Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE) or just lupus (from the Latin word meaning wolf), is one of many disorders of the immune system known as autoimmune diseases. In autoimmune diseases, the immune system turns against parts of the body it is designed to protect, leading to inflammation and damage to various body tissues. Lupus can affect many parts of the body, including the joints, skin, kidneys, heart, lungs, blood vessels, and brain.

Other Names

• SLE
• Lupus

Types

• Systemic lupus erythematosus (SLE) is the form of the disease that most people are referring to when they say "lupus." The word "systemic" means the disease can affect many parts of the body with symptoms that may be mild or serious. Although SLE usually first affects people between the ages of 15 and 45 years, it can occur in childhood or later in life as well.

• Discoid lupus erythematosus is a chronic skin disorder in which a red, raised rash appears on the face, scalp, or elsewhere. The raised areas may become thick and scaly and may cause scarring; this rash may last for days or years. A small percentage of people with discoid lupus have or develop SLE later.

• Subacute cutaneous lupus erythematosus refers to skin lesions that appear on parts of the body exposed to sun that do not cause scarring.

• Drug-induced lupus is a form of lupus caused by medications. Many different drugs can cause drug-induced lupus with symptoms that are similar to those of SLE (arthritis, rash, fever, and chest pain) and they typically go away completely when the drug is stopped. The kidneys and brain are rarely involved.

• Neonatal lupus is a rare disease that can occur in newborn babies of women with SLE, Sjögren syndrome, or no disease at all. Scientists suspect that neonatal lupus is caused by autoantibodies in the mother's blood called anti-Ro (SSA) and anti-La (SSB). Autoantibodies ("auto" means self) are blood proteins that act against the body's own parts. At birth, the babies have a skin rash, liver problems, and low blood counts. These symptoms gradually go away over several months. In rare instances, babies with neonatal lupus may have a serious heart problem that slows down the natural rhythm of the heart. All women who are pregnant and known to have anti-Ro (SSA) or anti-La (SSB) antibodies should be monitored by echocardiograms (a test that monitors the heart and surrounding blood vessels) during the 16th and 30th weeks of pregnancy. It is important for women with SLE or other related autoimmune disorders to be under a doctor's care during pregnancy. Physicians can now identify mothers at highest risk for complications, allowing for prompt treatment of the infant at or before birth. SLE can also flare during pregnancy, and prompt treatment can keep the mother healthier longer.

Sign and Symptoms

Each person with lupus has slightly different symptoms that can range from mild to severe and may come and go over time. However, some of the most common symptoms of lupus include painful or swollen joints (arthritis), unexplained fever, and extreme fatigue. A characteristic red skin rash—the so-called butterfly or malar rash—may appear across the nose and cheeks. Rashes may also occur on the face and ears, upper arms, shoulders, chest, and hands. Because many people with lupus are sensitive to sunlight (called photosensitivity), skin rashes often first develop or worsen after sun exposure.

Common symptoms:

Malar Rash, Lupus. Source: NIEHS-NIH

• Painful or swollen joints and muscle pain.
• Unexplained fever.
• Red rashes, most commonly on the face.
• Chest pain upon deep breathing.
• Unusual loss of hair.
• Pale or purple fingers or toes from cold or stress (Raynaud phenomenon).
• Sensitivity to the sun.
• Swelling (edema) in legs or around eyes.
• Mouth ulcers.
• Anemia (a decrease in red blood cells).
• Swollen glands.
• Extreme fatigue.

Some people also experience headaches, dizziness, depression, confusion, or seizures. New symptoms may continue to appear years after the initial diagnosis, and different symptoms can occur at different times. In some people with lupus, only one system of the body, such as the skin or joints, is affected. Other people experience symptoms in many parts of their body. Just how seriously a body system is affected varies from person to person. The following systems in the body also can be affected by lupus.

