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•	Highlights
•	Introduction
•	Causes
•	Risk Factors
•	Symptoms
•	Complications
•	Diagnosis
•	Treatment
•	Treatment for Cutaneous and...
•	Treatment for Severe SLE...
•	Lifestyle Changes
•	Resources
•	References

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•	Rheumatoid arthritis
•	Fibromyalgia

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Systemic lupus erythematosus

Highlights

Drug Research

• Mycophenolate mofetil (CellCept) works better than cyclophosphamide and has far fewer side effects, according to a major study in the New England Journal of Medicine. This study supports other recent research that suggests that CellCept should be a first-line treatment for patients with mild to moderate lupus kidney disease. However, the drug may not be appropriate for patients with advanced or rapidly progressing kidney disease. Unlike cyclophosphamide, which is delivered intravenously, CellCept is taken by mouth.
• Short-term hormone replacement therapy (HRT) is safe for women who experience early menopause due to immunosuppressant drugs. HRT does not appear to increase the risk of lupus flares.
• Stem cell transplantation may someday provide an alternative to blood-thinning drugs for patients with antiphospholipid syndrome (APS). The transplant uses stem cells cultivated from a patient’s own blood or bone marrow. Many patients with APS need to take blood-thinning drugs on a lifelong basis. The transplant procedure is still experimental but is showing promise in studies.

Systemic Lupus Erythematosus (SLE) and Pregnancy

• SLE during pregnancy raises the risk for premature and low birth weight babies.
• A 2005 study found that women who had lupus but did not know it were 10 times more likely to have a stillborn baby than healthy women. The risk of stillbirth was four times greater for women diagnosed with lupus.

SLE and Non-Hodgkin’s Lymphoma

Patients with lupus have a significantly higher risk of developing non-Hodgkin’s lymphoma (NHL) than healthy patients, suggests a review in the Archives of Internal Medicine. The risk for NHL is also greater for patients with other autoimmune disorders. NHL is a cancer of the lymph nodes.

Introduction

Systemic lupus erythematosus (SLE) is a chronic, often 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. SLE was first described in 1828. Its very name helps define the disease:

• Systemic is used because the disease can affect organs and tissue throughout the body.
• Lupus is Latin for wolf. It refers to the rash that extends across the bridge of the nose and upper cheekbones and was thought to resemble a wolf bite.
• Erythematosus is from the Greek word for red and refers to the color of the rash.

Lupus has many different symptoms. Common ones include:

• Fatigue
• Joint pain or swelling
• Skin rashes

Causes

Systemic lupus erythematosus is a complex disorder that occurs as a consequence of a number of independent processes and factors.

Environmental factors, such as viruses, exposure to chemicals, or sunlight trigger inflammatory or immune activity. This immune activation may begin as an appropriate response to an unwanted "invader." But, because of a combination of genetic factors, an individual with lupus develops an ongoing immune response that does not shut itself off appropriately. This leads to waxing and waning flares of inflammation that can involve various organs of the body, depending on specific features of this self-perpetuating immune response in individual patients.

The exact combination of genes that predispose individuals to SLE may differ somewhat from patient to patient, but probably share certain common features which tend to impair the ability of the body to rid itself of immune-triggering particles and which tend to prolong or increase the degree of immune responsiveness to these triggers.

A major characteristic of lupus is that it is an autoimmune response, in which immune factors, called autoantibodies, seem to attack the person's own cells. Some autoantibodies are normal in a well-balanced immune system, and serve various roles to help the body dispose of wastes, protect from invaders that have similarity to human structures, and to keep blood vessels clear. In healthy people, autoantibodies tend to be well-regulated and well "masked," or covered up, until needed. Therefore, it is probably the high activity and high detectability of autoantibodies that makes lupus unique, not the fact that they exist.

Many people who have viral syndromes or have reached the age of 50 test positive for the anti-nuclear autoantibody (ANA). Thus, this common screening test for lupus is actually an autoantibody which is found in many healthy people, and a positive ANA would never give someone a diagnosis of lupus in the absence of lupus symptoms or other disease features.

The Inflammatory Process and Autoimmunity

The Normal Immune System Response. The inflammatory process is a byproduct of the activity of the body's immune system, which fights infection and heals wounds and injuries:

• When an injury or an infection occurs, white blood cells are mobilized to rid the body of any foreign proteins, such as a virus.
• The masses of blood cells that gather at the injured or infected site produce factors to fight any infections.
• In the process, the surrounding area becomes inflamed and some healthy tissue is injured. The immune system is then called upon to repair wounds by clotting any bleeding blood vessels and initiating fiber-like patches to the tissue.
• Under normal conditions, the immune system has special factors that control and limit this inflammatory process.

The Infection Fighters. B cells and T cells are two important components of the immune system that play a role in the inflammation associated with lupus. Both B cells and T cells belong to a family of immune cells called lymphocytes. Lymphocytes help fight infection.

B cells and T cells are involved in the immune system's response to infection. Antigens are foreign bodies (such as bacteria and viruses) that stimulate the immune system to produce autoantibodies. When a T cell recognizes an antigen it will produce chemicals (cytokines) that cause B cells to multiply and release many immune proteins (antibodies). These antibodies circulate widely in the bloodstream, recognizing the foreign particles and triggering inflammation in order to rid the body of the invasion.

An antigen is a substance that can provoke an immune response. Typically antigens are substances not usually found in the body.

T cells can be further categorized as killer T-cells or helper T-cells. Killer T-cells directly attack antigens, such as viruses and tumor cells. Helper T-cells recognize antigens that are presented to them by special types of white blood cells (macrophages), and can stimulate B cells to mount various kinds of attacks on the antigen.

For reasons that are still not completely understood, both the T cells and B cells become overactive in lupus patients. In an immune response, it is normal for the antibody response to change over time, particularly if the first antibodies that are made do not eliminate the invading particles. Little by little, the types of antibodies being made undergo changes in an attempt to better recognize and fight an invader. In lupus, a complex interaction between activated immune cells and an impaired antigen-elimination process leads to a greater than normal range of what the antibodies recognize. Eventually, antibodies are made that recognize more of the body's own tissues in a stronger or more persistent manner than is healthy, and inflammatory responses are mounted in these tissues.

Autoantibodies. In the majority of patients with SLE, antinuclear antibodies (ANA) are detectable. Important research published in 2003 found that such autoantibodies may be present in individuals up to 7 years prior to their developing symptoms of lupus. Some subtypes of ANA are found in lupus patients and only rarely in people without lupus. These include:

• Anti-ds DNA. An autoantibody called anti-double stranded DNA (anti-ds DNA) may play an important role in some lupus patients. A 2001 study suggested that some of these antibodies specifically recognize a protein in the kidney called alpha-actinin, which researchers suspect may also occur in other tissues that are affected by SLE, such as in the skin, joints, and brain. A subset of anti-DNA has also been found to target nerve-cell receptors in the brains of patients with SLE.
• Anti-Sm antibodies. This antibody is found most often in lupus patients of African descent and is almost never detected in people without lupus. Although it is not usually seen in lupus patients, it almost always indicates SLE when it is detected.

