SÍNDROME DE STEVENS–JOHNSON Y NECRÓLISIS EPIDÉRMICA TÓXICA INDUCIDOS POR FÁRMACOS
Palabras clave:
Stevens–Johnson; necrólisis epidérmica tóxica; reacción adversa a medicamentos; farmacovigilancia; ALDEN; HLA; farmacogenéticaResumen
DOI: https://doi.org/10.46296/yc.v10i19.0989
Resumen
Introducción: El síndrome de Stevens–Johnson (SJS) y la necrólisis epidérmica tóxica (NET) constituyen un continuo de reacciones cutáneas adversas graves, predominantemente inducidas por medicamentos. Objetivo: sintetizar la evidencia contemporánea sobre fármacos desencadenantes, factores de susceptibilidad, características clínicas y desenlaces del SJS/NET farmacológico. Métodos: revisión sistemática conforme a PRISMA 2020. Se buscaron estudios humanos publicados entre enero de 2010 y el 30 de abril de 2026 en PubMed/MEDLINE, Google Scholar, SciELO y Scopus. Se incluyeron cohortes, estudios caso-control, series clínicas de al menos 10 pacientes, estudios farmacogenéticos y análisis de farmacovigilancia con texto completo verificable. Se excluyeron casos aislados, revisiones, editoriales y estudios sin datos separables de SJS/NET. Debido a heterogeneidad de diseño, exposición y definición de causalidad, se realizó síntesis narrativa estructurada. Resultados: se incluyeron 18 estudios primarios. La evidencia fue consistente en señalar a anticonvulsivantes aromáticos y lamotrigina, antibióticos —en especial trimetoprim/sulfametoxazol—, alopurinol y antiinflamatorios no esteroideos entre los desencadenantes más frecuentes. En FAERS, lamotrigina, trimetoprim/sulfametoxazol, alopurinol y fenitoína concentraron una proporción importante de notificaciones; los análisis de antiepilépticos mostraron señales desproporcionadas especialmente altas para lamotrigina, fenitoína y carbamazepina. Estudios poblacionales asociaron el riesgo con edad avanzada, diabetes, enfermedad vascular periférica, enfermedades autoinmunes, psoriasis, antecedente de alergia medicamentosa, malignidad y epilepsia. HLA-B*58:01 mostró una asociación fuerte con SJS/NET por alopurinol en población coreana. La mortalidad varió ampliamente según gravedad y nivel de referencia, con valores aproximados desde 6,9% hasta 46,7%, y fue mayor en NET, mayor desprendimiento cutáneo, sepsis y puntuaciones SCORTEN elevadas. Conclusiones: el SJS/NET inducido por fármacos permanece dominado por un grupo relativamente estable de medicamentos de alto riesgo, aunque emergen señales con terapias oncológicas modernas. La retirada inmediata del fármaco sospechoso, la evaluación sistemática de causalidad y el reconocimiento de susceptibilidad clínica/genética son esenciales para reducir morbimortalidad.
Palabras claves: Stevens–Johnson; necrólisis epidérmica tóxica; reacción adversa a medicamentos; farmacovigilancia; ALDEN; HLA; farmacogenética.
Abstract
Introduction: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) represent a continuum of severe adverse cutaneous reactions, predominantly drug-induced. Objective: To synthesize contemporary evidence regarding triggering drugs, susceptibility factors, clinical characteristics, and outcomes of drug-induced SJS/TEN. Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines. Human studies published between January 2010 and April 30, 2026, were searched in PubMed/MEDLINE, Google Scholar, SciELO, and Scopus. Included studies comprised cohorts, case-control studies, clinical series of at least 10 patients, pharmacogenetic studies, and pharmacovigilance analyses with verifiable full text. Case reports, reviews, editorials, and studies lacking data separable for SJS/TEN were excluded. Due to heterogeneity in study design, exposure, and causality definitions, a structured narrative synthesis was performed. Results: Eighteen primary studies were included. Evidence consistently identified aromatic anticonvulsants and lamotrigine, antibiotics—particularly trimethoprim/sulfamethoxazole—allopurinol, and non-steroidal anti-inflammatory drugs (NSAIDs) as the most frequent triggers. In the FAERS database, lamotrigine, trimethoprim/sulfamethoxazole, allopurinol, and phenytoin accounted for a significant proportion of reports; analyses of antiepileptic drugs revealed disproportionately high signals, particularly for lamotrigine, phenytoin, and carbamazepine. Population-based studies linked the risk to advanced age, diabetes, peripheral vascular disease, autoimmune diseases, psoriasis, a history of drug allergy, malignancy, and epilepsy. The HLA-B*58:01 allele showed a strong association with allopurinol-induced SJS/TEN in the Korean population. Mortality varied widely depending on severity and level of care, ranging from approximately 6.9% to 46.7%, and was higher in cases of TEN, extensive skin detachment, sepsis, and high SCORTEN scores. Conclusions: Drug-induced SJS/TEN remains driven by a relatively stable group of high-risk medications, although signals associated with modern oncological therapies are emerging. Immediate withdrawal of the suspected drug, systematic causality assessment, and recognition of clinical or genetic susceptibility are essential to reduce morbidity and mortality.
Keywords: Stevens–Johnson; toxic epidermal necrolysis; adverse drug reaction; pharmacovigilance; ALDEN; HLA; pharmacogenetics.
Información del manuscrito:
Fecha de recepción: 13 de mayo de 2026.
Fecha de aceptación: 20 de julio de 2026.
Fecha de publicación: 28 de agosto de 2026.
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