Abstract

Background

Toxic epidermal necrolysis is a rare condition where a drug reaction induces skin loss, similar to that seen in extensive burns. It is associated with high morbidity and mortality and there is no clear agreement on effective treatment.

Objectives

To assess the effects of all interventions for the treatment of toxic epidermal necrolysis.

Search methods

We searched the Cochrane Skin Group Specialised Register (March 2001), the Cochrane Controlled Trials Register (March 2001), MEDLINE (1966 to December 2001), EMBASE (1980 to December 2001), DARE (4th Quarter 2001) and CINAHL (1982 to October 2001).

Selection criteria

Randomised controlled trials of therapeutic and supportive interventions that included participants clinically diagnosed with toxic epidermal necrolysis were included.

Data collection and analysis

Two independent authors carried out study selection and assessment of methodological quality.

Main results

Only one randomised controlled trial of treatment was identified. This trial compared the effectiveness of thalidomide with placebo and included 22 patients, 12 in the treatment group and 10 in the placebo group. Patients on the treatment arm received thalidomide 200 mg twice daily for 5 days. The main end point was the measurement of the progression of skin detachment after seven days. Other end points were the overall mortality and severity of the disease evaluated with the simplified acute physiology score. The study was terminated as the mortality on the treatment arm was 83% compared to 30% on the control arm (relative risk 2.78, 95% confidence interval 1.04 to 7.40).- No randomised controlled trials of the most commonly used current treatments i.e. systemic steroids, cyclosporin A and intravenous immunoglobulins were found.

Authors' conclusions

Treatment with thalidomide was not shown to be effective and was associated with significantly higher mortality than placebo. There is no reliable evidence on which to base treatment for toxic epidermal necrolysis, a disease commonly associated with mortality rates of around 30%. More research is required to understand the mechanisms of toxic epidermal necrolysis. International multi‐centre studies are needed in the form of randomised controlled trials, to evaluate treatments for toxic epidermal necrolysis, especially those using high doses of steroid and intravenous immunoglobulins.

Author(s)

Samit Majumdar, Maja Mockenhaupt, Jean‐Claude Roujeau, Askari P Townshend

Abstract

Plain language summary

Interventions for toxic epidermal necrolysis

Toxic epidermal necrolysis (TEN or Lyell's disease) is a rare life‐threatening skin condition. It is probably an immune response triggered by some drugs or infection, which is more likely to happen in people with suppressed immunity. TEN causes extensive blistering and shedding of skin, similar to burns. Drugs used include oral steroids, thalidomide, immunosuppressants and immunoglobulins. This review of trials did not find any reliable evidence for the treatment of TEN. The only trial available used thalidomide, but this trial did not show any benefit from treatment compared against placebo but highlighted increased chances of dying from the treatment. Thalidomide is not safe or effective for the skin condition toxic epidermal necrolysis, but there is not enough evidence to show which treatments are effective.

Author(s)

Samit Majumdar, Maja Mockenhaupt, Jean‐Claude Roujeau, Askari P Townshend

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

Only one RCT looking at effectiveness of treatments for TEN was available. Thalidomide treatment was not shown to be effective and was associated with significantly high mortality. There is no reliable evidence on commonly used interventions, such as systemic steroids, immunoglobulins and cyclosporin A, for treating TEN, a disease associated with high mortality.

Implications for research 

More research is required to determine the exact pathophysiology of TEN. Multi‐centre, carefully designed, randomised controlled trials are needed, especially to evaluate the effects of treatment with high‐dose oral steroids and intravenous immunoglobulins compared against best supportive care. Comparison of standard supportive care in an acute hospital versus care in a special burns unit might also be worthwhile especially if the components of these complex interventions can be adequately defined. Other interventions that might improve prognosis such as early withdrawal of the suspected drug, types of skin care dressing and the role of infection prophylaxis are worthy of further study. Such trials need to take into account the variable severity of the condition as baseline severity may be the largest predictor of outcome. Other research could focus on the management of people who survive the acute phase e.g. by evaluating the impact of different educational strategies for subsequent medication use and modalities to prevent long term complications such as ocular scarring.

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