Other autoantibodies found in lupus patients include:

• Anti-Ro (SSA) and Anti-La (SSB). These autoantibodies may be involved in the sun-sensitive rashes sensitivity experienced by patients with SLE and are also found in association with neonatal lupus syndrome, in which a pregnant mothers' antibodies cross the placenta and cause inflammation in the developing child's skin or heart.
• Antiphospholipid antibodies. A quarter to a half of patients with SLE may have these antibodies. They attack blood clotting regulator proteins which stick to phospholipids, fatty compounds found in cell membranes throughout the body. Antiphospholipid antibodies increase the risks for blood clots and may be responsible for narrowing of and irregularities in blood vessels. Antiphospholipid antibodies are linked with miscarriages and other pregnancy complications, strokes, heart attacks and blood clots in almost any part of the body, including kidneys, legs, lungs, and eyes.

Cytokines. Most immune cells secrete or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are indispensable for maintaining the balance of the body during immune responses, infections, injuries, tissue repair, blood clotting, clearing of debris from inflamed blood vessels, and other aspects of healing. If overproduced, however, they can cause serious damage, including dangerous levels of inflammation and cellular injury. Specific cytokines called interferons and interleukins play a critical role in SLE by regulating the secretion of autoantibodies by B cells. Researchers are currently interested in interferon alpha; some evidence suggests high levels of this cytokine may underlie the autoimmune response in SLE.

Complement. Another immune factor of high interest in SLE is the complement system. This is comprised of more than 30 proteins and is important for defending and regulating the immune response. Inherited deficiencies in certain complement components (C1q, C1r, C1s, C4, and C2) have long been associated with SLE. Deficiencies may contribute to SLE in the following manner:

• The complement system may protect against autoimmune disease by normalizing apoptosis, the natural process by which cells self-destruct. This self-destruction process is an important part of the normal way in which the body cleans out damaged or no longer useful cells. In healthy people, autoantibodies may also play a role in regulating apoptosis so that dangerous antigens are not left in the bloodstream long enough to trigger a more global (dysregulated) immune response.
• Complement components are also necessary for clearing molecular rubble called immune complexes. These are the end product of the battle between autoantibodies and antigens. In the absence of complement, this debris accumulates and is deposited in the kidneys, blood vessels, joints, and other sites where it can cause the immune system to produce inflammation and tissue damage.

Genetic Defects

Researchers estimated that between 20 and 100 different genetic factors may be involved in the alterations of the immune system set point that could make a person susceptible to SLE.

• Research published in 2003 identified a particular set of genes, now commonly called the "interferon signature," that is activated by interferon in patients with severe lupus. This discovery may help doctors be able to identify patients at particular risk for severe disease before they develop symptoms.
• A genetic risk factor for lupus in African American women was identified in 2003. This defect causes increased production of nitric oxide, which may predispose individuals to lupus, and to severe disease in particular.
• Other research has identified defects in genes that regulate apoptosis, the natural process by which cells self-destruct.
• Another study identified an abnormal gene in some patients with SLE that promotes the build-up of immune complexes that can cause kidney damage. HLA (human leukocyte antigen) is a protein that presents antigens to T cells by holding them up from the surface of macrophages or other antigen-presenting cells. There are varieties of HLA molecules that are determined by the genes that are inherited. Small differences in HLA from person to person can determine which antigens are presented in triggering an immune response and how strongly the immune system will respond to these antigens. Among the types of HLA associated with lupus are HLA-DR2, -DR3, -A1, -B8, and DMA-0104.

Triggers of the Immune Response

In genetically susceptible people, there are various external factors that can provoke an immune response. Possible SLE triggers include colds, fatigue, stress, chemicals, sunlight, and certain drugs.

Viruses. Blood tests reveal that patients with SLE are more likely to have been exposed to certain viruses than the general population. These viruses include the Epstein-Barr virus (the cause of mononucleosis), cytomegalovirus, and parvovirus-B1.

Results from a 2005 study, conducted by researchers at the National Institute of Environmental Health Sciences, suggested a strong association between Epstein-Barr virus (EBV) and increased risk of lupus, particularly for African Americans. The study of 230 patients with lupus and matched controls assessed the seroprevalence of EBV antibodies. One particular antibody, EBV-IgA, was linked to a five times greater risk of SLE in African Americans. The association was not as strong for whites, but increased with age (patients over 50 years of age had four times higher risk.)

The researchers also observed that a genetic variation in CTLA-4, a protein that helps regulate T-cell immune system response, appeared to modify the risk of lupus associated with EBV-IgA antibodies. The Epstein-Barr virus settles into B cells after initial infection and can become dormant for long periods of time. T-cells trigger an immune response and help fight reactivation of infection. Therefore, an individual’s CTLA-4 genotype could determine the immune system’s responsiveness in fighting repeat episodes of EBV infection.

Click the icon to see an image of mononucleosis.

Some research suggests that different viruses may imprint specific types of SLE. For instance cytomegalovirus may affect blood vessels and cause problems such as Raynaud's phenomenon or blood abnormalities, but may not affect the kidney as much. These are speculations, however, and not a proven association.

Sunlight. Ultraviolet (UV) rays found in sunlight are important SLE triggers. When they bombard the skin, they can alter the structure of DNA in cells below the surface. The immune system may perceive these altered skin cells as foreign and trigger an autoimmune response against them. UV light is categorized as UVB or UVA depending on the length of the wave.

• UVB are short waves (280 to 320 nm). The shorter the wavelengths, the more damage they do.
• UVA are longer waves (320 to 400 nm). Some research suggests that UVA wavelengths in the longest range, known as UVA1 (340 to 400 nm), may actually repair DNA and normalize immune responses.

Chemicals. Clusters of SLE cases have occurred in populations with high exposure to certain chemicals. For example, in a 2001 study, citizens in a small town in Arizona had two to seven times the prevalence of SLE, which was associated with a high exposure to chlorinated pesticides. Crystalline silica is another suspect. A number of other chemicals are under investigation. However, it is very difficult to determine a causal role for any specific chemicals. (Silicone breast implants have been under intense scrutiny as a possible trigger of autoimmune diseases, including SLE. The weight of evidence to date, however, finds no support for this concern.) Some drugs have been associated with a temporary lupus syndrome (drug-induced lupus), which resolves when these drugs are stopped.

Hormones. Cytokines, major immune factors that are active in SLE, are directly affected by sex hormones. In general, estrogen enhances antibody production and testosterone reduces antibody production, although their exact role in SLE may be more complicated than that since there are various ways in which each hormone might influence various immune cells. Women with SLE may have lower levels of several active male hormones (androgens), and some men who are affected by SLE may also have abnormal androgen levels.

Oral Contraceptives. Female patients with SLE have long been cautioned against taking oral contraceptives due to the possibility that estrogen could trigger lupus flare-ups. Studies presented at the 2004 annual meeting of the American College of Rheumatology suggested that oral contraceptives are safe for most women with lupus. Women who were at high risk for blood clots due to antiphospholipid syndrome were excluded from these studies, and the researchers advised that such patients should not use oral contraceptives.

Risk Factors

The number of people diagnosed with lupus has more than tripled over the past 4 decades. Some experts believe this may simply indicate a greater degree of doctor training in recognizing the syndrome.

