Lupus is a condition characterized by chronic inflammation of body tissues caused by autoimmune disease. Autoimmune diseases are illnesses that occur when the body's tissues are attacked by its own immune system.
The immune system is a complex system within the body that is designed to fight infectious agents, for example, bacteria, and other foreign invaders. One of the mechanisms that the immune system uses to fight infections is the production of antibodies. Patients with lupus produce abnormal antibodies in their blood that target tissues within their own body rather than foreign infectious agents. Because the antibodies and accompanying cells of inflammation can involve tissues anywhere in the body, lupus has the potential to affect a variety of areas of the body. Sometimes lupus can cause disease of the skin, heart, lungs, kidneys, joints, and/or nervous system. When only the skin is involved, the condition is called discoid lupus. When internal organs are involved, the condition is called systemic lupus erythematosus (SLE).
Both discoid and systemic lupus are more common in women than men (about eight times more common). The disease can affect all ages but most commonly begins from age 20 to 45 years. It is more frequent in African-Americans and people of Chinese and Japanese descent.
What causes lupus ? Is it hereditary ?
The precise reason for the abnormal autoimmunity that causes lupus is not known. Inherited genes, viruses, ultraviolet light, and drugs may all play some role. Genetic factors increase the tendency of developing autoimmune diseases, and autoimmune diseases such as lupus, rheumatoid arthritis, and immune thyroid disorders are more common among relatives of patients with lupus than the general population. Some scientists believe that the immune system in lupus is more easily stimulated by external factors like viruses or ultraviolet light. Sometimes, symptoms of lupus can be precipitated or aggravated by only a brief period of sun exposure.
It also is known that some women with SLE can experience worsening of their symptoms prior to their menstrual periods. This phenomenon, together with the female predominance of SLE, suggest that female hormones play an important role in the expression of SLE. This hormonal relationship is an active area of ongoing study by scientists.
More recently, research has demonstrated evidence that a key enzyme's failure to dispose of dying cells may contribute the development of SLE. The enzyme, DNase1, normally eliminates what is called "garbage DNA" and other cellular debris by chopping them into tiny fragments for easier disposal. The researchers turned off the DNase1 gene in mice. The mice appeared healthy at birth but after six to eight months, the majority of mice without DNase1 showed signs of SLE. Thus, a genetic mutation in a gene that could disrupt the body's cellular waste disposal may be involved in the initiation of SLE.
What is drug-induced lupus ?
Dozens of medications have been reported to trigger SLE; however, more than 90% of this "drug-induced lupus" occurs as a side effect of one of the following six drugs: hydralazine (used for high blood pressure), quinidine and procainamide (used for abnormal heart rhythm), phenytoin (used for epilepsy), isoniazid [(Nydrazid, Laniazid), used for tuberculosis], d-penicillamine (used for rheumatoid arthritis). These drugs are known to stimulate the immune system and cause SLE. Fortunately, drug-induced SLE is infrequent (accounting for less than 5% of SLE among all patients with SLE) and usually resolves when the medications are discontinued.
What are the symptoms and signs of lupus?
In discoid lupus, only the skin is typically involved. The skin rash in discoid lupus often is found on the face and scalp. It usually is red and may have raised borders. Discoid lupus rashes are usually painless and do not itch, but scarring can cause permanent hair loss. Over time, 5%-10% of patients with discoid lupus may develop SLE.
Patients with SLE can develop different combinations of symptoms and organ involvement. Common complaints and symptoms include fatigue, low-grade fever, loss of appetite, muscle aches, arthritis, ulcers of the mouth and nose, facial rash ("butterfly rash"), unusual sensitivity to sunlight (photosensitivity), inflammation of the lining that surrounds the lung (pleuritis) and the heart (pericarditis), and poor circulation to the fingers and toes with cold exposure (Raynaud's phenomenon).
More serious organ involvement with inflammation occurs in the brain, liver, and kidney. White blood cells and blood clotting factors also can be decreased in SLE, thereby increasing the risk of infection and bleeding.
Over half of the patients with SLE develop a characteristic red, flat facial rash over the bridge of their nose. Because of its shape, it is frequently referred to as the "butterfly rash" of SLE. The rash is painless and does not itch. The facial rash, along with inflammation in other organs, can be precipitated or worsened by exposure to sunlight, a condition called photosensitivity. This photosensitivity can be accompanied by worsening of inflammation throughout the body, called a "flare" of disease.
