DEFINITION

Lupus is a disorder of the autoimmune disease. In autoimmune diseases, the body harms its own healthy cells and tissues. This leads to inflammation mage to various body tissues. Lupus can affect many parts of the body, including the joints, skin, kidneys, heart, lungs, blood vessels, and brain. Lupus is characterized by periods of illness, called flares, and periods of wellness (remission).
Although lupus is used as a broad term, several kinds of lupus exist.

Systemic lupus erythematosus is the most common form of the disease. The symptoms of SLE may be mild or serious.

Discoid lupus erythematosus refers to a skin disorder in which a red, raised rash appears on the face, scalp, or elsewhere. The raised areas may become thick and scaly and may cause scarring. The rash may last for days or years and may recur. A small percentage of persons with discoid lupus have or develop SLE.

Drug-induced lupus refers to a form of lupus caused by specific medications. Symptoms are similar to those of SLE and typically resolve when the drug is stopped.

Neonatal lupus is a rare form of lupus affecting newborn babies of women with SLE or certain other immune-system disorders. At birth, the babies have a skin rash, liver abnormalities, or low blood counts, which resolve entirely over several months. However, babies with neonatal lupus may have a serious heart defect. Physicians can now identify most at-risk mothers, allowing for prompt treatment of the infant at or before birth. Neonatal lupus is very rare, and most infants of mothers with SLE are entirely healthy.

At present, no cure for lupus exists. However, lupus can be very successfully treated with appropriate drugs, and most persons with the disease can lead active, healthy lives.

ETIOLOGY

Lupus is a complex disease, the cause of which is unknown. In addition, some autoantibodies join with substances from the body's own cells or tissues to form molecules called immune complexes. A buildup of these immune complexes in the body also contributes to inflammation and tissue injury in persons with lupus. Researchers do not yet understand all the factors that cause inflammation and tissue damage in lupus.

SYMPTOMS

Each person's experience with lupus is different, though patterns exist that permit accurate diagnosis. Symptoms can range from mild to severe and may come and go over time.

Common symptoms of lupus include painful or swollen joints, muscle pain, unexplained fever, skin rashes, and extreme fatigue. A characteristic skin rash may appear across the nose and cheeks-the so-called butterfly or malar rash. Other rashes may occur elsewhere on the face and ears, upper arms, shoulders, chest, and hands.

Other symptoms of lupus include chest pain, unusual hair loss, sensitivity to the sun, anemia, and pale or purple fingers or toes from cold and stress (Raynaud's phenomenon). Some persons also experience headaches, dizziness, depression, or seizures. New symptoms may continue to appear years after the initial diagnosis, and different symptoms can occur at different times.

The following systems in the body also can be affected by lupus.

 Kidneys: Inflammation of the kidneys can impair their ability to get rid of waste products and other toxins from the body effectively. Usually no pain is associated with kidney involvement, though some persons may notice that their ankles swell. Most often the only indication of kidney disease is an abnormal urine or blood test.

 Lungs: Some persons with lupus develop pleuritis. Persons with lupus also may get pneumonia.

 Central nervous system : In some persons, lupus affects the brain or central nervous system. This can cause headaches, dizziness, memory disturbances, vision problems, stroke, or changes in behavior.

 Blood vessels: Blood vessels may become inflamed, affecting the way blood circulates through the body. The inflammation may be mild or severe.

 Blood: Persons with lupus may develop anemia, leukopenia, or thrombocytopenia. Some persons with lupus may have abnormalities that cause an increased risk for blood clots.

  Heart: In some persons with lupus, myocarditis, endocarditis, or pericarditis can occur, causing chest pains or other symptoms. Lupus can also increase the risk of atherosclerosis

Despite the symptoms persons with lupus can maintain a high quality of life overall. One key to managing lupus is understanding the disease and its impact.

Learning to recognize the warning signs of a flare can help a person take steps to ward it off or reduce its intensity. Many persons with lupus experience increased fatigue, pain, a rash, fever, abdominal discomfort, headache, or dizziness just before a flare.

