Background: Cutaneous drug eruptions are a significant source of morbidity, mortality, and cost to the healthcare system. Identifying the culprit drug is essential; however, despite numerous methods being published, there are no consensus guidelines. Objectives: Conduct a scoping review to identify all published methods of culprit drug identification for cutaneous drug eruptions, compare the methods, and generate hypotheses for future causality assessment studies. Eligibility criteria: Peer-reviewed publications involving culprit drug identification methods. Sources of evidence: Medline, Embase, and Cochrane Central Register of Controlled Trials. Charting methods: Registered PRISMA-ScR format protocol on Open Science Forum. Results: In total, 135 publications were included comprising 656,635 adverse drug events, most of which were cutaneous. There were 54 methods of culprit drug identification published, categorized as algorithms, probabilistic approaches, and expert judgment. Algorithms had higher sensitivity and positive predictive value, but lower specificity and negative predictive value. Probabilistic approaches had lower sensitivity and positive predictive value, but higher specificity and negative predictive value. Expert judgment was subjective, less reproducible, but the most frequently used to validate other methods. Studies suggest that greater accuracy may be achieved by specifically assessing cutaneous drug eruptions and using combinations of causality assessment categories. Conclusions: Culprit drug identification for adverse drug reactions remains a challenge. Many methods have been published, but there are no consensus guidelines. Using causality assessment methods specifically for cutaneous drug eruptions and combining aspects of the different causality assessment categories may improve efficacy. Further studies are needed to validate this hypothesis.

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Background Cutaneous drug eruptions are a significant source of morbidity, mortality, and cost to the healthcare system. Identifying the culprit drug is essential; however, despite numerous methods being published, there are no consensus guidelines. Objectives Conduct a scoping review to identify all published methods of culprit drug identification for cutaneous drug eruptions, compare the methods, and generate hypotheses for future causality assessment studies. Eligibility criteria Peer-reviewed publications involving culprit drug identification methods. Sources of evidence Medline, Embase, and Cochrane Central Register of Controlled Trials. Charting methods Registered PRISMA-ScR format protocol on Open Science Forum. Results In total, 109 studies and 26 reviews were included comprising 656,635 adverse drug events, most of which were cutaneous. There were 54 methods of culprit drug identification published, categorized as algorithms, probabilistic approaches, and expert judgment. Algorithms had higher sensitivity and positive predictive value, but lower specificity and negative predictive value. Probabilistic approaches had lower sensitivity and positive predictive value, but higher specificity and negative predictive value. Expert judgment was subjective, less reproducible, but the most frequently used to validate other methods. Studies suggest that greater accuracy may be achieved by specifically assessing cutaneous drug eruptions and using combinations of causality assessment categories. Conclusions Culprit drug identification for adverse drug reactions remains a challenge. Many methods have been published, but there are no consensus guidelines. Using causality assessment methods specifically for cutaneous drug eruptions and combining aspects of the different causality assessment categories may improve efficacy. Further studies are needed to validate this hypothesis.

Background Identification of culprit drugs when managing cutaneous drug eruptions is essential. Causality assessment methods (CAMs) have been proposed, including lab-based techniques. However, no consensus guidelines exist. Objectives To identify and map the functionality and feasibility of lab-based CAMs. Methods A scoping review was conducted to identify culprit drug identification methods. Publications on lab-based methods were analyzed. Medline, Embase, and Cochrane Central Register of Controlled Trials databases were searched. Results Twenty-five publications met inclusion criteria. Nine lab-based CAMs were studied, including lymphocyte transformation test, cytokine measurement (ELISpot, ELISA, beads array assay), modified IFN-ɣ ELISpot, CellScan, histamine release, granzyme B-ELISpot, intracellular granulysin, lymphocyte toxicity assay, and HLA allele genotyping. Diagnostic accuracy was reported for 8/9 methods. Clinical assessment and operational algorithms were commonly used as validation benchmarks. Lab-based methods were assessed at different phases of a drug eruption including in the acute (18.1%), recovery (27.3%), acute and recovery (27.3%), or an unspecified phase (27.3%). Lymphocyte transformation test (specificity 30% to 100%, sensitivity 27% to 73%) and cytokine measurement (specificity 76% to 100%, sensitivity 20% to 84%) were the most common methods studied. Conclusions Lab-based CAMs can be low-risk, effective, and complementary of clinical methods. High-quality studies are needed to adequately develop and validate these tools for clinical practice.