Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

A Dangerous Reaction to Medication or Infection

Woman with allergic reaction looking herself in the mirror
SJS starts off as a blistering rash.

 

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Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are potentially life-threatening skin reactions caused by an abnormal immune response to medications or infections. The conditions typically begin with a fever and flu-like symptoms followed by the severe blistering of the skin and mucous membranes. If not treated immediately, SJS and TEN can cause severe scarring, vision loss, organ failure, and even death.

Stevens-Johnson syndrome and toxic epidermal necrolysis comprise a disease spectrum referred to as SJS/TEN. Of the two conditions, SJS is less severe. While both have similar immunological causes, they are differentiated by the percentage of skin involved.

By definition:

  • SJS involves less than 10 percent of the body.
  • SJS/TEN involves more than 10 percent but less than 30 percent of the body.
  • TEN involves more than 30 percent of the body.

SJS is a rare condition with an annual incidence of around 2.6 to 6.1 cases per one million people. TEN is even rarer, with an annual incidence of between 0.4 to 1.2 cases per million. Adults are more affected than children, while women are twice as likely to experience SJS or TEN than men.

Symptoms

Generally speaking, SJS and TEN manifest with flu-like symptoms in the early stages. Within a few days, the skin will develop a blistering and peeling rash. The initial symptoms tend to last from one to three days and typically include:

  • Headache
  • Fever
  • Sore throat
  • Cough
  • Burning or itchy eyes
  • Fatigue
  • Muscle aches
  • Joint pain
  • Diarrhea
  • Nausea
  • Vomiting

The initial symptoms will eventually give way to an intense burning sensation on the skin. This will be followed by the appearance of red or purplish lesions of up to an inch in size, usually starting on the face, trunk, arms, and/or legs.

Over the course of minutes and hours, the rash will begin to spread, blister, and peel, exposing large patches of raw and weeping skin. Painful lesions and ulcers will quickly form in the mouth and even the mucous membranes of the nose, eyelids, genitals, and anus. Conjunctivitis ("pink eye") is also common, particularly in children.

The development of SJS/TEN symptoms is considered a medical emergency.

Complications

Complications of SJS and TEN are common if treatment is delayed. Even if treatment is sought, TEN can cause devastating illness over a short period of time, causing the same level of injury as a second-degree burn.

Some of the possible complications of SJS and TEN include:

Causes

While SJS and TEN are usually caused by a reaction to medications or infection, as many as one-third of cases will have no known cause. For reasons poorly understood, exposure to these agents will trigger an abnormal immune response in which immune cells, called CD8 T-cells, suddenly target and attack skin cells known as keratinocytes.

Medications

Medications associated with SJS and TEN include:

  • Anticonvulsants, especially Tegretol (carbamazepine), Luminal (phenobarbital), Lamictal (lamotrigine), and Dilantin (phenytoin)
  • Aloprim and Zyloprim (allopurinol) used to treat gout and kidney stones
  • Sulfonamide antibiotics like Bactrim (sulfamethoxazole-trimethoprim), Azulfidine (sulfasalazine), Gantrisin (sulfisoxazole), and penicillin
  • Viramune (nevirapine) used to treat HIV
  • Pain relievers like Advil (ibuprofen), Tylenol (acetaminophen), and Aleve (naproxen)

SJS/TEN is not like a drug allergy that can occur after a single dose. The condition is associated with the continual and cumulative exposure to a medication over time. SJS and TEN symptoms will often develop within 10 to 14 days of starting a drug therapy but can take up to four weeks.

Infections

A number of infections can trigger an SJS and TEN episode, including:

Genetics

Genetics are believed to contribute significantly to a person's predisposition to SJS/TEN. The mutation of certain genes central to the immune response, especially the human leukocyte antigen B (HLA-B gene), have been implicated. For reasons unknown, certain immunologic "triggers" will overstimulate the immune system and set the HLA-B gene into overdrive.

This may explain why people with HIV, for example, are at greater risk given that the HLA-B gene is linked to the immune control of the virus.

Despite the fact that HLA-B mutations are commonly found in people with SJS and TEN, not everyone with these genetic anomalies will develop the condition, even when exposed to the same triggers. This suggests that environmental factors may also contribute.

Diagnosis

The diagnosis of SJS and TEN is based on both the physical symptoms and percentage of skin involvement. During an examination, your doctor will look for the so-called Nikolsky's sign, a dermatological finding in which the slight rubbing of skin will cause the outermost layer to peel away like parchment.

A skin biopsy is helpful but not required to return a positive diagnosis. If performed, the biopsy will aim to find evidence of degenerative inflammation and tissue necrosis (death).

The doctor will also review your medical history (including the drugs you take) to better determine the cause of the reaction. Additional tests may be ordered, including blood tests, cultures, or X-rays, if the cause is believed to be infectious.

Differential Diagnoses

To ensure the correct diagnosis, the doctor will need to exclude all other possible causes of the symptoms. The differential diagnoses may include:

  • Bullous drug eruption (a drug allergy characterized by blistering)
  • Chemical burn
  • Toxic shock syndrome
  • Bullous pemphigoid (an autoimmune blistering disease)
  • Paraneoplastic pemphigus (a cancer-related autoimmune blistering disease)

Treatment

If you're diagnosed with SJS or TEN, you will need to be hospitalized in a burn unit or the intensive care unit (ICU). The treatment will be similar to that for a burn victim and may include:

  • Immediate discontinuation of the suspected medication
  • Cool compresses, medicated ointments, and bandages to treat the blisters
  • Intravenous hydration with saline fluids
  • Intravenous antibiotics to prevent bacterial infection
  • Intravenous corticosteroids and tumor necrosis factor inhibitors like Remicade (infliximab) to temper the immune response
  • Immune suppressants like Sandimmune (cyclosporine)
  • Pain control medications
  • A feeding tube to aid in nutrition
  • Eye care from an ophthalmologist, if needed

In severe cases, a procedure called plasmapheresis may be performed to filter CD8 T-cells and other immune cells from the blood.

Prognosis

Recovery can take weeks or months, depending on how severe your symptoms were. Studies suggest that around 5 percent of people with SJS will die as a result of disease complications, while anywhere from 30 percent to 35 percent of people with TEN will die. Many of these deaths are related to delayed treatment, while others are simply the result of massive tissue loss.

Those who do recover may experience further health problems involving the skin, eyes, lungs, and other organ systems.

Skin

Because of the extensive skin involvement, people with SJS and TEN may have permanent scarring, discoloration, or disfigurement of the skin. While hair and nails will often fall out following an episode, they will generally grow back.

Eyes

Between 50 percent and 90 percent of people will develop eye problems following a bout of SJS or TEN. These may include dry eye syndrome, ingrown eyelashes, light sensitivity, and keratitis (corneal inflammation). Corneal scarring may cause significant vision loss and, in rare cases, blindness.

Mouth and Gums

Xerostomia (dry mouth), tooth decay, or gum infections are common following SJS and TEN. Young children may have problems with the way their teeth grow or develop abnormalities in the roots of their teeth.

Lungs

Damage to the lungs following a bout of SJS or TEN can lead to chronic bronchitis, chronic bronchiolitis, bronchiectasis, and other obstructive lung disorders.

Mental Health

Mood disorders like anxiety and depression are not uncommon after having had SJS or TEN. Much of this may be associated with the physical trauma and aftermath of the condition. Psychiatric care, along with emotional support and the appropriate drug therapy, may be needed to improve your long-term mental health.

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