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Systematic review

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The Effect of Intravenous Immunoglobulin Combined with Corticosteroid on the Progression of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Meta-Analysis.

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Authors Ye LP , Zhang C , Zhu QX
Journal PloS one
Year 2016
Links Pubmed DOI PubMed Central

This article includes 18 Primary studies 18 Primary studies (18 references)

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BACKGROUND: Intravenous immunoglobulin (IVIG) treatment is commonly used to treat Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with controversial therapeutic effect. METHODS: We conducted a comprehensive meta-analysis through combining the published eligible studies to evaluate the effectiveness of IVIG on SJS and TEN treatment. RESULTS: A total of 26 studies were selected from public available databases. The combination of IVIG and corticosteroid markedly reduced the recovery time (by 1.63 days, 95% CI: 0.83-2.43, P < 0.001), compared with solo corticosteroid group. The favorable effects were greater in Asian (2.19, 95% CI: 1.41-2.97, P < 0.001), TEN (2.56, 95% CI: 0.35-4.77, P = 0.023) and high-dose IVIG treated individuals (1.78, 95% CI: 0.42-3.14, P = 0.010). The hospitalization length reduced by 3.19 days (95% CI: 0.08-6.30, P = 0.045), though the outcome was proven to be unstable. We found heterogeneities, which sources were probably regional factors. Besides, IVIG was inclined to decrease SJS/TEN mortality (SMR 0.84, 95% CI: 0.66-1.08, P = 0.178). This impact was possibly more profound when patients were treated with high dose IVIG (SMR 0.74, 95% CI: 0.50-1.08, P = 0.116), or when patients were diagnosed as TEN (SMR 0.68, 95% CI: 0.45-1.01, P = 0.058). CONCLUSIONS: Our current meta-analysis suggests that IVIG combined with corticosteroid could reduce recovery time for SJS and TEN. This effect is greater among Asian patients. Whereas, its impact on reducing mortality is not significant.

Systematic review

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Intravenous immunoglobulin in the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis: a meta-analysis with meta-regression of observational studies.

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Journal International journal of dermatology
Year 2015
Links Pubmed DOI

This article is included in 1 Broad synthesis 13 Broad syntheses (1 reference)

This article includes 13 Primary studies 13 Primary studies (13 references)

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BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe disorders with significant morbidity and mortality. The therapeutic use of intravenous immunoglobulin (IVIG) is based on limited data. OBJECTIVES: This systematic review evaluates the existing literature to determine if IVIG impacts the standardized mortality rate (SMR) in patients with SJS or TEN. METHODS: The MEDLINE database was searched for the period 1966-2011 for pertinent studies. The bibliographies of selected references were also reviewed for additional studies. Inclusion criteria required the studies to refer to patients who received IVIG for SJS or TEN, the severity of which was determined using the SCORTEN system. Thirteen studies were used in the final analysis. Demographic data, IVIG dosing, SCORTEN score, and mortality rates were extracted. RESULTS: Of the 13 studies, eight included a control group. Meta-analysis revealed that differences in SMRs were not significant (-0.322, 95% confidence interval [CI] -0.766 to 0.122; P = 0.155). The overall SMR point estimate for all 13 studies was 0.814 (95% CI 0.617-1.076). Meta-regression demonstrated a strong inverse correlation between IVIG dosage and SMRs (slope: -0.59, 95% CI -0.14 to -1.03; P = 0.009). CONCLUSIONS: Intravenous IG at dosages of ≥2 g/kg appears to significantly decrease mortality in patients with SJS or TEN.

Systematic review

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The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis: a systematic review and meta-analysis.

Authors Huang YC , Li YC , Chen TJ
Journal The British journal of dermatology
Year 2012
Links Pubmed DOI

This article is included in 1 Broad synthesis 17 Broad syntheses (1 reference)

This article includes 17 Primary studies 17 Primary studies (17 references)

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BACKGROUND: Quantitative analysis of intravenous immunoglobulin (IVIg) treatment against toxic epidermal necrolysis (TEN) is lacking. OBJECTIVES: To provide a meta-analysis evidence-based examination of IVIg efficacy against TEN. METHODS: A systematic review and meta-analysis of literature published before 31 July 2011 was conducted. In observational controlled studies with at least eight patients with TEN receiving IVIg treatment, a pooled estimate of mortality risk was determined, comparing IVIg and supportive care. Statistical analyses were performed on raw data to compare the clinical differences between (i) high-dose and low-dose IVIg treatment in adult patients and (ii) paediatric and adult patients treated with IVIg. RESULTS: Seventeen studies met inclusion criteria. Overall mortality rate of patients with TEN treated with IVIg was 19.9%. The pooled odds ratio (OR) for mortality from six observational controlled studies comparing IVIg and supportive care was 1.00 [95% confidence interval (CI) 0.58-1.75; P=0.99]. The pooled OR for mortality in patients treated with high-dose IVIg vs. supportive care was 0.63 (95% CI 0.27-1.44; P=0.27). Adults treated with high-dose IVIg exhibited significantly lower mortality than those treated with low-dose IVIg (18.9% vs. 50%, respectively; P=0.022); however, multivariate logistic regression model adjustment indicated that IVIg dose does not correlate with mortality (high vs. low dose: OR 0.494; 95% CI 0.106-2.300; P=0.369). Paediatric patients treated with IVIg had significantly lower mortality than adults (0% vs. 21.6%; P=0.001). CONCLUSIONS: Although high-dose IVIg exhibited a trend towards improved mortality and children treated with IVIg had a good prognosis, the evidence does not support a clinical benefit of IVIg. Randomized controlled trials are necessary.

