Lymphocyte transformation test in pediatric drug hypersensitivity: case series report from a tertiary care hospital
Olga Rogozina1, Susana Martín-López1, Fiorela Cinthia Dueñas López1
1Clinical Pharmacology Department, La Paz University Hospital-IdiPAZ, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain.
Insights
The lymphocyte transformation test (LTT) shows high accuracy in diagnosing pediatric adverse drug reactions (ADRs), correlating with causality scores and drug provocation tests. LTT is a valuable non-invasive tool for identifying T-cell mediated reactions.
Area of Science:
- Pharmacology
- Immunology
- Pediatrics
Background:
- Diagnosing adverse drug reactions (ADRs) in children is complicated by concurrent infections.
- There is a critical need for reliable in vitro diagnostic methods for pediatric ADRs.
Purpose of the Study:
- To assess the lymphocyte transformation test (LTT) for supporting the Spanish Pharmacovigilance System (SPS) causality algorithm in pediatric ADRs.
- To determine the diagnostic accuracy of the SPS algorithm, LTT, skin tests, and drug provocation testing (DPT) for pediatric ADRs.
Main Methods:
- A retrospective case-series study (2018-2024) involving 81 children with adjudicated ADRs at a tertiary hospital.
- The reference standard was tolerance upon drug re-exposure to calculate sensitivity, specificity, and predictive values.
- Analysis included correlating LTT results with SPS causality scores and DPT outcomes.
Main Results:
- The study analyzed 81 children, with cutaneous and hepatic ADRs being most common.
- Frequent culprit drugs included amoxicillin, paracetamol, amoxicillin/clavulanic acid, and ibuprofen.
- LTT demonstrated 100% sensitivity and 100% negative predictive value, with 78% specificity. LTT positivity significantly correlated with SPS scores ≥4 (p<0.001) and DPT outcomes (p=0.008).
Conclusions:
- LTT positivity in children significantly correlates with high causality scores and drug provocation test results.
- The lymphocyte transformation test is a valuable, non-invasive tool for diagnosing T-cell mediated adverse drug reactions.
- LTT is particularly useful when drug provocation testing poses risks or is contraindicated in pediatric patients.
Background:
Diagnosing adverse drug reactions (ADRs) in children is challenging due to coexisting infections. Reliable in vitro methods are critically needed.
Objectives:
To evaluate the lymphocyte transformation test (LTT) in supporting the Spanish Pharmacovigilance System (SPS) causality algorithm for identifying culprit drugs in pediatric ADRs, and to estimate the diagnostic accuracy of the SPS algorithm, LTT, skin tests, and drug provocation testing (DPT).
Methods:
Retrospective case-series (2018-2024) at a tertiary hospital. Children with adjudicated ADRs were identified through pharmacovigilance programs and clinical referrals. Tolerance upon re-exposure served as the reference standard to estimate sensitivity, specificity, and predictive values.
Results:
We analyzed 81 children (mean age 9.2 ± 5.9 years; 46.9% female). Most had no prior drug allergies (88.9%). The ADR spectrum was primarily cutaneous and hepatic (rash 19.5%, urticaria 13.0%, liver injury 11.9%). Frequent culprit drugs included amoxicillin (8.4%), paracetamol (7.9%), amoxicillin/clavulanic acid (6.9%), and ibuprofen (6.4%). Using re-exposure as the reference standard, LTT demonstrated 100% sensitivity (95% CI: 51.0-100%) and 100% NPV (95% CI: 89.3-100%), with 78% specificity (95% CI: 12.6-57.6%). Significant associations were found between LTT positivity and SPS scores ≥4 (p<0.001), and between LTT and DPT outcomes (p=0.008).
Conclusion:
LTT positivity correlates significantly with high causality scores and DPT outcomes in children. LTT is a valuable, non-invasive tool for evaluating T-cell-mediated reactions, particularly when DPT is risky or contraindicated.
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