Lab-Based Culprit Drug Identification Methods for Cutaneous Drug Eruptions: A Scoping Review

Abstract

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.