Diagnostic Performance of the Lymphocyte Transformation Test and Patch Testing in Delayed Hypersensitivity Drug Reactions

Background: Cutaneous adverse drug reactions (CADRs) occur in 2–5% of inpatients, primarily due to delayed (T-cell-mediated) reactions, such as maculopapular exanthemas (MPEs). The lymphocyte transformation test (LTT) detects drug-specific T-cell responses with varied sensitivity. Patch testing may complement LTT, although in CADRs, its positivity could be low. There is a paucity of data about combined diagnostics, temporal association, and correlations in Mediterranean populations. Methods: We retrospectively analyzed patients with clinically suspected delayed CADRs, primarily maculopapular exanthema (MPE). Patients underwent LTT, with a stimulation index >3 considered positive, as well as patch testing with various drugs. Clinical information collected included demographics, type of reaction, latency, and the time interval between the reaction and testing. The performance of LTT and patch testing was evaluated in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Correlations between test results and clinical characteristics were assessed using Jamovi software (Windows Version 2.7.2). Results: Among 38 patients (79% female, mean age 55.2 ± 19.9 years), 143 agents were tested (49% antibiotics). LTT was positive in 44.7% per patient (21.7% per agent), patch testing in 15.8% (per patient). Combined positivity was 7.9%; both tests were negative in 50%. LTT showed sensitivity 64.3%, specificity 90.0%, PPV 90.0%, NPV 64.3%; patch testing: 21.4%, 100%, 100%, 47.6%, respectively. Combined sensitivity reached 71.4%. Highest LTT positivity was observed for contrast agents (60%), corticosteroids (47%), and NSAIDs (43%). LTT positivity correlated with atopy ( P = 0.004) and shorter reaction-to-testing intervals ( P = 0.013). Conclusions: LTT offers high specificity and PPV, particularly for the identification of non-antibiotic culprits in atopic patients with recent MPE. Early integration with patch testing enhances diagnostic yield and supports safe drug delabeling to minimize unnecessary avoidance and improve patient safety.