What is Stevens-Johnson Syndrome?

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are different types of the same condition, which used to be called Lyell syndrome. These should not be confused with other skin conditions like erythema multiforme major or staphylococcal scalded skin syndrome, and different kinds of drug rashes.

Stevens-Johnson syndrome or toxic epidermal necrolysis is a rare, sudden, serious, and potentially life-threatening skin condition. In this, the skin and the lining of the mouth, nose, and eyes (mucous membranes) shed off, similar to how a sheet peels off. In most cases – over 80% of the time – this is caused by a reaction to certain medications.

These conditions are classified based on how much skin is peeling off, or in medical terms, the percentage of ‘detached skin surface area’.

– If less than 10% of the body’s skin is affected, it’s called Stevens-Johnson syndrome.
– If between 10% and 30% of the skin is peeling, it’s referred to as overlap Stevens-Johnson syndrome/toxic epidermal necrolysis.
– If more than 30% of the skin is affected, it’s considered toxic epidermal necrolysis.
Stevens-Johnson syndrome/toxic epidermal necrolysis is a serious medical condition and should be treated as soon as possible to avoid any life-threatening complications.

What Causes Stevens-Johnson Syndrome?

Stevens-Johnson syndrome/toxic epidermal necrolysis is a rare and unpredictable reaction to certain medications. Though rare, the reaction can be severe, mainly caused due to certain parts of our immune system – namely CD8+ cytotoxic lymphocytes, Fas-Fas ligand (FasL) pathway, granule-mediated exocytosis, and the TNF–alpha/death receptor pathway.

Let’s break this down a bit:

1. Granulysin – This is a component found in destructive cells of our immune system. It’s believed to be the primary cause of damage to keratinocytes – the main cell type in our skin’s outermost layer.

2. Fas–FasL – These are proteins that, when activated, can also cause damage to keratinocytes. They do this by activating enzymes within the cells that lead to cellular self-destruction.

3. Cytotoxic T cells – Another group of immune cells, can release certain proteins like perforin and granzyme B that can create gaps in the target cell membranes and instigate them to self-destruct.

4. TNF–alpha is a type of signaling protein in the body that may either cause cells to self-destruct or protect them from doing so.

5. Nitrous oxide (NO) – This is a gas that, when stimulated by TNF–alpha and a substance called interferon (IFN)–alpha, may activate the enzymes that lead to cell self-destruction.

So, in summary, this reaction is thought to be an overdrive response of the body’s immune system to certain medications, leading to severe damage to the skin and mucous membranes.

Risk Factors and Frequency for Stevens-Johnson Syndrome

Stevens-Johnson syndrome/toxic epidermal necrolysis is a rare condition that affects around two to seven out of a million people every year. It has been observed that Stevens-Johnson syndrome is three times more common than toxic epidermal necrolysis. This condition can affect anybody, regardless of their age, gender, or race, but it’s typically seen more in older people and women.

People infected with the human immunodeficiency virus (HIV) are more likely to contract this disease, with around one in a thousand people getting affected. There are many medicines that have the potential to trigger Stevens-Johnson syndrome/toxic epidermal necrolysis. It is more common after drug usage rather than vaccinations or infections like mycoplasma, cytomegalovirus, and dengue.

  • The following medicines are known to cause this condition more frequently:
    • Anticonvulsants: lamotrigine, carbamazepine, phenytoin, phenobarbitone
    • Allopurinol, especially in doses of more than 100 mg per day
    • Sulfonamides: cotrimoxazole, sulfasalazine
    • Antibiotics: penicillins, cephalosporins, quinolones, minocycline
    • Paracetamol/acetaminophen
    • Nevirapine (non-nucleoside reverse-transcriptase inhibitor)
    • Nonsteroidal anti-inflammatory drugs (NSAIDs) (oxicam type mainly)
    • Contrast media

Individuals who have specific human leukocyte antigen (HLA) allotypes are at a higher risk of developing Stevens-Johnson syndrome/toxic epidermal necrolysis if they consume aromatic anticonvulsants and allopurinol. Because of this link, the relatives of a person with this condition are at risk and need to be careful about consuming medicines associated with this disease.

