Clinic and Pathogenesis of Severe Bullous Skin Reactions: Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis

Abstract

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the most severe forms of hypersensitivity reactions affecting the skin. They are best considered severity variants of a single disease on the basis of similar pathology (epidermal necrolysis), risk factors, causes and frequent progression from SJS to TEN in a few days. Most cases occur in patients with normal metabolic pathways, after taking for a mean of 2 weeks a normal dosage of a medication for the first time. A few 'high-risk' drugs account for half of the cases of SJS as well as of TEN. Drug-specific cytotoxic T lymphocytes (hypersensitivity type IVc) induce the diffuse apoptosis of epidermal cells, probably in conjunction with amplification mechanisms not yet deciphered. Animal models point to the resemblance of epidermal necrolysis with acute graft-versus-host disease. Since mortality and morbidity of epidermal necrolysis are high, patients should be referred to specialized wards, burn units for the most severe cases. Symptomatic treatment is of tremendous importance in the absence of any intervention proven yet as capable of stopping the disease. Recent observations suggest that corticosteroids, more than highdose immunoglobulins, may deserve a formal study.

CD94/NKG2C is a killer effector molecule in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis

“…Among them, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the most severe forms of druginduced skin diseases and are now considered variants of the same disease. 2 SJS and TEN are rare diseases with a prevalence of 1 to 2 cases per million persons per year in white subjects and a mortality rate ranging from 2% to 10% in patients with SJS and 30% in patients with TEN. The most common feature of these diseases is the formation of subepidermal blisters and detachment of the epidermis, which appears as scalded skin.…”

Differential gene expression in drug hypersensitivity reactions: induction of alarmins in severe bullous diseases

“…1,2 Nowadays SJS and TEN are best considered as severity variants of a single disease. 3,4 CDHR are considered type IV hypersensitivity reactions. Phenotypic diversity of the final expression of CDHR could be explained by the involvement of a variety of cytokines, inflammatory cells and regulatory mechanisms 5 whose precise nature is unknown so far.…”

“…1,3,5,12,15 Moreover, published data show differences in gene expression intensity between benign and severe clinical entities. 11,13 In an attempt to get more insight into the molecular mechanisms involved in CDHR, we analysed the gene expression profiles of PBMCs during the acute phase and upon resolution of CDHR.…”

Treatment of osteoporosis: recognizing and managing cutaneous adverse reactions and drug-induced hypersensitivity

“…TEN and SJS require specialist care due to the epidermal detachment, with procedures paralleling those applied in the burns unit [ 21]. Systemic corticosteroids and intravenous immunoglobulins have been tried in SJS, but their use in TEN remains controversial and not recommended in the absence of randomized trial evidence [22]. The potential of intravenous immunoglobulins and other experimental treatments in the management of severe cutaneous adverse reactions is currently under investigation.…”

“…Some authors have also found promising results with intravenous IgG in TEN patients [24], but other series were inconclusive. There is not enough evidence to support the use of IgG as part of the management strategy for these patients [22,25].…”