Use of intravenous immunoglobulin in toxic epidermal necrolysis and Stevens–Johnson syndrome: Our current understanding

https://doi.org/10.1016/j.intimp.2005.11.012Get rights and content

Abstract

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN, Lyell's disease, syndrome) are considered to be part of a spectrum of adverse cutaneous drug reactions with increasing severity and extent of skin detachment, ranging from SJS (less than 10% body surface area skin detachment, 1–5% mortality) to TEN (greater than 30% skin detachment, 25–35% mortality).

Both SJS and TEN are characterized morphologically by ongoing apoptotic keratinocyte cell death that results in the separation of the epidermis from the dermis. Recent evidence is supportive of a role for the death receptor Fas and its ligand FasL, in the pathogenesis of keratinocyte apoptosis during TEN. This Fas-mediated keratinocyte apoptosis that causes epidermal detachment in TEN can be inhibited in vitro by antagonistic monoclonal antibodies to Fas and by intravenous immunoglobulins (IVIG) which have been shown to contain natural anti-Fas antibodies.

Over the last 6 years, numerous case reports and 8 non-controlled clinical studies containing 9 or more patients have analyzed the therapeutic effect of IVIG in TEN. Taken together, although each study has its potential biases, 6 of the 8 studies point towards a benefit of IVIG used at doses greater than 2 g/kg on the mortality associated with TEN. Hopefully, these studies will serve as the basis for designing a prospective controlled trial in the near future; as such, an approach appears the only way to definitively determine the therapeutic potential of IVIG in TEN.

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Summary

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe adverse drug reactions characterized by a low incidence but high mortality. The incidence of SJS is approximately 6 cases per million persons per year, and that of TEN is approximately 2 cases per million persons per year [1]. However, SJS and TEN are idiosyncratic in nature and thereby have the potential to affect any individual taking a medication; the most frequently incriminated drugs being antibiotics,

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    However, the effect of IVIG is still controversial.31,32 In 2006, French et al. summarized the clinical studies reported and suggested that the use of more than 2 g/kg of body weight of intravenous immunoglobulin is beneficial on the mortality associated with TEN.9 Barron et al.33 conducted a meta-analysis with meta-regression of 13 observational studies conducted during the period of 1966–2011 to assess IVIG in the treatment of SJS/TEN based on the SCORTEN scoring system.

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    Since then, the use of IVIG has become more frequent in the treatment of TEN. A meta-analysis of nine studies evaluating the impact of IVIG on mortality concluded that at high doses of IVIG (>2 g/kg) a 59% reduction between expected and observed mortality rate was detected, compared to a 3% reduction in low doses of IVIG [56]. Considering the studies included in this review, we noted a rise in the use of IVIG since 1999.

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