Gender

About 90% of lupus patients are women, most of whom are diagnosed when they are in their childbearing ages, a fact that may be explained by hormones. After menopause, women are only 2.5 times as likely as men to contract SLE. Flares also become somewhat less common after menopause in women who have chronic SLE.

Ethnicity

African-Americans are three to four times more likely to develop the disease than Caucasians and to have severe complications. Hispanics and Asians are also more susceptible to the disease.

Family History

A family history plays a strong role in SLE. A brother or sister of a patient with the disorder has 20 times the risk as someone without an immediate family member with SLE.

Risk Factors in Children

The disease is rare in childhood. When it does occur, it is often associated with thrombotic thrombocytopenia purpura, a condition resulting from abnormally low levels of blood platelets. SLE in children may also be caused by certain medications, including minocycline and zafirlukast.

The Presence of Other Autoimmune Disorders

Rheumatoid Arthritis. One study investigated the relationship between hormones, SLE, and rheumatoid arthritis, another autoimmune disease. Higher levels of estrogen are associated with SLE, while lower levels are associated with rheumatoid arthritis. The study found that some patients, in fact, progress from one disease to the other, and that such transitions occur during major hormonal shifts, such as the onset of menopause or pregnancy.

Rheumatoid arthritis is a systemic autoimmune disease that initially attacks the lining, or synovium, of the joints. 

Fibromyalgia. Fibromyalgia, which some experts believe may be another autoimmune disorder, is also a common co-condition in patients with SLE.

Click the icon to see an image of fibromyalgia.

Drug-Induced Lupus

Many prescription drugs can cause lupus-like skin symptoms. In one study, the most common drugs causing these symptoms were hypertension medications, including hydrochlorothiazide, angiotensin-converting-enzyme inhibitors, and calcium-channel blockers. About 40 different drugs have been linked to lupus onset. Anyone diagnosed with cutaneous lupus erythematosus should be sure to tell their doctors all the medications (including herbs and supplements) that they are taking.

Lifestyle Factors

Smoking. A 2004 review found a small association between current smoking and SLE development. No association was observed for past cigarette use.

Symptoms

SLE symptoms may develop slowly over months or years, or they may appear suddenly. Symptoms tend to be worse during winter months, perhaps because prolonged exposure to sunlight in the summer causes a gradual build-up of factors that trigger symptoms months later.

Arthritic Pain

The most common symptom is joint pain, occurring in about 90% of patients with SLE. Characteristics of this symptom vary widely:

• It is often accompanied by swelling and redness.
• It can last from hours to months.
• It may be mild or severe.
• It can occur in one joint, move from one to another, or flare erratically.
• Pain often occurs in the morning and improves during the day, only to return later when the patient tires.
• The joints most affected are fingers, wrists, elbows, knees, and ankles. (Joints in the spine and neck are not affected.)

Children may experience these symptoms as growing pains, and, in all patients, they may be the only symptoms for many years.

Fever

Fever occurs in 90% of patients with SLE and is usually caused by the inflammatory process of the disease, not by infection. It is low-grade except during an acute lupus crisis.

Skin Rashes

Three-quarters of patients with SLE have skin inflammation and skin lesions (ulcers, rashes, or other injured areas). About half of these lesions are photosensitive; that is, they are aggravated by ultraviolet (UV) radiation from sunlight, even from light coming through a window. (UV radiation may even trigger systemic flares in patients with SLE.)

A number of different skin conditions have been described in patients with SLE.

Discoid Lupus Erythematosus. About 20% of patients have discoid lesions. In such cases, the condition is often known as discoid lupus erythematosus (DLE). Patients with this condition may have the following skin abnormalities:

• Discoid means coin-shaped, so these lesions are round and raised. They are also scaly. Untreated, the margins gradually extend outward as the center dries out and atrophies, causing severe scarring. If discoid lesions appear on the scalp, they can plug hair follicles and cause irreversible hair loss. Discoid lesions can also appear on the upper body .

Lupus, discoid - view of lesions on the chest: This close-up picture of the neck clearly shows the typical rounded appearance of discoid lupus. The whitish appearance is caused by scaling. The two dark spots are biopsy sites and are not part of the disease.

• A butterfly-shaped rash across the face may accompany this condition. This rash causes little scarring, although spidery, branching lines of swollen capillaries (the tiniest blood vessels) may appear.

Click the icon to see an image of systemic lupus erythematosus.

Most patients with this condition have only a limited skin disorder. In only about 10% of cases does discoid lupus develop into full-blown SLE.

Subacute Cutaneous Lupus Erythematosus. Subacute cutaneous lupus erythematosus (SCLE) can cause skin lesions on parts of the body that are exposed to sunlight. These lesions do not cause scarring.

Vasculitis. Patients with SLE sometimes develop inflammation in the blood vessels (vasculitis) that may have the following effects on the skin:

• Red welts may form across large areas of the body.
• Sometimes deep red bumps may appear, particularly on the leg, where they may ulcerate.
• In some people, reddish-purple lesions appear on the pads of fingers and toes or near the nails of fingers and toes.
• Lesions caused by vasculitis may ulcerate or blister if they erupt on mucous membranes in the mouth, nose, or vagina and can be painful if they occur on the throat.

Click the icon to see an image of vasculitis.

Other SLE Symptoms

Other symptoms include:

• Fatigue
• Loss of appetite, nausea, and weight loss
• Chest pain
• Bruising
• Menstrual irregularities
• Thought and concentration disturbances
• Personality changes
• Sleep disorders, such as restless legs syndrome and sleep apnea
• Dryness of the eyes and mouth
• Brittle hair or hair loss

Hair loss or breakage may also occur in about half of patients with SLE during severe flares or after pregnancy or severe illness. In such cases, hair grows back

Complications

Systemic lupus erythematosus (SLE) is one of the most serious rheumatic diseases. According to a 2002 government study, the annual number of deaths has risen from 879 to 1,406 since 1979. About third of these deaths occur in people aged 15 to 44 years, mostly women. Such numbers may be underestimates, since SLE can affect so many organs that a cause of death in some people with SLE may not have been directly attributed to the condition. A primary cause of death among patients with lupus is atherosclerosis, a disease of the coronary blood vessels resulting from accelerated buildup of plaque.

SLE is unpredictable and varies greatly form one individual to the next. Severity also appears to differ among ethnic groups and countries. In Europe and North American patients with SLE for example, overall 5-year survival rates are between 93 - 95%, while in Asia or Africa they are considerable lower (60 - 70%). Other research indicates that African American and Hispanic American patients suffer greater organ damage than Caucasian patients. Genetic factors appear to have some influence on specific effects of SLE on organ damage among ethnic groups. However, the poorer outlook among minority groups and in underdeveloped nations is probably due to less access to good health care.

Mild SLE. About 20 - 30% of cases are mild. For many of these patients, the only symptoms may be the skin rashes of discoid lupus erythematosus (DLE) or subacute cutaneous lupus erythematosus (SCLE) with or without joint aches. The number and intensity of symptoms in mild cases often decrease over time, as does the likelihood of major organ involvement. These skin conditions, however, are not absolute insurance against more severe disease, and patients with mild SLE should be tested for organ involvement.

