What is Toxic Epidermal Necrolysis?
Toxic epidermal necrolysis (TEN) is a severe and possibly deadly skin condition causing extensive peeling of the skin and inner lining of body openings, which might potentially lead to dangerous bodywide infections, and even death. The condition was first identified in 1956 by Alan Lyell, he compared it to severe skin burns.
In majority of cases, TEN comes about as a response from the body’s immune system to specific drugs. However, infections, growths like tumors and vaccinations have also been identified as potential causes. It has a lot in common with another drug-induced skin condition known as Steven-Johnson Syndrome (SJS). Both conditions involve skin peeling, but the main difference lies in the extent of skin peeling. In cases of TEN, more than 30% of the body’s total skin surface peels away, while with SJS, it is less than 10%.
What Causes Toxic Epidermal Necrolysis?
TEN, an abbreviation for a serious skin disorder, can be triggered by various factors like medications, infections, vaccines, or sometimes it happens without a known cause. Most commonly, it’s due to an adverse reaction to certain drugs. Numerous medications have been tied to TEN, which include types of antibiotics, antiepileptic drugs (used to treat seizures), non-steroidal anti-inflammatory drugs (used for pain and inflammation), antiviral drugs (used to treat viruses), and a medicine called allopurinol used for gout. A study in 2008 identified some drugs that have a higher risk of causing TEN. These include lamotrigine, carbamazepine, phenytoin, nevirapine, phenobarbital, sulfonamide, sulfasalazine, allopurinol, and some types of non-steroidal anti-inflammatory drugs. Most people who develop TEN do so within the first four weeks of starting these treatments.
Other possible causes of TEN could also be infections such as a type of pneumonia called mycoplasma pneumonia, hepatitis A, and a type of virus called human herpesvirus 7. Certain forms of cancer, like those affecting the liver and lungs, are linked to it too. Some vaccines, notably the vaccine for meningitis, might also trigger it. Recent reports have even linked TEN to COVID-19, triggered by either the virus itself or the medications used in its treatment.
Risk Factors and Frequency for Toxic Epidermal Necrolysis
In the United States, the occurrence rate of TEN is estimated at 1.9 per million adults yearly, and SJS affects about 9.3 per million people each year. Different regions of the world report varying figures. In 1996, a German study estimated the yearly rate of both SJS and TEN cases at around 1.9 per million people. Between 1995 and 2013, the United Kingdom reported as many as 5.76 cases per million residents each year. In Japan, about one in a million adults per year is affected by TEN.
Research indicates that individuals of Asian and African descent are more susceptible than the white population, with some studies pointing to a two-fold increased risk in these groups. Women are also more prone to these conditions than men, with a female to male ratio of 1.5 to 1. The majority of those affected by TEN are in their 50s to 70s, but it can happen at any age. Mostly, adults get these conditions due to reactions to drugs, while in children, infections are often the cause. Recent studies have found a link between certain HLA alleles and the development of TEN, particularly in the Southeast Asian population.
- In the United States, TEN affects about 1.9 per million adults yearly, and SJS affects approximately 9.3 per million people each year.
- A German study found the yearly rate of both SJS and TEN at around 1.9 per million people.
- The United Kingdom reported up to 5.76 cases per million residents each year, between 1995 and 2013.
- In Japan, TEN affects about one per million adults yearly.
- Individuals of Asian and African descent have a higher risk than the white population.
- Women are more likely to get these conditions than men, with a ratio of 1.5 to 1.
- Majority of those with TEN are aged between 50 to 70, though it can occur at any age.
- In adults, these conditions are mainly caused by drug reactions and infections in children.
- Certain HLA alleles have been linked with the development of TEN, especially in the Southeast Asian population.
Signs and Symptoms of Toxic Epidermal Necrolysis
TEN, or toxic epidermal necrolysis, is often caused by a reaction to medication, typically occurring 1 to 3 weeks after starting a new treatment. As such, it’s extremely important to keep track of any recent changes in medication. However, it’s worth noting that about 5% of cases occur without any recent drug use.
The early symptoms of TEN are similar to the flu and can include fever, general discomfort, joint pain, a runny nose, and headaches. This stage can last between 1 to 21 days. The next stage involves a skin rash that starts as a red or purple mottled area and develops into blisters. The blisters then merge to form large areas of loose skin, which eventually peels off, leaving a raw surface underneath. This rash usually starts on the face and upper chest before spreading to the rest of the body. The scalp is usually unaffected. Light pressure on the skin can cause it to peel – this is known as the Nikolsky sign, but it is not unique to TEN and can occur with other skin disorders. The speed at which the rash progresses can vary, but it typically happens over 2 weeks and can spread to cover the entire body within 24 hours. In severe cases, previously healed skin may be affected again.
