Erythema multiforme

Related Terms

Adenoviral conjunctivitis, allergic, allergic reaction, allergic response, antibodies, blister, bullous systemic lupus erythematosus, drug allergy, drug-induced, drug reaction, erythroderma ichthyosiform congenital, erythema multiforme, erythema multiforme major, idiopathic, immune-complex-mediated, immune defense system, immune system, immunoglobulin, immunosuppressant, intravenous immunoglobulin therapy, IVIG, lesion, mucocutaneous, pinkeye, rash, skin disease, skin disease, skin disorder, skin lesion, Stevens Johnson syndrome, systemic disorder.

Background

Stevens-Johnson syndrome (SJS) is a type of allergic reaction that usually occurs in response to medications. It is a severe type of erythema multiforme, which is a skin disease characterized by skin eruptions and blisters. SJS is a less severe form of another disease called toxic epidermal necrolysis (TENS).
Pediatricians, A.M. Stevens and S.C. Johnson, discovered the disease in 1922 when they treated two young male patients with skin lesions, fever, inflamed mucosa and conjunctivitis (pinkeye).
SJS is a systemic disorder that is potentially life threatening, especially if left untreated. About 3-15% of patients with severe SJS die. In severe cases, the lesions can cause significant scarring of the involved organs, which often leads to loss of function of the organ systems. For instance, restriction of the esophagus and of the respiratory tract can occur due to lesions and scaring.
SJS typically involves many areas of the body and extensive lesion formation. The lesions can extend to the mucous membranes and affect any organ, including the lungs, eyes, mouth, stomach and intestines. The disease can cause severe damage to the mouth, nose, eye, vagina, urethra, gastrointestinal tract and/or lower respiratory tract.
It is estimated that about one million Americans are diagnosed with SJS each year.
SJS is an immune-complex-mediated hypersensitivity disorder that may be caused by medications, viral infections and malignancies (cancers). In up to half of cases, no specific etiology has been identified.
The ratio of male to female occurrence is two to one. Since the causes of SJS are not well understood, it is unclear why it is more common among males.
Currently, there is no treatment for the specific disease. Instead, treatment focuses on alleviating the symptoms. In general, the condition lasts about two to six weeks.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Hebert AA, Bogle MA. Intravenous immunoglobulin prophylaxis for recurrent Stevens-Johnson syndrome. J Am Acad Dermatol 2004; 50(2): 286-288.
National Library of Medicine. .
Natural Standard: The Authority on Integrative Medicine. .
Stevens Johnson Syndrome Foundation. .

Causes

Drug-induced: Almost any medication, including over-the-counter medications, like ibuprofen (Motrin? or Advil?) may lead to SJS. Medications most often associated with SJS include penicillins and sulfa antibiotics.
Anticonvulsants (like phenytoin, carbamazepine, valproic acid and lamotrigine) and nonsteroidal ant-inflammatory drugs (NSAIDs) have also caused SJS.
In late 2002, the U.S. Food and Drug Administration (FDA) and the manufacturer Pharmacia noted that SJS had been reported in patients taking the cyclooxygenase-2 (COX-2) inhibitor valdecoxib.
There have also been recent reports of cocaine-induced SJS.
Herbs/supplements: Since many herbs or supplements have pharmaceutical properties, they may also cause SJS in some patients. SJS has been reported with the use of ginseng-containing products, as well as belladonna and Ginkgo biloba.
Infection: More than half of the patients with SJS report having had a recent upper respiratory tract infection before the onset of SJS. Viral diseases that are commonly associated with SJS include herpes simplex virus (HSV), AIDS, coxsackie viral infections, influenza, hepatitis, mumps, mycoplasmal infection, lymphogranuloma venereum (LGV), rickettsial infections and variola (smallpox).
Tumor-related: Various cancers and lymphomas have been associated with SJS. Tumor-related SJS is more common among adults than children.
Idiopathic: When the cause of SJS is unknown, it is considered idiopathic. About 25-50% of SJS cases are idiopathic.