Widespread SLE. Most commonly, SLE is a chronic, life-long disease, alternating between periods of symptom-relapse, (called flares), and remission. The disease may begin in any of the various systems of the body and progress unpredictably to others. The following are typical patterns:

• Symptom relapses, or flares, occur on the average of two or three times a year.
• Between flares, most patients with SLE function at about 90% of normal capacity.

The degree of severity depends on different factors:

• Severity of the inflammatory response
• Frequency of episodes
• The degree of organ or system involvement

Vital organs or systems, such as lungs, kidneys, nervous system, joints skin, and others are affected in 50 - 75% of patients with SLE. Infections followed by kidney failure are the chief causes of death in patients with SLE.

Because of more effective and aggressive treatment, the prognosis for SLE has improved markedly over the past two decades. Long-term progress of the disease is affected greatly by treatment in the initial acute phase of the disease, so a speedy and accurate diagnosis is all-important. The 10-year survival rate with treatment is now 85 - 95% and many people have a normal life span. SLE that develops later in life is generally less serious than SLE that strikes in childhood.

Complications of the Blood

Almost 85% of patients with SLE experience problems associated with abnormalities in the blood.

Anemia. About half of patients with SLE are anemic. Causes include:

• Iron deficiencies resulting from excessive menstruation
• Iron deficiencies from GI bleeding caused by some of the treatments
• A specific anemia called hemolytic anemia, which destroys red blood cells

Hemolytic anemia can occur with very high levels of the anticardiolipin antibody. It can be chronic or develop suddenly and severely (acute).

Antiphospholipid Syndrome. Between 34 - 42% of patients with SLE have the antiphospholipid syndrome (APS). This is a specific set of conditions related to the presence of autoantibodies called lupus anticoagulant and anticardiolipin. These autoantibodies react against fat molecules called phospholipids, and so are called antiphospholipids. Their actions have complex effects that include causing narrowing and abnormalities of blood vessels.

• Patients who have APS have a very incidence of blood clots, which most often occur in the deep veins in the legs (32%). Blood clotting in turn puts patients at higher risk for stroke (13%) and pulmonary embolism (clots in the lungs) (9%).

This picture shows a red and swollen thigh and leg caused by a blood clot (thrombus) in the deep veins in the groin (ileofemoral veins). Such a clot prevents normal return of blood from the leg to the heart.

• About 22% of patients have thrombocytopenia--a reduction in blood platelets, which can cause bleeding.
• The effects on blood vessels have also been associated with confusion, headaches, and seizures. Leg ulcers can also develop.
• Patients with APS who become pregnant have a high incidence of pregnancy loss, especially in the late term.

Not all patients with APS carry both of the autoantibodies, and they can also wax and wane and so have varying effects. APS also occurs without lupus in about half of patients with the syndrome.

Thrombocytopenia. In thrombocytopenia, antibodies attack blood platelets. In such cases, blood clotting is impaired, which causes bruising and bleeding from the skin, nose, gums, or intestines. (This condition can also occur in APS, but it is not considered to be one of the standard features of the syndrome.)

Neutropenia. Neutropenia is a drop in the number of white blood cells. Patients with SLE often neutropenia, but the condition is usually harmless unless the reductions are so severe that they leave the patient vulnerable to infections.

Acute Lupus Hemophagocyte Syndrome. A rare blood complication of SLE that occurs primarily in Asians is called acute lupus hemophagocytic syndrome. It is generally of short duration and characterized by fever and a sudden drop in blood cells and platelets.

Lymphomas. Patients with SLE and other autoimmune disorders have a greater risk for developing lymph system cancers such as non-Hodgkin’s lymphoma (NHL). A 2005 study reported that patients with SLE were over seven times more likely to develop NHL than healthy patients. .

Raynaud's Phenomenon

Raynaud's phenomenon is a condition in which cold or stress can cause spasms in impaired blood vessels resulting in pain in fingers and toes. It occurs as part of the inflammatory response in blood vessels, which can narrow them and reduce circulation. In extreme cases, gangrene can result.

Click the icon to see an image of Raynaud's phenomenon.

Heart and Circulation Complications

Heart disease is a primary cause of death in lupus patients. The immune response in SLE can cause inflammation and other damaging effects that can cause significant injury to the arteries and tissues associated with the circulation and the heart. In addition, SLE treatments (particularly corticosteroids) affect cholesterol, weight, and other factors that can also affect the heart. For decades ,experts questioned the extent to which the drugs used to treat SLE contributed to the high rate of atherosclerosis in such patients. Numerous studies now suggest that something about the disease process itself, possibly the chronic inflammation of the blood vessels, probably lies at the root of this dangerous problem. In any event, patients with SLE, have a higher chance for the following conditions, which put them at risk for heart attack or stroke:

• Atherosclerosis, or plaque buildup in the arteries
• Increased stiffness in the arteries
• Unhealthy cholesterol and lipid (fatty molecules) levels
• High blood pressure, most likely because of kidney injury and corticosteroid treatments
• Congestive heart failure
• Pericarditis, an inflammation of the tissue surrounding the heart (occurs in about 30% of patients)
• Myocarditis, an inflammation of the heart muscle itself (rare)

Click the icon to see an image of pericarditis.

• Abnormalities in the valves of the heart (rare)
• Elevated levels of homocysteine, which occurs with vitamin B6, B12 and folate deficiencies; homocysteine is now a strong suspect in heart attack, strokes, and blood clots
• Blood clots

The risk for cardiovascular disease, heart attack and stroke is much higher than average in younger women with SLE. The risks decline as such women age.

Lung Complications

SLE affects the lungs in about 60% of patients:

• Recurrent inflammation of the membrane lining the lung (pleurisy) is the most common problem.
• In some cases, fluid accumulates, a condition called pleural effusion, and can cause stabbing localized pain that worsens when coughing, sneezing, laughing, or taking a deep breath.
• Inflammation of the lung itself in SLE is called lupus pneumonitis. It can be caused by infections or by the SLE inflammatory process. Symptoms are the same in both cases: fever, chest pain, labored breathing, and coughing. Rarely, lupus pneumonitis becomes chronic and causes scarring in the lungs, which reduces their ability to deliver oxygen to the blood.
• A very serious and also rare condition called pulmonary hypertension occurs when high pressure develops in the vessels supplying blood to the lungs.

Click the icon to see an image of primary pulmonary hypertension.

Kidney Complications (Lupus Nephritis)

The kidneys are a crucial battleground in SLE because it is here that the debris left over from the immune attacks is most likely to be deposited. About 50% of patients with SLE exhibit inflammation of the kidneys (called lupus nephritis).This condition occurs in different forms and can vary widely in severity.

Click the icon to see an image of the kidney.

• Proliferative nephritis is a serious variant of lupus nephritis. It occurs when the inflammatory process causes widespread damage and scarring in the blood vessels of the kidneys, which filters waste products, water, and salts out of the blood. The condition is associated with high blood pressure and kidney deterioration.
• Membranous lupus nephritis is another variant that is often associated with a good outlook. In some cases, however, if the kidney is persistently exposed to high protein levels, the disorder can progress to fatal end-stage kidney (renal) disease.

