Longitudinal analysis of antibody profiles against plakins in severe drug eruptions: Emphasis on correlation with tissue damage in drug-induced hypersensitivity syndrome and drug reaction with eosinophilia and systemic symptoms

A. Takehara, Y. Aoyama, M. Kurosawa, Y. Shirafuji, H. Umemura, K. Kamiya, Y. Ushigome, Y. Kano, T. Shiohara, K. Iwatsuki

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10 Citations (Scopus)

Abstract

Background: The evidence for severe drug eruption as a trigger for autoimmune disease has recently increased. No information is available on how tissue damage in severe drug eruptions can induce autoimmune responses. Objectives: To investigate whether the generation of autoantibodies (autoAbs) against plakin family proteins could be the cause or result of tissue damage in patients with severe drug eruptions and whether the generation of autoAbs could be prevented by systemic corticosteroids during the acute stage. Methods: We retrospectively analysed alterations of serum levels of autoAbs against plakin family proteins in patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) during the acute stage and long after resolution over a period of more than 10 years. Results: AutoAbs against plakin family proteins were detected in patients with either SJS/TEN or DiHS/DRESS regardless of the epidermal damage in the acute stage, and were sustained even long after resolution in DiHS/DRESS, indicating that those autoAbs are neither the cause nor the consequence of epidermal damage, at least in DiHS/DRESS. Severe liver damage and noncorticosteroid therapy during the early and acute stages of DiHS/DRESS were associated with the subsequent generation of these autoAbs. Conclusions: These autoAbs are neither necessarily the cause nor the result of epidermal damage in DiHS/DRESS, because the presence of these autoAbs was not restricted to patients with SJS/TEN but was also observed in those with DiHS/DRESS, which is characterized by lack of epidermal damage. Severe liver damage and/or immune responses that could be prevented by corticosteroids in the acute stage of DiHS/DRESS are among the causal factors contributing to the generation of autoimmune responses.

Original languageEnglish
JournalBritish Journal of Dermatology
DOIs
Publication statusAccepted/In press - 2016

ASJC Scopus subject areas

  • Medicine(all)
  • Dermatology

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