  • Areas of elevated risk include:
    • Han Chinese, Thai, Malaysian, and South Indian people with HLA-B*1502 who take aromatic anticonvulsants.
    • Han Chinese individuals with HLA-B*5801 who take allopurinol.
    • Europeans with HLA-B*5701 who take abacavir, or those carrying HLA-A*3101 and taking carbamazepine.
Widespread early morbilliform eruption with flaccid bullae in patient with toxic
epidermal necrolysis
Widespread early morbilliform eruption with flaccid bullae in patient with toxic
epidermal necrolysis

Signs and Symptoms of Stevens-Johnson Syndrome

This condition starts with common symptoms such as a fever, feeling unwell, coughing, nose inflammation, sore eyes, and muscle pains. Over the next few days, a blistering rash and sores start developing on various parts of the body like the face, torso, limbs, and inside the mouth.

  • Red skin patches that might look like targets, rings, or spots
  • Loose blisters
  • Large painful sores
  • Nikolsky’s sign – the top layer of skin peels off easily if rubbed

At the beginning of toxic epidermal necrolysis, there’s widespread redness and skin sores, which can have a target-like rash. Stevens-Johnson syndrome is notable for its target-like rash, with less raw skin areas.

Sores and skin erosion can show up on the lips, inside the mouth, throat, food pipe, stomach, eyes, genitals, and upper respiratory tract. About half of the patients have these symptoms in three different places. Patients often feel very unwell, anxious, and experience pain. Stevens-Johnson syndrome and toxic epidermal necrolysis can also affect the liver, kidneys, lungs, bone marrow, and joints. The typical symptoms include:

  • Fever, feeling unwell, headache, loss of appetite, sore throat
  • Symptoms linked to sudden problems with the eyes, lungs, heart, stomach, kidneys, and blood cells

These symptoms can overlap with other severe skin reactions, such as acute generalized exanthematous pustulosis, which causes small pus-filled blisters, and drug hypersensitivity syndrome, which causes a measles-like rash and affects other organs.

Testing for Stevens-Johnson Syndrome

If your doctor suspects you have a condition called Stevens-Johnson syndrome or toxic epidermal necrolysis, they’ll likely order several tests to confirm their diagnosis and check how severe your condition is. Let’s break down these tests;

Firstly, they might do a skin biopsy. This test is urgent and involves removing a small sample of your skin that’s then quickly frozen and examined under a microscope to check for skin cell death.

Next, they might perform a direct immune fluorescence test. This test helps detect the presence of certain autoimmune diseases, and in this case, we expect it to come back negative.

Your doctor will also likely order a complete blood count (CBC). This test helps check various components of your blood and will be used to look for low blood cell counts and unusual blood cells.

A liver function test (LFT) might be done as well. This test measures certain enzymes and proteins in your blood to evaluate how well your liver is working. In this case, the doctor is checking for increased liver enzymes and decreased albumin, a protein made by the liver.

Next is a renal function test, which checks how well your kidneys are doing by looking for protein in your urine and measuring your blood’s creatinine and urea levels. In some instances, a check for low sodium levels or hyponatremia is also included.

Your doctor might also test for lung and heart problems using bronchoscopy, x-ray imaging, ECG, and other imaging techniques.

The severity of your condition is then evaluated using a scoring system called SCORTEN. This scores you on seven factors, including your age, presence of a malignancy (cancer), heart rate, how much of your skin is affected, and levels of certain chemicals in your blood. Each factor adds one point to your score, and the score is then used to estimate your risk of dying from your condition. Higher SCORTEN scores mean higher risks.

If you’re taking many drugs known to cause Stevens-Johnson syndrome/toxic epidermal necrolysis, your doctor might use an algorithm called ALDEN to figure out which one caused your reaction. This algorithm uses different scores based on the timing of drug intake, whether a drug was present in your body on the day you started showing symptoms, whether you’ve had this reaction to the same drug before, and whether the drug is known to often cause this reaction. Negative scores are given for certain factors like how long you’ve been taking the drug and any other potential causes of your reaction.