Most patients with SLE will develop arthritis during the course of their illness. Arthritis in SLE commonly involves swelling, pain, stiffness, and even deformity of the small joints of the hands, wrists, and feet. Sometimes, the arthritis of SLE can mimic that of rheumatoid arthritis (another autoimmune disease).
Inflammation of muscles (myositis) can cause muscle pain and weakness.
Inflammation of blood vessels, (vasculitis) that supply oxygen to tissues, can cause isolated injury to a nerve, the skin, or an internal organ. The blood vessels are composed of arteries that pass oxygen-rich blood to the tissues of the body and veins which return oxygen-depleted blood from the tissues to the lungs. Vasculitis is characterized by inflammation with damage to the walls of various blood vessels. The damage blocks the circulation of blood through the vessels and can cause injury to the tissues that the vessels supply.
Inflammation of the lining of the lungs (pleuritis) and of the heart (pericarditis) can cause sharp chest pain. The chest pain is aggravated by coughing, deep breathing, and certain changes in body position. The heart muscle itself rarely can become inflamed (carditis). It has also been shown that young women with SLE have a significantly increased risk of heart attacks from coronary artery disease.
Kidney inflammation in SLE can cause leakage of protein into the urine, fluid retention, high blood pressure, and even kidney failure. With kidney failure, machines are needed to cleanse the blood of accumulated poisons in a process called dialysis.
Involvement of the brain can cause personality changes, thought disorders (psychosis), seizures, and even coma. Damage to nerves can cause numbness, tingling, and weakness of the involved body parts or extremities. Brain involvement is called cerebritis.
Many patients with SLE experience hair loss (alopecia). Often, this occurs simultaneously with an increase in the activity of their disease.
Some patients with SLE have Raynaud's phenomenon. In these patients, the blood supply to the fingers and toes becomes interrupted upon exposure to cold, causing blanching, bluish discoloration, and pain in the exposed fingers and toes.
What are the symptoms and signs of lupus ?
In discoid lupus, only the skin is typically involved. The skin rash in discoid lupus often is found on the face and scalp. It usually is red and may have raised borders. Discoid lupus rashes are usually painless and do not itch, but scarring can cause permanent hair loss. Over time, 5%-10% of patients with discoid lupus may develop SLE.
Patients with SLE can develop different combinations of symptoms and organ involvement. Common complaints and symptoms include fatigue, low-grade fever, loss of appetite, muscle aches, arthritis, ulcers of the mouth and nose, facial rash ("butterfly rash"), unusual sensitivity to sunlight (photosensitivity), inflammation of the lining that surrounds the lung (pleuritis) and the heart (pericarditis), and poor circulation to the fingers and toes with cold exposure (Raynaud's phenomenon).
More serious organ involvement with inflammation occurs in the brain, liver, and kidney. White blood cells and blood clotting factors also can be decreased in SLE, thereby increasing the risk of infection and bleeding.
Over half of the patients with SLE develop a characteristic red, flat facial rash over the bridge of their nose. Because of its shape, it is frequently referred to as the "butterfly rash" of SLE. The rash is painless and does not itch. The facial rash, along with inflammation in other organs, can be precipitated or worsened by exposure to sunlight, a condition called photosensitivity. This photosensitivity can be accompanied by worsening of inflammation throughout the body, called a "flare" of disease.
Most patients with SLE will develop arthritis during the course of their illness. Arthritis in SLE commonly involves swelling, pain, stiffness, and even deformity of the small joints of the hands, wrists, and feet. Sometimes, the arthritis of SLE can mimic that of rheumatoid arthritis (another autoimmune disease).
Inflammation of muscles (myositis) can cause muscle pain and weakness.
Inflammation of blood vessels, (vasculitis) that supply oxygen to tissues, can cause isolated injury to a nerve, the skin, or an internal organ. The blood vessels are composed of arteries that pass oxygen-rich blood to the tissues of the body and veins which return oxygen-depleted blood from the tissues to the lungs. Vasculitis is characterized by inflammation with damage to the walls of various blood vessels. The damage blocks the circulation of blood through the vessels and can cause injury to the tissues that the vessels supply.
Inflammation of the lining of the lungs (pleuritis) and of the heart (pericarditis) can cause sharp chest pain. The chest pain is aggravated by coughing, deep breathing, and certain changes in body position. The heart muscle itself rarely can become inflamed (carditis). It has also been shown that young women with SLE have a significantly increased risk of heart attacks from coronary artery disease.
