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What is Systematic Lupus Erythematosus (SLE)?
SLE is an autoimmune disease that causes a chronic inflammatory condition. The inflammation triggered by SLE can affect many organs in the body, including skin, joints, kidneys, lung, and nervous system. Women (especially African-American and Asian women) have a higher risk than men for developing SLE.
Symptoms and Diagnosis
SLE has a wide range of symptoms. The most common symptoms are joint pain, skin rash, and fever. Symptoms can develop slowly or appear suddenly. Many patients with SLE have "flares," in which symptoms suddenly worsen and then settle down for long periods of time. Diagnosing SLE is complicated because symptoms vary widely and can resemble other conditions. A doctor will base an SLE diagnosis on certain specific criteria including symptom history and the results of blood tests for antinuclear antibodies.
No drug can cure SLE, but many different drugs can help control symptoms and relieve discomfort. The choice of drugs depends on the severity of the condition as well as other factors. Patients with mild SLE may be helped by nonsteroidal anti-inflammatory drugs (NSAIDs) while patients with more severe SLE may require corticosteroids or immunosuppressants. Belimumab (Benlysta) is a biologic drug that is used along with standard drug treatments for patients with active lupus. Researchers are working to develop new drugs and treatments for SLE.
Living with SLE
Patients can make lifestyle changes to help cope with SLE. These include:
Guidelines for Lupus Nephritis
The American College of Rheumatology has guidelines for the treatment of lupus-associated kidney disease (lupus nephritis). Recommendations include:
Systemic lupus erythematosus (SLE) is a chronic life-long, autoimmune disease. It can be mild to severe, and affects mostly women. SLE may affect various parts of the body, but it most often manifests in the skin, joints, blood, and kidneys. The name describes the disease:
There are several different forms of lupus. SLE is the most common type and is the type of lupus that can lead to serious systemic complications. Other forms of lupus include:
Systemic lupus erythematosus (SLE) is an autoimmune disorder. In a normal immune system, the body releases proteins (antibodies) to fight viruses, toxins and other potentially harmful foreign substances (antigens). With lupus and other autoimmune diseases, the immune system does not work properly. It produces autoantibodies that mistakenly attack and destroy the body's own healthy cells and tissue. These autoantibodies also trigger inflammation, which can lead to organ damage.
Autoantibodies called antinuclear antibodies (ANA) are detectable in most, although not all, patients with SLE. Tests for the presence of ANA are used as part of the diagnostic work-up for the condition. (For more information, see "ANA Tests" in Diagnosis section of this report.)
Scientists do not know exactly what causes the abnormal immune response associated with autoimmune disorders. It is most likely a combination of genetic and environmental factors. People who develop an autoimmune disease may have a genetic predisposition that is triggered by some environmental factor such as sunlight, stress hormones, or viruses. It does not appear that one gene alone is responsible for lupus. Researchers estimate that 20 to 100 different genetic factors may make a person susceptible to SLE.
About 90% of lupus patients are women, most diagnosed when they are in their childbearing years (20s and 30s). (Female hormones may play a role.) Men are at higher risk for lupus before age 18 and after age 50.
Most people develop SLE between the ages of 15 to 44. About 15% of patients experience the onset of symptoms before age 18.
African-Americans are three to four times more likely to develop the disease than Caucasians and to have severe complications. Hispanics, Asians, and Native American women are also more susceptible to the disease.
Lupus very often runs in families but people without a family history of lupus can also develop it. Lupus is also more common in families whose members have other autoimmune disorders.
In genetically susceptible people, there are various external factors that can trigger symptoms (flares). Possible SLE triggers include colds, fatigue, stress, chemicals, sunlight, and certain drugs.
Viruses. Some research suggests an association between Epstein-Barr virus (EBV), the cause of mononucleosis, and increased risk of lupus. Other viruses or infections can also trigger SLE.
Sunlight. Ultraviolet (UV) rays found in sunlight are important SLE triggers. UV light is categorized as UVB or UVA depending on the length of the wave. Shorter UVB wavelengths cause the most harm.
Stress. Emotional or physical stress can trigger SLE flares.
Smoking. Smoking is a risk factor for SLE and can increase the risk for skin and kidney problems in women who have the disease. Long-term heavy smokers are at highest risk.
