Stevens-Johnson syndrome/toxic epidermal necrolysis

Alternate names

SJS/TEN; Drug-induced Stevens Johnson syndrome; Stevens-Johnson syndrome; Toxic epidermal necrolysis; Stevens-Johnson syndrome toxic epidermal necrolysis spectrum; Susceptibility to severe cutaneous adverse reaction ITY TO

Definition

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a very severe reaction, most commonly triggered by medications, that causes skin tissue to die (necrosis) and detach. The mucous membranes of the eyes, mouth, and/or genitals are also commonly affected.

Summary

SJS and TEN previously were thought to be separate conditions, but they are now considered part of a disease spectrum. SJS is at the less severe end of the spectrum, and TEN is at the more severe end. It is considered SJS when skin detachment involves less than 10% of the body surface, and TEN when skin detachment involves more than 30% of the body surface. People with skin detachment involving 10-30% of the body surface are said to have "SJS/TEN overlap." All forms of SJS/TEN are a medical emergency that can be life-threatening.

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  Mucosal desquamation in a person with Stevens–Johnson syndrome

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  Inflammation and peeling of the lips—with sores presenting on the tongue and the mucous membranes in SJS.

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  Conjunctivitis in SJS

Epidemiology

• SJS/TEN is a rare disease, affecting 1 to 2 per million people each year. Stevens-Johnson syndrome (the less severe form of the condition) is more common than toxic epidermal necrolysis.
• People who are HIV-positive and those with a chronic inflammatory disease called systemic lupus erythematosus are more likely to develop SJS/TEN than the general population.
• The reason for the increased risk is unclear, but immune system factors and exposure to multiple medications may play a role.

Cause

• Several genetic changes have been found to increase the risk of SJS/TEN in response to triggering factors such as medications. Most of these changes occur in genes that are involved in the normal function of the immune system.
• The genetic variations most strongly associated with SJS/TEN occur in the HLA-B gene.
• This gene is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria).
• The HLA-B gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins.
• Certain variations in this gene occur much more often in people with SJS/TEN than in people without the condition.
• Studies suggest that the HLA-B gene variations associated with SJS/TEN cause the immune system to react abnormally to certain medications.
• In a process that is not well understood, the drug causes immune cells called cytotoxic T cells and natural killer (NK) cells to release a substance called granulysin that destroys cells in the skin and mucous membranes.
• The death of these cells causes the blistering and peeling that is characteristic of SJS/TEN.
• Variations in several other HLA and non-HLA genes have also been studied as potential risk factors for SJS/TEN.
• However, most people with genetic variations that increase the risk of SJS/TEN never develop the disease, even if they are exposed to drugs that can trigger it.
• Researchers believe that additional genetic and nongenetic factors, many of which are unknown, likely play a role in whether a particular individual develops SJS/TEN.

Medications most commonly associated with SJS/TEN include:

• Pain medicines, particularly a class of non-steroidal anti-inflammatory drugs (NSAIDs) called oxicams.
• Cough and cold medications.
• Medications used to treat seizures, such as carbamazepine, lamotrigine, and phenytoin.
• Allopurinol, which is used to treat kidney stones and a form of arthritis called gout.
• Nevirapine, which is used to treat HIV infection.
• Antibiotics, but this association is unclear

Infections that may be associated with SJS/TED include:

• Viral infections such as herpes (simplex or zoster), pneumonia, HIV, hepatitis, Coxsackie, influenza, mumps, CMV, and Epstein-Barr. Many people with the condition report a recent upper respiratory tract infection.
• Bacterial infections such as strep, diphtheria, Brucellosis, Mycobacteria, and Mycoplasma pneumoniae.

Riskfactors

Some people may have an increased risk of developing SJS/TED. Most people with one or more risk factors never develop the condition, even if they are exposed to medications or infections that may trigger it. Factors that may increased a person's risk of developing SJS/TED include:

• Having HIV. The incidence of the condition among people with HIV is about 100 times greater than among people in the general population.
• Having cancer.
• Having a weakened immune system.
• Having a personal or family history of SJS/TED.
• Having certain variations of a gene called HLA-B, which is part of a family of genes called the human leukocyte antigen (HLA) complex.

Inheritance

SJS/TEN is not an inherited condition. However, the genetic changes that increase the risk of developing SJS/TEN can be passed from one generation to the next.

Signs and symptoms

SJS/TEN often begins with a fever and flu-like symptoms. Within a few days, the skin begins to blister and peel, forming very painful raw areas called erosions that resemble a severe hot-water burn. The skin erosions usually start on the face and chest before spreading to other parts of the body. In most affected individuals, the condition also damages the mucous membranes, including the lining of the mouth and the airways, which can cause trouble with swallowing and breathing. The painful blistering can also affect the urinary tract and genitals. SJS/TEN often affects the eyes as well, causing irritation and redness of the conjunctiva, which are the mucous membranes that protect the white part of the eye and line the eyelids, and damage to the clear front covering of the eye (the cornea).