• Kidneys: Inflammation of the kidneys (nephritis) can impair their ability to get rid of waste products and other toxins from the body effectively. There is usually no pain associated with kidney involvement, although some patients may notice swelling in their ankles. Most often, the only indication of kidney disease is an abnormal urine or blood test. Because the kidneys are so important to overall health, lupus affecting the kidneys generally requires intensive drug treatment to prevent permanent damage.
• Lungs: Some people with lupus develop pleuritis, an inflammation of the lining of the chest cavity that causes chest pain, particularly with breathing. Patients with lupus also may get pneumonia.
• Central nervous system: In some patients, lupus affects the brain or central nervous system. This can cause headaches, dizziness, memory disturbances, vision problems, seizures, stroke, or changes in behavior.
• Blood vessels:Blood vessels may become inflamed (vasculitis), affecting the way blood circulates through the body. The inflammation may be mild and may not require treatment or may be severe and require immediate attention.^[1]
• Blood: People with lupus may develop anemia, leukopenia (a decreased number of White Blood Cells), or thrombocytopenia (a decrease in the number of platelets in the blood, which assist in clotting). Some people with lupus may have an increased risk for blood clots.
• Heart: In some people with lupus, inflammation can occur in the heart itself (myocarditis and endocarditis) or the membrane that surrounds it (pericarditis), causing chest pains or other symptoms. Lupus can also increase the risk of atherosclerosis (hardening of the arteries).

Causes

Lupus is a complex disease, and its cause is unknown. It is likely that a combination of genetic, environmental, and possibly hormonal factors work together to cause the disease.^[2] Scientists are making progress in understanding lupus. Some research has suggested a relationship between EBV (Epstein-Barr Virus) infection and lupus. ^[3] The fact that lupus can run in families indicates that its development has a genetic basis. Recent research suggests that genetics plays an important role; however, no specific "lupus gene" has been identified yet. Studies suggest that several different genes may be involved in determining a person's likelihood of developing the disease, which tissues and organs are affected, and the severity of disease.^{[4] [5]} However, scientists believe that genes alone do not determine who gets lupus and that other factors also play a role. Some of the factors scientists are studying include sunlight, stress, certain drugs, and infectious agents such as viruses.

In lupus, the body's immune system does not work as it should. A healthy immune system produces proteins called antibodies and specific cells called lymphocytes that help fight and destroy viruses, bacteria, and other foreign substances that invade the body. In lupus, the immune system produces antibodies against the body's healthy cells and tissues. These antibodies, called autoantibodies, contribute to the inflammation of various parts of the body and can cause damage to organs and tissues. The most common type of autoantibody that develops in people with lupus is called an antinuclear antibody (ANA) because it reacts with parts of the cell's nucleus (command center). Doctors and scientists do not yet understand all of the factors that cause inflammation and tissue damage in lupus, and researchers are actively exploring them.

Diagnosis

Diagnosing lupus can be difficult and may take months or even years for doctors to piece together the symptoms to diagnose this complex disease accurately. Making a correct diagnosis of lupus requires knowledge and awareness on the part of the doctor and good communication on the part of the patient.

Diagnostic Criteria for Systemic Lupus Erythematosus

No single test can determine whether a person has lupus, but several laboratory tests may help the doctor to make a diagnosis. The most useful tests identify certain autoantibodies often present in the blood of people with lupus. For example, the antinuclear antibody (ANA) test is commonly used to look for autoantibodies that react against components of the nucleus, or "command center," of the body's cells. Most people with lupus test positive for ANA; however, there are a number of other causes of a positive ANA besides lupus, including infections, other autoimmune diseases, and occasionally as a finding in healthy people. The ANA test simply provides another clue for the doctor to consider in making a diagnosis. In addition, there are blood tests for individual types of autoantibodies that are more specific to people with lupus, although not all people with lupus test positive for these and not all people with these antibodies have lupus. These antibodies include anti-DNA, anti-Sm, anti-RNP, anti-Ro (SSA), and anti-La (SSB). The doctor may use these antibody tests to help make a diagnosis of lupus.

Some tests are used less frequently but may be helpful if the cause of a person's symptoms remains unclear. The doctor may order a biopsy of the skin or kidneys if those body systems are affected or a test for anticardiolipin (or antiphospholipid) antibody. The presence of this antibody may indicate increased risk for blood clotting and increased risk for miscarriage in pregnant women with lupus. Again, all these tests merely serve as tools to give the doctor clues and information in making a diagnosis. The doctor will look at the entire picture—medical history, symptoms, and test results—to determine if a person has lupus.

Other laboratory tests are used to monitor the progress of the disease once it has been diagnosed. A [Complete Blood Count|complete blood count], urinalysis (urine test), blood chemistries, and the erythrocyte sedimentation rate (ESR) test can provide valuable information. Another common test measures the blood level of a group of substances called complement. People with lupus often have increased ESRs and low complement levels, especially during flares of the disease. X rays and other imaging tests can help doctors see the organs affected by SLE.