Chemicals. While no chemical has been definitively linked to SLE, occupational exposure to crystalline silica has been studied as a possible trigger. (Silicone breast implants have been investigated as a possible trigger of autoimmune diseases, including SLE. The weight of evidence to date, however, finds no support for this concern.) Some prescription medications are associated with a temporary lupus syndrome (drug-induced lupus), which resolves after these drugs are stopped.
Hormone Replacement Therapy. Premature menopause, and its accompanying symptoms (such as hot flashes), is common in women with SLE. Hormone replacement therapy (HRT), which is used to relieve these symptoms, increases the risk for blood clots and heart problems as well as breast cancer. It is not clear whether HRT triggers SLE flares. Women should discuss with their doctors whether HRT is an appropriate and safe choice. Guidelines recommend that women who take HRT use the lowest possible dose for the shortest possible time. Women with SLE who have active disease, antiphospholipid antibodies, or a history of blood clots or heart disease should not use HRT.
Oral Contraceptives. Female patients with lupus used to be cautioned against taking oral contraceptives (OCs) due to the possibility that estrogen could trigger lupus flare-ups. However, recent evidence indicates that OCs are safe, at least for women with inactive or stable lupus. Women who have been newly diagnosed with lupus should avoid OCs. Lupus can cause complications in its early stages. For this reason, women should wait until the disease reaches a stable state before taking OCs. In addition, women who have a history of, or who are at high risk for, blood clots (particularly women with antiphospholipid syndrome) should not use OCs. The estrogen in OCs increases the risk for blood clots.
Systemic lupus erythematosus (SLE) can cause complications throughout the body.
Blood problems are common with SLE.
Anemia. About half of patients with SLE are anemic. Causes include:
Hemolytic anemia can occur with very high levels of the anticardiolipin antibody. It can be chronic or develop suddenly and be severely (acute).
Antiphospholipid Syndrome. Many patients with SLE have antiphospholipid syndrome (APS). This is a disorder of blood coagulation related to the presence of autoantibodies called lupus anticoagulant and anticardiolipin. APS can cause blood clots, which most often occur in the deep veins of the legs, a condition called deep vein thrombosis. Blood clots increase the risk for stroke and pulmonary embolism (clots in the lungs). Patients with APS are also at high risk for pregnancy complications, including miscarriage (see Pregnancy Complications below).
Vasculitis. Vasculitis is an inflammation of the blood vessels. If it becomes severe, it can cause blood to stop flowing to organs and tissues, resulting in potentially life-threatening complications.
Thrombocytopenia. In thrombocytopenia, antibodies attack and destroy blood platelets. In such cases, blood clotting is impaired, which causes bruising and bleeding from the skin, nose, gums, or intestines.
Leukopenia and Neutropenia. These conditions cause a drop in the number of white blood cells. Severe reductions in white blood cell counts can increase the risk for infections.
Blood Cancers. Patients with SLE and other autoimmune disorders have a greater risk for developing lymph system cancers such as Hodgkin's disease and non-Hodgkin's lymphoma (NHL).
The risk for coronary artery disease, heart attack, and stroke is much higher than average in patients with SLE, and heart disease is a primary cause of death. The chronic inflammation associated with SLE can cause plaque build-up in the heart's arteries (atherosclerosis), which can lead to coronary heart disease and heart attack. SLE also affects blood vessels and circulation. In addition, SLE treatments (particularly corticosteroids) can affect cholesterol, weight, and other factors that harm the heart.
Patients with SLE have an increased risk for developing the following conditions, which put them at risk for heart attack or stroke:
SLE affects the lungs in several ways:
Kidney complications such as inflammation of the kidneys (lupus nephritis) are common in SLE. About a third of patients have lupus nephritis at the time of diagnosis and more than half develop it within 10 years after lupus symptoms begin. In its early stages, lupus nephritis can cause fluid build-up leading to swelling in the extremities (feet, legs, hands, arms) and overall weight gain. If left untreated, lupus nephritis may progress to complete kidney failure (end-stage renal disease).
Nearly all patients with SLE report some symptoms relating to problems that occur in the central nervous system (CNS), which includes the spinal cord and the brain. SLE can also affect the peripheral nervous system, which transmits and receives motor and sensory information from the central nervous system.