Serious complications occur eventually in about 30% of patients. If kidney injury develops, it almost always occurs within 10 years of the onset of SLE, rarely after that.

Central Nervous System Complications

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. Most of these symptoms are minor and some, such as headache, may be related to depression rather than the disease itself. CNS involvement is more likely to occur in the first year, usually during flare-ups in other organs. Symptoms vary widely and may be indistinguishable from psychiatric or neurologic disorders or from the side effects of some medications used for SLE. Central nervous system symptoms are usually mild, but there is little effective treatment available for them. CNS symptoms get worse as the disease progresses.

The most serious CNS disorder is inflammation of the blood vessels in the brain, which occurs in 10% of patients with SLE. Fever, seizures, psychosis, and even coma can occur. Other CNS side effects include:

• Irritability
• Emotional disorders (anxiety, depression)
• Mild impairment of concentration and memory
• Migraine and tension headaches
• Problems with the reflex systems, sensation, vision, hearing, and motor control

Infections

Infections are a common complication and a major cause of death in all stages of SLE. The immune system is indeed overactive in SLE, but it is also abnormal and reduces the ability to fight infections. Patients are not only prone to the ordinary streptococcal and staphylococcal infections, but they are also susceptible to fungal and parasitic infections (called opportunistic infections), which are common in people with weakened immune systems. They also face an increased risk for herpes, salmonella, and yeast infections. Corticosteroid and immunosuppressants, treatments used for SLE, also increase the risk for infections, thereby compounding the problem.

Gastrointestinal Complications

About 45% of patients with SLE suffer gastrointestinal problems, including nausea, weight loss, mild abdominal pain, and diarrhea. Severe inflammation of the intestinal tract occurs in less than 5% of patients and causes acute cramping, vomiting, diarrhea, and, rarely, intestinal perforation, which can be life-threatening. Fluid retention and swelling can cause intestinal obstruction, which is much less serious but causes the same type of severe pain. Inflammation of the pancreas can be caused by the disease and by corticosteroid therapy.

Joint, Muscle, and Bone Complications

Arthritis caused by SLE almost never leads to destruction or deformity of joints. The inflammatory process can, however, damage muscles and cause weakness. 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 are known risk factors for osteoporosis).

Click the icon to see an image of osteoporosis.

Eye Complications

Inflamed blood vessels in the eye can reduce blood supply to the retina, resulting in degeneration of nerve cells and a risk of hemorrhage in the retina. The most common symptoms are cotton-wool-like spots on the retina. In about 5% of patients sudden temporary blindness may occur.

Socioeconomic Consequences

In one study, 40% of patients with SLE quit work within four years of diagnosis, and many had to modify their work conditions. Significant factors that predicted job loss included high physical demands from the work itself, a more severe condition at the time of diagnosis, and lower educational levels. People with lower income jobs were at particular risk for leaving them.

Diagnosis

No single test can definitively confirm or rule out SLE. A number of tests are required before SLE can be diagnosed definitively. The first symptoms of SLE can resemble one of many syndromes or disorders, including rheumatoid arthritis, Still's disease, rheumatic fever, Lyme disease, multiple sclerosis, thrombotic thrombocytopenia purpura, cryoglobulinemia, Weber-Christian disease, viral infections, vasculitis, psychosis, and other conditions. Other autoimmune disorders, such as Sjogrens syndrome or scleroderma, may even be present at the same time as SLE.

Ruling out Other Conditions

The doctor should first rule out common conditions that might be causing the symptoms. The doctor may test the synovial fluid (the lubricating liquid surrounding joints) to rule out rheumatoid arthritis, which is also an autoimmune disease and can occur with SLE. Certain eye and saliva tests may be used if Sjögren's syndrome is suspected.

A number of conditions may resemble SLE:

• Scleroderma: Hardening of the skin caused by overproduction of collagen
• Multiple sclerosis: Fatigue, heaviness or clumsiness in the arms and legs
• Rheumatoid arthritis: Inflammation of the lining of the joints
• Sjögren's syndrome: Characterized by dry eyes and dry mouth
• Mixed connective tissue disorder: Similar to SLE, but milder
• Myositis: Inflammation and degeneration of muscle tissues
• Fibromyalgia: Chronic muscle pain
• Rosacea: Flushed face with pus-filled blisters
• Seborrheic dermatitis: Sores on lips and nose
• Lichen planus: Swollen rash that itches, typically on scalp, arms, legs, or in the mouth
• Leukoplakia: White spots on tongue or cheek
• Dermatomyositis: Bluish-red skin eruptions on face and upper body
• Lyme Disease: Bulls-eye rash, joint inflammation, and flu-like symptoms

Lyme disease is an acute inflammatory disease that is caused by the bacterium Borrelia burgdorferi. The bacteria is transmitted by the bite of a deer tick. Symptoms may go away in 3 to 4 weeks even without treatment, but other diseases may develop if the initial infection is not treated.

Click the icon to see an image of dermatomyositis.

Tests for Autoantibodies

Methods for measuring the antibodies involved with SLE vary and the range of results can be bewildering. Repeat tests may be needed.

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. A number of other conditions, however, also cause high levels of ANA, so a positive test is not a definite diagnosis for SLE:

• Antinuclear antibodies may be strongly present in other autoimmune diseases (such as scleroderma, Sjögren's syndrome, or rheumatoid arthritis).
• They also may be weakly present in about 20 - 40% of healthy women.
• Some drugs can also produce positive antibody tests, including hydralazine, procainamide, isoniazid, and chlorpromazine.

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:

• If SLE symptoms are present and the ANA test is positive, other tests for SLE will be administered.
• If SLE symptoms are not present and the test is positive, the doctor will look for other causes, or the results will be ignored if the patient is feeling healthy.

ANA Subtypes. In some cases, doctors may test for specific ANA subtypes.

• Anti-double stranded DNA (Anti-ds DNA) is usually found only in patients with SLE. It may play an important role in injury to blood vessels found in SLE and high levels often indicate kidney involvement. Anti-ds DNA levels tend to fluctuate over time and may even disappear.
• Anti-Sm antibodies are also usually found only with SLE. They are more constant and are more likely to be detected in African-American patients.
• When the ANA is negative but the diagnosis is still strongly suspected a test for anti-Ro anti-La antibodies may identify patients with a rare condition called ANA negative, Ro lupus.

Antibodies to SR Proteins. An advance in diagnosing SLE has been the detection of antibodies to molecules called SR proteins, which are carried by most patients. The test accurately detects lupus in 50% to 70% of patients who test positive for these antibodies.

Antiphospholipid Antibodies. In patients with SLE in whom blood abnormalities are suspected, tests will be administered to detect the presence of the two major antiphospholipid antibodies:

• The test for the lupus anticoagulant antibody measures the time it takes blood to clot. A longer than normal blood clotting time indicates a higher chance for clotting in the body and, therefore, the presence of lupus anticoagulant.
• An ELISA test (enzyme-linked immunosorbent assay) is performed to detect the anticardiolipin antibody.

As with the ANA, these antibodies also have a tendency to appear and disappear in a single patient. Patients who have these autoantibodies as well as blood clotting problems or frequent miscarriage are diagnosed with antiphospholipid syndrome (APS), which often occurs in SLE but can also develop independently.