Symptoms

About 3-15% of patients with severe SJS die. SJS is potentially life threatening because in severe cases, the lesions can cause significant scarring of the involved organs, which often leads to loss of function of the organ systems.
The disease typically starts with a nonspecific upper respiratory tract infection. The patient may experience flu-like symptoms, including, fever, sore throat, chill, headache and malaise (generally feeling of discomfort) for anywhere from one to 14 days. Some individuals will also experience diarrhea and vomiting.
As the disease progresses, mucocutaneous (mucus membrane and the skin) lesions quickly develop. Patients may experience extensive sloughing (shedding of the skin). Skin lesions may occur anywhere, but they are most common on the palms, soles of the feet, back of the hands and extremities. Mucosal involvement may include erythema (reddening of the skin), edema (fluid in body tissues), blistering, ulceration (open sore on the skin) and necrosis (dead skin). Clusters of outbreaks generally last about two to four weeks.
Lesions may become bullous and rupture, making the skin vulnerable to secondary infection. The lesions usually do not itch.
Lesions in the mouth and/or mucous membranes may make it difficult for the patient to eat or drink. Patients who experience symptoms in the genitourinary tract may also experience painful urination.
Other common symptoms of SJS include, persistent fever, swelling of eyelids or red eyes, conjunctivitis (pinkeye), flu-like symptoms, tachycardia, low blood pressure, epistaxis (nosebleeds), seizures or coma.
SJS is a life-threatening reaction, if left untreated. Complications may include permanent blindness, dry-eye syndrome, photophobia (sensitivity to light), lung damage, chronic obstructive pulmonary disease (COPD), asthma, permanent loss of nail beds, scarring of the esophagus and other mucous membranes, arthritis and chronic fatigue syndrome. Extensive skin involvement may cause the loss of large quantities of body fluids, causing shock in addition to the risk of infection.

Treatment

If the condition is drug-induced, the affected individual should stop taking the offending medication immediately. No specific drug treatment exists for SJS. Recovery may take two to six weeks. Severe cases may require hospitalization in an intensive care unit or burn unit, where the patient will receive intravenous fluids and nutritional supplements.
Acetaminophen: Acetaminophen (Tylenol?) has been used to reduce fever and discomfort associated with SJS.
Antibiotics: Antibiotics are prescribed to treat secondary infections that are often associated with SJS. Commonly prescribed antibiotics include penicillin, amoxicillin, erythromycin and cefadroxil.
Corticosteroids: The use of systemic corticosteroids is controversial. High doses taken early in the reaction have been effective. However, they might increase risk of secondary infections because of their immunosuppressive properties.
Immunosupressants: Immunosuppressants like cyclophosphamide and cyclosporine have been used to treat allergic symptoms.
IVIG: Human intravenous immunoglobulin (IVIG) has been used to treat severe cases of SJS. IVIG may help prevent secondary infections in patients suffering from SJS by increasing immunoglobulin levels in the bloodstream.
Moist compress: For mild symptoms, a moist compress has been applied to skin lesions. Areas of denuded skin should be covered with compresses of saline or burow solution.
Oral rinse: Analgesic mouth rinse has been used to treat mouth ulcers associated with SJS.
Topical anesthetics: Topical anesthetics like lidocaine (Lidoderm?) have been applied to the skin to relieve pain associated with lesions.

Prevention

Avoid exposure to known antigens that have caused SJS in the past.
Consider wearing a medical alert ID bracelet or necklace.

Adverse effect vs. allergic reaction

Not all adverse reactions to drugs are allergies. In fact, less than 10 percent of adverse drug reactions are allergic because most drug side effects are not related to the immune system. Instead, the drug directly affects various organs throughout the body.
For instance, a nasal decongestant constricts the capillaries in the nose in order to reduce nasal swelling and open the airway passages. However, a side effect is that it also constricts the capillaries in other regions of the body, which may lead to an increased heart rate, headache, dizziness or increased blood pressure. Since a decongestant is not specific to a single part of the body or one single action, many people could experience side effects. Therefore, it is a non-allergic reaction because the body's immune system is not involved.
Other causes of adverse reactions include interactions between two or more drugs, overdose or the body's inability to break the drug down completely as a result of liver or kidney damage.
Allergic reactions can be classified into four immunopathologic categories using various classification systems. These classifications are based on the immune system's response to the allergen, not on the severity of the reaction.
SJS is technically an immune-complex-mediated hypersensitivity (allergic) condition. Therefore, SJS is a type III allergic reaction. This category involves the formation of an antigen-antibody immune complex, which deposits on blood vessel walls and activates cell components known as complements. This causes a serum-sickness like syndrome, involving fever, swelling, skin rash and enlargement of the lymph nodes in about three to eight hours. It may be caused by a variety of allergens, including penicillins, sulfonamides, intravenous (IV) contrast media and hydantoins.

Support for patients

The Steven Johnson Syndrome Foundation is an online resource for SJS patients and their families. The organization aims to provide support services, information about SJS treatments and therapies to both healthcare professionals and the public. The goal of the organization is to promote awareness about the disease so that a quick diagnosis can be made and quality treatment can begin.
More information can be found at the Steven Johnson Syndrome Foundation website, www.sjsupport.org.