Treatment

At present, there is no cure for lupus. However, lupus can be effectively treated with drugs, and most people with the disease can lead active, healthy lives. Lupus is characterized by periods of illness, called flares, and periods of wellness, or remission. Understanding how to prevent flares and how to treat them when they do occur helps people with lupus maintain better health.

Diagnosing and treating lupus are often a team effort between the patient and several types of health care professionals. A person with lupus can go to his or her family doctor or internist, or can visit a rheumatologist. A rheumatologist is a doctor who specializes in rheumatic diseases (arthritis and other inflammatory disorders, often involving the immune system). Clinical immunologists (doctors specializing in immune system disorders) may also treat people with lupus. As treatment progresses, other professionals often help. These may include nurses, psychologists, social workers, nephrologists (doctors who treat kidney disease), hematologists (doctors specializing in blood disorders), dermatologists (doctors who treat skin disease), and neurologists (doctors specializing in disorders of the nervous system).

The range and effectiveness of treatments for lupus have increased dramatically, giving doctors more choices in how to manage the disease. It is important for the patient to work closely with the doctor and take an active role in managing the disease. Once lupus has been diagnosed, the doctor will develop a treatment plan based on the patient's age, sex, health, symptoms, and lifestyle. Treatment plans are tailored to the individual's needs and may change over time. In developing a treatment plan, the doctor has several goals: to prevent flares, to treat them when they do occur, and to minimize organ damage and complications. The doctor and patient should reevaluate the plan regularly to ensure it is as effective as possible.

• NSAIDs: For people with joint or chest pain or fever, drugs that decrease inflammation, called nonsteroidal anti-inflammatory drugs (NSAIDs), are often used. Many NSAIDs, such as aspirin and ibuprofen, are available without a prescription. NSAIDs may be used alone or in combination with other types of drugs to control pain, swelling, and fever.

• Antimalarials: Antimalarials are another type of drug commonly used to treat lupus. These drugs were originally used to treat malaria, but doctors have found that they also are useful for lupus. A common antimalarial used to treat lupus is hydroxychloroquine (Plaquenil)*. It may be used alone or in combination with other drugs and generally is used to treat fatigue, joint pain, skin rashes, and inflammation of the lungs. Clinical studies have found that continuous treatment with antimalarials may prevent flares from recurring and are beneficial to use with pregnant patients with lupus. ^{[8] [9]}

• Corticosteroids: The mainstay of lupus treatment involves the use of corticosteroid hormones, such as prednisone, hydrocortisone, methylprednisolone, and dexamethasone. Corticosteroids are related to cortisol, which is a natural anti-inflammatory hormone and work by rapidly suppressing inflammation. Corticosteroids can be given by mouth, in creams applied to the skin, or by injection. Because they are potent drugs, the doctor will seek the lowest dose with the greatest benefit. It is dangerous to stop taking corticosteroids suddenly, so it is very important that the doctor and patient work together in changing the corticosteroid dose. Sometimes doctors give very large amounts of corticosteroid by vein over a brief period of time (days) ("bolus" or "pulse" therapy). With this treatment, the typical side effects are less likely and slow withdrawal is unnecessary. ^[10]Long-term side effects of corticosteroids can include stretch marks on the skin, weakened or damaged bones (osteoporosis and osteonecrosis), high blood pressure, damage to the arteries, high blood sugar (diabetes), infections, and cataracts. Typically, the higher the dose and the longer they are taken, the greater the risk and severity of side effects. Researchers are working to develop ways to limit or offset the use of corticosteroids. For example, corticosteroids may be used in combination with other, less potent drugs, or the doctor may try to slowly decrease the dose once the disease is under control. People with lupus who are using corticosteroids should talk to their doctors about taking supplemental calcium and vitamin D or other drugs to reduce the risk of osteoporosis (weakened, fragile bones).

• Immunosuppressants: For some patients whose kidneys or central nervous systems are affected by lupus, a type of drug called an immunosuppressant may be used. Immunosuppressives, such as cyclophosphamide and mycophenolate mofetil, restrain the overactive immune system by blocking the production of immune cells. These drugs may be given by mouth or by infusion (dripping the drug into the vein through a small tube). Side effects may include nausea, vomiting, hair loss, bladder problems, decreased fertility, and increased risk of cancer and infection. The risk for side effects increases with the length of treatment. As with other treatments for lupus, there is a risk of relapse after the immunosuppressives have been stopped.