Almost all patients with TEN suffer from red and eroded areas on their mucous membranes, which typically appear 1 to 3 days before the skin rash. The most commonly affected areas are the mouth, eyes, and genitals, but other areas like the respiratory and digestive tracts can also be affected. A normal chest x-ray doesn’t rule out harm to the lungs. Eye complications can be serious and range from redness and swelling of the eyelids and conjunctivitis to ulcers on the cornea. Additionally, the disease can trigger a massive release of immune system chemicals (cytokines), leading to severe health problems such as infection, organ failure, and severe bleeding from the digestive system. These complications contribute to the high mortality rate associated with TEN, which is about 30%.
Testing for Toxic Epidermal Necrolysis
To diagnose TEN, or toxic epidermal necrolysis, doctors usually have to examine a small piece of the affected skin under a microscope. This procedure, known as a skin biopsy, helps confirm the diagnosis and establish a treatment plan. Even though no specific blood tests can diagnose TEN, basic screenings like complete blood count and liver function tests are necessary. These tests help in planning the supportive treatment, spotting any organ failures, and determining the overall prognosis or likely course of the disease.
Anemia, a condition where your body lacks enough healthy red blood cells, and lymphopenia, a low level of a certain type of white blood cell, are commonly seen in people with TEN. But if the patient has neutropenia, which means a too low level of a certain kind of white blood cell called a neutrophil, it could indicate a less favorable outcome.
It’s important to keep certain elements of the patient’s blood within normal levels, especially for patients suffering from extensive mucosal affection, marked by damage to the thin, moist tissues that line some parts of the inside of your body. This is because they might be at risk of severe bleeding, particularly from the gastrointestinal system. In such cases, the patient might even need a transfusion of blood or blood products.
Medical imaging studies, like X-rays, are not crucial for diagnosing TEN, but they might be used to check for complications like lung issues. Another useful test could be the patch test, which might help identify the cause of the TEN in around half of the patients by exposing the skin to small amounts of various substances and checking for an allergic reaction.
The severity of TEN and the mortality rate, or likelihood of death, are often gauged using a tool known as the SCORTEN scale. This assesses seven factors during the first 24 hours of presentation at the hospital, including age, heart rate, presence of cancer or blood cancer, extent of body area affected on the first day, and levels of certain substances in the blood. Based on these factors, a patient’s death rate can vary from 3.2% for one risk factor to over 90% for five or more risk factors.
Treatment Options for Toxic Epidermal Necrolysis
In the treatment of TEN (Toxic Epidermal Necrolysis), the primary goal is to provide supportive care as the skin repairs itself. This involves steps like rehydrating the body, managing pain, caring for the wounds and providing dietary support. At the early stages of this condition, the most important things to do includes stopping the use of the medication causing the condition and referring the patient to a specialist hospital unit for burns or intensive care.
During the treatment, doctors will have to frequently check the patient’s airways, providing additional oxygen with a face mask if necessary. If the patient is struggling to breathe, an expert might perform a procedure called endotracheal intubation to help their breathing. Doctors also make sure that the body gets enough fluid to function properly. Care should be taken for managing the patient’s pain, often with the use of potent painkillers. Dressings are used on the damaged skin areas, and preventive measures are taken to ensure that the patient doesn’t fall into a dangerously low body temperature state.
It’s important to provide nutritional support to patients with TEN as this condition can increase the body’s metabolic rate. Dietary support can be provided either through the mouth or, if the oral cavity is badly affected, via a nasal feeding tube. The energy requirements and nutritional supplements will be calculated carefully.
Doctors will provide aseptic wound care to prevent infections as the skin recovers, with skin lesions usually healing within two weeks. In case the doctor decides to clean the wound (debridement), this is usually done under general anesthesia. There are various options for dressing the wound, such as biological dressing (like allo-, xeno-, and homografts), biosynthetic dressing (like biobrane), or silver-impregnated dressing. Good wound care can also lessen the patient’s need for painkillers.
Infections are common in TEN and can be fatal. Routine antibiotics are not recommended as a preventive measure as they do not change survival rates, but doctors will routinely assess the skin for signs of early infection. If the doctor suspects an infection based on the skin swab results, the patient’s general health, or their body temperature, they might decide to administer antibiotics to counter the infection.
Although various treatment options have been suggested, including different medications and procedures, their effectiveness has not been definitively proven. For instance, plasmapheresis (a procedure that filters the blood), anti-TNF (a treatment that targets inflammation), or IVIG (immune-strengthening treatment) might be used. However, the benefits of these therapies are based primarily on anecdotal evidence and are typically based on small-scale observational studies. The effectiveness of these treatments is difficult to establish due to the rarity of TEN.
