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Disease Profile

Stevens-Johnson syndrome/toxic epidermal necrolysis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

All ages

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ICD-10

L51.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

SJS/TEN; Drug-induced Stevens Johnson syndrome; Stevens-Johnson syndrome;

Categories

Immune System Diseases; Skin Diseases

Summary

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.[1] 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.[2] 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."[1] All forms of SJS/TEN are a medical emergency that can be life-threatening.[2][3]

The first symptoms of SJS/TEN often include fever and flu-like symptoms (such as general ill feeling, body aches, and cough).[1][3] Within about 1 to 3 days, a red or purplish rash forms, and then the skin begins to blister and peel, leading to "raw" areas of skin that are painful.[1][2] This often starts on the face and then spreads to other parts of the body.[1][2] The mucous membranes may also become involved during this time, which can lead to symptoms such as severe conjunctivitis (when the eyes are affected), trouble swallowing and breathing (when the mouth and airway are affected), and difficulty urinating and genital pain (when the genitals are affected).[1][2]

SJS/TEN often is triggered by certain medications including  allopurinol, anti-epileptics, pain relievers, cancer therapies, or antibiotics (sometimes up to 2 weeks after stopping the medication). SJS/TEN can also be triggered by infections such as pneumonia, herpes virus, and hepatitis A. In many cases the cause cannot be identified.[2][3] People that may be at increased risk to develop SJS/TEN include those with HIV, a weakened immune system, a personal or family history of the condition, and certain variations of a gene called HLA-B.[2][3] There are no universal diagnostic criteria for SJS/TEN. Currently the diagnosis is based on the person's medical history and symptoms.[1] People suspected of having SJS/TEN should be admitted to the hospital to confirm the diagnosis and assess severity.[4] 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.[1]

Treatment needs should be assessed in the hospital to determine severity and where treatment should be provided (e.g. intensive care unit, burn unit, or dermatology unit). Treatment may involve stopping a triggering medication (for those suspected of having medication-induced SJS/TEN), standard therapies used for major burns, various eye treatments (for those with eye involvement), pain control, and preventing and treating infections.[4] The overall mortality 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. Those that survive may experience recurrence (particularly if re-exposed to a trigger) and/or long-term complications involving the skin and affected mucous membranes.[4]

Symptoms

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) often begins with a fever and flu-like symptoms, such as cough, sore throat, body aches, tiredness, and a general ill feeling.[1][3] Within about 1 to 3 days, a reddish or purplish rash forms and the skin begins to blister and peel (detach), leading to "raw" areas of skin that are painful.[1][2] These skin symptoms usually begin on the face and chest, and then spread to other parts of the body.[1][2] The percentage of body surface area affected can vary significantly from person to person. When skin detachment occurs on less than 10% of the body surface, the condition is classified as Stevens-Johnson syndrome (SJS). When skin detachment occurs on over 30% of the body surface, the condition is classified as toxic epidermal necrolysis (TEN). People with 10% to 30% of the body surface affected are said to have "SJS/TEN overlap."[1]

The mucous membranes (thin, moist tissues that line body cavities) of the mouth, throat, genitals, eyes, and/or digestive tract usually also are involved, and may become affected before or after the skin.[1] Early symptoms of mucous membrane involvement may include light sensitivity, itching or burning of the eyes, and pain when swallowing.[1] As the condition progresses, eye symptoms may include pain, severe conjunctivitis, discharge, iritis, and corneal blisters. Eye involvement can lead to long-term eye complications, including vision loss.[1][2][5] Symptoms of mouth and throat involvement may include painful blisters, and trouble swallowing and breathing. Symptoms of genital involvement may include inflammation of the urethra, vaginitis, painful blisters, and difficulty urinating.[1][2] Gastrointestinal symptoms may include diarrhea, black or tarry stools, and other complications.[1]

Symptoms may persist or worsen for up to two weeks before the skin and mucous membranes begin to start healing themselves. Skin that remained attached may gradually peel during this time, and the nails may shed in some cases.[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal blistering of the skin
Blistering, generalized
Blisters

[ more ]

0008066
Acantholysis
0100792
Diarrhea
Watery stool
0002014
Erythema
0010783
Fatigue
Tired
Tiredness

[ more ]

0012378
Fever
0001945
Macule
Flat, discolored area of skin
0012733
Nausea and vomiting
0002017
Weight loss
0001824
30%-79% of people have these symptoms
Abnormality of neutrophils
0001874
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
Excessive salivation
Mouth watering
Oversalivation
Watery mouth

[ more ]

0003781
5%-29% of people have these symptoms
Abdominal pain
Pain in stomach
Stomach pain

[ more ]