• Monoclonal Antibody Therapy: For patients who do not respond to traditional medication as listed above, a therapy initiated at University College of London, involves administering anti-CD20 antibody Rituximab which kills antibody producing B cells in the blood. Ongoing studies show that this may be beneficial for those not responding to traditional treatment.^[11]

• Other Therapies: In some patients, methotrexate, a disease-modifying antirheumatic drug, may be used to help control the disease. Working closely with the doctor helps ensure that treatments for lupus are as successful as possible. Because some treatments may cause harmful side effects, it is important to report any new symptoms to the doctor promptly. It is also important not to stop or change treatments without talking to the doctor first.

• Alternative and Complementary Therapies: Because of the nature and cost of the medications used to treat lupus and the potential for serious side effects, many patients seek other ways of treating the disease. Some alternative approaches people have tried include special diets, nutritional supplements, fish oils, ointments and creams, chiropractic treatment, and homeopathy. Although these methods may not be harmful in and of themselves, and may be associated with symptomatic or psychosocial benefit, no research to date shows that they affect the disease process or prevent organ damage. Some alternative or complementary approaches may help the patient cope or reduce some of the stress associated with living with a chronic illness. If the doctor feels the approach has value and will not be harmful, it can be incorporated into the patient's treatment plan. However, it is important not to neglect regular health care or treatment of serious symptoms. An open dialogue between the patient and physician about the relative values of complementary and alternative therapies allows the patient to make an informed choice about treatment options.^[12]

Living with Systemic Lupus Erythematosus

Despite the symptoms of lupus and the potential side-effects of treatment, people with lupus can maintain a high quality of life overall. One key to managing lupus is to understand the disease and its impact. Learning to recognize the warning signs of a flare can help the patient take steps to ward it off or reduce its intensity. Many people with lupus experience increased fatigue, pain, a rash, fever, abdominal discomfort, headache, or dizziness just before a flare. Developing strategies to prevent flares can also be helpful, such as learning to recognize your warning signals and maintaining good communication with your doctor.

It is also important for people with lupus to receive regular health care, instead of seeking help only when symptoms worsen. Results from a medical exam and laboratory work on a regular basis allows the doctor to note any changes and to identify and treat flares early. The treatment plan, which is tailored to the individual's specific needs and circumstances, can be adjusted accordingly. If new symptoms are identified early, treatments may be more effective. Other concerns also can be addressed at regular checkups. The doctor can provide guidance about such issues as the use of sunscreens, stress reduction, and the importance of structured exercise and rest, as well as birth control and family planning. Because people with lupus can be more susceptible to infections, the doctor may recommend yearly influenza vaccinations or pneumococcal vaccinations for some patients.

Women with lupus should receive regular preventive health care, such as gynecological and breast examinations. Men with lupus should have the prostate-specific antigen (PSA) test. Both men and women need to have their blood pressure and cholesterol checked on a regular basis. If a person is taking corticosteroids or antimalarial medications, an eye exam should be done at least yearly to screen for and treat eye problems.

Learning to recognize the warning signs of a flare can help the patient take steps to ward it off or reduce its intensity.

Warning signs of a flare

• Increased fatigue
• Pain
• Rash
• Fever
• Abdominal discomfort
• Headache
• Dizziness

Preventing a flare

• Learning to recognize warning signals
• Maintaining good communication with the doctor
• Adjusting medication to symptoms

Pregnancy for women with lupus

Although a lupus pregnancy is considered high risk, most women with lupus carry their babies safely to the end of their pregnancy. Women with lupus have a higher rate of miscarriage and premature births compared with the general population. In addition, women who have antiphospholipid antibodies are at a greater risk of miscarriage in the second trimester because of their increased risk of blood clotting in the placenta. Lupus patients with a history of kidney disease have a higher risk of preeclampsia (hypertension with a buildup of excess watery fluid in cells or tissues of the body). Pregnancy counseling and planning before pregnancy are important. Ideally, a woman should have no signs or symptoms of lupus and be taking no medications for at least six months before she becomes pregnant.^[13]

Some women may experience a mild to moderate flare during or after their pregnancy; others do not. Pregnant women with lupus, especially those taking corticosteroids, also are more likely to develop high blood pressure, diabetes, hyperglycemia (high blood sugar), and kidney complications, so regular care and good nutrition during pregnancy are essential. It is also advisable to have access to a neonatal (newborn) intensive care unit at the time of delivery in case the baby requires special medical attention.

