, while the other group had negative SPT and negative intradermal testing for Timothy and Bermuda grass. In both groups, 11% of individuals had a positive nasal challenge with Timothy grass.

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Int Forum Allergy Rhinol . Author manuscript; available in PMC 2020 June 10.