Active clinical trials for "Stevens-Johnson Syndrome"

The investigators' aim is to study the effects of mechanical expression of meibomian glands on eyelid disease, ocular surface health in the subacute phase of SJS/TEN. The primary outcome is to use meibomian gland imaging to assess the health and caliber of the meibomian glands of both lower eyelids, between the treated and non-treated eyes before and after the intervention. Monitoring of outcomes will be measured by comparing the results of meibography at the initial visit and at the 6-month follow-up. The secondary outcome assessed will be patient symptoms. The Ocular Surface Disease Index survey will be administered before each treatment and patients will be asked to differentiate their symptoms between the two eyes, both before and after the intervention. The investigators hypothesize that mechanical expression of meibomian glands within the first 6 months of SJS/TEN onset will significantly improve ocular surface disease and symptoms in those patients.

Toxic epidermal necrolysis (TEN) including Stevens Johnson (SJS) and Lyell syndromes represent the most severe drug eruptions. It is an allergic disorder caused by cytotoxic T lymphocytes, specific of drugs, responsible for the destruction of keratinocytes by apoptosis. Regulatory T cell (CD25 high CD4+), normally responsible for controlling the activation of cytotoxic T lymphocytes, have altered function. Despite the progress made in the pathophysiological understanding of TEN, there is currently no effective treatment. The main symptom is bullous and skin peeling > 10% giving the appearance of great burns. The death rate is estimated between 30 and 40% due to visceral inflammatory injuries and bacterial superinfection. The risk of mortality is estimated during the initial treatment by calculating the SCORTEN (mortality>10% if SCORTEN>2, mortality>90% if SCORTEN>5). The morbidity is also very important (92% at 1 year), especially ophthalmologic with high risk of blindness... The therapeutic potential of G-CSF (Granulocyte-Colony Stimulating Factor) in TEN is supported by several observations. The G-CSF promotes skin healing. This has been shown in human burns, with a significant reduction in healing time under G-CSF. The mechanisms associate the growth factor effect on keratinocytes, macrophages stimulation and metalloprotease activity allowing tissue remodeling limiting sequels onset. Otherwise, healing altered in deficient G-CSF mice is corrected by the growth factor injection. The G-CSF is an immunomodulator whose activities appear to justify use in TEN : Polarization of immune response to Th2 non-cytotoxic (anti Th1), Preferential differentiation of naive LT (T lymphocytes) in regulator LT (CD25 high CD4+) and mobilization of regulator LT of the spinal cord to altered tissues. The G-CSF was used in a few cases of TEN with great efficacy. No data is available concerning sequels of SJS/TEN in treated patients. This clinical trial program, by providing proof of the efficacy of filgrastim in SJS/TEN, should allow progress in care of this serious toxics diseases. In the future, it could thus reduce the significant morbidity of these syndromes with a high rate of sequelae.

