Effectiveness, safety and tolerability of cyclosporine versus supportive treatment in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: A record-based study.

BACKGROUND: Toxic epidermal necrolysis and Stevens-Johnson syndrome comprise life-threatening, drug-induced mucocutaneous disease spectrum. Interest in cyclosporine, a calcineurin inhibitor that can block the function of T-cells, has increased with the discovery of the importance of granulysin in apoptosis in toxic epidermal necrolysis. In our hospital, cyclosporine is given to Stevens-Johnson syndrome/toxic epidermal necrolysis patients as an adjunctive therapy. AIMS: This study is an observational, record-based study comparing the effectiveness and safety of patients receiving cyclosporine versus only supportive therapy. METHODOLOGY: Medical records as bed-head tickets and laboratory investigation reports of Stevens-Johnson syndrome/toxic epidermal necrolysis patients admitted in the hospital over a period of 1 year were collected. Data regarding clinico-demographic profile, suspected drug causing Stevens-Johnson's syndrome/toxic epidermal necrolysis, SCORTEN, body surface area involved, treatment received and outcome were obtained. RESULTS: Twenty-eight patients were analyzed. Nineteen belonged to the cyclosporine group (supportive treatment + cyclosporine), nine to supportive treatment only group. Among the suspected drugs, antiepileptics formed the major group (28.6%). Five patients in the supportive only group and one in the cyclosporine group died. Time for stabilization and reepithelialization and duration of recovery were significantly lower in the cyclosporine group (P < 0.001, P= 0.007, P= 0.01, respectively). The standardized mortality ratio was 0.32 in cyclosporine group which is nearly 3.3 times lower than the only supportive treatment. LIMITATIONS: As it was a record-based study, certain confounding factors (serum blood urea nitrogen) could not be adjusted. CONCLUSION: Cyclosporine (5 mg/kg/day) for 10 days from onset of Stevens-Johnson syndrome/toxic epidermal necrolysis may decrease the risk of dying, may provide faster healing of lesions and might lead to early discharge from hospital.

Cyclosporine in Stevens Johnson syndrome and toxic epidermal necrolysis and retrospective comparison with systemic corticosteroid.

BACKGROUND: Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening dermatological emergencies. Many immunosuppressive modalities have been tried with variable results. AIMS: To determine the efficacy of cyclosporine in cases of SJS and TEN and compare the efficacy with systemic corticosteroid in the same condition. METHODS: Study was conducted at a tertiary hospital during 01 July 2011 to 30 June 2012. SCORTEN was assessed at the time of admission. Total body surface area (TBSA) assessment was like any burn patients. Cyclosporine was administered in the dose of 3 mg/kg body weight in three divided dosage for 07 days and then tapered over another 07 days. Data were compared to a historical series of SJS/TEN patients, managed by systemic steroids a year ago. RESULTS: A total of 11 consecutive patients with a mean age of 32.09 and standard deviation (SD 16.17) were enrolled in to cyclosporine group, which were retrospectively compared to 6 patients with a mean age of 27.87 (SD 13.97) years in the corticosteroid group. The mean duration of re-epithelialization was 14.54 (SD 4.08) and 23 days (SD 6.68) in cyclosporine and corticosteroid group respectively (P = 0.009956). Mean hospital stay was 18.09 (SD 5.02) and 26 (SD 6.48) days in cyclosporine and corticosteroid group respectively (P = 0.02597). A total of 1.11 and 0.51 patients were expected to die against no death and two deaths in cyclosporine and corticosteroid group respectively (Standardized mortality ratio = 3.92) (P = 0.04321). CONCLUSION: This study definitely suggests that cyclosporine has encouraging role in the management of uncomplicated cases of SJS, SJS-TEN overlap or TEN.

Low dose intravenous immunoglobulins and steroids in toxic epidermal necrolysis: a prospective comparative open-labelled study of 36 cases.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe adverse drug reaction associated with high mortality. Though different modalities of treatment are advocated, there is no consensus regarding specific therapy. Corticosteroids have shown conflicting results and for high dose intravenous immunoglobulins (IVIG), cost is a limiting factor. AIM: To find out the effectiveness of combination therapy with low-dose IVIG and steroids versus steroids alone in our TEN patients. METHODS: After obtaining Ethical Committee approval, 36 consecutive TEN patients (2008-2012) were alternately allocated to 2 groups - Group A was given combination of low-dose IVIG (0.2-0.5 g/kg) and rapidly tapering course of steroids (intravenous dexamethasone 0.1- 0.3 mg/kg/day tapered in 1-2 weeks) while Group B was given same dose of steroids alone. Outcome parameters assessed were time taken for arrest of disease progression, time taken for re-epithelization, duration of hospital stay and mortality rates. RESULTS: Both groups had 18 patients. Baseline characteristics like age, sex ratio, SCORTEN, body surface area involvement and treatment interval were comparable. Time for arrest of disease progression and for re-epithelization was significantly lowered in Group A (P = 0.0001, P = 0.0009 respectively). Though duration of hospital stay and deaths were less in Group A, difference was not statistically significant. SCORTEN based standardized mortality ratio (SMR) analysis revealed that combination therapy reduced the probability of dying by 82% (SMR = 0.18 ± 0.36) and steroids by 37% (SMR = 0.63 ± 0.71). Difference in SMR was statistically significant (P = 0.00001). No significant side effects due to either modality were found in any of the patients. CONCLUSION: Combination therapy with low-dose IVIG and steroids is more effective in terms of reduced mortality and faster disease resolution when compared to steroids alone in TEN.

Treatment of toxic epidermal necrolysis with intravenous immunoglobulin: a series of three cases.

Stevens-Johnson's syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening dermatoses, that lead to keratinocyte apoptosis induced by interactions between Fas (cell death receptor) and soluble Fas-ligand, present in serum of Stevens-Johnson's syndrome / toxic epidermal necrolysis patients. Anti-Fas antibodies in intravenous immunoglobulin (IVIG) would block the apoptosis cascade. Three cases of toxic epidermal necrolysis occurred in one male and two female patients, after use of allopurinol, leprosy multidrug therapy concomitant with dipyrone, and diclofenac. The cases were treated with intravenous immunoglobulin 2-3 mg/kg and prednisone 20-50 mg/day. The interruption of new lesions outbreak and reepithelization were extremely fast after the use of intravenous immunoglobulin, without adverse effects. Controlled studies are needed to confirm the efficacy of intravenous immunoglobulin in Stevens-Johnson's syndrome / toxic epidermal necrolysis, but the results seem promising.

Simultaneous occurrence of toxic epidermal necrolysis and neuroleptic malignant syndrome.

Toxic epidermal necrolysis (TEN) is an acute life-threatening blistering disease characterized by involvement of the skin, multiple mucous membranes and internal organs. It is most commonly precipitated by the administration of medications like anticonvulsants. Neuroleptic malignant syndrome (NMS) is a rare complication of neuroleptic therapy characterized by catatonic behavior, generalized muscular rigidity, hyperthermia and autonomic dysfunction. An 18-year-old girl presenting with simultaneous appearance of TEN and NMS following anti-psychotic drugs given for bipolar mood disorder, is reported for the rare association and her complete recovery.