Treatment Options for Stevens-Johnson Syndrome

If you’re diagnosed with Stevens-Johnson syndrome or toxic epidermal necrolysis, you will likely receive care from an expert team in a specialized hospital environment. This team may include doctors specializing in intensive care, dermatology, plastic surgery or burns, eye health, women’s health, urinary health, and lung conditions. Additionally, physical therapists and nutritionists will assist with your recovery.

The primary focus of treatment includes supportive care, which involves several key aspects:

  • Stops what might be causing the syndrome, such as certain medications.
  • Admits you to a hospital – usually to an intensive care or burn unit for expert care.
  • Replaces lost fluids: This addresses any dehydration that might have occurred due to the condition.
  • Nutritional assessment: Some patients may need to be fed through a tube that goes down their nose and into their stomach.
  • Manages body temperature: A warm environment is typically created, and an emergency blanket may be used.
  • Offers pain relief as needed.
  • Supplemental oxygen: Some patients may need help breathing. In severe cases, a machine called a ventilator might be used for breathing assistance.
  • Ensures cleanliness: All procedures are performed in a sterile (germ-free) manner to avoid the risk of infections.

As part of your care, your skin will be checked daily for signs of infection. Non-sticking dressings will be used to cover any open areas, and it’s crucial to avoid any further skin injury. Areas inside your body, like the mouth, will be carefully cleaned, and medications that numb pain may be used topically.

Extra precautions include:

  • Gently removing dead skin or tissue from inside the mouth.
  • Regular skin cultures – a type of test to check for infections – usually from the armpits and groin area.

Secondary infections might be treated with antibiotics, but these are generally avoided unless necessary. Although some doctors prescribe high-dose corticosteroids (a type of medication that reduces inflammation), it’s unclear if they’re beneficial. In some cases, other medications could be used. These include ciclosporin, N-acetylcysteine, intravenous immunoglobulins, and TNF-alpha inhibitors. However, whether or not these drugs should be used remains a topic of debate.

When dealing with acute skin peeling conditions, doctors need to take into account other possible causes. These could include:

  • Severe adverse skin reactions to drugs, like drug hypersensitivity syndrome (DHS) or acute generalized exanthematous pustulosis (AGEP)
  • Different kinds of drug eruptions
  • A serious form of skin rash called erythema multiforme major
  • A bacterial infection causing skin to blister and peel, known as staphylococcal scalded skin syndrome
  • Autoimmune skin diseases like pemphigus vulgaris and pemphigus foliaceus
  • Acute graft versus host disease, a complication that can occur after a bone marrow transplant.

What to expect with Stevens-Johnson Syndrome

Stevens-Johnson syndrome/toxic epidermal necrolysis is a very serious condition that can lead to high mortality rates (i.e., death rates), with outcomes often depending on how severe the condition is when detected.

According to a study conducted throughout the US from 2009-2012, about 4.8% of patients with Stevens-Johnson syndrome (SJS), 19.4% with overlapping SJS/toxic epidermal necrolysis (TEN), and 14.8% with TEN died from the condition.

In another study conducted in Créteil, France, out of 361 patients diagnosed with either SJS or TEN, 66 people unfortunately passed away. That’s a mortality rate of 18%: 2% among those with SJS, 12% among those with overlapping SJS/TEN, and a notably higher 26% among those with TEN.

However, there is some good news. In recent years, the mortality rate for SJS/TEN has shown a declining trend, mainly due to improved supportive care compared to earlier decades.

Possible Complications When Diagnosed with Stevens-Johnson Syndrome

In the early stages, the biggest risk of Stevens-Johnson Syndrome (a severe skin reaction) is sepsis, a potentially life-threatening condition caused by the body’s response to an infection. Other risks include failure of the lungs, liver, and kidneys.

The long-term complications of Stevens-Johnson Syndrome can affect the eyes (even leading to blindness), skin (causing changes in color and scarring), and kidneys. The skin and mucous membranes can form blisters and sores which may result in strictures (abnormal narrowing) and scars.