Miscellaneous Blood Tests

Complement. Blood tests of patients with SLE often show low levels of serum complement, a protein in the blood that aids 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. There is some evidence that complete deficiencies of C1q may be a key factor in the inability of the immune system to contain the autoimmunity process. Complement levels are especially low if there is kidney involvement or other disease activity.

LE Cell Tests. The first blood test ever used for SLE called LE (lupus erythematosus) cell test is positive in only about half of patients with SLE and is no longer used that often.

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.

Click the icon to see an image of the formed elements of blood.

Skin Tests

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 antibodies known as immunoglobulin G (IgG), which are located just below the outer layer of the tissue sample. They are present in about 80% of patients with active SLE and in between 30 - 40% of those with inactive disease. The biopsy will not differentiate between systemic and discoid lupus, but it can rule out other diseases. Tests for other antibodies will rule out or confirm discoid lupus and subacute cutaneous lupus.

Tests for Serious Complications of SLE

Kidney Damage and Lupus Nephritis. Kidney damage in patients already diagnosed with SLE may be detected from the following tests:

• Blood tests that measure creatinine, a protein metabolized in muscles and excreted in the urine. High levels suggest kidney damage, although it can also be present with normal creative levels.
• Tests for detecting anti-ds DNA antibodies and complement. High levels of anti-ds DNA and low levels of complement C3 suggest kidney damage. (It should be noted, however, that some patients with severe kidney damage show low levels of anti-ds DNA.) Testing for anti-C1q antibodies now appears to be an even more reliable indicator of lupus nephritis.
• Urine analyses. They should be performed at 4- to 6-month intervals to check for signs of kidney involvement.
• A kidney biopsy. This may be performed to determine if lupus nephritis is present when less invasive tests indicate kidney involvement. It is not absolutely accurate but it helps determine treatment. Electron microscopy (very high-powered electronic microscopes) may be especially important in obtaining critical information on the degree of kidney damage.

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.

Click the icon to see an image of an electrocardiogram.

Central Nervous System Complications. SLE occurring in the central nervous system (CNS) can be difficult to diagnose because its symptoms are easily confused with other psychiatric and neurologic conditions.

• Tests of the cerebrospinal fluid (CSF) for elevated levels of autoantibodies are the most reliable ways to detect CNS complications caused by a faulty immune system.
• Additional tests, including electroencephalograms (EEGs), magnetic resonance imaging (MRI), computed tomography (CT), or x-rays may be useful when blood vessel blockage in the brain is suspected.
• If the doctor suspects that CNS symptoms are caused by infection, especially for patients who are receiving immunosuppressant therapy, a lumbar puncture should be performed.

Osteoporosis. To detect early osteoporosis in patients with SLE whose disease has lasted more than 3.5 years, experts recommend an imaging test called dual energy x-ray absorptiometry (DEXA) to measure bone mineral density.

Treatment

No treatment cures systemic lupus erythematosus, but many therapies can suppress symptoms and relieve discomfort. Treatment of SLE varies depending on the extent and severity of the disease.

Only three drugs are technically FDA-approved for the treatment of lupus:

• Prednisone
• Aspirin
• Hydroxychloroquine

However, none of these are the standard of care. In everyday practice, numerous other, more effective drugs are commonly used. A new surge of interest has spurred numerous clinical studies and the development of many new therapeutic drugs. Genetic research in lupus is progressing very rapidly, and several new drugs are likely to be approved in the near future. There are also different drugs available to treat some of the conditions associated with lupus.

Treating Mild Systemic Lupus Erythematosus

Less intensive treatments may be effective for symptoms of mild lupus. They include:

• Creams and sunblocks for rashes
• Nonsteroidal anti-inflammatory drugs for fever, arthritis, and headache
• Antimalarial drugs for pleurisy, mild kidney involvement, and inflammation of the tissue surrounding the heart

Treating Severe Systemic Lupus Erythematosus

More aggressive treatment is needed if there is serious disease progression, evidenced by the following:

• Hemolytic anemia
• Low platelet count with an accompanying rash (thrombocytopenia purpura)
• Major involvement in the lungs or heart
• Significant kidney damage
• Acute inflammation of the small blood vessels in the extremities or gastrointestinal tract
• Severe central nervous system symptoms

The primary approach to treating severe SLE is to suppress the immune factors, most often first with corticosteroids and other immunosuppressant drugs. Investigative drugs and procedures are also showing promise.

Treating Specific Complications

The major complications of the disease must be treated as separate problems, keeping in mind the specific aspects of SLE. They are discussed in another section.

Treatment for Cutaneous and Mild SLE

Creams. Steroid creams are often used for skin lesions. However, many patients with discoid lupus do not respond to steroids, particularly if they have eruptions that are caused by sun sensitivity. A cream derived from vitamin A (Tegison) has been beneficial for 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.

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Common NSAIDs. NSAIDs block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. There are dozens of NSAIDs.

• Over-the-counter NSAIDs include aspirin, ibuprofen (Motrin IB, Advil, Nuprin, Rufen), naproxen (Aleve), ketoprofen (Actron, Orudis KT).
• Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), dexibuprofen (Seractil).

Regular, long-term use of NSAIDs has been associated ulcers and gastrointestinal bleeding. [See Box: NSAID-induced Ulcers and Gastrointestinal bleeding.] 

An ulcer is a crater-like lesion on the skin or mucous membrane caused by an inflammatory, infectious, or malignant condition. Patients can take certain medicines to suppress the acid in the stomach causing the the erosion of the stomach lining. Endoscopic therapy can be used to stop bleeding from the ulcer.

NSAIDs may also cause increases in blood pressure. The highest risks have been observed with piroxicam (Feldene), naproxen (Aleve), and indomethacin (Indocin). People with hypertension, severe vascular disease, kidney, or liver problems and those taking diuretics must be closely monitored if they need to take NSAIDs.

Other NSAID said effects can include:

• Delayed emptying of the stomach, which could interfere with the actions of other drugs (elderly are at special risk)
• Dizziness
• Tinnitus (ringing in the ear)
• Headache
• Skin rash
• Confusion or bizarre sensation (in some higher-potency NSAIDs, such as indomethacin)

As with acetaminophen, high daily doses of aspirin have been associated with an increased risk of kidney failure, although the risk remains low in those with healthy kidney function. Kidney abnormalities have been reported in people taking other NSAIDs as well, which resolve when the drugs are withdrawn. Any sudden weight gain or swelling should be reported to a doctor. Anyone with kidney disease should avoid these drugs.

Diabetics taking oral hypoglycemics may need to adjust the dosage if they also need to take NSAIDs because of possible harmful interactions between the drugs.

Note: Some studies have reported that ibuprofen (but not other NSAIDs) may blunt the heart-protective effects of low-dose aspirin, Additional research is needed to confirm these findings.

Investigative Alternatives to NSAIDs

NO-NSAIDS. Experimental drugs are being developed that combine nitric oxide with NSAIDs (NO-NSAIDs). Nitric oxide increases blood flow in the mucous lining and secretions of mucus and bicarbonate.

