Stevens Johnson Syndrome/Toxic Epidermal Necrolysis and It’s Interface with Coagulation Activation

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis are rare but life-threatening, immune-mediated adverse drug reaction characterized by fever, bullae formation and dermal necrosis. Eyes are most often involved and may lead to corneal blindness. The role of cytotoxic lymphocytes in initiating the specific immune reaction in SJS/TEN via a human leukocyte antigen allele restricted pathway is well known. Following an IRB approved protocol, blood samples were obtained from subjects suspected of SJS/TEN and normal healthy volunteers. In addition, exudates from mucosal swabs were isolated following addition of 0.25 ml of saline and double centrifugation. The discharges and plasma samples were analyzed using SELDITOF Bio. Rad. Richmond, CA. In addition to blood samples, confirmatory biopsies were performed in all SJS/TEN subjects, with 4 subjects having confirmed SJS/TEN and 7 subjects having suspected SJS/TEN. Immunohistochemical staining was performed on these skin biopsy sections using antibodies against granulysin. This study highlights the immune-mediated activation of coagulation. Although the platelet microparticle levels, PAI-1 levels, Protein C levels, and antithrombin levels did not show a significant difference between the study groups, however there was a wider range in all four parameters in the confirmed/unconfirmed SJS/TEN patients. Furthermore, there were statistically significant increases in monocyte chemotactic protein-1 (p = .0078), IL-6 (p= .0078), and TNF-alpha (p=.0078) in the tissue biopsies of confirmed SJS patients when compared to normal human plasma. Analysis of mucosal swab exudates of confirmed SJS patients, using surface enhanced laser desorption-time of flight (SELDI-TOF) technique revealed distinct peaks at 15.1 kDA and 14.2 kDA while a control cohort of an adverse drug reaction group exhibited a peak at 11.2 kDA. Immunofluorescent staining of the skin biopsy slides revealed increased expression of granulysin at the epidermal-dermal layer in biopsy confirmed SJS/TEN patients when compared to the controls.