The patient may also experience complications involving the eyes or the genital and urinary systems. Early consultation with an eye specialist is crucial, alongside treatments like topical lubricants or antibiotic or steroid eye drops. For complications related to the genital and urinary systems, topical estrogen is applied to promote mucosal healing. In serious situations, the menstrual cycle might have to be stopped to reduce the risk of a condition called vaginal adenosis. Depending on their symptoms, the patient might also need to see other specialists, like urologists and ear, nose, and throat specialists. After treatment, patients with TEN might also need psychological support.
What else can Toxic Epidermal Necrolysis be?
Stevens-Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN) are essentially different severity levels of the same disease. The difference boils down to how much skin is affected. If less than 10% of the total skin area is affected, it’s classified as SJS. If more than 30% of the skin is affected, it’s considered TEN. If the affected skin area falls between 10 to 29%, it’s a combination of both conditions. Another similar condition is erythema multiform major (EMM), which mainly impacts less than 10% of skin and is identified by certain target-like skin changes, possibly with or without blistering. Unlike EMM, SJS and TEN usually start with red spots or blemishes on the skin that turn into blisters, mainly located on the face and body. In 90% of SJS and TEN cases, at least 2 mucus-lined tissues, such as mouth or eyes, are involved.
Other conditions that could be mistaken for SJS or TEN include:
- Other drug-induced skin conditions
- Toxic shock syndrome, which often starts off with organ failures and specific skin rashes that later peel off
- Paraneoplastic pemphigus, a skin condition linked to cancer
- Exfoliative erythroderma, which only affects the skin and doesn’t cause pain in most cases
- Staphylococcal scalded skin syndrome in children, which is linked to a certain type of bacterial infection and typically doesn’t affect the mucous membranes
A skin biopsy is a useful method to help differentiate SJS and TEN from these other conditions.
What to expect with Toxic Epidermal Necrolysis
The death rate for Toxic Epidermal Necrolysis (TEN), a serious skin condition, is reported to be between 25 and 30%. This is quite high when compared to Stevens-Johnson Syndrome (SJS) where the percent of patient deaths is between 1 to 5%. How severe the TEN case might be often depends on how much of the skin is affected; the more skin that is damaged, the higher the risk of death. The primary cause of death in these cases often comes from infections. Other life-threatening complications may include adult respiratory distress syndrome (problems with breathing), pulmonary embolism (blockage in the lungs), kidney and heart failure, and gastrointestinal bleeding (bleeding in the stomach and intestines).
In determining the severity of the disease and the chances of survival for each patient, specialists use a system known as SCORTEN. Developed by Bastuji-Garin and her team, this system measures seven variables within the first 24 hours of being admitted to the hospital. These variables include the patient’s age, how much of the body’s surface area is affected, heart rate, whether the patient has cancer (malignancy), and levels of three substances in the blood: urea, glucose, and bicarbonate.
Possible Complications When Diagnosed with Toxic Epidermal Necrolysis
Patients diagnosed with TEN (Toxic Epidermal Necrolysis) can deal with a range of complications because it affects the skin and the lining of the mouth, nose, and other parts of the body. Early symptoms often include painful mouth sores, which can make eating and drinking a challenge, leading to dehydration. When the disease affects the outer layer of the skin, it increases the possibility of infection and blood poisoning. This can progress to a severe drop in blood pressure and failure of multiple organs.
Long-term issues might involve changes in skin color to either lighter or darker than usual. The lining of the body could heal in a constricted way, leading to narrowness and potential issues with bodily functions. Complications for women often include narrowing of the reproductive parts, changes in the cells of the vulva, and painful intercourse. For men, the most common issue is a difficulty pulling back the foreskin.
There could be serious complications related to the eyes in TEN patients. Hence, it’s advised that they consult with an eye specialist early on. These might include cornea damage, dry eye, a certain type of eyelid infection, inflammation of the entire eyeball, or even complete blindness.
The complications may extend to the lungs causing blood clots, acute respiratory distress syndrome, and pneumonia. There might also be complications in the digestive system such as extensive internal bleeding, gum adhesions, and dry mouth due to affected salivary glands.
Effects of TEN:
- Dehydration from painful mouth sores
- Increased risk of infection and blood poisoning
- Potential low blood pressure and multiple organ failure
- Changes in skin color
- Narrowed physical areas due to constrictions
- Painful intercourse in women
- Difficulty pulling back the foreskin in men
- Potential eye complications, including blindness
- Pulmonary embolism, ARDS, and pneumonia
- Internal bleeding, gum adhesions, and dry mouth
Preventing Toxic Epidermal Necrolysis
Patients who have been diagnosed with Toxic Epidermal Necrolysis (TEN) in the past should be advised not to use the drug that caused this condition again and any similar types of medicine. This is because there’s a risk the same reaction might occur with similar drugs. Patients also need to understand the importance of protecting their skin from the sun and using sunscreen to prevent changes in skin color that can happen after inflammation. Some patients might need emotional support for a long time after this experience, and this should be assessed for each patient before they leave the hospital.
