Predictive biomarkers for the progression of ocular complications in chronic Stevens-Johnson syndrome and toxic Eeidermal necrolysis

Yamato Yoshikawa,Tsunehiko Ikeda,Shigeru Kinoshita,Mayumi Ueta,Hiromi Nishigaki,Chie Sotozono

doi:10.1038/s41598-020-76064-8

Abstract

This study aimed to clarify predictive biomarkers of mild and severe ocular complications of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) by examining the cytokines in tears. In 121 chronic-phase SJS/TEN eyes, cytokines in tear samples collected using Schirmer test strips were measured, and ocular sequelae severity was evaluated using an Ocular Surface Grading Score (OSGS) involving 7 components (conjunctivalization, neovascularization, opacification, keratinization, symblepharon, and upper/lower conjunctival-sac shortening), with findings categorized into grades 0–3 (maximum total OSGS: 21). Changes in cytokines between the mild and severe groups (mild: total OSGS of 10 or less, severe: total OSGS of 11 or more), and changes between SJS/TEN cases with and without each of the 7 components, were compared. In the severe group, there was significant upregulation of interleukin (IL)-8 (P < 0.01) and Granzyme B (GrzB) (P < 0.05). IL-8 was significantly upregulated in eyes with conjunctivalization, neovascularization, or opacification, GrzB was upregulated in eyes with keratinization, interferon-γ-inducible protein 10 (IP-10) was downregulated in eyes with conjunctivalization or neovascularization, and IL-1α was upregulated in eyes with opacification (all: P < 0.05). IL-8 and IP-10 was involved in conjunctivalization and neovascularization, while GrzB was involved in keratinization. IL-8 and GrzB in tears may reflect SJS/TEN-related ocular sequelae severity.

Highlights

This study aimed to clarify predictive biomarkers of mild and severe ocular complications of StevensJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN) by examining the cytokines in tears
We investigated the cytokines in tears of SJS/TEN cases with severe ocular complications (SOC), and found that in the acute phase, interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) were dramatically increased[13], while in the chronic phase, there was a significant downregulation of interferon-γ-induced protein 10 (IP-10), as well as upregulation of IL-6, IL-8, eotaxin, and macrophage inflammatory protein-1 beta (MIP-1β) compared with the tears of normal control subjects[14]
Compared to the mild group tears, the severe group tears had significant upregulation of IL-8 (P < 0.01) and Granzyme B (GrzB) (P < 0.05) (Fig. 2). This finding suggested that focusing on IL-8 and GrzB might be the predictive biomarkers for the progression of SOC in SJS/TEN

Summary

Introduction

This study aimed to clarify predictive biomarkers of mild and severe ocular complications of StevensJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN) by examining the cytokines in tears. In the acute phase of SJS/TEN, severe ocular complications (SOC) reportedly occur in 50% of the patients[7,8,9,10,11,12], and in the chronic phase, acute ocular surface damage causes severe scarring and symblepharon. We investigated the cytokines in tears of SJS/TEN cases with SOC, and found that in the acute phase, interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) were dramatically increased[13], while in the chronic phase, there was a significant downregulation of interferon-γ-induced protein 10 (IP-10), as well as upregulation of IL-6, IL-8, eotaxin, and macrophage inflammatory protein-1 beta (MIP-1β) compared with the tears of normal control subjects[14]. It remains unknown as to whether or not the inflammatory cytokines in tears differ depending on their severity of scarring of the ocular surface

Objectives

Methods

Results

Conclusion