Symptoms vary widely and may overlap with psychiatric or neurologic disorders. They may also be caused by of some medications used for treating SLE.
CNS side effects associated with SLE include:
Infections are a common complication and a major cause of death in all stages of SLE. Patients are not only prone to the ordinary bacterial and viral infections, but they are also susceptible to fungal and parasitic infections, which are common in people with weakened immune systems. They also face an increased risk for urinary tract, herpes, salmonella, and yeast infections. Corticosteroid and immunosuppressant drug treatments used for SLE also increase the risk for infections.
Many patients with SLE suffer gastrointestinal problems, including nausea, weight loss, mild abdominal pain, diarrhea, and gastroesophageal reflux disorder (heartburn). SLE can also affect organs located in the gastrointestinal system, such as the liver, gallbladder, pancreas, and bile ducts.
Patients with SLE often experience muscle aches and weakness. Lupus can also cause pain, stiffness, and swelling in the joints. However, unlike rheumatoid arthritis, the arthritis caused by SLE almost never leads to destruction or deformity of joints. Patients with SLE also commonly experience reductions in bone mass density (osteoporosis) and have a higher risk for fractures, whether or not they are taking corticosteroids (which can increase the risk for osteoporosis). Women who have SLE should have regular bone mineral density scans to monitor bone health.
Many patients with SLE have problems with dry eyes. Retinal vascular lesions (blood vessel damage due to reduced blood flow) are also common and may affect vision. Nerve damage in the eyes can also cause poor vision as well as droopy eyelids. It is not uncommon for patients with SLE to also have Sjögren's syndrome, another type of autoimmune disorder characterized by dry eyes. Certain antimalarial drugs used to treat SLE can also cause eye complications.
Women with lupus face a higher risk for pregnancy complications, including miscarriage, premature birth, and preeclampsia. The risk for miscarriage is highest for patients with antiphospholipid antibodies, which can cause blood clotting in the placenta. Lupus patients with active kidney disease are at increased risk for preeclampsia (a pregnancy complication that includes high blood pressure and fluid build-up). Pregnant women who take corticosteroids face increased risks of gestational diabetes and high blood pressure.
Despite these obstacles, many women with lupus have healthy pregnancies and deliver healthy babies. To increase the odds of a successful pregnancy, it is important for women to plan carefully before becoming pregnant. (See "Pregnancy and SLE" in Treatment section of this report.)
SLE is a chronic and relapsing inflammatory disease. It is marked by periods of remission (no symptoms) that alternate with flares of active disease when symptoms suddenly worsen. Flares tend to diminish after menopause.
Symptom-free periods can sometimes last for years, but the course of SLE is unpredictable and varies greatly from person to person. Some patients have a mild form of lupus with occasional skin rashes, fever, fatigue, or joint and muscle aches. Sometimes lupus remains in a mild form, other times it may progress to a more severe form. Severe lupus involves serious health complications and extensive internal organ damage (such as the heart, lungs, kidneys, and brain).
Because of more effective and aggressive treatment, the prognosis for SLE has improved markedly over the past two decades. Treatment early in the course of the illness that controls the initial inflammation can help to improve long-term outlook. Over 95% of people with lupus survive at least 10 years, and many patients have a normal lifespan.
SLE symptoms may develop slowly over months or years, or they may appear suddenly. Symptoms tend to vary among patients and different symptoms can occur at different times.
Common symptoms of SLE include:
A number of conditions overlap with or resemble SLE:
SLE can be difficult to diagnose. Symptoms can fluctuate and mimic those of other diseases. A doctor will make a diagnosis of SLE based on symptoms, medical history, physical exam, and blood test for antinuclear antibodies. The doctor may also order other types of laboratory tests.
The American College of Rheumatology (ACR) has a classification system for helping doctors diagnose, or exclude, SLE. According to the ACR, at least four of the 11 criteria should be present for a diagnosis of lupus.
