Toxic epidermal necrolysis treated with N-acetylcysteine

Vélez, Antonio; Moreno, José-Carlos

doi:10.1067/mjd.2002.118557

Cited by 45 publications

(33 citation statements)

References 12 publications

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“…NAC also increases the clearance of several drugs and their metabolites. Only a few patients have been treated with high-dose intravenous NAC in open studies, with an apparent clinical effectiveness [93, 94]. However, a randomized trial has shown a lack of effectiveness of NAC in the prevention of hypersensitivity reactions to trimethoprim-sulfamethoxazole in patients with HIV infection [48].…”

Section: Ten Treatmentsmentioning

confidence: 99%

Novel Treatments for Drug-Induced Toxic Epidermal Necrolysis (Lyell’s Syndrome)

Paquet

Pierard

Quatresooz³

2005

Int Arch Allergy Immunol

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Drug-induced toxic epidermal necrolysis (TEN) is a life-threatening disease characterized by extensive destruction of the epidermis. It apparently results from the formation of specific toxic drug metabolites by the keratinocytes. The mortality rate which averages 25–30% is mainly due to secondary septicemia, and to ionic and metabolic disturbances following loss of epidermal integrity. Apoptosis is the likely mechanism leading to massive keratinocyte death in TEN. Dysregulations in the tumor necrosis factor-α (TNF-α) pathway, CD95 system (Fas ligand, CD95L; Fas receptor, CD95R) and calcium homeostasis in the epidermis are involved in this apoptotic process. An active role has also been ascribed to T lymphocytes, macrophages and factor XIIIa-positive dermal dendrocytes. Despite progress, treatment of TEN remains controversial. In the past, systemic glucocorticoids were used in order to target the inflammatory reaction in TEN. However, there was no evidence for improvement of the healing process, while corticosteroids worsened the prognosis by increasing the risk of septicemia. Only a few cases have been treated with other drugs including cyclophosphamide, pentoxyfilline, thalidomide, anti-TNF-α antibodies and cyclosporin A. In the recent past, some TEN patients were treated with intravenous human immunoglobulins (IVIG). The rationale for such a treatment was to block the CD95 system on keratinocytes. The early promising clinical results of IVIG treatment in TEN were subsequently challenged. This review compares the effectiveness and drawbacks of the major drugs presently used in TEN treatment. Some future prospects in TEN management are also discussed.

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Section: Ten Treatmentsmentioning

confidence: 99%

Novel Treatments for Drug-Induced Toxic Epidermal Necrolysis (Lyell’s Syndrome)

Paquet

Pierard

Quatresooz³

2005

Int Arch Allergy Immunol

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“…It has been clinically demonstrated that the prompt withdrawal of the culprit drug is associated with a better prognosis in TEN (44). In addition, some chemical agents like N-acetylcysteine may be useful in the treatment of TEN because they react with oxidative compounds and replenish intracellular cysteine levels necessary for the production of GSH (45,46). Conversely, treatments that only block the activities of the proinflammatory cytokines and receptors produced in TEN, without acting on the deregulation of the electron transport chain in mitochondriae will probably have a limited effect on the course of TEN.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

Toxic epidermal necrolysis: Revisiting the tentative link between early apoptosis and late necrosis (Review)

Paquet

Pierard

2007

Int J Mol Med

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Abstract. Toxic epidermal necrolysis (TEN) is a dramatic drug-induced reaction that may lead to full destruction of the epidermis and epithelial mucosae. The keratinocytes themselves seem to play a major role in the pathogenic mechanism. Biochemical and morphological studies performed on early epidermal lesions demonstrated that keratinocytes undergo apoptosis, but histological and clinical data show evidence of necrosis of the epidermis later in the disease evolution. Based on the limited information currently available about TEN pathomechanism, we present a 'mitochondrial hypothesis' that may explain both early apoptosis and late necrosis in TEN epidermis. Strong electrophilic drug metabolites are generated in TEN-affected keratinocytes due to an impaired detoxication pathway. These compounds presumably disrupt the electron transfer chain in the mitochondriae resulting in a decline in ATP production, loss of electrochemical gradient across the inner membrane (Δψm), and partial reduction in O 2 with production of reactive oxygen species (ROS). The latter compounds directly damage cell membranes and act as intracellular chemical messengers stimulating proapoptotic systems such as CD95 and TNF-·, which in turn can activate nitric oxide (NO) metabolism. NO interacts with ROS to enhance their toxic effects. These proapoptotic events represent swift processes in the involved cells. The loss of Δψm and the opening of permeability transition pores in the mitochondrial membrane lead to osmotic swelling and rupture of these organelles with subsequent necrosis of the cell. The necrotic events follow apoptosis when both phenomena are present.

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“…Administration of N-acetylcysteine enhances the oxidant buffering capacity of glutathione, which enhances the detoxification of a range of drugs, as well as inhibiting NF-ĸB. Two case reports have shown a beneficial response but larger studies are clearly required before it is readily applied in clinical practice [174], [175].…”

Section: N-acetylcysteinementioning

confidence: 99%

Severe Cutaneous Adverse Reactions

Fernando¹

2013

Skin Biopsy - Diagnosis and Treatment

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Toxic epidermal necrolysis treated with N-acetylcysteine

Cited by 45 publications

References 12 publications

Novel Treatments for Drug-Induced Toxic Epidermal Necrolysis (Lyell’s Syndrome)

Novel Treatments for Drug-Induced Toxic Epidermal Necrolysis (Lyell’s Syndrome)

Toxic epidermal necrolysis: Revisiting the tentative link between early apoptosis and late necrosis (Review)

Severe Cutaneous Adverse Reactions

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