Severe damage to the skin and mucous membranes makes SJS/TEN a life-threatening disease. Because the skin normally acts as a protective barrier, extensive skin damage can lead to a dangerous loss of fluids and allow infections to develop. Serious complications can include pneumonia, overwhelming bacterial infections (sepsis), shock, multiple organ failure, and death. About 10 percent of people with Stevens-Johnson syndrome die from the disease, while the condition is fatal in up to 50 percent of those with toxic epidermal necrolysis.

Among people who survive, long-term effects of SJS/TEN can include changes in skin coloring (pigmentation), dryness of the skin and mucous membranes (xerosis), excess sweating (hyperhidrosis), hair loss (alopecia), and abnormal growth or loss of the fingernails and toenails. Other long-term problems can include impaired taste, difficulty urinating, and genital abnormalities. A small percentage of affected individuals develop chronic dryness or inflammation of the eyes, which can lead to increased sensitivity to light (photophobia) and vision impairment.

Diagnosis

There are no universal diagnostic criteria for SJS/TEN. Currently the diagnosis is based on the person's medical history and symptoms. People suspected of having SJS/TEN should be admitted to the hospital to confirm the diagnosis and assess severity. As mentioned earlier, whether a person is diagnosed specifically with SJS, TEN, or SJS/TEN overlap depends on the percentage of body surface area affected.

Treatment

A person suspected of having Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) should be admitted to the hospital immediately because it can be life-threatening. When the diagnosis is confirmed, the extent of the disease should be determined quickly so that the most appropriate place for treatment can be decided. People with SJS/TEN may be best treated in an intensive care unit, burn unit, or specialized dermatology unit. Several studies show that the chance of recovery is better for those moved promptly to a burn care unit or intensive care unit. Treatment should ideally be managed by a team of doctors experienced in treating the condition.

Treatment aims to address symptoms and prevent complications (supportive care). People thought to have medication-induced SJS/TEN should discontinue the medication as soon as possible.

Generally, treatment of skin symptoms is similar to that of major burns, and includes wound care, pain control, fluids and electrolytes, nutritional support, temperature management, and monitoring for or treating secondary infections.

Eye involvement needs immediate treatment to reduce the risk of permanent eye damage and vision loss. Eye inflammation can worsen quickly within a few days, so daily eye evaluations (by an ophthalmologist) and aggressive treatment are needed. Treatment depends on the extent of eye involvement and may involve any of several strategies either alone or in combination, including:

• Saline rinses to clean the eyes and eyelids.
• Lubrication multiple times per day with preservative-free eye drops or ointments (including for those with no apparent eye involvement).
• Eye medicines with topical corticosteroids and broad-spectrum antibiotics.
• Amniotic membrane transplantation (AMT) to try to prevent vision loss and complications involving the mucous membranes. Some people need multiple procedures. The amniotic membrane is the innermost layer of the placenta, and can been used as a graft or dressing to aid in repairing the surface of the eyes and promote healing.

Beyond supportive care, various therapies have been tried by doctors, including systemic corticosteroids, intravenous immune globulin (IVIG), cyclosporine, plasmapheresis, and anti-tumor necrosis factor (TNF) monoclonal antibodies. However, with the exception of thalidomide (which was found to be harmful), none have been adequately studied in randomized trials. There is, however, increasing evidence that cyclosporine may slow the progression of the condition.

Prognosis

The long-term outlook and chance of recovery varies from person to person. Regrowth of the affected skin typically occurs in two to three weeks, but recovery can take weeks to months, depending on the severity of symptoms. Feelings of overwhelming tiredness may persist for months. Depression may also develop. For some, complications may develop within weeks to months of an acute episode, and there may be long-term complications involving the skin and affected mucous membranes, which can severely impact quality of life. SJS/TEN may recur if there is re-exposure to a medication known to have triggered the condition originally. However recurrent episodes due to different medications or infections have also been reported. The overall risk of recurrence is not known, but it seems to be higher in children with SJS/TEN that is associated with infections. In some people, SJS/TEN is fatal. The overall mortality (death) rate is about 25%, ranging from about 10% for SJS to over 30% for TEN. The most common causes of death include sepsis, acute respiratory distress syndrome, and multiple organ failure.

NIH genetic and rare disease info

• NIH info on Stevens-Johnson syndrome/toxic epidermal necrolysis

Stevens-Johnson syndrome/toxic epidermal necrolysis is a rare disease.

Stevens-Johnson syndrome/toxic epidermal necrolysis Resources
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