According to published data, allergic rhinitis is the most common form of allergy worldwide, affecting 10% to 30% of adults and as many as 40% of children. The effectiveness of interventions to treat allergic rhinitis, such as immunotherapy, avoidance, and pharmacotherapy, are largely dependent on ascertaining an accurate diagnosis. Through properly assigned treatment, a correct diagnosis helps alleviate financial burden and loss of quality of life for millions of patients affected by this condition.
Skin-prick tests—followed by intradermal testing to confirm negative test results—are recommended by professional medical societies and associations for diagnosing allergic rhinitis due to ease of administration and low level of invasiveness. However, researchers have yet to come to a consensus on the accuracy of skin testing for allergies, particularly when seeking to detect allergic rhinitis.
Reviewing the Literature
Due to concern that skin-prick testing was being overused and inflicting significant costs into the Canadian healthcare system, the Ontario Ministry of Health and Long-Term Care recently asked Health Quality Ontario to evaluate published evidence on the utility of the test in the diagnosis of allergic rhinitis. “We conducted a systematic review and meta-analysis of published studies on the diagnostic accuracy of skin-prick testing in children or adults with suspected symptoms of allergic rhinitis, using nasal provocation as the reference standard,” says Dr. Nevis. “We also evaluated the diagnostic accuracy of intradermal testing for the same patient group as a secondary objective.”
For the analysis, the authors screened more than 2,000 citations and 56 full-text articles reporting on both sensitivity and specificity of skin-prick testing in at least 10 subjects, published between 1964 and March 2015. Of the 56 full-text articles, 42 were excluded due to relevancy, insufficient information on outcomes, or being case control studies. The systematic review included eight studies, amounting to 430 patients. Only seven studies were included in the meta-analysis because one study restricted the tested allergen to alternaria, which was not evaluated in the other studies. That investigation also had findings that deviated substantially from the other studies.
“We found inconsistencies across studies in terms of quality, reported diagnostic accuracy, and other study characteristics,” explains Dr. Nevis. “We also found no other systematic reviews or meta-analyses, so our research proved to be a great opportunity for us to evaluate published evidence and present data so that the Ontario Ministry of Health and Long-Term Care can make decisions based on the best available evidence. Importantly, we believe our evidence is influential beyond the province of Ontario.”
Overall, skin-prick testing appeared to be moderately accurate in diagnosing patients with allergic rhinitis, says Dr. Nevis. The researchers reported pooled estimates of sensitivity and specificity for skin-prick testing for allergic rhinitis of about 88% and 77%, respectively (Figure). When the study that tested for alternaria was included in the meta-analysis, estimates for accuracy changed only slightly. Five studies that restricted their analyses of skin-prick testing to single-allergen extracts had sensitivities that ranged from 79% to 100% and specificities that ranged from 79% to 91%. Three studies that examined multiple-allergen extracts reported sensitivities ranging from 68% to 97% and specificities ranging from 70% to 84%.
As part of Dr. Nevis and colleague’s secondary analysis, the authors reviewed four studies reporting on the sensitivity and specificity of intradermal testing. When used to confirm negative skin-prick testing results, intradermal testing estimates for sensitivity ranged from 27% to 50%; estimates for specificity ranged from 69% to 100%. When intradermal testing was evaluated as a stand-alone tool for diagnosing allergic rhinitis, estimates for sensitivity ranged from 60% to 79%; overall specificity was estimated to be 68%. Overall, there was insufficient evidence to determine the accuracy of intradermal testing due to limitations in the four included studies.
More Research Needed
“According to the evidence we collected, there is insufficient evidence to determine the accuracy to skin-prick testing among children,” Dr. Nevis explains. While current guidelines provide no age limits for skin-prick testing, prior research suggests that skin reactions diminish for young children, with a 3 mm threshold for wheal size likely to yield high rates of false positives in this age group. Dr. Nevis notes that the authors were unable to assess the accuracy of skin-prick testing in patients younger than age 9 because the minimum age for eligible studies in the review was 9 years.
“Across the studies we reviewed, there was substantial variation in allergen extracts used in skin-prick testing,” Dr. Nevis says. “Most studies included similar types of allergens, but a few used uncommon allergens. More research is needed to establish accuracy among children and to better avoid study heterogeneity. Nonetheless, skin-prick testing results remained fairly accurate regardless of the allergen extract type.”
Nevis I, Binkley K, Kabali C. Diagnostic accuracy of skin-prick testing for allergic rhinitis: a systematic review and meta-analysis. Allergy Asthma Clin Immunol. 2016;12:20. Available at: https://aacijournal.biomedcentral.com/articles/10.1186/s13223-016-0126-0.
Bernstein I, Li J, Bernstein D, et al. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol. 2008;100:S1-S148.
Kwong K, Jean T, Redjal N. Variability in measurement of allergen skin testing results among allergy-immunology specialists. J Allergy Ther. 2014;5:1-5.
Gungor A, Houser S, Aquino B, et al. A comparison of skin endpoint titration and skin-prick testing in the diagnosis of allergic rhinitis. Ear Nose Throat J. 2004;83:54-60.