Steven Johnsons Syndrome SJS

Mild to moderate rash diffuse maculopapular rash with or without pruritus severe rash see section on Stevens-Johnson syndrome (SJS)... 

Statistical design, 54 Stereotypes, health-provider, 276-277 Sterilization experiments, 199 Stevens-Johnson syndrome (SJS), 93 STI-571,154... 

Steven-Johnson syndrome (SJS, erythema multiforme) and toxic epidermal necrolysis (TEN or Lyell syndrome) with apoptosis of keratinocytes and bullous detachment of the epidermis from the dermis. When more than 30% of the body surface is affected, TEN is present. Its course is dramatic and the outcome not rarely fatal. 

Adverse hypersensitivity may start 1 to 8 weeks after start of drug use and clinically display as anaphylaxis, fever, rash and various cutaneous reactions (exanthema s, bullous responses, etc.), blood dyscrasias and involve multiple internal organs, including liver, kidney and lungs (Sullivan and Shear, 2001 Gomes and Demoly, 2005). Occasionally drug hypersensitivity results in very serious and life-threatening conditions, such as Steven Johnsons Syndrome (SJS) and toxic epidermal necrolysis (TEN). 

Type IVc. T cells themselves can also act as effector cells. They migrate to the tissue and can kill tissue cells such as hepatocytes or keratinocytes in a perforin/ granzymeB- and FasL-dependent manner (Schnyder et al. 1998 Nassif et al. 2002, 2004 Kuechler et al. 2004). Such reactions occur in most drug-induced delayed hypersensitivity reactions, mostly together with other type IV reactions (monocyte, eosinophil, or neutrophil recruitment and activation). Cytotoxic T cells thus play an important role in maculopapular or bullous skin diseases as well as in conditions characterized by neutrophilic inflammation (acute generalized exanthematous pustulosis, AGEP), and in contact dermatitis. Type IVc reactions appear to be dominant in bullous skin reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), where activated CD8-t T cells kill keratinocytes (Schnyder et al. 1998 Nassif et al. 2002, 2004). They may also be the dominant cell type in hepatitis or interstitial nephritis. 

Acute generalized exanthematous pustulosis (AGEP) Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) Drag induced hypersensitivity syndrome/Drag rash with eosinophilia and systemic symptoms (DiHS/DRESS) ... 

Bullous Exanthema, Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)... 

Carbamazepine (CBZ) is a widely used anticonvulsant that can cause rashes in up to 10% of patients, and in occasional cases this may be the precursor to the development of a hypersensitivity syndrome characterized by systemic manifestations such as fever and eosinophilia (Feeder 1998 Vittorio and Muglia 1995). Rarely, CBZ can induce blistering skin reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis, two conditions associated with a high fatality rate (Rzany et al. 1999). There is now increasing laboratory evidence to show that... 

Another noteworthy adverse drug reaction (ADR) with a higher incidence in Asian patients on the anticonvulsant drugs carbamazepine and phenytoin is the Stevens-Johnson syndrome (SJS) (Locharernkul et al., 2008). SJS is a serious and potentially life-threatening skin condition. There is a conjecture that this higher risk in SJS is associated with a higher presence of the HLA-B 1502 allele in the Asian population. Phillips et al. (2011) argued that carriers of this allele could also avoid other structurally similar anticonvulsants. 

Another subdivision of type IV hypersensitivity reactions has categories distinguished by the effector cells and mediators involved together with the resulting associated cutaneous reactions. Four subdivisions are defined type IVa, mediated by monocytes with IFN-y as dominant cytokine type IVb, mediated by eosinophils with IL-5 and IL-4 involvement type IVc, mediated by T cells with perforin and granzyme B as important effector molecules and type IVd, mediated by neutrophils with IL-8 involvement. Representative skin reactions for the so-called types IVa, b, c, and d are, respectively, maculopapular rash, maculopapular rash with eosinophilia, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). 

In the Han Chinese population, genetic polymorphisms at HLA-B 1502 are associated with an increased risk for carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS), while HLA-A 3101 polymorphisms are associated with an increased risk for drug hypersensitivity to CBZ [1 ]. Studies on Caucasian populations did not consistently reproduce the same associations [2,3 ] although a more recent multiethnic study population in Canada demonstrated similar associations to those seen in the Han Chinese population In addition, HLA-A 2402 allele is linked... 

Nevirapine is a non-nucleoside reverse transcriptase inhibitor used to treat HIV-infected patients that causes mild to severe skin rash and even Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) in a substantial proportion (16%) of patients. Nevirapine also induces hepatotoxicity. These adverse clinical symptoms may also occur in non-HIV subjects taking the drug as postoperative prophylaxis [15]. 

Erythema multiforme (Stevens-Johnson syndrome, or SJ) is life-threatening and shows ocular involvement in 69% of cases (mild in 40%, moderate in 25%, and severe in 4%). Late complications can occur usually in the form of severe ocular surface disease and trichiasis. 

Parrillo SJ, Parrillo CV. Stevens-Johnson syndrome. eMedicine online 2006 . 

Current evidence suggests that cytokines play an important role in many skin ADRs (Naisbitt et al. 2007 Roychowdhury and Svensson 2005), ranging from nuld rashes to life-threatening reactions such as Steven s Johnson Syndrome (SJS) or toxic epidermal necrolysis (TEN). Skin reactions can be broadly classified into two major categories based on time-to-onset immediate (within 24 h) and delayed reactions (greater than 48 h). Because the type of immune response and the cytokines involved in immediate versus delayed skin reactions varies, each category will be discussed separately. 

Steel SJ, Moffatt JL (1954) Stevens-Johnson syndrome and granulocytopenia after phenylbutazone. Br Med J 795... 

Table 1 A comparison of patients with Stevens-Johnson syndrome or toxic epidermal necrolysis (SJS/TEN) and patients with antiepileptic drug-related hypersensitivity syndrome...

AGEP acute generalized exanthematous pustulosis, DRESS drug reaction with eosinophilia and systemic symptoms, EM erythema multiforme, FDE fixed drug eruption, niAbs monoclonal antibodies, NMBDs neuromuscular blocking drugs, NSAIDs nonsteroidal anti-inflammatory drugs, SJS Stevens-Johnson syndrome, TEN toxic epidermal necrolysis... 

SJS Stevens-Johnson syndrome, TEN tonic epidermal necrolysis... 

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