Clinical Trials

Here are some recruiting clinical trials in Lupus: Lupus Clinical Trials

Research

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a component of the Department of Health and Human Services' National Institutes of Health (NIH), has a major focus on lupus research in its on campus program in Bethesda, Maryland. By evaluating patients with lupus and their relatives, researchers on campus are learning more about how lupus develops and changes over time. The NIAMS also funds many lupus researchers across the United States. Some of these researchers are studying the genetic factors that increase a person's risk for developing lupus. To help scientists gain new knowledge, the NIAMS also has established Specialized Centers of Research devoted specifically to lupus research. In addition, the NIAMS is funding lupus registries that gather medical information as well as blood and tissue samples from patients and their relatives. This gives researchers across the country access to information and materials they can use to help identify genes that determine susceptibility to the disease.

It is thought that autoimmune diseases, such as lupus, occur when a genetically susceptible individual encounters an unknown environmental agent or trigger. In this circumstance, an abnormal immune response can be initiated that leads to the signs and symptoms of lupus. Research has focused on both the genetic susceptibility and the environmental trigger. Although the environmental trigger remains unknown, microbial agents such as Epstein-Barr virus and others have been considered.

Future research

With research advances and a better understanding of lupus, the prognosis for people with lupus today is far brighter than it was even 20 years ago. It is possible to have lupus and remain active and involved with life, family, and work. As current research efforts unfold, there is continued hope for new treatments, improvements in quality of life, and, ultimately, a way to prevent or cure the disease. The research efforts of today may yield the answers of tomorrow, as scientists continue to unravel the mysteries of lupus.

History

The disease now known as SLE was probably first described by Hippocrates, who called it "herpes esthiomenos," which translates as "gnawing dermatosis." In the Middle Ages, the disfigurement brought on by SLE flares brought the myth of werewolves to the minds of people. These were feared to be human beings who had strange powers to transform themselves into animals. The name lupus may derive from the suggestion that the sufferer has been injured by a wolf, or resembles a wolf.^[14]

The destructive lesions of the face and nose were first described as lupus by the British dermatologist Robert Willan (1757-1808), and the systemic manifestations of SLE (fever, weight loss, lymphadenopathy, anemia, and arthritis) were described in 1872 by Moriz Kaposi in Vienna.^[15] (Kaposi also described a type of cancer, Kaposi sarcoma.)

In 1951, the first antimalarial (quinacrine) was used in the treatment of lupus; soon afterwards, the related drugs chloroquine and hydroxychloroquine were tried and found to be clinically useful. The use of immunosuppressives began in 1952 with low doses of nitrogenous mustard, a poison previously used as a war gas. Another modern approach is exemplified by biologic agents like rituximab, a monoclonal antibody that interferes with B-lymphocyte activation.

Epidemiology

Women of childbearing age, between 15 and 40 years, are at the highest risk for SLE.^{[16] [17]} 2006; 15: 753–6 Lupus is three times more common in African American women than in Caucasian women and is also more common in women of Hispanic, Asian, and Native American descent. The lowest incidences of SLE are seen among Caucasian Americans, Canadians and Spaniards with incidences of 1.4, 1.6 and 2.2 cases per 100,000 people respectively. Throughout Europe, the highest incidences are found in France (5 cases/100,000), Sweden (4.7 cases/100,000), and in Asian (10.0 cases/100,000) and Afro-Caribbean (21.9 cases/100,000) residents of the UK. ^[18] In addition, lupus can run in families, but the risk that a child or a brother or sister of a patient will also have lupus is still quite low. ^[19]

Interesting Facts

The composer Ludwig van Beethoven suffered from a wide range of illnesses, not least of which was a "hideously disfiguring skin condition"; SLE may have been the unifying diagnosis.^[20] The author Flannery O'Connor was also affected by SLE.^[21]

