Recent Therapeutic Advances in Dermatology

Lipper, Graeme; Arndt, Kenneth A.; Dover, Jeffrey S.

doi:10.1001/jama.283.2.175

Cited by 15 publications

(4 citation statements)

References 19 publications

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“…SCORTEN has been shown to be effective in predicting mortality rates in patients with TEN based on 7 independent risk factors (age, Ͼ40 years; presence of malignancy; body surface area involved, Ͼ10%; serum urea nitrogen level, Ͼ28 mg/dL [Ͼ10 mmol/L]; glucose level, 3 ] level, Ͻ20 mEq/L [Ͻ20mmol/L]; and heart rate, Ͼ120 beats per minute within the first 24 hours of admission). 9 The mortality rate for patients is based on the number of risk factors each patient has.…”

Section: Commentmentioning

confidence: 99%

“…1 In a large case-controlled study, the drugs most commonly associated with TEN were found to be sulfonamides, anticonvulsant agents, allopurinol, and oxicam nonsteroidal anti-inflammatory drugs. 1,3 There is also substantial association with antibiotics such as cephalospor-ins, quinolones, aminopenicillins, tetracyclines, and imidazole antifungal agents. Recently, a study suggested that the sooner the drug treatment was halted, the fewer skin lesions would occur, and consequently the lower the mortality rate would be.…”

Section: Commentmentioning

confidence: 99%

“…OXIC EPIDERMAL necrolysis (TEN) is a rare, life-threatening condition, the result of a hypersensitivity reaction to various drugs. [1][2][3] The incidence of TEN varies between 0.4 and 1.2 cases per million per year, and more than 100 different drugs have been associated with TEN. 1 The mortality rate associated with TEN varies from 15% to 40%, with a large portion of patients dying from infections or multiorgan failure.…”

mentioning

confidence: 99%

“…1 The mortality rate associated with TEN varies from 15% to 40%, with a large portion of patients dying from infections or multiorgan failure. [2][3][4] Toxic epidermal necrolysis often begins with symptoms of fever, sore throat, and burning eyes, usually 1 to 3 days prior to any cutaneous lesions. 4 The cutaneous signs emerge as poorly defined erythematous macules with darker purpuric centers that tend to merge and cause extensive epidermal necrosis and detachment (Figure).…”

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confidence: 99%

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Analysis of Intravenous Immunoglobulin for the Treatment of Toxic Epidermal Necrolysis Using SCORTEN

Trent¹,

Kirsner²,

Romanelli³

et al. 2003

Arch Dermatol

208

122

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Background: Toxic epidermal necrolysis (TEN) is a rare, life-threatening condition caused by certain medications. Keratinocytes affected by TEN have been found to undergo apoptosis mediated by Fas-FasL interactions. Treatment with intravenous immunoglobulin (IVIG) has been proposed to inhibit this interaction.Objective: To demonstrate the effectiveness of IVIG therapy in reducing mortality in patients with TEN.Design: A retrospective analysis of 16 consecutive patients with TEN who were treated with IVIG. The SCORTEN system, a validated predictor of TEN mortality, was used to analyze the data of these patients. Using SCORTEN, we compared the predicted mortality of our patient population with observed mortality.Setting: Dermatology inpatient unit at a universityaffiliated hospital.Intervention: All 16 patients received IVIG treatment daily for 4 days. Fifteen patients received 1 g/kg per day and 1 patient received 0.4 g/kg per day.Main Outcome Measures: For each patient, causes of TEN and other medical problems were documented prior to IVIG therapy, as were the 7 independent SCORTEN risk factors.Results: One patient died. Based on the SCORTEN system, 5.81 patients were expected to die. These mortality rates were compared using the standardized mortality ratio (SMR) analysis ([⌺ observed deaths/⌺ expected deaths] ϫ 100) to determine the efficacy of this treatment, which showed that patients with TEN treated with IVIG were 83% less likely to die than those not treated with IVIG (SMR = 0.17; 95% confidence interval, 0.0-0.96). Conclusion:Based on comparison of our observed mortality rate with the SCORTEN-predicted mortality rate, treatment with IVIG significantly decreased mortality in patients with TEN.

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Section: Commentmentioning

confidence: 99%

Section: Commentmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Analysis of Intravenous Immunoglobulin for the Treatment of Toxic Epidermal Necrolysis Using SCORTEN

Trent¹,

Kirsner²,

Romanelli³

et al. 2003

Arch Dermatol

208

122

View full text Add to dashboard Cite

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Drug Hypersensitivity Reactions Involving Skin

Hausmann¹,

Schnyder²,

Pichler

2009

Handbook of Experimental Pharmacology

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Immune reactions to drugs can cause a variety of diseases involving the skin, liver, kidney, lungs, and other organs. Beside immediate, IgE-mediated reactions of varying degrees (urticaria to anaphylactic shock), many drug hypersensitivity reactions appear delayed, namely hours to days after starting drug treatment, showing a variety of clinical manifestations from solely skin involvement to fulminant systemic diseases which may be fatal. Immunohistochemical and functional studies of drug-specific T cells in patients with delayed reactions confirmed a predominant role for T cells in the onset and maintenance of immune-mediated delayed drug hypersensitivity reactions (type IV reactions). In these reactions, drug-specific CD4+ and CD8+ T cells are stimulated by drugs through their T cell receptors (TCR). Drugs can stimulate T cells in two ways: they can act as haptens and bind covalently to larger protein structures (hapten-carrier model), inducing a specific immune response. In addition, they may accidentally bind in a labile, noncovalent way to a particular TCR of the whole TCR repertoire and possibly also major histocompatibility complex (MHC)-molecules - similar to their pharmacologic action. This seems to be sufficient to reactivate certain, probably in vivo preactivated T cells, if an additional interaction of the drug-stimulated TCR with MHC molecules occurs. The mechanism was named pharmacological interaction of a drug with (immune) receptor and thus termed the p-i concept. This new concept may explain the frequent skin symptoms in drug hypersensitivity to oral or parenteral drugs. Furthermore, the various clinical manifestations of T cell-mediated drug hypersensitivity may be explained by distinct T cell functions leading to different clinical phenotypes. These data allowed a subclassification of the delayed hypersensitivity reactions (type IV) into T cell reactions which, by releasing certain cytokines and chemokines, preferentially activate and recruit monocytes (type IVa), eosinophils (type IVb), or neutrophils (type IVd).

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