Toxic epidermal necrolysis: Effector cells are drug-specific cytotoxic T cells

Nassif, Amal; Bensussan, Armand; Boumsell, Laurence; Deniaud, Aurélien; Moslehi, Homayoun; Wolkenstein, Pierre; Bagot, Martine; Roujeau, Jean‐Claude

doi:10.1016/j.jaci.2004.07.047

Cited by 360 publications

(306 citation statements)

References 21 publications

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“…[4][5][6] More recently, several lines of evidence have accumulated to show that the final steps of the adverse drug reaction depend on an immunological process, that seems directed against the parent form of the drug more often than against a metabolite. 7 Azukizawa et al 8 generated transgenic mice in which ovalbumin was specifically expressed in keratinocytes. Transfer of ovalbumin-specific CD8 þ T cells into these transgenic mice resulted in rapid proliferation of these cells in lymph nodes and migration to the skin leading to a degeneration of the epidermis and hair follicles, which was reminiscent of TEN.…”

Section: Introductionmentioning

confidence: 99%

A marker for Stevens-Johnson syndrome …: ethnicity matters

Thomas²,

et al. 2006

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Section: Introductionmentioning

confidence: 99%

A marker for Stevens-Johnson syndrome …: ethnicity matters

Thomas²,

et al. 2006

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“…The existence of drug-specific cytotoxic CD8+ lymphocytes was reported in two studies (13,14). Presence of CD8+ T-lymphocytes expressing cutaneous lymphocyte antigen (CLA), responsible for skin homing, is already evident in the early stages of TEN (13,14). It has been demonstrated that cytotoxicity of T-cells in TEN is mediated by TEN: sulfonamides, allopurinol, carbamazepine, phenobarbitone, phenytoin and oxycam group of nonsteroidal anti-inflammatory drugs, as well as new drugs nevirapine and lamotrigine (8).…”

Section: Epidemiology Etiology and Pathogenesismentioning

confidence: 93%

“…The pathogenic substrate of toxic epidermal necrolysis is a massive, drug-induced apoptosis of keratinocytes, activated by drug-specific CD8+ cytotoxic lymphocytes (not by its metabolites, as previously assumed). The existence of drug-specific cytotoxic CD8+ lymphocytes was reported in two studies (13,14). Presence of CD8+ T-lymphocytes expressing cutaneous lymphocyte antigen (CLA), responsible for skin homing, is already evident in the early stages of TEN (13,14).…”

Section: Epidemiology Etiology and Pathogenesismentioning

confidence: 95%

“…An increased risk of developing TEN was reported in persons with reduced acetylating capacity (slow acetylators), in immunocompromised (HIV infection and lymphoma), and in individuals with brain tumors, undergoing radiotherapy and receiving anticonvulsants (5,12). the granzyme, which causes programmed cell death by activating procaspase-8 and perforin, leading to formation of pores in the cells being in contact with T-lymphocytes (13)(14)(15). An increased expression of IL-6, TNF-α, IL-18, interferon-γ and FasL was reported in TEN lesions, originating from T-lymphocytes, monocytes/macrophages and keratinocytes (5,16).…”

Section: Epidemiology Etiology and Pathogenesismentioning

confidence: 99%

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An update on diagnosis and treatment of toxic epidermal necrolysis / Novine u dijagnostici i lečenju toksične epidermalne nekrolize

Kandolf-Sekulović¹

2011

Serbian Journal of Dermatology and Venerology

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Toxic epidermal necrolysis is an idiosyncratic drug reaction which manifests with extensive epidermal detachment due to the massive keratinocyte apoptosis, mucous membrane involvement, and potentially lethal outcome. It is caused by adverse reactions to drugs, mostly idiosyncratic, unpredictable and independent of the applied dose, which develops 7-21 days after initiation of the drug, and is most commonly caused by the following drugs: sulfonamides, allopurinol, carbamazepine, phenobarbitone, phenytoin and oxycam group of nonsteroidal anti-inflammatory drugs. The treatment outcome depends on several factors, while older age, multiple drug use, late exclusion of the drug inducing toxic epidermal necrolysis, raised serum levels of urea, creatinine and cytopenia are poor prognostic indicators which are rated in SCORTEN scoring which proved to be of great help in the assessment of disease outcome. The basic approach to the treatment is early diagnosis, immediate suspension of the probable inducing drug, and emergency transport to the closest burn center, since treatment in burn units is associated with a lower risk of infection and mortality of these patients. Exclusion of the drug that induced toxic epidermal necrolysis, and supportive therapy, is the first and only therapy for which there is a consensus in different centers. Various forms of adjuvant therapy are also applied: in France, supportive therapy is a standard of care, in Germany it is short-term use of high-dose corticosteroids, while in USA, in the last decade high-dose intravenous immunoglobulins are the most widely accepted treatment modalities. Case reports and small patients' series described therapeutic effects of plasmapheresis, cyclosporine and other immunosuppressants. In conclusion, elimination of the possible causal agent, rapid transport to the burn unit, and multidisciplinary approach to treatment are of utmost importance for favorable outcome of the disease with 20-30% mortality rate. An update on diagnosis and the treatment of toxic epidermal necrolysis is provided in this review.

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“…The detachment of the epidermis in TEN is caused by the necrosis of keratinocytes following apoptosis [22]. The cells responsible for apoptosis are CD8+ T lymphocytes [23]. The exposure to a drug induces their maturation into cytotoxic T lymphocytes.…”

Section: Immunopathogenesismentioning

confidence: 99%

Zespół toksycznej nekrolizy naskórka

Hinc-Kasprzyk¹,

Polak-Krzemińska²,

Ożóg-Zabolska³

2015

Anaesthesiol Intensive Ther

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Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, are rare, life-threatening diseases that are characterised by extensive epidermal detachment, erosion of mucous membranes and severe systemic symptoms. In the majority of cases, the development of symptoms can be attributed to the use of drugs; therefore, the disease pathology is thought to be caused by a severe adverse reaction to drugs. The high mortality rate results primarily from the development of complications in the form of systemic infections and multiple organ failure. TEN and SJS affect all age groups, including newborns, infants and older children. The rarity of these syndromes has not permitted large, randomised studies, which has resulted in numerous difficulties in their diagnosis and management. Because the pathogenesis has not yet been established, the management and systemic treatment of these syndromes have not been standardised. The efficacy of the treatment options suggested has not been confirmed by clinical studies involving suitably large groups of patients, especially children.

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Toxic epidermal necrolysis: Effector cells are drug-specific cytotoxic T cells

Cited by 360 publications

References 21 publications

A marker for Stevens-Johnson syndrome …: ethnicity matters

A marker for Stevens-Johnson syndrome …: ethnicity matters

An update on diagnosis and treatment of toxic epidermal necrolysis / Novine u dijagnostici i lečenju toksične epidermalne nekrolize

Zespół toksycznej nekrolizy naskórka

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