Kidney inflammation in SLE can cause leakage of protein into the urine, fluid retention, high blood pressure, and even kidney failure. With kidney failure, machines are needed to cleanse the blood of accumulated poisons in a process called dialysis.
Involvement of the brain can cause personality changes, thought disorders (psychosis), seizures, and even coma. Damage to nerves can cause numbness, tingling, and weakness of the involved body parts or extremities. Brain involvement is called cerebritis.
Many patients with SLE experience hair loss (alopecia). Often, this occurs simultaneously with an increase in the activity of their disease.
Some patients with SLE have Raynaud's phenomenon. In these patients, the blood supply to the fingers and toes becomes interrupted upon exposure to cold, causing blanching, bluish discoloration, and pain in the exposed fingers and toes.
How is lupus diagnosed ?
Since patients with SLE can have a wide variety of symptoms and different combinations of organ involvement, no single test establishes the diagnosis of systemic lupus. To help doctors improve the accuracy of the diagnosis of SLE, eleven criteria were established by the American Rheumatism Association. These 11 criteria are closely related to the symptoms discussed above. Some patients suspected of having SLE may never develop enough criteria for a definite diagnosis. Other patients accumulate enough criteria only after months or years of observation. When a person has four or more of these criteria, the diagnosis of SLE is strongly suggested. Nevertheless, the diagnosis of SLE may be made in some settings in patients with only a few of these classical criteria. Of these patients, a number may later develop other criteria, but many never do.
The 11 criteria used for diagnosing systemic lupus erythematosus are :
i) malar (over the cheeks of the face) "butterfly" rash;
ii) discoid skin rash : patchy redness that can cause scarring;
iii) photosensitivity : skin rash in reaction to sunlight exposure;
iv) mucus membrane ulcers : ulcers of the lining of the mouth, nose or throat;
v) arthritis : two or more swollen, tender joints of the extremities;
vi) pleuritis/pericarditis : inflammation of the lining tissue around the heart or lungs, usually associated with chest pain with breathing;
vii) kidney abnormalities : abnormal amounts of urine protein or clumps of cellular elements called casts
viii)brain irritation : manifested by seizures (convulsions) and/or psychosis
ix) blood count abnormalities : low counts of white or red blood cells, or platelets
x) immunologic disorder : abnormal immune tests include anti-DNA or anti-Sm(Smith) antibodies, falsely positive blood test for syphilis, anticardiolipin antibodies, lupus anticoagulant, or positive LE prep test
xi) antinuclear antibody : positive ANA antibody testing
In addition to the 11 criteria, other tests can be helpful in evaluating patients with SLE to determine the severity of organ involvement. These include routine testing of the blood to detect inflammation (for example, a test called the sedimentation rate), blood chemistry testing, direct analysis of internal body fluids, and tissue biopsies. Abnormalities in body fluids and tissue samples (kidney, skin, and nerve biopsies) can further support the diagnosis of SLE. The appropriate test procedures are selected for the patient individually by the doctor.
What is the treatment for systemic lupus ?
There is no permanent cure for SLE. The goal of treatment is to relieve symptoms and protect organs by decreasing inflammation and/or the level of autoimmune activity in the body. Many patients with mild symptoms may need no treatment or only intermittent courses of antiinflammatory medications. Those with more serious illness involving damage to internal organ(s) may require high doses of corticosteroids in combination with other medications that suppress the body's immune system.
Patients with SLE need more rest during periods of active disease. Researchers have reported that poor sleep quality was a significant factor in developing fatigue in patients with SLE. These reports emphasize the importance for patients and physicians to address sleep quality and the effect of underlying depression, lack of exercise, and self-care coping strategies on overall health. During these periods, carefully prescribed exercise is still important to maintain muscle tone and range of motion in the joints.
Nonsteroidal antiinflammatory drugs (NSAIDs) are helpful in reducing inflammation and pain in muscles, joints, and other tissues. Examples of NSAIDs include aspirin, ibuprofen (Motrin), naproxen (Naprosyn), and sulindac (Clinoril). Since the individual response to NSAIDs varies among patients, it is common for a doctor to try different NSAIDs to find the most effective one with the fewest side effects. The most common side effects are stomach upset, abdominal pain, ulcers, and even ulcer bleeding. NSAIDs are usually taken with food to reduce side effects. Sometimes, medications that prevent ulcers while taking NSAIDs, such as misoprostol (Cytotec), are given simultaneously.