Risks:

  • Sepsis (serious body-wide infection) in the early stages
  • Failure of lungs, liver, and kidneys
  • Long-term complications affecting the eyes (including blindness)
  • Skin complications leading to changes in color and scarring
  • Kidney complications
  • Blisters and sores on the skin and mucous membranes leading to strictures and scars
Frequently asked questions

The prognosis for Stevens-Johnson syndrome (SJS) can vary depending on the severity of the condition when detected. However, it is a serious condition that can lead to high mortality rates. According to studies, the mortality rate for SJS ranges from 2% to 26%, with overlapping SJS/toxic epidermal necrolysis (TEN) having a higher mortality rate compared to SJS alone. The mortality rate for SJS/TEN has shown a declining trend in recent years due to improved supportive care.

Stevens-Johnson Syndrome can be triggered by certain medications, including anticonvulsants, allopurinol, sulfonamides, antibiotics, paracetamol/acetaminophen, nevirapine, nonsteroidal anti-inflammatory drugs (NSAIDs), and contrast media. It can also occur in individuals with specific human leukocyte antigen (HLA) allotypes who consume aromatic anticonvulsants and allopurinol.

The types of tests that are needed for Stevens-Johnson Syndrome include: 1. Skin biopsy: This involves removing a small sample of skin to check for skin cell death. 2. Direct immune fluorescence test: This helps detect the presence of certain autoimmune diseases. 3. Complete blood count (CBC): This test checks various components of the blood, including low blood cell counts and unusual blood cells. 4. Liver function test (LFT): This measures enzymes and proteins in the blood to evaluate liver function. 5. Renal function test: This checks kidney function by looking for protein in the urine and measuring blood creatinine and urea levels. 6. Lung and heart tests: These may include bronchoscopy, x-ray imaging, ECG, and other imaging techniques. 7. SCORTEN scoring system: This evaluates the severity of the condition based on factors such as age, presence of malignancy, heart rate, skin involvement, and blood chemical levels. 8. ALDEN algorithm: This helps determine which drug caused the reaction in cases where multiple drugs are being taken. 9. Skin checks for signs of infection and regular skin cultures to check for infections. 10. Additional tests and medications may be used depending on the specific case and symptoms.

The doctor needs to rule out the following conditions when diagnosing Stevens-Johnson Syndrome: - Severe adverse skin reactions to drugs, like drug hypersensitivity syndrome (DHS) or acute generalized exanthematous pustulosis (AGEP) - Different kinds of drug eruptions - A serious form of skin rash called erythema multiforme major - A bacterial infection causing skin to blister and peel, known as staphylococcal scalded skin syndrome - Autoimmune skin diseases like pemphigus vulgaris and pemphigus foliaceus - Acute graft versus host disease, a complication that can occur after a bone marrow transplant.

When treating Stevens-Johnson Syndrome, there are several side effects that may occur. These include sepsis (serious body-wide infection) in the early stages, failure of the lungs, liver, and kidneys, long-term complications affecting the eyes (including blindness), skin complications leading to changes in color and scarring, kidney complications, and the formation of blisters and sores on the skin and mucous membranes, which can result in strictures (abnormal narrowing) and scars.

You should see doctors specializing in intensive care, dermatology, plastic surgery or burns, eye health, women's health, urinary health, and lung conditions for Stevens-Johnson Syndrome.

Stevens-Johnson Syndrome is a rare condition that affects around two to seven out of a million people every year.

Stevens-Johnson Syndrome is treated through supportive care in a specialized hospital environment. The treatment involves stopping the cause of the syndrome, admitting the patient to a hospital for expert care, replacing lost fluids, conducting nutritional assessments, managing body temperature, providing pain relief, offering supplemental oxygen if needed, ensuring cleanliness to avoid infections, and checking the skin daily for signs of infection. Extra precautions include gently removing dead skin or tissue from inside the mouth and conducting regular skin cultures to check for infections. Secondary infections may be treated with antibiotics if necessary, and other medications such as corticosteroids, ciclosporin, N-acetylcysteine, intravenous immunoglobulins, and TNF-alpha inhibitors may be used in some cases, although their use is still a topic of debate.

Stevens-Johnson Syndrome is a rare, serious, and potentially life-threatening skin condition where the skin and mucous membranes shed off, caused by a reaction to certain medications.

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