Stevens-Johnson Syndrome

Stevens-Johnson syndrome is a rare but serious skin reaction that can threaten your life. It usually starts with symptoms similar to the flu, followed by a painful rash that spreads, blisters, and causes the skin to peel off. Most cases are triggered by medications, though infections can also be responsible.

Table of contents

• What is Stevens-Johnson syndrome?
• Other names for this condition
• What causes Stevens-Johnson syndrome?
• Who gets Stevens-Johnson syndrome?
• Signs and symptoms
• How is it diagnosed?
• Treatment and hospital care
• Recovery and long-term effects
• Prevention and risk factors

What is Stevens-Johnson syndrome?

Stevens-Johnson syndrome (SJS) is a rare, serious disorder of the skin and mucous membranes (the moist areas of tissue such as the eyes, mouth, throat, and genitals). It is usually a reaction to medication that starts with flu-like symptoms, followed by a painful rash that spreads and blisters. Then the top layer of affected skin dies, sheds, and begins to heal after several days.^[1]

Stevens-Johnson syndrome is considered a medical emergency that usually requires hospitalization. Without treatment, the symptoms can become life-threatening.^[3]

A more severe form of the condition is called toxic epidermal necrolysis (TEN). The difference between SJS and TEN depends on how much of the body’s skin surface is affected. When less than 10% of the body surface area has skin detachment, the diagnosis is Stevens-Johnson syndrome. When more than 30% of the body surface is affected, the diagnosis is toxic epidermal necrolysis. When between 10% and 30% is affected, doctors call it SJS/TEN overlap.^[2][6]

Lyell’s syndrome, toxic epidermal necrolysis, Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum

Other names for this condition

Stevens-Johnson syndrome is also known by several other names. It may be called Lyell’s syndrome, Stevens-Johnson syndrome/toxic epidermal necrolysis, or Stevens-Johnson syndrome toxic epidermal necrolysis spectrum. If doctors know what caused it, they might call it drug-induced Stevens-Johnson syndrome or mycoplasma-induced Stevens-Johnson syndrome.^[2]

What causes Stevens-Johnson syndrome?

Medications are the cause in most cases of Stevens-Johnson syndrome, especially in adults. The most common medication triggers include:^[2][3][8]

• Antibacterial sulfa drugs (such as sulfamethoxazole)
• Anti-epileptic drugs, including phenytoin, carbamazepine, lamotrigine, and phenobarbital
• Allopurinol (a drug used to treat gout and kidney stones)
• Non-steroidal anti-inflammatory drugs (NSAIDs), particularly oxicam-type drugs such as piroxicam and meloxicam
• Antibiotics, including aminopenicillins, fluoroquinolones, and cephalosporins
• Nevirapine (used to treat HIV)

If your case of Stevens-Johnson syndrome is caused by a drug, symptoms typically appear about one to three weeks after you start taking the medication. However, reactions may occur during the use of a medication or up to two weeks after stopping it.^[1][2]

In children, infections are the most likely cause of Stevens-Johnson syndrome. Common infectious triggers include cold or flu viruses, cold sores, glandular fever, herpes, mumps, and mycoplasma pneumonia (a type of lung infection).^[2][3][5]

In about 20% of cases, no drug or infection can be identified as the cause.^[8]

Who gets Stevens-Johnson syndrome?

Stevens-Johnson syndrome is very rare. It affects approximately 1 to 2 people per million each year for SJS, and 0.4 to 1.2 people per million each year for the more severe form, TEN.^[8][9]

Many cases of Stevens-Johnson syndrome happen in children and adults younger than 30 years old, but the condition can also occur in older people, especially the elderly. More cases occur in females than in males.^[2]

You’re more likely to get Stevens-Johnson syndrome if:^[3]

• You’ve had it before after taking a certain medicine—you’re more likely to get it again if you take that medicine again or other similar medicines
• You have a weakened immune system—for example, from having a condition like HIV or AIDS, or treatments like chemotherapy
• A close family member has had Stevens-Johnson syndrome—sometimes your genes can mean you’re at higher risk of getting it

Genetic factors are important in determining who develops Stevens-Johnson syndrome. Certain human leukocyte antigens (HLAs), which are markers in your immune system, may increase your risk of developing SJS or TEN when taking specific medications. For example, there is a strong association in people of Han Chinese and South Asian Indian descent between a genetic marker called HLA-B*1502 and Stevens-Johnson syndrome induced by carbamazepine.^[2][9]

Stevens-Johnson syndrome is rare, and the risk of getting it is low, even if you’re taking a medicine that can cause it.^[3]

Signs and symptoms

Stevens-Johnson syndrome can start with flu-like symptoms, such as a high temperature (fever), sore throat, cough, headache, joint pain, fatigue, and burning eyes. These early warning signs usually appear one to three days before a rash develops.^[1][3]

As the condition develops, other signs and symptoms include:^[1][2]

• Unexplained widespread skin pain
• A red or purple rash that spreads across the body
• The rash is made up of circular patches that are darker in the middle and lighter around the outside, sometimes described as looking like a target
• Blisters on your skin and the mucous membranes of the mouth, nose, throat, eyes, genitals, and anus
• Blisters that burst to leave painful sores
• Shedding of skin within days after blisters form—the skin often peels very easily

