The use of cyclosporine for Stevens-Johnson syndrome-toxic epidermal necrolysis spectrum at the University of Louisville: A case series and literature review.

INTRODUCTION: Cyclosporine therapy for Stevens-Johnson syndrome-toxic epidermal necrolysis (SJSTEN) was first reported in the literature by Renfro et al. in 1989. Herein we report an additional 4 cases of SJS-TEN treated with cyclosporine. METHODS: Case information was collected retroactively at the University of Louisville Hospital in Louisville, KY. All cases had a diagnosis of SJS or TEN by a dermatologist. All patients were ≥18 years of age and treated with cyclosporine during their admission. RESULTS: Three of four patients re-epithelialized within an average of 3.67 days of starting 3-4 mg/kg/day of cyclosporine. One patient passed away, likely due to advanced endometrial cancer. DISCUSSION: We provide a review of the literature on cyclosporine use for SJS/TEN, including various outcome measures - stabilization (cessation of new lesions), time to re-epithelialization, mortality rate, and hospital length of stay and, where available, comparison to other systemic agents. CONCLUSION: The outcomes appear to be consistent with rapid re-epithelialization and low mortality as seen in many previous reports. Treating SJS-TEN with systemic agents including cyclosporine will remaincontroversial because the vast majority of data comes from case reports, case series, or small open prospective trials.

Low dose ouabain stimulates NaK ATPase α1 subunit association with angiotensin II type 1 receptor in renal proximal tubule cells.

Our laboratory has recently demonstrated that low concentrations of ouabain increase blood pressure in rats associated with stimulation of NaK ATPase activity and activation of the Src signaling cascade in NHE1-dependent manner. Proteomic analysis of human kidney proximal tubule cells (HKC11) suggested that the Angiotensin II type 1 receptor (AT1R) as an ouabain-associating protein. We hypothesize that ouabain-induced stimulation of NaK ATPase activity is mediated through AT1R. To test this hypothesis, we examined the effect of ouabain on renal cell angiotensin II production, the effect of AT1R inhibition on ouabain-stimulated NKA activity, and the effect of ouabain on NKA-AT1R association. Ouabain increased plasma angiotensin II levels in rats treated with ouabain (1µg/kg body wt./day) for 9days and increased angiotensin II levels in cell culture media after 24h treatment with ouabain in human (HKC11), mouse (MRPT), and human adrenal cells. Ouabain 10pM stimulated NKA-mediated 86Rb uptake and phosphorylation of EGFR, Src, and ERK1/2. These effects were prevented by the AT1R receptor blocker candesartan. FRET and TIRF microscopy using Bodipy-labeled ouabain and mCherry-NKA or mCherry-AT1R demonstrated association of ouabain with AT1R and NKA. Further our FRET and TIRF studies demonstrated increased association between AT1R and NKA upon treatment with low dose ouabain. We conclude that ouabain stimulates NKA in renal proximal tubule cells through an angiotensin/AT1R-dependent mechanism and that this pathway contributes to cardiac glycoside associated hypertension.