Accuracy of Penicillin Allergy Diagnostic Tests: A Systematic Review and Meta-analysis.

Abstract Background Having a penicillin allergy label associates with higher risk for antibiotic resistance and increased healthcare use. Objective To assess the accuracy of skin tests and specific IgE quantification in the diagnostic evaluation of patients reporting a penicillin/β-lactam allergy. Methods We performed a systematic review and diagnostic accuracy meta-analysis, searching on MEDLINE, Scopus and Web of Science. We included studies conducted in patients reporting a penicillin allergy and in whom skin tests and/or specific IgE quantification were performed and compared with drug challenge results. We quantitatively assessed the accuracy of diagnostic tests with bivariate random-effects meta-analyses. Meta-regression and subgroup analyses were performed to explore causes of heterogeneity. Studies’ quality was evaluated using QUADAS-2 criteria. Results We included 105 primary studies, assessing 31,761 participants. Twenty-seven studies were assessed by bivariate meta-analysis. Skin tests had a summary sensitivity of 30.7% (95%CI=18.9-45.9%) and specificity of 96.8% (95%CI=94.2-98.3%), with a partial area under the summary ROC curve of 0.686 (I2=38.2%). Similar results were observed for subanalyses restricted to patients reporting non-immediate maculopapular exanthema or urticaria/angioedema. Specific IgE had a summary sensitivity of 19.3% (95%CI=12.0-29.4%) and specificity of 97.4% (95%CI=95.2-98.6%), with a partial area under the summary ROC curve of 0.420 (I2=8.5%). Projected predictive values mainly reflect the low frequency of true penicillin allergy. Conclusion Skin tests and specific IgE quantification appear to have low sensitivity and high specificity. As current evidence is insufficient for assessing the role of these tests in stratifying patients for delabeling, we identified key requirements needed for future studies.