Macrophages and tumor necrosis factor alpha in toxic epidermal necrolysis

“…It has been suggested that several pathways are implicated in the widespread apoptosis of keratinocytes in SJS/TEN (24)(25)(26)(27). Involvement of cytotoxic T cells and the molecular cytotoxicity of Fas and cytotoxic enzymes, including granzyme B, perforin, and granulysin have been shown in SJS/TEN (25,27).…”

Section: Discussionmentioning

confidence: 99%

Severe Obliterative Bronchitis Associated with Stevens-Johnson Syndrome

et al. 2011

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We report a case of Stevens-Johnson syndrome (SJS) in which the patient had been diagnosed with severe obliterative bronchitis. A 29-year-old woman was admitted with a high fever and a widespread vesicular rash. She was diagnosed with SJS and betamethasone administration was started. After one month, her vesicular skin rash improved; however, she developed respiratory failure and was assisted with mechanical ventilation.Computed tomography of the chest demonstrated a hyperlucent lung with narrowing of the peripheral vessels. Bronchoscopy revealed an occlusion of the bronchus when the patient exhaled. The flow-volume curve revealed a severe obstructive pattern. The patient was diagnosed with obliterative bronchitis following SJS. She was treated with a bronchodilator and steroids, but could not breathe adequately without the ventilator. During the following year, her PaCO2 increased to 100 torr and her heart function also continued to worsen. Despite intensive treatment, she died one year and seven months after the onset of SJS. In SJS and toxic epidermal necrolysis (TEN) patients, chronic pulmonary complications are rare, but there is no effective therapy for obliterative bronchitis following SJS/TEN. Therefore, early awareness of this condition is needed and lung transplantation must be considered at an early stage of this disease.

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“…In keratinocytes, ROS induce IL-6, IL-8 and TNF-· production (32). Indeed, a high expression of these cytokines has been found early in the course of TEN in keratinocytes and in blister fluid (7,33,34). The production of these proinflammatory cytokines, especially TNF-· could act as an autocrine or paracrine factor to spread TEN epidermal destruction.…”

Section: Tentative Physiopathological Pathway Of Ten Epidermal Destrumentioning

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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Macrophages and tumor necrosis factor alpha in toxic epidermal necrolysis

Cited by 99 publications

References 11 publications

Cutaneous Manifestations of Diabetes Mellitus

Cutaneous Manifestations of Diabetes Mellitus

Severe Obliterative Bronchitis Associated with Stevens-Johnson Syndrome

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

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