Corticosteroids are more potent than NSAIDs in reducing inflammation and restoring function when the disease is active. Corticosteroids are particularly helpful when internal organs are involved. Corticosteroids can be given by mouth, injected directly into the joints and other tissues, or administered intravenously. Unfortunately, corticosteroids have serious side effects when given in high doses over prolonged periods, and the doctor will try to monitor the activity of the disease in order to use the lowest doses that are safe. Side effects of corticosteroids include weight gain, thinning of the bones and skin, infection, diabetes, facial puffiness, cataracts, and death (necrosis) of large joints.
Hydroxychloroquine (Plaquenil) is an antimalarial medication found to be particularly effective for SLE patients with fatigue, skin, and joint disease. Side effects include diarrhea, upset stomach, and eye pigment changes. Eye pigment changes are rare, but require monitoring by an ophthalmologist (eye specialist) during treatment with Plaquenil. Researchers have found that Plaquenil significantly decreased the frequency of abnormal blood clots in patients with systemic SLE. Moreover, the effect seemed independent of immune suppression, implying that Plaquenil can directly act to prevent the blood clots. This fascinating work highlights an important reason for patients and doctors to consider Plaquenil, especially for those SLE patients who are at some risk for blood clots in veins and arteries, such as those with phospholipid antibodies (cardiolipin antibodies, lupus anticoagulant, and false positive VDRL). This means not only that Plaquenil reduces the chance for reflares of SLE, but it can also be beneficial in 'thinning' the blood to prevent abnormal excessive blood clotting.
For resistant skin disease, other antimalarial drugs, such as chloroquine (Aralen) or quinacrine, are considered, and can be used in combination with hydroxychloroquine. Alternative medications for skin disease include dapsone and retinoic acid (Retin-A). Retin-A is often effective for an uncommon wart-like form of lupus skin disease. For more severe skin disease, immunosuppressive medications are considered as below.
Medications that suppress immunity (immunosuppressive medications) are also called cytotoxic drugs. Immunosuppressive medications are used for treating patients with more severe manifestations of SLE with damage to internal organ(s). Examples of immunosuppressive medications include methotrexate (Rheumatrex, Trexall), azathioprine (Imuran), cyclophosphamide (Cytoxan), chlorambucil (Leukeran), and cyclosporine (Sandimmune). All immunosuppressive medications can seriously depress blood cell counts and increase risks of infection and bleeding. Other side effects are peculiar for each drug. For examples, Rheumatrex can cause liver toxicity, while Sandimmune can impair kidney function.
In recent years, mycophenolate mofetil (Cellcept) has been used as an effective medication for lupus, particularly when it associated with kidney disease. Cellcept has been helpful in reversing active lupus kidney disease (lupus renal disease) and in maintaining remission after it is established. It's lower side effect profile has advantage over traditional immune suppression medications.
In SLE patients with serious brain or kidney disease, plasmapheresis is sometimes used to remove antibodies and other immune substances from the blood to suppress immunity. Some SLE patients can develop seriously low platelet levels, thereby increasing the risk of excessive and spontaneous bleeding. Since the spleen is believed to be the major site of platelet destruction, surgical removal of the spleen is sometimes performed to improve platelet levels. Other treatments have included plasmapheresis and the use of male hormones. Plasmapheresis has also been used to remove proteins (cryoglobulins) that can lead to vasculitis. Endstage kidney damage from SLE requires dialysis and/or a kidney transplant.
Most recent research is indicating benefits of rituximab (Rituxan) in treating lupus. Rituximab is an intravenously infused antibody that suppresses a particular white blood cell, the B cell, by decreasing their number in the circulation. B cells have been found to play a central role in lupus activity, and when they are suppressed, the disease tends toward remission.
At the 2007 national Rheumatology meeting, there was a paper presented suggesting that low dose dietary supplementation with omega-3 fish oils could help patients with lupus by decreasing disease activity and possibly decreasing heart disease risk.
How can a lupus patient help prevent disease activity (flares) ?
