A systematic review of case-control studies of cytokines in blister fluid and skin tissue of patients with Stevens Johnson syndrome and toxic epidermal necrolysis.

in The Australasian journal of dermatology by Thomas Jonathan Stewart, Joshua Farrell, John Walter Frew

TLDR

  • Stevens Johnson syndrome and toxic epidermal necrolysis are severe skin reactions that can be life-threatening. The study looked at the levels of certain proteins in the skin and fluid of people with these conditions. They found that some of these proteins were higher in people with SJS/TEN than in healthy people or people with other skin conditions. These proteins may be involved in the cause of SJS/TEN and could be used to diagnose or treat the condition. More research is needed to understand the proteins better and to find new ways to treat SJS/TEN.

Abstract

Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions characterised by keratinocyte apoptosis, necroptosis and epidermal detachment. Several cytokines and cytotoxic proteins have been shown to be elevated in the blood and skin of SJS/TEN sufferers and biologics such as intravenous immune globulin and tumour necrosis factor (TNF)-alpha inhibitors have demonstrated good therapeutic potential. The exact pathogenic model of SJS/TEN however remains elusive. This systematic review aimed to evaluate the case-control studies of cytokines and cytotoxic proteins in the blister fluid and skin of adults with Stevens Johnson syndrome and/or toxic epidermal necrolysis. This review was registered with INPLASY and conducted in accordance with the PRISMA reporting guidelines. Potential bias was assessed using the NIH criteria. Eleven articles describing results from 96 cases and 170 controls were included. Fas, Fas ligand, Interleukin (IL)-8 and B-cell lymphoma (Bcl)-2 were elevated in SJS/TEN blister fluid and skin tissue, compared with healthy controls. IL-2, IL-6, TNF-alpha, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon-gamma and matrix metalloproteinase-2 were elevated in SJS/TEN blister fluid compared with fluid sampled from lesional controls. Granulysin, IL-33, TGF-beta-1 and IL-13 were elevated in SJS/TEN skin tissue compared with lesional lichen planus tissue, as was IL-13, IFN-gamma, IL-2 and IL-5, when compared with erythema multiforme tissue. A wide array of cytokines and cytotoxic proteins are present at higher concentrations in the blister fluid and skin tissue of SJS/TEN patients compared with healthy and lesional controls. Our findings suggest that these proteins may be pathogenic, as well as possibly markers for diagnosis, disease severity and course. They may also prove to be useful therapeutic targets. More research is needed.

Overview

  • The study aims to evaluate the case-control studies of cytokines and cytotoxic proteins in the blister fluid and skin of adults with Stevens Johnson syndrome and/or toxic epidermal necrolysis. The exact pathogenic model of SJS/TEN remains elusive, but several cytokines and cytotoxic proteins have been shown to be elevated in the blood and skin of SJS/TEN sufferers. The study was conducted in accordance with the PRISMA reporting guidelines and potential bias was assessed using the NIH criteria. Eleven articles describing results from 96 cases and 170 controls were included. The primary objective of the study is to identify cytokines and cytotoxic proteins that may be pathogenic, as well as possibly markers for diagnosis, disease severity and course, and useful therapeutic targets.

Comparative Analysis & Findings

  • The study found that Fas, Fas ligand, Interleukin (IL)-8 and B-cell lymphoma (Bcl)-2 were elevated in SJS/TEN blister fluid and skin tissue, compared with healthy controls. IL-2, IL-6, TNF-alpha, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon-gamma and matrix metalloproteinase-2 were elevated in SJS/TEN blister fluid compared with fluid sampled from lesional controls. Granulysin, IL-33, TGF-beta-1 and IL-13 were elevated in SJS/TEN skin tissue compared with lesional lichen planus tissue, as was IL-13, IFN-gamma, IL-2 and IL-5, when compared with erythema multiforme tissue. A wide array of cytokines and cytotoxic proteins are present at higher concentrations in the blister fluid and skin tissue of SJS/TEN patients compared with healthy and lesional controls. The findings suggest that these proteins may be pathogenic, as well as possibly markers for diagnosis, disease severity and course. They may also prove to be useful therapeutic targets.

Implications and Future Directions

  • The study's findings have significant implications for the field of research and clinical practice. The identified cytokines and cytotoxic proteins may be useful for the diagnosis, monitoring and treatment of SJS/TEN. Further research is needed to validate the findings, identify the specific pathogenic mechanisms and develop targeted therapies. Possible future research directions include larger studies, longitudinal studies, and studies on the role of these proteins in the pathogenesis of SJS/TEN.
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