DIAGNOSIS

The diagnosis of lupus can be difficult. It may take months or even years for physicians to piece together the symptoms to diagnose this complex disease accurately.

No single test can determine whether a person has lupus, but several laboratory tests may aid in the diagnosis. Most persons with lupus test positive for ANA. However, there are a number of other causes of positive ANA results, including infections and other rheumatic or immune diseases-occasionally they even are found in healthy adults. The ANA test simply provides another clue for the physician to consider in making a diagnosis.

In addition, blood tests for individual types of autoantibodies exist that are more specific to persons with lupus, though not all persons with lupus test positive for these, and not all persons with these antibodies have lupus. These antibodies include anti-DNA, anti-Sm, anti-RNP, anti-Ro (SSA), and anti-La (SSB). These antibody tests may help in the diagnosis of lupus.

Some tests are used less frequently but may be helpful if the cause of a person's symptoms remains unclear. A biopsy of the skin or kidneys may be indicated if those body systems are affected. A test for syphilis or the anticardiolipin antibody may also be useful. Positive test results do not mean that a person has syphilis; however, the presence of this antibody may increase the risk of blood clotting and can increase the risk of miscarriages in pregnant women with lupus. Again, all these tests merely serve as tools in making a diagnosis.

Other laboratory tests are used to monitor the progress of the disease once it has been diagnosed. A complete blood count, urinalysis, blood chemistries, and erythrocyte sedimentation rate test can provide valuable information. Another common test measures the blood level of a group of substances called complement. Persons with lupus often have increased erythrocyte sedimentation rates and low complement levels, especially during flares of the disease.

Persons diagnosed with systemic lupus erythematosus (SLE) have autoantibodies in their blood years before any symptoms appear, according to an article in the October 16, 2003, issue of The New England Journal of Medicine.

The early detection of autoantibodies may facilitate the recognition of those persons who will develop SLE and may allow physicians to monitor them before the disease might otherwise be noticed.

THINK ABOUT THESE 

A cataract cannot return because all or part of the lens has been removed. However, in some people who have had extracapsular surgery or phacoemulsification, the lens capsule becomes cloudy after a year. It causes the same vision problems as a cataract does. To correct this, laser capsulotomy can be performed. In laser (YAG) capsulotomy a laser (light) beam is used to make a tiny hole in the capsule to let light pass. This surgery is painless and does not require stay in the hospital.

Full Source Title:American Journal of Medicine 
   
 Abstract
 
  PURPOSE:We sought to assess the nephritogenic antibody profile of patients with systemic lupus erythematosus (SLE), and to determine which antibodies were most useful in identifying patients at risk of nephritis. METHODS: We studied 199 patients with SLE, 78 of whom had lupus nephritis. We assayed serum samples for antibodies against chromatin components (double-stranded deoxyribonucleic acid [dsDNA], nucleosome, and histone), C1q, basement membrane components (laminin, fibronectin, and type IV collagen), ribonucleoprotein, and phospholipids. Correlations of these antibodies with disease activity (SLE Disease Activity Index) and nephropathy were assessed. Patients with no initial evidence of nephropathy were followed prospectively for 6 years. RESULTS: Antibodies against dsDNA, nucleosomes, histone, C1q, and basement membrane components were associated with disease activity (P <0.05). In a multivariate analysis, anti-dsDNA antibodies (odds ratio [OR] = 6; 95% confidence interval [CI]: 2 to 24) and antihistone antibodies (OR = 9.4; 95% CI: 4 to 26) were associated with the presence of proliferative glomerulonephritis. In the prospective study, 7 (6%) of the 121 patients developed proliferative lupus glomerulonephritis after a mean of 6 years of follow-up. Patients with initial antihistone (26% [5/19] vs. 2% [2/95], P = 0.0004) and anti-dsDNA reactivity (6% [2/33] vs. 0% [0/67], P = 0.048) had a greater risk of developing proliferative glomerulonephritis than patients without these autoantibodies.