SLE is undoubtedly a potentially serious illness with involvement of numerous organ systems. However, it is important to recognize that most patients with SLE lead full, active, healthy lives. Periodic increases in disease activity (flares) can usually be managed by varying medications. Since ultraviolet light can precipitate and worsen flares, patients with systemic lupus should avoid sun exposure. Sunscreens and clothing covering the extremities can be helpful. Abruptly stopping medications, especially corticosteroids, can also cause flares and should be avoided. Patients with SLE are at increased risk of infections, especially if they are taking corticosteroids or immunosuppressive medications. Therefore, any unexpected fever should be reported and evaluated.
The key to successful management of SLE is regular contact and communication with the doctor, allowing monitoring of symptoms, disease activities, and treatment side effects.
How can lupus affect pregnancy or the newborn ?
Patients with SLE who become pregnant are considered "high risk." Women with SLE who are pregnant require close observation during pregnancy and delivery. This includes fetal monitoring by the obstetrician during later pregnancy. These women can have an increased risk of miscarriages (spontaneous abortions) and can have flares of SLE during pregnancy. The presence of phospholipid antibodies, such as cardiolipin antibodies or lupus anticoagulant, in the blood can identify patients at risk for miscarriages. Cardiolipin antibodies are associated with a tendency toward blood clotting. Patients with SLE who have cardiolipin antibodies or lupus anticoagulant may need blood thinning medications (aspirin with or without heparin) during pregnancy to prevent miscarriages. Other reported treatments include the use of intravenous gamma globulin for selected patients with histories of premature miscarriage and those with low blood-clotting elements (platelets) during pregnancy. Pregnant women who have had a previous blood clotting event may benefit by continuation of blood thinning throughout and after pregnancy for up to six to 12 weeks, at which time the risk of clotting associated with pregnancy seems to diminish. Plaquenil has now been found to be safe for use to treat SLE during pregnancy.
Lupus antibodies can be transferred from the mother to the fetus and result in lupus illness in the newborn ("neonatal lupus"). This includes the development of low red cell (anemia) and/or white blood cell and platelet counts, and skin rash. Problems can also develop in the electrical system of the baby's heart (congenital heart block). Occasionally, a pacemaker for the baby's heart is needed in this setting. Neonatal lupus and congenital heart block are more common in newborns of mothers with SLE who carry antibodies referred to as anti-Ro (or SS-A) and anti-La (or SS-B). (It is wise for the newborn baby's doctor to be made aware if the mother is known to carry these antibodies. Risk of heart block is 2%, risk of neonatal lupus is 5%.) Neonatal lupus usually clears after six months of age as the mother's antibodies are slowly metabolized by the baby.
What does the future hold for patients with lupus ?
Overall, the outlook for patients with systemic lupus is improving each decade with the development of more accurate monitoring tests and treatments.
The role of the immune system in causing diseases is becoming better understood through research. This knowledge will be applied to design safer and more effective treatment methods. For example, completely revising the immune system of patients with extremely aggressive treatments that virtually temporarily wipe out the immune system is being evaluated. Current studies involve immune eradication with or without replacement of cells that can re-establish the immune system (stem cell transplantation).
It should be noted that patients with SLE are at a somewhat increased risk for developing cancer. The cancer risk is most dramatic for blood cancers, such as leukemia and lymphoma, but is also increased for breast cancer. This risk probably relates, in part, to the altered immune system that is characteristic of SLE.
Women with SLE appear to be at increased risk for heart disease (coronary artery disease) according to recent reports. Women with SLE should be evaluated to minimize risk factors for heart disease, such as elevated blood cholesterol, quitting smoking, high blood pressure, and obesity.
DHEA (dehydroepiandrosterone) has been helpful in reducing fatigue, improving thinking difficulties, and improving quality of life in patients with SLE. Recent research indicates that DHEA has been shown to improve or stabilize signs and symptoms of SLE. DHEA is commonly available in health food stores, pharmacies, and many groceries.
Landmark research has shown clearly that oral contraceptives do not increase the rate of flares of systemic lupus erythematosus. This important finding is opposite to what has been thought for years. Now we can reassure women with lupus that if they take birth control pills, they are not increasing their risk for lupus flares. NOTE: Birth control pills or any estrogen medications still should be avoided by women who are at increased risk of blood clotting, such as lupus women who have phospholipid antibodies (including cardiolipin antibody or lupus anticoagulant).
Individuals with SLE can improve their prognosis by learning about the many aspects of the illness as well as closely monitoring their own health with their doctors.
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