IVIg in TEN: time to re-evaluate the efficacy of intravenous immunoglobulin in the management of toxic epidermal necrolysis
Authors: S. Walsh, D. Creamer
Journal: British Journal of Dermatology (2012)

For clinicians involved in the care of patients with toxic epidermal necrolysis (TEN) the identification of a therapeutic intervention with unequivocal benefit remains a ‘holy grail’. The mortality rate for TEN (characterized by > 30% epidermal detachment) is high – more than one in three patients perish.1 Survival of the acute episode is often followed by long-term sequelae, the most profound of which is blindness. Consequently, there is considerable impetus to uncover pathogenetic pathways in TEN which are amenable to pharmacological manipulation. In 1998, Viard et al.2 demonstrated the reversal of Fas-mediated keratinocyte apoptosis by human immunoglobulin. The in vitro studies by Viard et al.2 were accompanied by a clinical report of 10 patients with TEN treated with intravenous immunoglobulin (IVIg), all of whom responded well and survived. Since 1998, IVIg has been administered for TEN across the developed world, yielding dozens of reports indicating efficacy. However, this trend may reflect a reporting or publication bias. In addition the quality of these studies is mostly poor; the majority are case reports or uncontrolled series. There have been no controlled trials. More recently, however, scepticism surrounding the role of IVIg has surfaced, and meta-analytical methods, such as those employed by Huang et al.3 in this issue, have indicated that there is less certainty regarding the efficacy of IVIg in TEN. Assessment of TEN studies is complicated by a lack of homogeneity in many key clinical areas. Variations in disease severity, patient comorbidities, dose of IVIg and timing of IVIg administration all complicate comparison of clinical outcome in differently designed studies. However, Huang et al.’s paper3 has revealed no statistical heterogeneity for outcome, indicating that results were statistically similar enough for valid analysis of pooled mortality rates. Proponents of IVIg argue the need for high doses in TEN. In Huang et al.’s paper univariate analysis shows that high dosage in adults (>2 g kg−1) is associated with lower mortality rates, but once data are adjusted by a multivariate logistic regression model, dose no longer correlates with mortality. The benefits of supportive care in TEN also confound reported efficacy of IVIg. In some studies outcome with IVIg is compared either to historical cases or to patients receiving supportive care only. Advances in intensive care medicine have improved the calibre of supportive care; this further confounds comparison of outcomes in patients treated with IVIg and historical cases managed with supportive care alone. At a 2011 symposium devoted to severe cutaneous drug reactions, attended by 140 U.K. dermatologists, a show-of-hands poll revealed that almost all clinicians gave IVIg to their most recent case of TEN. Although the use of IVIg is supported by some published data, there may be other less tangible reasons for its use, such as a need to administer an active therapy of some sort in a clinical scenario which is acute and life-threatening. However, Huang et al.’s meta-analysis indicates a lack of clear benefit for IVIg, a message which will be echoed in the forthcoming BAD guidelines on SJS/TEN. None declared.