B TEN with an extensive cutaneous involvement marked by detached and detachable apoptotic skin erosions on the trunk. These include cutaneous hyperpigmentation and hypopigmentation In most cases of TEN, a strong, direct association of the disease with preceding drug consumption can be established. Approximately compounds have been identified as the likely triggers of TEN so far, the most frequent being allopurinol, antibiotics, nonsteroidal anti-inflammatory drugs, and anticonvulsants 1 , It is thought to be initiated by an immune response to an antigenic drug-host tissue complex 9 , 17 — The first, the well-known hapten model, is far less likely to be HLA restricted.
However, the two remaining concepts do favor specific HLA phenotypes. In the case of the p-i concept, the mere pharmacological interaction of certain drugs with immune receptors would be sufficient to induce a drug hypersensitivity reaction 21 — Additionally, recent publications have shown that the HLA-peptide repertoire can be modified by abacavir and carbamazepine, resulting in enhanced peptide presentation and increased autoimmune reactivity altered peptide model 24 , However, the identification of specific drug-related HLA alleles that strongly increase the likelihood of developing SJS or TEN strengthens the hypothesis of the genetic susceptibility of patients to TEN, supporting the concept of HLA-restricted drug presentation 28 — Evidence suggests that immune activation by the drug-host tissue complex induces a strong expression of Fas-L, a cytolytic molecule, on keratinocytes as well as granulysin and annexin A1 secretion by CTLs, NK cells, NKT cells, and monocytes 32 — 37 Figure 3.
This indicates that the disturbance of the balance between pro-inflammatory and immunomodulatory mechanisms may critically determine the clinical outcome in cutaneous inflammation. Recent findings suggest that Th17 cells may alter their phenotype and become regulatory T cells This hypothesis should be examined in future studies.
A Drugs inducing an adverse skin reaction are not antigenic by themselves. Instead, their immunogenicity may result from binding to carrier proteins, which allows the formation of neoantigens that are recognized by T cells upon presentation by antigen-presenting cells APCs. B The p-i concept is based on the pharmacological interactions of drugs with immune receptors.
C The association of peptides with HLA molecules is highly specific. This may result in increased autoimmunity. A The causative medication might induce upregulation of Fas-L by keratinocytes constitutively expressing Fas, leading to activation of a death receptor-mediated apoptotic pathway.
C Drug-activated monocytes secrete annexin A1, which induces necroptosis in keratinocytes. This figure has been modified from French et al.
The suspect drug should be discontinued immediately and supportive therapy should be ensured in the burn or intensive care unit However, valid data on effective therapeutic options are poor, and prospective controlled clinical trials, which can clearly show the benefit of certain treatment options, are lacking. Alternatively, cyclosporine has shown excellent efficacy for the treatment of TEN in a recent study However, as the supporting data for each treatment modality with regard to decreased mortality in TEN are highly controversial, further evidence based on multicenter, randomized, controlled clinical trials is still to be defined.
The allergologic work-up to identify the causative agents includes skin tests epicutaneous testing 47 , in vitro assays lymphocyte transformation tests [LTTs] 48 — 50 , and drug-induced cytokine production assays e. Skin tests have been shown to be safe in TEN patients, but their specificity and sensitivity are rather low In a recent report, Barbaud et al.
Concerning in vitro tests, it should be noted that the LTT is not a standardized procedure and merely demonstrates the proliferation of lymphocytes in the presence of various compounds. Since the time TEN was first described by Dr. There is an unmet need to study the pathophysiology of TEN in more detail, which is complicated by the rarity of this disease and the lack of appropriate mouse models. Additionally, effective therapeutic options validated by prospective, randomized, controlled trials remain to be discovered.
The most important therapeutic measure so far remains the rapid identification and withdrawal of the causative drug in addition to supportive care.
TEN is a life-threatening condition that affects people of all ages. TEN is usually treated in a hospital. While the skin heals, supportive care includes controlling pain, caring for wounds and making sure you're getting enough fluids.
Recovery can take weeks to months. If your condition was caused by a medication, you'll need to permanently avoid that drug and those related to it.
If you have symptoms, seek immediate medical attention. You'll likely need care from a skin specialist dermatologist and other experts in a hospital.
The symptoms are likely to start showing up one to four weeks after you start taking a new drug. People at highest risk of TEN complications are those over age 70 and those who have liver cirrhosis or spreading metastatic cancer. Complications of TEN include:. To prevent another episode of TEN , learn whether it was caused by a medicine. Epub Mar 5. HLA associations and clinical implications in T-cell mediated drug hypersensitivity reactions: an updated review.
J Immunol Res. Epub May 8. Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis. Nat Med. Epub Nov Recent advances in the genetics and immunology of Stevens-Johnson syndrome and toxic epidermal necrosis.
J Dermatol Sci. Epub Apr Toxic epidermal necrolysis: the year in review. In children with Stevens-Johnson syndrome, an infection is the most likely cause.
These disorders occur in all age groups. These disorders are more likely to occur in people with an abnormal immune system, such as those with a bone marrow transplant, systemic lupus erythematosus Systemic Lupus Erythematosus SLE Systemic lupus erythematosus is a chronic autoimmune inflammatory connective tissue disorder that can involve joints, kidneys, skin, mucous membranes, and blood vessel walls.
Problems in the HIV is transmitted The tendency to develop one of these disorders can run in families. Stevens-Johnson syndrome and toxic epidermal necrolysis usually begin 1 to 3 weeks after the start of a drug if caused by a drug with fever, headache, cough, keratoconjunctivitis inflammation of the conjunctiva and the cornea in the eyes , and body aches.
Then the skin changes begin, with a flat red rash on the face, neck, and trunk, often spreading later to the rest of the body in an irregular pattern. The areas of rash enlarge and spread, often forming blisters in their center. The skin of the blisters is very loose and easy to rub off, often with just a gentle touch or pull, and the blisters peel off over a period of 1 to 3 days.
The affected areas are painful, and the person feels very ill with chills and fever. In some people, the hair and nails fall out. The palms and soles may be affected. This photo shows a red rash and blisters on the skin and on the mucous membranes lining the eyes and mouth in a person who has SJS. In both disorders, sores appear on the mucous membranes lining the mouth, throat, anus, genitals, and eyes. The damage to the lining of the mouth makes eating difficult, and closing the mouth may be painful, so the person may drool.
The eyes may become very painful and swell and become so crusted that they seal shut. The corneas can become scarred. The opening through which urine passes urethra may also be affected, making urination difficult and painful. Sometimes the mucous membranes of the digestive and respiratory tracts are involved, resulting in diarrhea and cough, pneumonia, and difficulty breathing.
The skin loss in toxic epidermal necrolysis is similar to a severe burn and is equally life threatening.
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