The rash usually starts on the upper body before quickly spreading to the face, arms, legs, and other areas of the body, such as the genitals. The rash is not usually itchy.^[3]

You can also get blisters and sores:^[3]

• On your lips and in your mouth and throat—this can make swallowing painful
• In the tube that carries urine out of your body—this can cause pain when urinating
• On your eyes—this can cause eye pain, pain when looking at bright lights, and problems with your sight

Other symptoms may include drooling (because closing the mouth is painful) and eyes sealed shut due to blisters and swelling.^[2]

Stevens-Johnson syndrome requires immediate medical attention. You should call emergency services or go to the emergency department if you or your child has a circular rash that’s darker in the middle and lighter around the outside after having an infection or starting a new medicine, or if you have a rash and the skin is itchy, red, swollen, blistered, or peeling.^[3]

How is it diagnosed?

Stevens-Johnson syndrome has a characteristic appearance, so doctors often can identify it based on your medical history, including a review of your current and recently stopped medications, and a physical examination.^[10]

To confirm the diagnosis and rule out other possible causes, your doctor may perform several tests:^[10]

Skin biopsy: Your doctor removes a small sample of skin for examination under a microscope. This test typically shows full-thickness death of the top layer of skin due to extensive cell death.^[4][10]

Culture: To rule out an infection, your doctor takes a sample of skin, tissue, or fluid for laboratory testing.^[10]

Blood tests: These are used to confirm infection or other possible causes.^[10]

Imaging: Depending on your symptoms, your doctor may have you undergo imaging such as a chest X-ray to check for pneumonia.^[10]

One important physical sign doctors look for is called the Nikolsky sign. This is when rubbing the skin lightly causes the top layer to slip away from the lower layers, indicating that the skin is detaching.^[5]

Treatment and hospital care

Stevens-Johnson syndrome is treated in hospital, often in an intensive care unit or burn center. Treatment focuses on removing the cause, caring for wounds, controlling pain, and minimizing complications as skin regrows.^[1][3]

The first and most important step in treating Stevens-Johnson syndrome is to stop taking any medications that may be causing it. If you’re taking more than one drug, it may be hard to tell which drug is causing the problem, so your doctor may have you stop taking all nonessential medications. Timing of withdrawal has been linked to outcome—the sooner the triggering medication is stopped, the better.^[10][14]

Supportive care you’re likely to receive while in the hospital includes:^[3][10][14]

• Fluid replacement and nutrition: Because skin loss can result in significant loss of fluid from your body, replacing fluids is an important part of treatment. You may receive fluids and nutrients through a vein or through a tube inserted in the nose and guided to the stomach.
• Wound care: Cool, wet compresses might help soothe blisters while they heal. Your care team may gently remove dead skin and apply creams and dressings to moisturize and protect the skin.
• Pain control: Strong painkillers are provided to help ease any pain.
• Infection prevention: Medicines to control inflammation and prevent infection, including broad-spectrum antibiotics.
• Eye care: Treatment of eye manifestations to prevent long-term damage.

Some doctors may consider additional treatments such as:^[10][13][14]

• Corticosteroids (such as prednisone or methylprednisolone) to control inflammation
• Cyclosporine, an immunosuppressive medication
• High-dose intravenous immunoglobulin therapy

However, there is no consensus on the best treatment approach, and care should be individualized on a case-by-case basis.^[16]

Recovery and long-term effects

It can take weeks to months to fully recover from Stevens-Johnson syndrome. You’ll likely feel very tired for a few weeks after leaving the hospital.^[3][12]

After the skin heals, there may be discoloration of the skin, which may take a long time to improve. Some people may experience permanent scarring.^[5]

More than 50% of patients surviving Stevens-Johnson syndrome and toxic epidermal necrolysis suffer from long-term complications of the disease.^[9] These can include:^[2]

• Visual impairment and eye problems, including dry eye syndrome
• Risk of blindness
• Respiratory problems, including asthma
• Scarring and changes to the skin
• Loss of nail beds
• Problems with the mouth and throat, including swallowing difficulties
• Chronic fatigue
• Post-traumatic stress disorder (PTSD)

The average reported death rate of Stevens-Johnson syndrome is 1 to 5%, and of toxic epidermal necrolysis is 25 to 35%. It can be even higher in elderly patients and those with a large surface area of skin detachment.^[9]

If your condition was caused by a medication, you’ll need to permanently avoid that drug and others like it. It is very important to keep a detailed list of trigger medications and inform all healthcare providers about your history of Stevens-Johnson syndrome.^[1]

Prevention and risk factors

The best way to prevent Stevens-Johnson syndrome is to avoid medications that have triggered the condition in the past. If you’ve had Stevens-Johnson syndrome before after taking a certain medicine, you’re more likely to get it again if you take that medicine again or other similar medicines.^[3]

For people of certain ethnic backgrounds, genetic testing may be available before starting high-risk medications. For example, people of Han Chinese or South Asian Indian descent may be tested for the HLA-B*1502 genetic marker before starting carbamazepine, as this can help identify those at higher risk.^[9]

If you develop any signs of a skin reaction after starting a new medication, contact your doctor immediately. Early recognition and stopping the medication can improve outcomes.^[14]