Abstract
Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), are drug-induced acute inflammatory vesiculobullous reactions of the skin and mucous membranes, including the ocular surface. Even after recovery from skin symptoms, some SJS/TEN patients continue to suffer with severe ocular complications (SOCs). Therefore, this study aims to understand the pathophysiology of chronic SOCs. Because plasma lipid profiling has emerged as a useful tool to understand pathophysiological alterations in the body, we performed plasma lipid profiling of 17 patients who suffered from SJS/TEN-associated chronic SOCs. A lipidomics approach yielded 386 lipid molecules and demonstrated that plasma levels of inflammatory oxylipins increased in patients with SJS/TEN-associated chronic SOCs. In addition, oxidized phosphatidylcholines and ether-type diacylglycerols increased in the patients with chronic SOCs, while phosphoglycerolipids decreased. When we compared these lipidomic profiles with those of patients with atopic dermatitis, we found that patients with chronic SOCs, specifically, had decreased levels of ether-type phosphatidylcholines (ePCs) containing arachidonic acid (AA), such as PC(18:0e/20:4) and PC(20:0e/20:4). To confirm our finding, we recruited additional patients, who suffered from SOC associated with SJS/TEN (up to 51 patients), and validated the decreased plasma levels of AA-containing ePCs. Our study provides insight into the alterations of plasma lipidomic profiles in chronic SOCs and into the pathophysiology of SJS/TEN-associated chronic SOCs.
Highlights
Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), are drug-induced acute inflammatory vesiculobullous reactions of the skin and mucous membranes, including the ocular surface [1,2]
Plasma lipid profiling of 17 patients with SJS/TEN-associated chronic severe ocular complications (SOCs), 24 patients with atopic dermatitis, and 32 healthy volunteers were determined by lipidomic analysis using a combination of two LC/MS platforms
We first demonstrated that plasma lipids are altered in patients with SJS/ TEN-associated chronic SOCs
Summary
Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), are drug-induced acute inflammatory vesiculobullous reactions of the skin and mucous membranes, including the ocular surface [1,2]. 40% of SJS/TEN patients develop severe ocular complications (SOCs), severe conjunctivitis with ocular surface epithelial defects and pseudomembrane, in the acute stage [5,6]. Our recent work has demonstrated that HLA-AÃ02:06 and -BÃ44:03 were associated with the incidence of SOCs in CM-related SJS/ TEN patients [10]. Even after recovery from skin symptoms, some SJS/ TEN patients continue to suffer with SOCs [11], and sometimes the ocular condition worsens due to inflammation. Chronic SOCs is one of the major conditions observed in SJS/ TEN patients
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