CONCLUSION: In addition to routine anti-dsDNA antibody assay, antihistone antibody measurement may be useful for identifying patients at increased risk of proliferative glomerulonephritis. 

Full Source Title:Arthritis and Rheumatism

Abstract:

OBJECTIVE: To determine the degree to which changes in C3 and C4 precede or coincide with changes in systemic lupus erythematosus (SLE) activity, as measured by 5 global activity indices, the physician's global assessment (PGA), modified SLE Disease Activity Index (M-SLEDAI), modified Lupus Activity Index (M-LAI), Systemic Lupus Activity Measure (SLAM), and the modified British Isles Lupus Assessment Group (M-BILAG), and to evaluate the association between changes in C3 and C4 levels and SLE activity in individual organ systems. RESULTS: Lupus flares occurred at 12% of visits based on the PGA, 19% based on the M-SLEDAI, 25% based on the M-LAI, 13% based on the SLAM, and 12% based on the M-BILAG. Recent changes in C3 and C4 levels were not associated with flares based on 3 of the 5 activity indices. Flares defined by the M-LAI were more frequent when there was a concurrent decrease in C3 (odds ratio [OR] 1.9, 95% confidence interval [95% CI] 1.1-3.1) or C4 (OR 2.1, 95% CI 1.3-3.6). Higher flare rates, as defined by the SLAM, were associated with previous increases in C3 (OR 1.6, 95% CI 1.0-2.6) and C4 (OR 2.2, 95% CI 1.2-3.9). When individual organ systems were analyzed, decreases in C3 and C4 were associated with a concurrent increase in renal disease activity (OR 2.2, 95% CI 1.4-3.5 and OR 1.9, 95% CI 1.1-3.4, respectively). Decreases in C3 were also associated with concurrent decreases in the hematocrit (OR 4.6, 95% CI 1.7-12.3), platelet (OR 2.5, 95% CI 1.5-4.1), and white blood cell (OR 2.2, 95% CI 1.3-3.6) counts. Previous increases in C3 levels were associated with a decrease in platelets (OR 1.7, 95% CI 1.1-2.7). A decrease in C4 was associated with a concurrent decrease in the hematocrit level (OR 3.2, 95% CI 1.3-7.5) and platelet count (OR 1.6, 95% CI 1.0-2.5).

CONCLUSION: Decreases in complement levels were not consistently associated with SLE flares, as defined by global measures of disease activity. However, decreasing complement was associated with a concurrent increase in renal and hematologic SLE activity

TREATMENT OF SLE

 

 

 

 

 

 

 

 

 

 

 

 

CONSERVATIVE MANAGEMENT

Arthritis, Arthralgia, and Myalgia
 
Arthritis, arthralgia, and myalgia are the most common manifestations of SLE. Severity ranges from mild to disabling. For patients with mild symptoms, administration of analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), or salicylates may provide adequate relief, although none of these is as effective as glucocorticoids.

In many SLE patients, musculoskeletal symptoms are not well controlled by salicylate or NSAID therapy. A trial of antimalarial drugs may be useful in such individuals.

Hydroxychloroquine is the preferred antimalarial agent in the United States (chloroquine may be more effective but has a higher incidence of retinal toxicity: quinacrine is often effective but rarely can cause aplastic anemia). The usual dose of hydroxychloroquine for SLE patients with arthritis is 400 mg daily. If response does not occur within 6 months, the patient can be considered a nonresponder and the drug stopped. If hydroxychloroquine is used for more than 6 months or chloroquine is used for more than 3 months, regular examination by an ophthalmologist for retinal damage is mandatory. If antimalarials are effective, the maintenance dose should be reduced periodically if possible, or the drug should be withdrawn when a patient is doing well, because the retinal toxicity is cumulative.

Some patients with arthritis or arthralgia do not benefit from NSAIDs or salicylates with or without antimalarials. Administration of dihydroandrosterone (DHEA), 100 to 200 mg daily, lowers activity of SLE in some patients, including arthritis/arthralgias.