ACR Criteria for Diagnosing Systemic Lupus Erythematosus
1. Butterfly (malar) rash across cheeks and nose
2. Discoid (skin) rash, which appears as scaly raised red patches
3. Photosensitivity -- skin rash or flare of other lupus symptoms that results from ultraviolet light and sun exposure
4. Oral (mouth) ulcers
5. Arthritis in two or more joints; joints will have tenderness and swelling but will not have become deformed
6. Inflammation of the lining around the lungs (pleuritis) or the heart (endocarditis)
7. Evidence of kidney disease
8. Evidence of severe neurologic disease, such as seizures or psychosis not due to other causes
9. Blood disorders, including low red and white blood cell and platelet counts
10. Immunologic abnormalities as evidenced by positive tests for anti-double stranded DNA (anti-dsDNA), anti-Smith (anti-SM), antiphospholipid antibodies, or a false-positive blood test for syphilis
11. Positive antinuclear antibody (ANA) test
Note: A patient must experience four of the criteria before a doctor can classify the condition as SLE. These criteria, proposed by the American College of Rheumatology, are not exclusive criteria for diagnosis, however.
Antinuclear Antibodies (ANAs). A primary test for SLE checks for antinuclear antibodies (ANA), which attack the cell nucleus.
High levels of ANA are found in more than 98% of patients with SLE. Other conditions, however, also cause high levels of ANA, so a positive test is not a definite diagnosis for SLE:
A negative ANA test makes a diagnosis of SLE unlikely but not impossible. High or low concentrations of ANA also do not necessarily indicate the severity of the disease, since antibodies tend to come and go in patients with SLE.
In general, the ANA test is considered a screening test:
ANA Subtypes. Doctors may also test for specific ANA subtypes.
Antiphospholipid Antibodies. Up to half of patients with SLE have antiphospholipid antibodies, which increase the risk for blood clots, strokes, and pregnancy complications. If a doctor suspects SLE blood abnormalities, tests may be able to detect the presence of the two major antiphospholipid antibodies: lupus coagulant antibody and anticardioplin antibody.
As with the ANA, these antibodies have a tendency to appear and disappear. Patients who have these autoantibodies as well as blood clotting problems or frequent miscarriages are diagnosed with antiphospholipid syndrome (APS), which often occurs in SLE but can also develop independently.
Complement. Blood tests of patients with SLE often show low levels of serum complement, a group of proteins in the blood that aid the body's infection fighters. Individual proteins are termed by the letter "C" followed by a number. Common complement tests measure C3, C4, C1q, and CH50. Complement levels are especially low if there is kidney involvement or other disease activity.
Blood Count. White and red blood cell and platelet counts are usually lower than normal and, depending on severity, are used to determine complications, such as anemia or infection.
Erythrocyte Sedimentation Rate (ESR). An erythrocyte sedimentation rate (ESR or sed rate) measures how fast red blood cells (erythrocytes) fall to the bottom of a fine glass tube that is filled with the patient's blood. A high sed rate indicates inflammation.
C-Reactive Protein (CRP). High levels of this blood protein indicate inflammation. Like the ESR, the CRP test cannot tell where the inflammation is located or what is causing it.
If a skin rash is present, the doctor may take a biopsy (a tissue sample) from the margin of a skin lesion. A test known as a lupus band detects immunoglobulin G (IgG) antibodies, which are located just below the outer layer of the tissue sample. They are much more likely to be present with active SLE than with inactive disease.
Kidney Damage (Lupus Nephritis). Kidney damage in patients already diagnosed with SLE may be detected from the following tests:
Patients who are diagnosed with lupus nephritis should continue to receive urine and blood tests every 1 to 3 months to monitor their condition. Regular blood pressure measurements are also important to ensure that the patient's blood pressure does not go above 130/80 mm Hg.
Lung and Heart Involvement. A chest x-ray may be performed to check lung and heart function. An electrocardiogram and an echocardiogram are administered if heart disease is suspected.
No treatment cures systemic lupus erythematosus, but many therapies can suppress symptoms and relieve discomfort. There are also different treatments for the complications associated with lupus. Treatment of SLE varies depending on the extent and severity of the disease.
Four drugs are specifically FDA-approved for the treatment of lupus:
Belimumab (Benlysta) is the newest of these drugs. Approved by the FDA in 2011, it is the first new lupus drug in over 50 years and the first drug developed specifically for treating lupus. Belimumab is a biologic monoclonal antibody drug that inhibits a protein called B lymphocyte stimulator. It is given by infusion in a doctor’s office. Most other lupus drug treatments are pills taken by mouth.
