# Evaluation of drug causality in SJS/TEN: The role of the lymphocyte transformation test and conventional/modified IFN-γ ELISpot assays

## TL;DR

This study compares tests to identify drugs causing severe skin reactions, finding one test more effective than others.

## Contribution

The study introduces a modified IFN-γ ELISpot assay as a more sensitive diagnostic tool for drug-induced hypersensitivity.

## Key findings

- Modified IFN-γ ELISpot showed 80% sensitivity and 88.2% NPV, outperforming LTT and conventional ELISpot.
- All assays had 100% specificity and PPV, indicating strong reliability in identifying true positives.
- Carbamazepine and ciprofloxacin triggered stronger immune responses, confirming drug-specificity.

## Abstract

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), are life-threatening hypersensitivity reactions often triggered by specific drugs. Accurate detection of drug culprits is critical for patient management and prevention of similar conditions. This study evaluates and compares the diagnostic performance of the Lymphocyte Transformation Test (LTT), Conventional IFN-γ ELISpot, and Modified IFN-γ ELISpot assays (anti-CD3/CD28 and IL-2) in detecting drug-induced immune responses in SJS/TEN patients.

The study involved 20 SJS/TEN patients who were diagnosed based on clinical features, causality assessment using the Naranjo algorithm, and SCORTEN scoring for severity. Blood samples were collected to isolate peripheral blood mononuclear cells (PBMCs), which were subjected to LTT and IFN-γ ELISpot assays that was assessed by conventional and modified assays, the latter involving T-cell pre-activation using anti-CD3/CD28 and IL-2. Drugs tested included carbamazepine, ciprofloxacin, phenytoin, sulphamethoxazole, clozapine, and gatifloxacin. Diagnostic parameters, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were calculated. The influence of systemic corticosteroid use on assay performance was also evaluated.

The Modified IFN-γ ELISpot assay demonstrated significantly higher sensitivity (80%) and NPV (88.2%) compared to the LTT (sensitivity: 30%, NPV: 68.2%) and Conventional IFN-γ ELISpot assay (sensitivity: 20%, NPV: 65.2%). All assays exhibited high specificity (100%) and PPV (100%). Among the 20 SJS/TEN patients, 7 (35%) were receiving systemic corticosteroids at the time of testing. Patients receiving systemic corticosteroids showed no significant differences in the 3 assays. Culprit drugs such as carbamazepine and ciprofloxacin elicited stronger immune responses compared to irrelevant drugs, highlighting assay specificity.

The Modified IFN-γ ELISpot assay outperformed the LTT and Conventional IFN-γ ELISpot in detecting drug-induced immune responses in SJS/TEN patients, particularly for high-risk drugs such as carbamazepine and sulphamethoxazole. Its superior sensitivity and reliability suggest it its role in identifying the culprit drugs in these patients.