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Erythema multiforme

Stevens-Johnson syndrome (SJS) is a severe and potentially life-threatening (15% of cases) disease, it is a hypersensitivity complex affecting the skin and the mucous membranes, a severe expression of erythema multiforme (EM) (and so SJS is also called erythema multiforme major). more...

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Symptoms

SJS is characterized by fever, sore throat, and headache leading to the sudden development of circular mucocutaneous lesions (target lesions) that can cover the majority of the skin. These lesions begin as macules and can develop into papules, vesicles, blisters, or urticarial plaques. The most extreme cases are termed Toxic Epidermal Necrolysis Syndrome (TENS) or Lyell's Syndrome, in these cases the entire skin is affected.

Treatment

Treatment is initially similar to that of patients with thermal burns, and continued care can only be supportive (e.g. IV fluids) and symptomatic (e.g. analgesic mouth rinse for mouth ulcer); there is no specific drug treatment (2002). An ophthalmologist should be consulted if eyes are involved. Treatment with corticosteroids is controversial since it might aggravate the condition.

Cause

The cause of SJS is either infections (usually following viral infections such as herpes simplex virus, influenza, mumps, cat-scratch fever, histoplasmosis, Epstein-Barr virus, or similar), drug-induced (valdecoxib, penicillins, barbiturate, sulfas, phenytoin, lamotrigine, nevirapine), malignancy-related (carcinomas and lymphomas), or idiopathic (50% of the time)

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Toxic epidermal necrolysis
From Gale Encyclopedia of Medicine, 4/6/01 by Richard H. Camer

Definition

Toxic epidermal necrolysis is a rare condition that causes large portions of the epidermis, the skin's outermost layer, to detach from the layers of skin below. A reaction to a medication is the primary cause.

Description

Toxic epidermal necrolysis (TEN) begins with fever, cough, and other nonspecific symptoms, and is soon followed by purplish, bloody-looking lesions on the skin and mucous membranes. These early lesions, typically found on the head, neck, and upper chest, soon merge and blister. Sheets of epidermis then begin to detach from the skin layers below. In time, the entire surface of the skin may be involved, with detachment of 100% of the epidermis.

Causes & symptoms

The main cause of TEN is a severe drug reaction. Some investigators believe there may be additional infectious causes. A severe reaction in transplant patients, called graft-vs.-host disease, can also produce TEN. One study reported more than 100 different drugs as causes of TEN. The drugs most commonly implicated, however, include antibacterial sulfonamides such as sulfadiazine, antibiotics such as aminopenicillins and cephalosporins, and anticonvulsants like phenytoin. TEN is extremely rare. Researchers estimate that there are 0.2 cases per million users of aminopenicillins and 4.5 cases per million users of sulfonamides.

Exactly what leads to detachment of the epidermis remains unclear. People with TEN seem to have difficulty metabolizing the offending drug. Some researchers suggest that certain substances that should be cleared from the body instead get deposited on the outer shell of the epidermis, causing an immune response that leads the body to "reject" the skin.

Diagnosis

Diagnosis is made primarily on the appearance and spread of the skin lesions, and on a history that includes introduction of a new medication within the previous one to three weeks. A biopsy of the early lesions will confirm the diagnosis. Physicians will consider other potential diseases that cause similar symptoms before reaching a diagnosis of TEN. One is erythema multiforme, a recurrent skin disorder that produces lesions similar in appearance to TEN. However, this disorder is not caused by a drug reaction and does not lead to sheet-like shedding of the skin. Another disease, Stevens-Johnson syndrome, is a drug-induced skin disease that some experts believe is really a milder form of TEN. Staphylococcal scalded skin syndrome (SSSS) also looks like TEN, but it is caused by a staphylococcal infection. Unlike TEN, which occurs rarely in children, SSSS primarily affects infants, young children, and adults with weakened immune systems.

Treatment

There is no specific treatment for TEN. Patients are typically treated in an intensive care unit or in a burn unit and receive treatment similar to that given to patients with major burns. With the loss of skin, severe dehydration is a major risk, so health care workers will attempt to replace fluids intravenously. Nutritional supplementation from a tube routed through the nose to the stomach may also be contemplated to promote the healing of the skin. Infection is a major risk, so some physicians "paint" the open lesions with topical antiseptics. Others use skin grafts taken from cadavers or cultured skin substitutes to cover large open areas until healing can occur. Some investigators believe system corticosteroids are useful in the treatment of TEN. But since these medications have also been implicated as a cause in some cases of TEN and are known to supress the immune system, their use should be considered carefully.

Prognosis

About 25-30% of patients with TEN die. Elderly patients, those with extensive skin lesions, and those with AIDS have the worst prognosis. Widespread systemic infection (sepsis) is the primary cause of death. Survivors, however, will be completely healed in three to four weeks.

Prevention

There is no prevention for TEN. No reliable test can indicate that a specific drug may cause TEN in a specific patient. Some researchers believe skin tests of potentially offending drugs may prove useful in the future.

Key Terms

Epidermis
The outermost layer of the skin.
Erythema multiforme
A recurrent skin disorder that produces lesions similar in appearance to TEN, but is not caused by a drug reaction and does not lead to sheet-like shedding of the skin.
Staphylococcal scalded skin syndrome
A disease caused by in which large sheets of skin may peel away from the body. It most often affects infants, young children, and people with weakened immune systems.
Stevens-Johnson syndrome
A drug-induced skin disease that some experts believe is really a milder form of TEN.

Further Reading

For Your Information

    Books

  • Fitzpatrick, Thomas B., et al. Color Atlas and Synopsis of Clinical Dermatology. New York: McGraw-Hill, 1997.
  • Helm, Klaus F., and James G. Marks, Jr. Atlas of Differential Diagnosis in Dermatology. New York: Churchill Livingstone, 1996.

    Periodicals

  • Revuz, Jean E., and Jean Claude Roujeau. "Advances in Toxic Epidermal Necrolysis." Seminars in Cutaneous Medicine and Surgery 15 (December 1996): 258-266.
  • Weightman, Warren. "Toxic Epidermal Necrolysis." Australasian Journal of Dermatology 37 (November 1996): 167-177.

    Organizations

  • American Academy of Dermatology. 930 N. Meacham Road, PO Box 4014, Schaumburg, IL 60168-4014. (847) 330-0230. http://www.aad.org.

Gale Encyclopedia of Medicine. Gale Research, 1999.

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