Current Perspectives on Severe Drug Eruption

Abstract

Adverse drug reactions involving the skin are commonly known as drug eruptions. Severe drug eruption may cause severe cutaneous adverse drug reactions (SCARs), which are considered to be fatal and life-threatening, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS). Although cases are relatively rare, approximately 2% of hospitalized patients are affected by SCARs. There is an incidence of 2 to 7 cases/million per year of SJS/TEN and 1/1000 to 1/10,000 exposures to offending agents result in DRESS. However, the mortality rate of severe drug eruptions can reach up to 50%. SCARs represent a real medical emergency, and early identification and proper management are critical to survival. The common pathogenesis of severe drug eruptions includes genetic linkage with HLA-and non-HLA-genes, drug-specific T cell-mediated cytotoxicity, T cell receptor restriction, and cytotoxicity mechanisms. A multidisciplinary approach is required for acute management. Immediate withdrawal of potentially causative drugs and specific supportive treatment is of great importance. Immunoglobulins, systemic corticosteroids, and cyclosporine A are the most frequently used treatments for SCARs; additionally, new biologics and plasma exchange are reasonable strategies to reduce mortality. Although there are many treatment methods for severe drug eruption, controversies remain regarding the timing and dosage of drug eruption. Types, dosages, and indications of new biological agents, such as tumor necrosis factor antagonists, mepolizumab, and omalizumab, are still under exploration. This review summarizes the clinical characteristics, risk factors, pathogenesis, and treatment strategies of severe drug eruption to guide clinical management. Keywords Severe drug eruption • Stevens-Johnson syndrome • Toxic epidermal necrolysis • Acute generalized exanthematous pustulosis • Drug reaction with eosinophilia and systemic symptoms Abbreviations AGEP Acute generalized exanthematous pustulosis ALT Alanine aminotransferase APCs Antigen-presenting cells AST Aspartate aminotransferase CBZ Carbamazepine CCR CC-chemokine receptor COVID-19 Coronavirus disease 2019 CTL Cytotoxic T cells CXCR CXC chemokine receptor DiHS

Toxic epidermal necrosis associated with afatinib: A case report and literature review

“…The typical latency period from drug exposure to symptoms ranges from 4 to 28 days ( 8 ). The incidence of SJS/TEN is 1-6 per 1,000,000, with a mortality rate of approximately 15% ( 9 ), most commonly resulting from sepsis ( 10 ). The histopathology of lesions in SJS/TEN varies from keratinocyte apoptosis to epidermal necrosis, with a partial infiltration of perivascular lymphocytes, histiocytes, and a few eosinophils being observed in the dermis ( 7 ).…”

Síndrome De Stevens-Johnson - Revisão De Literatura

“…-Anticonvulsivantes: fenitoína, carbamazepina, lamotrigina, fenobarbital; -Anti-inflamatórios não esteroidais: diclofenaco e fenilbutazona; -Antibióticos: sulfonamidas, penicilinas, quinolonas, macrolídeos; -Antirretrovirais: nevirapina; -Medicamentos para tratamento de tuberculose: isoniazida, etambutol; -Ansiolítico: alprazolam (ZHANG et al,2021). Observa-se que indivíduos imunossuprimidos e aqueles diagnosticados com doenças autoimunes e neoplasias hematológicas apresentam risco aumentado para SSJ/NET (CHAR-LTON et al, 2020).…”

“…Atualmente, existem três hipóteses sobre as interações do complexo droga-tecido, que são as seguintes: no modelo precursor hapteno/prohapteno, drogas ou seus metabólitos ligam-se covalentemente a proteínas endógenas no corpo para formar complexos de antígenos, que são considerados como substâncias estranhas ao organismo e passam por processamento por células apresentadoras de antígenos (APCs) para formar "complexos principais de histocompatibilidade (MHC)-peptídeo de antígeno" para reconhecimento dos receptores de células T (TCR); no modelo farmacológico de interação com o receptor imunológico, drogas inertes que não podem se ligar covalentemente a proteínas endógenas no corpo ligam-se ao TCR e desencadeiam uma resposta de células T devido à sua configuração especial; e no modelo peptídico, drogas ou metabólitos são diretamente ligados ao slot covalente das proteínas do MHC, alterando assim a especificidade das moléculas do MHC para os peptídeos (ZHANG et al,2021).…”

Drug eruptions: an emergency room approach

“…Las RAMC están dentro de las reacciones adversas a medicamentos más comunes y las más habituales son el exantema morbiliforme y la urticaria. Su frecuencia difiere según el medicamento usado, siendo más alta con algunos antibióticos, con los que puede presentarse hasta en el 8 % de los pacientes expuestos (5) . En un estudio observacional local, los patrones clínicos más frecuentes fueron el exantema morbiliforme (76,3 %) y la urticaria (13,6 %) y los menos frecuentes fueron los más graves, como el síndrome de Stevens-Johnson (SSJ; 0,6 %), lo que es similar a las cifras reportadas en la literatura mundial.…”

“…El grupo farmacológico más implicado fue los antibióticos (54,4 %), seguido de los analgésicos (22,5 %) y los antiepilépticos (8,9 %); sin embargo, al discriminar por cada medicamento, el más comúnmente implicado fue la dipirona (17,2 %) (4) . Aunque las RAMC graves no son las más frecuentes, se calcula que hasta un 2 % de los pacientes hospitalizados podrían verse afectados por estas y su mortalidad asciende hasta el 50 % en los peores casos (5) .…”