Comparison of effectiveness of interventions in reducing mortality in patients of toxic epidermal necrolysis: A network meta-analysis.

BACKGROUND: Limited evidence is available about effectiveness and choice of immunomodulating treatment modalities for toxic epidermal necrolysis (TEN). AIMS: To compare the effectiveness of interventions to reduce mortality in patients of toxic epidermal necrolysis through network meta-analysis. METHODS: Studies were retrieved using PubMed, Google Scholar and Cochrane Database of Systematic Reviews from inception to September 18, 2018. Only English language articles were considered. Observational and randomized controlled studies having ≥ 5 TEN patients in each intervention arm were included. Two investigators independently extracted study characteristics, intervention details and mortality data. Bayesian network meta-analysis was performed using the Markov chain Monte Carlo (MCMC) approach through the random effect model. The ranking analysis was done to provide a hierarchy of interventions. The consistency between direct and indirect evidence was assessed through node spit analysis. The primary outcome was to compare the mortality [Odds ratio OR (95% credibility interval CrI)] among all treatment modalities of TEN. RESULTS: Twenty-four studies satisfying the selection criteria were included. The network analysis showed improved survival with cyclosporine as compared to supportive care [OR- 0.19 (95% CrI: 0.05, 0.59)] and intravenous immunoglobulin [OR- 0.21 (95% CrI: 0.05, 0.76)]. The hierarchy of treatments based on "surface under the cumulative ranking curves" (SUCRA) value were cyclosporine (0.93), steroid+intravenous immunoglobulin (0.76), etanercept (0.59), steroids (0.46), intravenous immunoglobulin (0.40), supportive care (0.34) and thalidomide (0.02). No inconsistencies between direct and indirect estimates were observed for any of the treatment pairs. LIMITATIONS: Evidence is mainly based on retrospective studies. CONCLUSION: The use of cyclosporine can reduce mortality in TEN patients. Other promising immunomodulators could be steroid+intravenous immunoglobulin combination and etanercept.

A systematic review of the drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Indian population.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous drug reactions. No large scale epidemiological data are available for this disorder in India. AIMS: To carry out a systematic review of the published evidence of the drug-induced SJS and TEN in Indian population. METHODS: Publications from 1995 to 2011 describing SJS and TEN in Indian population were searched in PubMed, MEDLINE, EMBASE and UK PUBMED Central electronic databases. Data were collected for the causative drugs and other clinical characteristics of SJS and TEN from the selected studies. RESULTS: From 225 references, 10 references were included as per selection criteria. The major causative drugs were antimicrobials (37.27%), anti-epileptics (35.73%) and non-steroidal anti-inflammatory drugs (15.93%). Carbamazepine (18.25%), phenytoin (13.37%), fluoroquinolones (8.48%) and paracetamol (6.17%) were most commonly implicated drugs. Regional differences were observed for fluoroquinolones, sulfa drugs and carbamazepine. Total 62.96% of patients showed systemic complications. Most common complications were ocular (40.29%) and septicemia (17.65%). Higher mortality was observed for TEN as compared to SJS (odd ratio-7.19; 95% confidence interval (CI) 1.62-31.92; p = 0.0023). Observed mortality is higher than expected as per SCORTEN score 3. Duration of hospital stay was significantly higher in TEN (20.6 days; 95% CI 14.4-26.8) as compared to SJS (9.7 days; 95% CI 5.8-13.6; p = 0.020). Cost of management was significantly higher in TEN (Rs. 7910; 95% CI 5672-10147; p < 0.0001) as compared to SJS (Rs 2460; 95% CI 1762-3158). No statistical data were described for steroid use in the studies included. CONCLUSION: Carbamazepine, phenytoin, fluoroquinolones and paracetamol were the major causative drugs. TEN is showing higher mortality, morbidity and economic burden than SJS.

SCORTEN: does it need modification?