The NATIENS study is a phase III randomized study to examine the optimal treatment and mechanisms of each of two treatments (cyclosporine 5 mg/kg bid for 14 days versus etanercept 50 mg subcutaneously at day 0 and day 3) versus the current standard of care which is harmonized supportive care for the treatment of Stevens-Johnson Syndrome and toxic epidermal necrolysis (SJS/TEN). SJS/TEN is typically a drug-induced disease in adults with a mortality of up to 50% or higher in elderly adults. Although progress has been made in elucidating strong genetic risk factors that have led to pre-prescription screening and prevention the risk factors for most drugs and ethnicities represented in the United States are currently unknown. Currently there are a number of small observational studies and a non-blinded small randomized study however there is no strong or definitive evidence base to support any one treatment intervention over supportive care alone and this remains considered a standard of care for SJS/TEN. The primary objective of the study is to conduct a randomized double-blind double dummy stratified multicenter phase III study across 24 sites across the Unites States to determine whether two therapeutic interventions (etanercept versus cyclosporine) will improve short-term outcomes associated with SJS/TEN. The primary hypothesis of this study is that both etanercept and cyclosporine will show benefit over supportive care alone and that single dose etanercept 50 mg sc at days 0 and repeated 72 hours following initial dosing will show significant benefit over cyclosporine 5 mg/kg bid and supportive care alone. Our secondary outcomes are to determine the clinical outcomes at 3 and 12 months following initial presentation and to determine the molecular and cellular mechanisms of SJS/TEN through collection of timed samples to include DNA, RNA, PBMCs, blister cells and supernatant and skin. We hypothesize that patients will have significant sequelae identified at 3 and 12 months that will differ between treatment arms and that treatment interventions will significantly impact cytotoxic and cytokine signals with these biomarkers correlating with primary and secondary outcome. We also hypothesize that significant genetic associations will be found in association with drug-induced SJS/TEN. Eligible patients are >/= 18 who meet evidence for SJS/TEN clinical criteria as evidence by erythematous/dusky macules coalescing or denuded skin and blistering with positive Nikolsky sign which is mandatory criteria associated with mucous membrane involvement, prodromal symptoms including fever, myalgia and headache, increasing number of lesions and history of a medication. To continue with the study patients must meet pathological criteria. Randomization will occur by a secure central online computer-generated random number system through REDCap. Subjects will be allocated 1:1:1 to cyclosporine plus best supportive care, etanercept plus best supportive care or best supportive care alone. Patients, treating physician and outcome assessors will be blinded to the allocated treatment. The primary outcome of the study is time to complete re-epithelialization as defined by complete absence of erosion and compromised skin. Time to expected re-epithelialization of 21 days is the maximum healing time with supportive care in SJS/TEN patients which reflects the healing time of adult skin. The primary outcome will be independently assessed by the treating team to include any of a burn surgeon, dermatologist or wound specialist. Disagreement will be solved by independent adjudication by a minimum of two reviewers. Patients who have to discontinue a study medication will be analyzed by intent-to-treat analysis and followed for complications of SJS/TEN as per study protocol. Secondary outcomes of the study include: 1)time to halting of progression of SJS/TEN skin disease. Progression will be considered significant if there are any new blisters or erosions and halting of progression is defined as absence of these criteria with any new lesions; 2) all-cause mortality at 30 days, 3 months and 1 year following symptoms onset; 3) composite cause-specific mortality - outcome including death from sepsis, multi-organ failure and acute respiratory distress syndrome; 4) actual mortality versus expected mortality (as calculated by SCORTEN); 5) Time to cessation of acute ocular involvement (this will be tracked by the same serial photography evaluated by two independent Ophthalmology experts in SJS/TEN eye disease; 6) incidence of infections; 7) hospital length of stay; 8) adverse events due to therapy; 9) serial plasma granulysin, IL-15 concentrations (and other relevant biomarkers);10) Follow-up 3 months and 1 year from initial presentation for physical and mental health complications. For aims 2 and 3 a number of mechanistic studies will be performed on paired samples (DNA, RNA, PBMCs, plasma, blister fluid and skin).

A phase IIa, open label, non controlled clinical trial to assess the feasibility and safety of allogeneic adipose-derived mesenchymal stem cells (ASC) in the treatment of cicatricial conjunctivitis associated with Lyell's syndrome, Stevens-Johnson's syndrome and mucous membrane pemphigoid with ocular involvement

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions (SCARs) to drugs. To date, no curative drug has demonstrated with a good level of evidence its ability to promote SJS and TEN healing and could contribute to earlier reepithelialisation. Mesenchymal stroma cells (MSCs) therapy represents a new therapeutic approach. eg, in patients with cardiovascular diseases, neurological diseases, renal transplantation, lung diseases as acute respiratory distress syndrome. Recently, MSCs have been proposed in both burn wound healing with a significantly decrease of the unhealed burn area and in cutaneous radiation. Moreover, MSCs have immunomodulation properties potentially effective in refractory acute and chronic graft versus host disease (GVHD) by improving thymic function and induction of Tregs. Indeed, MSCs are able to migrate to inflamed tissues after stimulation by pro-inflammatory cytokines and to modulate the local inflammatory reactions. MSCs have also demonstrated their ability to promote tissue remodelling, angiogenesis and immunomodulation through either differentiation or secretion of several growth factors such as VEGF, basic FGF and various cytokines. Therefore, combining their immunomodulation effect and secretion of soluble factors involved in wound repair, MSCs might be valuable as a cell therapy strategy for promoting cutaneous healing in SJS-TEN syndrome and subsequently decrease the morbi-mortality.

