Toxic epidermal necrolysis (TEN; Lyell syndrome)/ Stevens–Johnson syndrome (SJS)

Version: 2.1
Published: 06 July 2016
Condition for which Ig has an emerging therapeutic role.

This medical condition has either been superseded or has become inactive
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Specific Conditions
  • Toxic epidermal necrolysis/Stevens–Johnson syndrome
Indication for Ig Use
  • To limit progression of TEN or SJS/TEN when administered in early stages.
Level of Evidence Insufficient data (Category 4a)
Description and Diagnostic Criteria Toxic epidermal necrolysis (TEN) is a rare, life-threatening hypersensitivity reaction to certain medications, such as sulphonamides, antibiotics, non-steroidal anti-inflammatory drugs and anti-convulsants. Drug-induced epidermal apoptosis has been proposed as possible pathogenesis. Stevens–Johnson syndrome (SJS) is a less extensive manifestation of the same phenomenon.

TEN and SJS are characterised by severe bullous reaction, with extensive destruction of the epidermis, and morphologically by ongoing apoptotic keratinocyte cell death that results in the separation of the epidermis from the dermis.

The term SJS is now used to describe patients with blistering and skin detachment involving a total body surface area of <10%. SJS/TEN describes patients with 10–30% detachment, and TEN describes patients with >30% skin detachment.
 
Justification for Evidence Category The Biotext (2004) review identified one small cohort study (20 patients) without a control group, which found that there appeared to be no significant effect from intravenous immunoglobulin (IVIg) therapy and that the death rate seemed to be higher than had been previously reported.

The Frommer and Madronio (2006) review found one small randomised study (four patients) with a control group of two patients (supportive care only). This study found that there was some improvement in epithelialisation and prominent difference in CD95 receptor between treated patients and controls. However, neither IVIg nor its comparison group could completely stop the TEN process.
Diagnosis Requirements

A diagnosis must be made by a Dermatologist.
Qualifying Criteria for Ig Therapy
  • TEN or SJS/TEN overlap with body surface area (erythema and/or erosions) of 10% or more.
  • AND
  • Evidence of rapid evolution.
     
IVIg should be initiated as early as possible, preferably within 24 hours of diagnosis.

Urgent skin biopsy should be performed for confirmation, but should not delay IVIg therapy if indicated.

The Adverse Drug Reactions Advisory Committee should be notified of the inciting medication.
Exclusion Criteria SJS alone.
Review Criteria for Assessing the Effectiveness of Ig Use
Clinical effectiveness of Ig therapy may be demonstrated by:
  • Clinical assessment one month after immunoglobulin treatment.
Dose
  • Dose (IVIg) - 2 g/kg as a single dose, or divided over three consecutive days.

Dosing above 1 g/kg per day is contraindicated for some IVIg products.

The aim should be to use the lowest dose possible that acheives the appropriate clinical outcome for each patient.

Refer to the current product information sheet for further information.
Bibliography
Bachot, N, Revuz, J & Roujeau, JC 2003, ‘Intravenous immunoglobulin treatment for Stevens–Johnson syndrome and toxic epidermal necrolysis: a prospective non-comparative study showing no benefit on mortality or progression’ (comment), Archives of Dermatology, vol. 139, no. 1, pp. 85–6.

Biotext 2004, ‘Summary data on conditions and papers’, in A systematic literature review and report on the efficacy of intravenous immunoglobulin therapy and its risks, commissioned by the National Blood Authority on behalf of all Australian Governments, pp. 242–7. Available from: http://www.nba.gov.au/pubs/pdf/report-lit-rev.pdf.

Campione, E, Marulli, GC, Carrozzo, AM, et al 2003, ‘High-dose intravenous immunoglobulin for severe drug reactions: efficacy in toxic epidermal necrolysis’, Acta Dermato-venereologica, vol. 83, no. 6, pp. 430–2.

Frommer, M & Madronio, C 2006, The use of intravenous immunoglobulin in Australia. A report for the National Blood Authority, Part B: systematic literature review, Sydney Health Projects Group, University of Sydney, Sydney, pp. 55–6.

Paquet, P, Jacob, E, Damas, P, et al 2005, ‘Analytical quantification of the inflammatory cell infiltrate and CD95R expression during treatment of drug-induced toxic epidermal necrolysis’, Archives of Dermatological Research, vol. 297, no. 6, pp. 266–73.

Prins, C, Vittorio, C, Padilla, RS, et al 2003, ‘Effect of high-dose intravenous immunoglobulin therapy in Stevens–Johnson syndrome: a retrospective, multicentre study’, Dermatology, vol. 207, no. 1, pp. 96–9.

Trent, J, Halem, M, French, LE, et al 2006, ‘Toxic epidermal necrolysis and intravenous immunoglobulin: a review’, Seminars in Cutaneous Medicine and Surgery, vol. 25, no. 2, pp. 91–3.