Other drugs that have not been specifically approved for lupus are also commonly used to treat the condition. Researchers are conducting many investigational drug studies, including trials of new biologic drugs.
Less intensive treatments may be effective for symptoms of mild lupus. They include:
More aggressive treatment is needed if there is serious disease progression, as indicated by:
The main approach to treating severe SLE is to suppress the inflammation and overactive immune system with corticosteroids or immunosuppressant drugs. Other types of medications, such as drugs to control high blood pressure, may also be prescribed.
The major complications of the disease must be treated as separate disorders, keeping in mind the specific aspects of SLE.
Women with lupus who conceive face high-risk pregnancies that increase the risks for themselves and their babies. It is important for women to understand the potential complications and plan accordingly. The most important advice is to try to avoid becoming pregnant when lupus is active. Research suggests that the following factors predict a successful pregnancy:
Creams. Steroid creams are often used for skin lesions. However, many patients with cutaneous lupus do not respond to steroids, particularly if they have eruptions that are caused by sun sensitivity. A cream derived from vitamin A (Tegison) may help some lesions that do not clear up with steroid creams.
Sun Protection. Sun protection is essential. Patients should always use sunblock creams (not just sunscreens) and always wear hats and clothing made of tightly woven fabrics.
NSAIDs block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. They can help relieve joint pain and swelling, and muscle pain. There are dozens of NSAIDs.
Side Effects. Long-term, regular use of NSAIDs (with the exception of aspirin) can increase the risk for heart attack, especially for people who have a heart condition. Long-term use of NSAIDs also increases the risk of ulcers and gastrointestinal bleeding. This risk can be reduced by taking antacid medication such as omeprazole (Prilosec, generic) along with the NSAID. To reduce the risks associated with NSAIDs, take the lowest dose possible for pain relief. To avoid stomach problems, it's best to take NSAIDs with food or immediately after a meal.
Other NSAID side effects may include:
Patients who have kidney problems associated with lupus (lupus nephritis) should be especially cautious about using NSAIDs. Patients with lupus who take NSAIDs on a regular basis should have their liver and kidney function tested every 3 to 4 months.
A doctor may prescribe antimalarial drugs for mild SLE when skin problems and joint pains are the predominant symptoms:
Treatment may start initially with high doses in order to accumulate high levels of the drug in the bloodstream. It is not known exactly why antimalarials work. They may block the immune response or interfere in some way with inflammation.
Side Effects. Side effects of antimalarials may include:
The most serious side effect is damage to the retina, although this is very uncommon at low doses. Eye damage after taking hydroxychloroquine is reversible when caught in time and treated. But it is not reversible if the damage develops after taking chloroquine. An eye exam is advisable when starting the drug and then every year after taking it for more than 5 years.
Antimalarials may also be used in combination with other anti-SLE drugs, including immunosuppressants and corticosteroids. It should be noted that smoking significantly reduces the effectiveness of antimalarial drugs.
Severe SLE is treated with corticosteroids, also called steroids, which suppress the inflammatory process. Steroids can help relieve many of the complications and symptoms, including anemia and kidney involvement.
Oral prednisone (Deltasone, Orasone, generic) is usually prescribed. Other drugs include methylprednisolone (Medrol, Solu-Medrol, generic), hydrocortisone, and dexamethasone (Decadron, generic).
Some people need to take oral prednisone for only a short time; others may require it for a long duration. An intravenous administration of methylprednisolone using "pulse" therapy for 3 days can help reduce flare-ups in the joints. Combinations with other drugs, particularly immunosuppressants such as azathioprine, may be beneficial.
Regimens vary widely, depending on the severity and location of the disease. Most patients with SLE can eventually function without prednisone, although some may have to choose between the long-term toxicity of corticosteroids and the complications of active disease. In certain situations (for example, at the start of treatment for lupus nephritis), steroids may be given intravenously for a few days.
Side Effects of Long-Term Oral Corticosteroids. Serious side effects are associated with long-term use of oral steroids. Doctors recommend taking as low a dose as possible. (However, side effects can still occur with daily use of low doses.)
Osteoporosis is a common and particularly severe long-term side effect of prolonged steroid use. Other adverse effects include weight gain, fat deposits, fluid retention and swelling, increased appetite and weight gain, bruising, acne, high blood pressure, cataracts, glaucoma, diabetes, susceptibility to infections, muscle wasting, menstrual irregularities, and mood swings.