Antimalarial Drugs

Antimalarial drugs may be prescribed for discoid lupus or for mild lupus when skin problems and joint pains are the predominant symptoms:

• The most common antimalarial drug used for SLE is hydroxychloroquine (Plaquenil). This drug is effective as maintenance therapy to reduce flares in patients with mild or inactive disease. Hydroxychloroquine may help protect against blood clots in people with antiphospholipid syndrome, high cholesterol levels, and bone loss.
• Other antimalarial drugs include chloroquine (Aralen) or quinacrine (Atabrine).

High doses may be prescribed initially in order to accumulate high levels of the drug in the blood stream. It is not known why antimalarials work. Some researchers believe they inhibit the immune response and others think they interfere specifically with inflammation.

Side Effects. Side effects of antimalarials may include:

• Skin rash.
• Change in skin color (yellow in the case of quinacrine)
• Gastrointestinal problems
• Headache.
• Hair loss
• Muscle aches
• Eye damage

The most serious is damage to the retina, although this is very uncommon when low doses are used. Eye damage after taking hydroxychloroquine is reversible when caught in time and treated, but it is not reversible if it develops after taking chloroquine. An eye exam is advisable every 6 months or so.

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.

Thalidomide

Thalidomide inhibits a number of potent cytokines and reduces the formation of new blood vessels that allow the disease to progress. In low doses it has been found to be safe and effective for severe cutaneous lupus in many patients. It does not appear to have any benefits for systemic complications of lupus.

A major side effect of thalidomide is peripheral neuropathy, which can cause numbness, tingling, or other altered sensation in the nerves of limbs (feet, legs, hands, fingers). The drug should be taken for the shortest time possible. The drug is also notorious for producing very serious birth defects in children. Women who are in their reproductive years must be sure they are not pregnant before taking thalidomide and they must use very reliable birth control while taking it.

Treatment for Severe SLE

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) is usually prescribed. Other drugs include methylprednisolone (Medrol, Solumedrol), hydrocortisone, and dexamethasone (Decadron).

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 is proving useful for flare-ups in the joints. Combinations with other drugs, particularly immunosuppressants, 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.

Side Effects of Long-Term Oral Corticosteroids. Unfortunately, serious and even life-threatening complications have been associated with long-term steroid use. Osteoporosis is a common and particularly severe long-term side effect of prolonged steroid use. Medications that can prevent osteoporosis include calcium supplements, parathyroid hormone, alendronate etidronate, risedronate, or hormone replacement therapy in post-menopausal women. Vitamin C and E may help reduce the risk of cataracts.

Other side effects associated with prolonged use of oral steroids include:

• Cataracts
• Glaucoma
• Diabetes
• Fluid retention
• Susceptibility to infections
• Weight gain
• High blood pressure
• Acne
• Excess hair growth
• Wasting of the muscles
• Menstrual irregularities
• Irritability
• Insomnia
• Psychosis

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 so-called 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. There have been a few cases of severe adrenal insufficiency that occurred when switching from oral to inhaled steroids, which, in rare cases, has resulted in death.

No one should stop taking any steroids without consulting a doctor first, and if steroids are withdrawn, regular follow-up monitoring is necessary. Patients should discuss with their doctor measures for preventing adrenal insufficiency during withdrawal, particularly during stressful times, when the risk increases.

Immunosuppressant Drugs

Drugs known as immunosuppressants are often used, either alone or with corticosteroids for very active SLE, particularly 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. About a third of patients take immunosuppressants at some point in the course of the disease.

Specific Immunosuppressants. The most common immunosuppressants are:

• Cyclophosphamide (Cytoxan) used to be considered the gold standard of treatment for lupus kidney disease (lupus nephritis). Cyclophosphamide is given intravenously and is sometimes used in combination with corticosteroids or other drugs. It has been used for lupus since the 1970s. Side effects are very severe and include nausea, vomiting, hair loss, infertility, and infections.
• Mycophenolate mofetil (CellCept) is now becoming the new standard. Many recent studies have shown that CellCept works better than cyclophosphamide and causes far fewer severe side effects (diarrhea is the main side effect). Unlike cyclophosphamide, it is taken by mouth. A 2005 study reported that 23% of patients treated with CellCept for lupus kidney disease went into remission after 6 months, compared with 6% of patients treated with cyclophosphamide. Experts are now recommending CellCept as a first-line treatment for newly diagnosed patients with mild or moderate lupus kidney disease. It may not be appropriate for patients with kidney failure or rapidly progressing kidney disease.
• Azathioprine (Imuran) has the lowest toxicity, but is also less effective than others.
• Methotrexate (Rheumatrex) may be helpful for patients with moderate SLE who do not have kidney insufficiency or very severe complications of SLE.
• Cyclosporine (Sandimmune) has been used for years, mostly for SLE associated with kidney involvement. High blood pressure is common, however, with this drug.

The most frequent side effects of immunosuppressants include:

• Stomach and intestinal problems
• Skin rash
• Mouth sores
• Hair loss

Serious side effects of immunosuppressants include:

• Low blood cell counts
• Anemia
• Menstrual irregularity
• Early menopause
• Ovarian failure
• Infertility
• Herpes zoster (shingles)
• Liver and bladder toxicity
• Increased risk of cancer

A 2005 study suggested that short-term hormone replacement therapy is safe for women with SLE and does not increase the risk of disease flares. Sterility in female patients may be avoided by administering pulsed doses at the time of menstruation. In general, immunosuppressants should not be used alone unless corticosteroids are ineffective or inappropriate. Grapefruit juice has an enzyme that may enhance the effects of some immunosuppressants

Hormone Treatments

Dehydroepiandrosterone (DHEA). Dehydroepiandrosterone (DHEA) is a natural steroid hormone that is produced by the adrenal glands and converted into estrogen and androgen. Some evidence suggests that DHEA deficiencies may play a role in SLE. Although DHEA is sold as a dietary supplement, and has been proclaimed as a cure for a wide variety of ailments, there is little scientific evidence to support most of these claims. In addition, because natural supplements are unregulated, there is no guarantee of quality control..

However, the synthetic equivalent of DHEA, prasterone, is being investigated as a potential treatment for SLE and several clinical trials have indicated promising, although mixed, results. In a 2004 randomized, double-blind, placebo-controlled trial of women with active lupus, prasterone significantly improved or stabilized lupus symptoms and reduced disease flare-ups. Women who received prasterone also experienced reductions in total cholesterol and triglyceride levels. A 2005 trial of women with SLE found that prasterone prevented bone loss and increased spinal and hip BMD, but additional trials have failed to confirm the benefit. Women in both trials were also taking other SLE drug treatments, such as prednisone. Prasterone is still in the drug development stage and it is not clear when, or if, it will be commercially available.

Danazol. Researchers are also investigating the use of danazol (Danocrine), a male hormone. One study reported long-term remission of thrombocytopenia when it was used with the corticosteroid prednisone. As with DHEA, side effects include male characteristics such as acne and hair growth.

Plasmapheresis

Plasmapheresis is a process in which the fluid part of the blood, called plasma, is removed from blood cells. The procedure involves first taking blood from the patient. The plasma, which contains the inflammatory antibodies and other immunologically active substances, is discarded and replaced with other fluids. The blood is then returned. Plasmapheresis is not useful for routine management of patients but may have some benefits for patients who do not respond to standard treatments or in specific cases, such as lupus patients with hemolytic anemia.

