toxic epidermolysis necrosis Students ; - Amal Aldawish - Suha Almokayid - Alaa Alenazi - Ola Wahbi - Munirah Alrubaian

background Toxic epidermal necrolysis (TEN) is a potentially life-threatening dermatologic disorder characterized by widespread erythema, necrosis, and bullous detachment of the epidermis and mucous membranes, resulting in exfoliation and possible sepsis and/or death. Mucous membrane involvement can result in gastrointestinal hemorrhage, respiratory failure, ocular abnormalities, and genitourinary complications.

pathophysiology of ten The pathophysiology of TEN has not been fully known, however various theories have received wide acceptance. 1-TEN is believed to be an immune-related cytotoxic reaction aimed at destroying keratinocytes that express a foreign antigen. 2-TEN mimics a hypersensitivity reaction, with its characteristic delayed reaction to an initial exposure and an increasingly rapid reaction with repeated exposure. 3- The widespread epidermolysis and blistering of TEN results from keratinocyte apoptosis—(an organized series of biochemical reactions leading to cell changes and cell death). 

pathophysiology of ten 4- Several immunopathologic pathways leading to keratinocyte apoptosis in TEN, including the following: A- Fas ligand activation on keratinocyte membranes leading to death receptor–mediated apoptosis  B- Release of destructive proteins (perforin and granzyme B) from cytotoxic T lymphocytes (CTLs) generated from an interaction with cells expressing major histocompatability complex (MHC) class  C- Overproduction of T cell– and/or macrophage-derived cytokines (interferon-γ [INF-γ], tumor necrosis factor-α [TNF-α], and various interleukins)  D- Drug-induced secretion of granulysin from CTLs, natural killer cells, and natural killer T cells  Precisely how the inciting agent triggers the proposed pathways is yet unknown.

Morbidity of TEN TEN is most commonly drug induced. However, the disorder has other potential etiologies, including infection, malignancy, and vaccinations. TEN is idiosyncratic, and its occurrence is not easily predicted

The estimated mortality associated with TEN varies widely in different reports, from 10-70%. Outcome depends in part on the quality of care and the rapidity with which treatment is initiated

Some believe that Stevens-Johnson syndrome is a manifestation of the same process involved in TEN, with the latter involving more extensive necrotic epidermal detachment. TEN involves more than 30% of the body surface, whereas SJS involves less than 10% 

toxic epidermolysis necrosis prognosis Score 0-1 – 3.2% mortality 2 – 12.2% mortality 3 – 35.3% mortality 4 – 58.3% mortality ≥5 – 90% mortality

mortality and morbidity of ten Mortality rates in children are much lower than in adults Septicemia and multisystem organ failure are the primary causes of death. Epithelial loss results in vulnerability to bacterial and fungal infections. Sloughing of stratified epithelium of mucosal membranes can result in GI hemorrhage, respiratory failure, Ocular abnormalities, and genitourinary lesions. Significant fluid loss from extensive skin exfoliation and an inability to tolerate oral intake can lead to hypovolemia, acute tubular necrosis, and shock.

management of toxic epidermolysis necrosis

management of ten The mainstay of treatment is supportive care until the epithelium regenerates. Supportive measures includes; Isolation Fluid and electrolyte balance Nutritional support Pain management Protective dressings Then early transfer of patients to a burn or intensive care unit to reduce the risk of infection .

pre-hospital care of ten - Supplement with oxygen by face-mask as needed - Prevent hypothermia with rewarming devices and blankets. - In severe TEN, contamination and evaporation must be minimized. - application of sterile coverings. - Fluid and pulmonary status must be carefully monitored.

emergency department care of ten Maintaining fluid and electrolyte homeostasis Mitigating temperature loss Providing adequate analgesia Preventing secondary infection

treatment of ten No specific treatment modality has been proven effective, but the following thought to be effective: Plasmapheresis Corticosteroids Cyclophosphamide Cyclosporine Tumor necrosis factor–alpha (TNF-alpha) inhibitors Intravenous immune globulin (IVIg)

Questions? References: http://emedicine.medscape.com/article/229698-treatment#d11 hopkinsmedicine.org