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Risk of progression to autoimmune disease in severe drug eruption: risk factors and the factor-guided stratification

Published:November 19, 2021DOI:


      The identification of risk factors is key not only to uncover the pathogenesis of autoimmune disease but also to predict progression to autoimmune disease. Drug-induced hypersensitivity syndrome (DiHS)/ drug reaction with eosinophilia and systemic symptoms (DRESS) is likely the best prototypic example for analyzing the sequential events. We conducted a retrospective study of 55 patients with DiHS/DRESS followed for the possibility of later development of autoimmune disease ∼18 years after resolution. Nine patients progressed to autoimmune sequelae regardless of treatment. The generation of autoantibodies preceded by 8 years in 8 of the 9 patients. The combination of increases in lymphocyte counts, severe liver damage, a rebound increase in globulin, persistent reactivations of Epstein-Barr virus and human herpesvirus-6, and low interleukin (IL)-2 and IL-4 at the acute/subacute phases, were significant risk factors for the future development of autoimmune disease. Based on these factors, we established a scoring system that can identify high-risk patients. When stratified these patients into three risk categories (low/intermediate/high), occurrence of autoimmune disease was exclusively detected in the high group. Our data represent the new scoring system to identify patients at high-risk of developing autoimmune disease, although a larger study is required to validate the scoring system.

      Key words

      Abbreviations used:

      Abs (antibodies), Ad (autoimmune disease group), AF (autoimmune-free group), ALT (alanine aminotransferase), ANA (anti-nuclear antibody), AP score (autoimmune predictive score), Ap (autoimmune-positive group), AP (autoimmune-positive group including Ad and Ap), CI (confidence interval), CMV (cytomegalovirus), CRP (C-reactive protein), DDS score (drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms severity score), DiHS/DRESS (drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms), EBV (Epstein-Barr virus), G-CSF (granulocyte colony-stimulating factor), HHV-6 (human herpesvirus-6), IAP (initially autoimmune-positive), IFN (interferon), IL (interleukin), IVIg (intravenous immunoglobulin), MIP (macrophage inflammatory protein), NLR (neutrophil-to-lymphocyte ratio), NPV (negative predictive value), PCR (polymerase chain reaction), PPV (positive predictive value), RRs (Relative risks), SJS/TEN (Stevens-Johnson syndrome/toxic epidermal necrolysis), SLE (systemic lupus erythematosus), Th1 (T-helper 1), TNF (tumor necrosis factor), TPO (thyroid peroxidase), Tregs (regulatory T cells)
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