Withdrawal from Long-Term Use of Oral Corticosteroids. Long-term use of oral steroid medications suppresses secretion of natural steroid hormones by the adrenal glands. After withdrawal from these drugs, this adrenal suppression persists and it can take the body a while (sometimes up to a year) to regain its ability to produce natural steroids again.
No one should stop taking any steroids without first consulting a doctor, and if steroids are withdrawn, regular follow-up monitoring is necessary. Patients should discuss with their doctors measures for preventing adrenal insufficiency during withdrawal, particularly during stressful times, when the risk increases.
Drugs known as immunosuppressants are often used, either alone or with corticosteroids, for very active SLE. Immunosuppressants are particularly recommended when kidney or neurologic involvement or acute blood vessel inflammation is present. These drugs suppress the immune system by damaging cells that grow rapidly, including those that produce antibodies.
Specific Immunosuppressants. The main immunosuppressants used for treating lupus are:
For treating patients with lupus nephritis, the choice of immunosuppressant depends on the severity of the condition and the patient's race. The American College of Rheumatology's guidelines recommend:
Side Effects. The most frequent side effects of immunosuppressants include:
Serious side effects of immunosuppressants include:
Belimumab (Benlysta) is a monoclonal antibody drug that is used along with standard lupus drug treatments such as corticosteroids, antimalarials, immunosuppressants, and NSAIDs. Approved in 2011, belimumab is the first new lupus drug in over 50 years and was the first drug developed specifically for treating lupus. The drug works by targeting and reducing the abnormal B cells that are thought to play a role in lupus.
Belimumab is given directly into a vein by intravenous infusion. The infusion is given in a doctor's office or other clinical setting and takes about an hour. The patient receives an infusion every 2 weeks for the first three treatments. After that, the patient receives an infusion once every 4 weeks.
Studies suggest that belimumab may reduce the likelihood of severe flares and may possibly help patients reduce their doses of steroid medicine. However, in these studies, African-Americans and other patients of African descent did not seem to respond to belimumab. Additional studies are being conducted to determine if belimumab is safe and effective for these patients.
Belimumab has many side effects. The most common ones are nausea, diarrhea, and fever. Serious side effects may include infections, heart problems, and depression including thoughts of suicide. The drug is very expensive and some insurers may not pay for it.
Lupus is a chronic disease, marked by symptom-free periods of remission interrupted by flare-ups of active disease. Lifestyle changes can help you prevent flares and promote better overall physical and emotional health.
Lupus flare-ups can often be unpredictable and are always unwelcome. Although specific flare symptoms and triggers vary from person to person, these are some basic strategies for preventing flares:
Patients should be sure they are fully immunized and should minimize their exposure to crowds or people with contagious illnesses. Careful hygiene, including dental hygiene, is also important. Be sure to call your doctor if you have a fever over 100 degrees or any sudden signs or symptoms that may indicate an infection.
It's important for people with SLE to maintain a healthy diet, especially if the disease has caused problems with high blood pressure, cholesterol, kidney function, or other complications. Discuss with your doctor if you need to make any dietary changes based on your specific health profile. Ask your doctor whether you should take a vitamin D supplement -- many people with lupus have low levels of vitamin D because they need to avoid exposure to sunlight.
People with SLE should try to maintain a healthy and active lifestyle. Light-to-moderate exercise, interspersed with rest periods, is good for the heart, helps fight depression and fatigue, and can help keep joints flexible.
Chronic stress has profound physical effects and influences the progression of SLE including triggering flares. Getting adequate rest of at least 8 hours and possibly napping during the day may be helpful. Maintaining social relationships and engaging in healthy activities are important for reducing stress and preventing depression and anxiety. Explore exercises that also have a relaxation component (such as yoga and tai chi) and learn more about relaxation techniques such as deep breathing and meditation.
Like all chronic illnesses, SLE poses many frustrations and challenges -- physical, emotional, financial, and otherwise. It affects all dimensions of a person's life including work, family, and relationships. It is absolutely normal and natural for patients to feel overwhelmed, especially after first receiving a diagnosis.
The following are some tips for living and coping with SLE:
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