Villanueva-Paz, MarinaNiu, HaoSegovia-Zafra, AntonioMedina-Caliz, InmaculadaSanabria-Cabrera, JudithLucena, M. IsabelAndrade, Raúl J.Alvarez-Alvarez, Ismael2022-04-132022-04-132021-11-15Villanueva-Paz M, Niu H, Segovia-Zafra A, Medina-Caliz I, Sanabria-Cabrera J, Lucena MI, et al. Critical Review of Gaps in the Diagnosis and Management of Drug-Induced Liver Injury Associated with Severe Cutaneous Adverse Reactions. J Clin Med. 2021 Nov 15;10(22):5317http://hdl.handle.net/10668/3535Drug-induced liver injury (DILI) encompasses the unexpected damage that drugs can cause to the liver. DILI may develop in the context of an immunoallergic syndrome with cutaneous manifestations, which are sometimes severe (SCARs). Nevirapine, allopurinol, anti-epileptics, sulfonamides, and antibiotics are the most frequent culprit drugs for DILI associated with SCARs. Interestingly, alleles HLA-B*58:01 and HLA-A*31:01 are associated with both adverse reactions. However, there is no consensus about the criteria used for the characterization of liver injury in this context, and the different thresholds for DILI definition make it difficult to gain insight into this complex disorder. Moreover, current limitations when evaluating causality in patients with DILI associated with SCARs are related to the plethora of causality assessment methods and the lack of consensual complementary tools. Finally, the management of this condition encompasses the treatment of liver and skin injury. Although the use of immunomodulant agents is accepted for SCARs, their role in treating liver injury remains controversial. Further randomized clinical trials are needed to test their efficacy and safety to address this complex entity. Therefore, this review aims to identify the current gaps in the definition, diagnosis, prognosis, and management of DILI associated with SCARs, proposing different strategies to fill in these gaps.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Drug-induced liver injurySevere cutaneous adverse reactionsHypersensitivityGapsCausality assessmentDiagnosisManagementClinical trialImmune responseEnfermedad hepática inducida por sustancias y drogasHipersensibilidadRelaciones intergeneracionalesDiagnósticoEnsayo clínicoInmunidadMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Purines::AllopurinolMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyridines::NevirapineMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::AllelesMedical Subject Headings::Anatomy::Tissues::Connective Tissue::Granulation Tissue::CicatrixMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::Histocompatibility Antigens Class I::HLA-B AntigensMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Membrane Glycoproteins::Histocompatibility Antigens Class I::HLA-A AntigensMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::PrognosisMedical Subject Headings::Diseases::Skin and Connective Tissue Diseases::Skin DiseasesMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::SulfonamidesMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial AgentsMedical Subject Headings::Chemicals and Drugs::Pharmaceutical Preparations::Pharmaceutical Preparations, Dentalreview article34830594Acceso abierto10.3390/jcm102253172077-0383PMC8618381