References

1. ↑ Cieślik P, Hrycek A, Kłuciński P. Vasculopathy and vasculitis in systemic lupus erythematosus. Pol Arch Med Wewn. 2008 Jan-Feb;118(1-2):57-63. Abstract PDF
2. ↑ Monticielo OA, Mucenic T, Xavier RM, Brenol JC, Chies JA. The role of mannose-binding lectin in systemic lupus erythematosus. Clin Rheumatol. 2008 Apr;27(4):413-9 Abstract
3. ↑ Niller HH, Wolf H, Minarovits J. Regulation and dysregulation of Epstein-Barr virus latency: implications for the development of autoimmune diseases. Autoimmunity. 2008 May;41(4):298-328. Abstract Full Text PDF
4. ↑ Horiuchi T, Kiyohara C, Tsukamoto H, et al. A functional M196R polymorphism of tumour necrosis factor receptor type 2 is associated with systemic lupus erythematosus: a case-control study and a meta-analysis. Ann Rheum Dis. 2007 Mar;66(3):320-4 Abstract Full text PDF
5. ↑ Sestak AL, Nath SK, Sawalha AH, Harley JB. Current status of lupus genetics. Arthritis Res Ther. 2007;9(3):210. Abstract Full Text PDF
6. ↑ Tan EM, Cohen AS, Fries JF, Masi AT, The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271-7. Abstract
7. ↑ Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997 Sep;40(9):1725PDF
8. ↑ Ruiz-Irastorza G, Ugarte A, Egurbide MV, et al. Antimalarials may influence the risk of malignancy in systemic lupus erythematosus. Ann Rheum Dis. 2007 Jun;66(6):815-7. Abstract Full Text PDF
9. ↑ Clowse ME, Magder L, Witter F, Petri M. Hydroxychloroquine in lupus pregnancy. Arthritis Rheum. 2006 Nov;54(11):3640-7. Abstract Full Text PDF
10. ↑ Tseng CE, Buyon JP, Kim M, et al. The effect of moderate-dose corticosteroids in preventing severe flares in patients with serologically active, but clinically stable, systemic lupus erythematosus: findings of a prospective, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2006 Nov;54(11):3623-32. Abstract Full Text PDF
11. ↑ Leandro, M., Edwards, J., Cambridge, G., Ehrenstein, M., Isenberg, D. An Open Study of B Lymphocyte Depletion in Systemic Lupus Erythematosus.Arthritis & Rheumatism. 2002 Vol.46, No.10, 2673 - 2677. [1]
12. ↑ Clarke JO, Mullin GE. A review of complementary and alternative approaches to immunomodulation. Nutr Clin Pract. 2008 Feb;23(1):49-62. Abstract Full Text PDF
13. ↑ Dhar JP, Sokol RJ. Lupus and pregnancy: complex yet manageable. Clin Med Res. 2006 Dec;4(4):310-21. Abstract Full Text PDF
14. ↑ Blotzer JW. Systemic lupus erythematosus I: historical aspects. Md State Med J. 1983 Jun;32(6):439-41. Citation
15. ↑ Mallavarapu RK, Grimsley EW. The history of lupus erythematosus. South Med J. 2007 Sep;100(9):896-8. Abstract
16. ↑ Masi AT, Kaslow RA. Sex effects in systemic lupus erythematosus: a clue to pathogenesis. Arthritis Rheum 1978; 21: 480–4
17. ↑ Lockshin MD. Sex differences in autoimmune disease. Lupus Abstract
18. ↑ Danchenko N, Satia JA, Anthony MS. Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden. Lupus 2006; 15: 308–18. Abstract
19. ↑ Grennan DM, Parfitt A, Manolios N et al. Family and twin studies in systemic lupus erythematosus. Dis Markers 1997; 13: 93–8. Abstract
20. ↑ Larkin E. Beethoven's illness-a likely diagnosis. Proc R Soc Med. 1971 May;64(5):493-6. Citation | [PDF
21. ↑ Caldwell AL. Flannery O'Connor: life with lupus. J Med Assoc Ga. 2003 Summer;92(2):15-7. Citation

External Links

• National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov
• American College of Rheumatology (ACR)http://www.rheumatology.org
• Alliance for Lupus Research, Inc. http://www.lupusresearch.org
• American Autoimmune-Related Diseases Association, Inc. (AARDA)http://www.aarda.org
• Arthritis Foundation http://www.arthritis.org
• Lupus Foundation of America (LFA) http://www.lupus.org
• Lupus Research Institute www.lupusresearchinstitute.org
• Rheuminations, Inc. http://www.dxlupus.org

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