Investigative Treatments

Monoclonal Antibodies (MAbs). A MAb is a laboratory-made protein that targets specific immune cells, such as B cells. B-cell overactivation has been identified a key component of the SLE disease process.

• Epratuzumab is being investigated for treatment of moderate to severe SLE. The FDA granted the drug Fast Track status (a designation that speeds up the approval process for promising drugs that address an unmet need). Phase III trials began in 2005.
• Lymphostat-B has also received Fast Track status. Phase II trial data showed mixed results, but the drug will enter Phase III trials.
• Rituximab, a lymphoma cancer drug, is currently in Phase I/II trials to evaluate the safety of higher doses. Initial results in several small trials indicate significant B-cell reduction with symptom improvement lasting at least one year.

Leflunomide. Leflunomide (Arava), an anti-rheumatic drug, blocks autoimmune antibodies and reduces inflammation in patients with rheumatoid arthritis. The drug is now being used for lupus with good results, but requires further study.

Sitaxsenten. Sitaxsenten, an endothelin receptor antagonist, is being investigated for treatment of pulmonary hypertension as a complication of lupus. A study presented at the 2004 annual scientific meeting of the American College of Rheumatology indicated that sitaxsentan improved patients’ ability to perform a walking test.

Riquent. Riquent is being developed to treat lupus patients with kidney disease (lupus nephritis). Initial trial results appeared promising, with fewer side effects than current treatments, but in October 2004 the FDA requested an additional clinical trial before approval would be considered.

Autologous Stem Cell Transplantation. Some patients with severe SLE have achieved at least short term remission after undergoing autologous transplantation of stem-cells and high-dose drug therapy to suppress the damaging immune factors. Stem cells are the early forms for all blood cells in the body. An autologous transplant is one in which marrow or blood cells used are the patient's own. (The advantage to an autologous transplant is that the patient's own cells are not at risk for rejection by the immune system.)

The procedure itself first removes the cells from the patient, who then receives high-dose immunotherapy. The stem cells are then reintroduced. Early results of small studies are encouraging, especially for treatment of antiphospholipid syndrome. Evidence suggests that these re-introduced stem cells do not repeat the original autoimmune errors. In some cases, SLE has remained inactive for more than 2 years. In 2004, the NIH launched a pilot 5-year study of autologous blood stem cell transplantation. Fourteen patients will be followed to see if they remain in remission and relapse-free. Researchers will also compare the “before” and “after” activity of the patients’ B and T cells.

UVA-1 Phototherapy. A promising treatment uses ultraviolet A-1 (UVA-1) radiation, which are long UVA wave lengths that do not promote sunburn and may actually block inflammatory immune factors. Small studies have suggested that UVA-1 phototherapy may have some benefits for lowering disease activity in SLE.

The spleen is an organ that helps produce and maintain red blood cells. It also aids the body's immune system by producing white blood cells that destroy harmful substances in the body. Removal of the spleen makes a person more susceptible to infection.

Click the icon to see an illustrated series detailing kidney transplant.

Lifestyle Changes

The following are some tips for maintaining a healthy diet:

• Eat a diet low in saturated fats. Not all fats are unhealthy. Some studies suggest that omega-3 fatty acids, which are fat compounds found in fish oil, black currant or primrose seed oils, and flax seed, have anti-inflammatory and nerve protecting actions.

Omega-3 fatty acids are essential acids. Medical research suggests they may have anti-inflammatory properties.  

• Choose whole grains and fresh vegetables and fruits. According to some studies, a diet rich in fruits and vegetables can lower homocysteine levels, which are elevated in patients with SLE and may be a risk factor for heart disease. Researchers are also investigating compounds called indoles, also known as mustard oil, which are found in broccoli, cabbage, brussels sprouts, cauliflower, kale, kohlrabi, collard and mustard greens, rutabaga, turnips, and bok choy. Indoles stimulate enzymes that convert estrogen to a more benign type. Eating vegetables certainly will not cure SLE, but they offer many general health benefits.
• Get most proteins from vegetables, particularly soy.
• Avoiding dairy and meat products may help protect the kidneys.
• Take extra calcium and vitamin D (this is particularly useful for patients taking corticosteroids).
• Supplements of vitamins B12, B6, and folate may be necessary, especially in people whose blood tests show high levels of homocysteine.
• Exercise is safe, but patients should not expect it to improve symptoms, including joint aches and fatigue.
• Restrict salt (particularly for patients with signs of high blood pressure and kidney disease).

Of possible interest to patients with SLE is a 2002 report that patients with rheumatoid arthritis (also an inflammatory autoimmune condition) experienced improvement when they went on the Mediterranean diet, which stresses fish (which contains anti-inflammatory factors), olive oil, garlic, whole grains, nuts, and fresh fruits and vegetables. In any case, such a diet is heart-healthy, which is important for patients with SLE.

Prevention Against Infections

Patients should minimize their exposure to crowds or people with contagious illnesses. Careful hygiene, including dental hygiene, is also important.

Avoiding SLE Triggers

Simple preventive measures include avoiding overexposure to ultraviolet rays and wearing protective clothing and sunblocks. There is some concern that allergy shots may cause flare ups in certain cases. Patients who may benefit from them should discuss risks and benefits with an SLE specialist. In general, patients with SLE should use only hypoallergenic cosmetics or hair products.

Reducing Stress

Chronic stress has profound physical effects and influences the progression of SLE. According to one 1999 study, patients with SLE differ from healthy individuals in their immune responses to stress, and psychological stress can induce flare-ups in patients with SLE. Patients should try to avoid undue emotional or physical stress. Getting adequate rest of at least 8 hours and possibly napping during the day may be helpful. Maintaining social relationships and healthy activities helps prevent the depression and anxiety associated with the disease.

Resources

• www.lupus.org -- Lupus Foundation of America
• www.lupusny.org -- SLE Foundation of America
• www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
• www.rheumatology.org -- American College of Rheumatology
• www.clinicaltrials.gov -- Find clinical trials

References

Buyon JP, Petri MA, Kim MY, Kalunian KC, Grossman J, Hahn BH, et al. The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus: a randomized trial. Ann Intern Med. 2005;142(12 Pt 1):953-962.

Dhar JP, Essenmacher LM, Ager JW, Sokol RJ. Pregnancy outcomes before and after a diagnosis of systemic lupus erythematosus. Am J Obstet Gynecol. 2005;193(4):1444-1455.

Ginzler EM, Dooley MA, Aranow C, Kim MY, Buyon J, Merrill JT, et al. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med. 2005;353(21):2219-2228.

Statkute L, Traynor A, Oyama Y, Yaung K, Verda L, Krosnjar N, et al. Antiphospholipid syndrome in patients with systemic lupus erythematosus treated by autologous hematopoietic stem cell transplantation. Blood. 2005;106(8):2700-2709.

Zintzaras E, Voulgarelis M, Moutsopoulos HM. The risk of lymphoma development in autoimmune diseases: a meta-analysis. Arch Intern Med. 2005;165(20):2337-2344.

Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr. 2002 Dec;21(6):495-505.

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