0002027
Abnormal myocardium morphology
0001637
Abnormal pleura morphology
0002103
Abnormality of the urethra
Urethra issue
0000795
Acute hepatic failure
Acute liver failure
0006554
Anemia
Low number of red blood cells or hemoglobin
0001903
Conjunctivitis
Pink eye
0000509
Corneal erosion
Damage to outer layer of the cornea of the eye
0200020
Cough
Coughing
0012735
Dyspareunia
0030016
Dyspnea
Trouble breathing
0002094
Dysuria
Painful or difficult urination
0100518
Elevated hepatic transaminase
High liver enzymes
0002910
Entropion
Eyelid turned in
0000621
Esophageal stricture
Narrowing of esophagus due to inflammation and scar tissue
0002043
Gastrointestinal hemorrhage
Gastrointestinal bleeding
0002239
Hypokalemic metabolic alkalosis
0001960
Myocardial infarction
Heart attack
0001658
Pancreatitis
Pancreatic inflammation
0001733
Photophobia
Extreme sensitivity of the eyes to light
Light hypersensitivity

[ more ]

0000613
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

0002205
Renal insufficiency
Renal failure
Renal failure in adulthood

[ more ]

0000083
Restrictive ventilatory defect
Stiff lung or chest wall causing decreased lung volume
0002091
Sepsis
Infection in blood stream
0100806
Sudden cardiac death
Premature sudden cardiac death
0001645
Thrombocytopenia
Low platelet count
0001873
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

0000505

Cause

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is most often a reaction to a medication or infection.[3][6][7] Some researchers suspect that a combination of medication and infection may trigger the condition in some people. In many cases, no particular trigger of any kind is identified.[2]

Medications most commonly associated with SJS/TEN include:[1][2][6]

  • 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 [1] 

Infections that may be associated with SJS/TED include:[2][3][6]

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:[1][2][3][6]

  • 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.

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.[4]

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.[4][6]

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.[6][4]

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:[4][6]

  • 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.[4]

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • MayoClinic.com has an information page on Stevens-Johnson syndrome/toxic epidermal necrolysis.
  • MedlinePlus Genetics contains information on Stevens-Johnson syndrome/toxic epidermal necrolysis. This website is maintained by the National Library of Medicine.
  • The Merck Manuals Online Medical Library provides information on this condition for patients and caregivers.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
    Stevens-Johnson syndrome
    Toxic Epidermal Necrolysis (TEN)
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Stevens-Johnson syndrome/toxic epidermal necrolysis. Click on the link to view a sample search on this topic.

References

  1. High WA. Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis. UpToDate. Waltham, MA: UpToDate; Updated March 12, 2019; https://www.uptodate.com/contents/stevens-johnson-syndrome-and-toxic-epidermal-necrolysis-pathogenesis-clinical-manifestations-and-diagnosis.
  2. Stevens-Johnson syndrome/toxic epidermal necrolysis. Genetics Home Reference (GHR). July 2015; https://ghr.nlm.nih.gov/condition/stevens-johnson-syndrome-toxic-epidermal-necrolysis.
  3. Stevens-Johnson syndrome. MayoClinic.com. March 9, 2018; https://www.mayoclinic.org/diseases-conditions/stevens-johnson-syndrome/symptoms-causes/syc-20355936.
  4. High WA, Roujeau J-C. Stevens-Johnson syndrome and toxic epidermal necrolysis: Management, prognosis, and long-term sequelae. UpToDate. Waltham, MA: UpToDate; May 25, 2018; https://www.uptodate.com/contents/stevens-johnson-syndrome-and-toxic-epidermal-necrolysis-management-prognosis-and-long-term-sequelae.
  5. Kang MH. Ocular Manifestations of Stevens Johnson Syndrome and Toxic Epidermal Necrolysis. Hanyang Med Rev. 2016; 36:174-81. https://synapse.koreamed.org/pdf/10.7599/hmr.2016.36.3.174.
  6. Foster CS. Stevens-Johnson Syndrome. Medscape Reference. December 29, 2017; https://emedicine.medscape.com/article/1197450-overview#showall.
  7. Harr T, French LE. Stevens-Johnson syndrome. Orphanet Journal of Rare Diseases. 2010; 5:39:https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-39.
  8. Creamer D, Walsh SA, Dziewulski P, Exton LS, Lee HY, Dart JK, Setterfield J, Bunker CB, Ardern-Jones MR, Watson KM, Wong GA, Philippidou M, Vercueil A, Martin RV, Williams G, Shah M, Brown D, Williams P, Mohd Mustapa MF, Smith CH. U.K. guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016. Br J Dermatol. June 2016; 174(6):1194-227. https://www.ncbi.nlm.nih.gov/pubmed/27317286.

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