Systematic review

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Systematic review of treatments for Stevens-Johnson syndrome and toxic epidermal necrolysis using the SCORTEN score as a tool for evaluating mortality.

Journal Therapeutic advances in drug safety
Year 2011
Links Pubmed DOI PubMed Central

This article is included in 1 Broad synthesis 13 Broad syntheses (1 reference)

This article includes 13 Primary studies 13 Primary studies (13 references)

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Epidermal necrolysis, whether involving limited, that is, Stevens-Johnson syndrome (SJS), or large, that is, toxic epidermal necrolysis (TEN), areas of the skin surface, is associated with high mortality. A specific prognosis score (SCORTEN) accurately predicts mortality. Management of SJS and TEN mainly relies on supportive care but several treatments have been proposed, particularly corticosteroids and intravenous immunoglobulins (IVIG), to block the progression of the disease. The aim of this study was a pooled analysis of published series addressing the question of treatment efficacy by comparing the mortality observed to the mortality predicted by the SCORTEN score. A literature search was carried out through PubMed from January 2001 to December 2009. It found 47 original series including at least 10 patients. Among these, 13 containing a clear description of treatment(s) and an evaluation of SCORTEN score were analyzed allowing the calculation of a mortality ratio (MR) for each series and a pooled MR with 95% confidence interval (CI) for each treatment. The analyzed series comprised a total of 439 patients. Supportive care was used only in 199 patients with a pooled MR of 0.89 (CI 0.67-1.16, p = 0.43), corticosteroids were administered to 78 patients with a pooled MR of 0.92 (CI 0.53-1.48, p = 0.84), and IVIG in 162 with a pooled MR of 0.82 (CI 0.58-1.12, p = 0.23). In conclusion, even though this analysis had some limitations, it strongly suggested that neither corticosteroids nor IVIG provide any important reduction in the risk of dying from SJS and TEN.

Systematic review

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A systematic review of treatment of drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in children.

Journal Journal of population therapeutics and clinical pharmacology = Journal de la thérapeutique des populations et de la pharamcologie clinique
Year 2011
Links Pubmed

This article is included in 2 Broad syntheses 29 Broad syntheses (2 references)

This article includes 29 Primary studies 29 Primary studies (29 references)

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Stevens-Johnson (SJS) and Toxic Epidermal Necrolysis (TEN) are two uncommon mucocutaneous diseases usually considered as severe drug reactions and are characterized by different grades of epidermal necrosis. Several treatment modalities have been proposed with variable results but the lack of controlled studies makes difficult to analyze them objectively especially in children. All publications describing management for SJS and TEN in children were searched in MEDLINE, EMBASE, and the Cochrane Library. Reports included were divided in two categories: A, studies with 5 or more patients and observational studies; and B, reports with less than 5 patients. A formal meta-analysis was not feasible. Description was made using central tendency measures. From 1389 references only 31 references with a total of 128 cases were included, 88 category A and 40 category B. The 4 main treatment modalities were: intravenous immunoglobulin (IVIG), steroids (prednisolone, methylprednisolone, dexamethasone), dressings with or without surgical debridement, and support treatment alone. Miscellaneous treatments: Of 12 patients, 3 received ulinastatin, 4 patients plasmapheresis, 2 patients IV pentoxifylline and the last three patients received different treatment each (cyclosporine, methylprednisone/G-CSF and methylprednisolone/IVIG). Patients receiving IVIG and steroids showed similar findings while patients treated with dressing and support treatment alone, reported both longer time to achieve remission and hospitalization stays and appear to be associated with more complications and deaths. There is scant quality literature about management of SJS and TEN in children. Steroids and IVIG seem to improve the outcome of SJS and TEN patients but results from different reports are variable. Patients treated only with care support seem to have higher morbidity and mortality. Further studies are necessary to define optimal management.

Systematic review

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Treatment of epidermal necrolysis with high-dose intravenous immunoglobulins (IV Ig): clinical experience to date.

Authors Faye O , Roujeau JC
Journal Drugs
Year 2005
Links Pubmed DOI

This article is included in 1 Broad synthesis 9 Broad syntheses (1 reference)

This article includes 9 Primary studies 9 Primary studies (9 references)

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High-dose human intravenous immunoglobulins (IV I ) have now been used as a treatment for epidermal necrolysis for several years. We have reviewed all series involving more than nine patients treated with high-dose IV Ig for toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome (SJS) published in indexed journals. Nine series included a total of 156 patients; among the 156 reported cases, 32 patients died (20.5%). When the analysis was restricted to the five series that included some comparison with expected deaths, the mortality rate observed in patients treated with IV Ig was 27% versus an expected rate of 30%. Because of high diversity in study designs and dosages of IV Ig used, and because several series included duplicate cases, it was not possible to make more detailed statistical analyses, including individual prognostic factors and IV Ig dosages. In the absence of randomised controlled trials, this review does not provide a definite conclusion on the usefulness of IV Ig in SJS or TEN; however, the analysis of published data does not suggest a dramatic efficacy. We conclude that, in the absence of further studies, IV Ig cannot yet be considered the standard of care for SJS or TEN.