BACKGROUND: Toxic epidermal necrolysis (TEN) is a drug induced acute life threatening condition with mortality ranging from about 15 to 60%. A 'severity of illness' score termed as SCORTEN has been developed to predict mortality in TEN cases at the time of admission. It is calculated by giving one point for each of predetermined seven variables, evaluated during first 24 hours of admission. Total score ranging from 1-7 predicts a probability of mortality from 0.03 to 0.90. AIM: A prospective study was conducted to analyze efficacy of 'SCORTEN' in TEN cases to predict mortality during their management. METHODS: All cases of TEN reporting for management to the hospital were assessed using 'SCORTEN' on day one and day five to predict probable mortality, this data was then compared with ultimate outcome. RESULTS: During the study period, we treated 10 cases of TEN, all induced by drugs, patient's age ranging from 03 to 70 years and body surface area (BSA) involvement from 10 to 95%. Three cases succumbed to death. These cases were analyzed with SCORTEN to predict probability of mortality at the time of admission and day five. We encountered some variations from the original study. It was observed that if patients are analyzed with SCORTEN on a daily/alternate day basis, it will serve as a better predictor of mortality. CONCLUSION: Body surface area (BSA) involvement and age probably need more weightage in calculations. Besides malignancy, tuberculosis and pre-existing diabetes also need to be included while predicting mortality.

Adverse cutaneous reactions to thiacetazone for tuberculosis treatment in Tanzania.

Because thiacetazone has been linked with serious adverse cutaneous reactions, we undertook 1 year of systematic surveillance for cutaneous thiacetazone-associated adverse reactions within the national tuberculosis programme of Tanzania. For individual cases, we collected information on age, sex, interval between commencing thiacetazone-containing treatment and occurrence of adverse reaction, most severe clinical presentation (toxic epidermal necrolysis, rash without necrolysis, itching without rash), and outcome (dead or alive) within 2 weeks of onset. Univariate and multivariate analyses were done of variables relevant to outcome. 1273 patients with adverse reactions were reported. The frequency of fatal outcome from any cutaneous reaction was 3.1 per 1000 among all tuberculosis patients, and 19.1% among patients with toxic epidermal necrolysis. About 60% of all adverse reactions and deaths occurred within 20 days of starting thiacetazone. Case fatality from adverse cutaneous reactions was considerably less frequent than reported previously, suggesting that improved management might allow retention of thiacetazone in the armamentarium of national tuberculosis programmes even where infection with HIV is prevalent.

PIP: Thiacetazone is a useful and inexpensive companion drug in the treatment of tuberculosis (TB). Its main contribution is its ability to prevent failure and relapse in patients with initially isoniazid-resistant strains. Early toxicity studies showed that the drug was generally better tolerated in East Africa than in many other countries. Thiacetazone is an essential drug in the Tanzania National Tuberculosis/Leprosy Program. Under trial conditions in Tanzania, before the HIV epidemic, adverse reactions associated with thiacetazone were uncommon. Serious, and occasionally fatal, toxic cutaneous reactions to sulphur-containing drugs in HIV-infected patients have been recognized for several years. Recently, the use of thiacetazone in HIV-infected patients has been linked with serious adverse cutaneous reactions, including toxic epidermal necrolysis. Most reports, however, concerned only patients admitted to referral hospitals, so the Tanzania National Tuberculosis Program began a nationwide one-year systematic surveillance study to determine the frequency and severity of adverse cutaneous reactions. Individual-level data were collected on each case's age, sex, interval between commencing thiacetazone-containing treatment and occurrence of adverse reaction, most severe clinical presentation, and outcome within two weeks of onset. The study identified 1273 patients with adverse reactions. The frequency of fatal outcome from any cutaneous reaction was 3.1 per 1000 among all tuberculosis patients and 19.1% among patients with toxic epidermal necrolysis. Approximately 60% of all adverse reactions and deaths occurred within twenty days of starting thiacetazone. Case fatality from adverse cutaneous reactions was considerably less frequent than previously reported, suggesting that improved management may allow the retention of thiacetazone as a weapon against TB even where infection with HIV is prevalent.