Pemphigus is a rare autoimmune life-threatening blistering condition affecting skin and mucous membranes. Pemphigus belongs to a family of polygenic disorders. Several different genes encoding molecules regulate pemphigus autoimmunity. Many trials focused on HLA investigation. Increased levels of certain HLA class II alleles frequencies in pemphigus have been reported in various populations. However, they were not investigated in the Russian population. The aim of our study is to investigate HLA class II alleles and haplotypes in Russian patients with pemphigus. Methods Patients and controls We are recruiting 120 patients with pemphigus. The diagnosis was based on clinical and histopathological findings and confirmed by immunofluorescent techniques (direct and indirect immunofluorescent tests). Before sampling, written consent was obtained from each subject. A single blood sample for HLA typing was obtained from all subjects. This study has been approved by the Ethics Committee of Sechenov University, Russia. Phenotypic and allelic frequencies were compared with healthy blood donors (n=100) registered in Sechenov University blood center.

Intro: Dermatology department of Henri Mondor Hospital (Creteil, France), is a reference center for toxic bullous diseases and severe cutaneous drug reactions (Stevens-Johnson syndrome (SJS), Lyell syndrome (toxic epidermal necrolysis (TEN)), generalized bullous fixed drug reactions, AGEP, DRESS, drug induced immunoglobulin A (IgA) bullous dermatosis, and erythema multiforme). In order to conduct clinical and biological research studies in drug reactions, it is necessary for the investigator's department to implement a collection of clinical data and biological samples. Hypothesis/Objective: To collect clinical data and cutaneous and biological samples for immunological, biological and genetic studies to improve knowledge about pathophysiology of drug reactions. Method: The following samples will be performed in addition to the routine practice samples: one skin punch biopsy (6mm); 43 mL of blood; blister fluid aspiration; oral and nose mucous membrane and skin eSWABs, stool samples. These samples will be stored in a dedicated biological sampling department ("Platform of biological resources"). Conclusion: The implementation of this collection should allow us to conduct pathophysiological studies about drug reactions.

To test the ability of palifermin (a recombinant human keratinocyte growth factor) to decrease mucocutaneous injury and to promote epithelial repair in Toxic Epidermal Necrolysis and Stevens-Johnson Syndrome-Toxic Epidermal Necrolysis Overlap, diseases in which there is extensive sloughing of the skin and mucosa, including that of the eyes, gastrointestinal tract, respiratory and genitourinary systems.

Patients diagnosed with Stevens-Johnson syndrome and Toxic Epidermal Necrolysis were confirmed based on the investigators national diagnostic criteria. Patients who meet all inclusion criteria and do not conflict with the exclusion criteria will receive NPB-01 (intravenous immunoglobulin) 400mg/kg/day for five consecutive days. Subsequently, efficacy of NPB-01 for therapy of Stevens-Johnson syndrome and Toxic Epidermal Necrolysis will be evaluated the disease evaluation score et al. As a safety endpoint, the safety of NPB-01 will be investigated the occurrence of adverse events by 20 days after the start of the study treatment.

PRF in orabase will be applied as a pack material on chronic oral ulcers of chronic multiple oral lesions compared to conventional topical steroid therapy with clobetasol propionate 0.05% in orabase. The outcomes measured are Pain alleviation as Primary outcome and Clinical improvement in terms of Ulcer size, Number and Mucositis score as Secondary outcomes. Time frame for outcomes assessment will be Daily for 7 Days regarding pain score and weekly for 2 weeks regarding clinical improvement.