Methotrexate in weekly oral or parenteral doses of 10 to 20 mg may also be considered, because there are reports of its efficacy in some cases.

However, none of these interventions is as reliable as glucocorticoid therapy in suppressing lupus arthritis and arthralgia. If quality of life is seriously impaired by pain (or by the deformities that develop in about 10 percent of individuals with lupus arthritis), the physician should consider institution of low-dose glucocorticoids, not to exceed 15 mg each morning.
 
Rare patients require high-dose glucocorticoids or even cytotoxic drugs. Such interventions should be avoided if possible. In fact, if arthritis is the major manifestation of disease that compels the physician to choose high-dose immunosuppressive treatments, it may be preferable to use around-the-clock non-narcotic or narcotic analgesics to control pain, rather than to risk life-threatening side effects of aggressive immunosuppression.

Cutaneous Lupus

As many as 70 percent of patients with SLE are photosensitive..Patients should begin with preparations that block UVA and UVB. Sunscreens can be locally irritating (especially those that contain PABA); patients may need to try several preparations to find one that is not irritating.

Local glucocorticoids, including topical creams and ointments and injections into severe skin lesions, are also helpful in lupus dermatitis. [ Patients with disfiguring (discoid) or extensive lesions should be seen by a dermatologist, because management of severe lupus dermatitis can be difficult.

Antimalarial agents are useful in some patients with lupus dermatitis, whether the lesions are those of SLE, subacute cutaneous lupus, or discoid lupus. Antimalarials have multiple sunblocking, anti-inflammatory, and immunosuppressive effects. They also bind melanin and serve as sunscreens, and they have antiplatelet and cholesterol-lowering effects. All these properties may be beneficial to patients with SLE.

Responses to chloroquine and quinacrine are usually demonstrable within 1 to 3 months; responses to hydroxychloroquine may require 3 to 6 months. Antimalarials may be steroid sparing. Recommended initial doses of antimalarials are hydroxychloroquine, 400 mg daily, chloroquine phosphate, 500 mg daily, and quinacrine, 100 mg daily. Higher doses can be given for brief periods (2 to 4 weeks). After disease is well controlled, the drugs can be slowly tapered. Daily doses can be reduced, or the drug can be given less frequently (e.g., a few days each week). The combination of hydroxychloroquine (or chloroquine) and quinacrine is probably synergistic and can be used in patients refractory to single-drug therapy.

Toxicities of these agents are important but infrequent in comparison with other agents used to treat SLE. Retinal damage is the most important; it can occur in up to 10 percent of patients receiving chronic chloroquine therapy but is much less frequent in those receiving hydroxychloroquine. Regular ophthalmologic examinations with appropriate special testing identify retinal changes early. If changes occur, antimalarial therapy should be stopped or the daily dose decreased. This strategy substantially lowers the incidence of clinically important retinal toxicity. Retinopathy is rare in patients treated with quinacrine.

For individuals with lupus rash resistant to antimalarials and other conservative strategies, etretinate has been beneficial. The retinates are teratogenic, cause cheilitis in most patients, and elevate cholesterol and triglyceride levels in some. Patients resistant to antimalarials and retinates may require systemic glucocorticoids, which improve lupus skin lesions of any type. Additional treatments, which should be considered experimental for dermatologic lupus, include dapsone, thalidomide, and cytotoxic drugs.

Dapsone has been used in discoid lupus, urticarial vasculitis, and bullous LE lesions with some success. It has significant hematologic toxicities (including methemoglobinemia, sulfhemoglobinemia, and hemolytic anemia) and can occasionally worsen the rashes of LE. Some steroid-resistant cases have improved when treated with cytotoxic drugs such as azathioprine or methotrexate.

Successful treatment of refractory lupus rashes with thalidomide has been reported. Development of peripheral neuropathy associated with thalidomide is not uncommon. This highly teratogenic drug is available on special request from the manufacturer, with appropriate assurances that the patient cannot become pregnant.

Fatigue and Systemic Complaints

Fatigue is common in patients with SLE and may be the major disabling complaint. It reflects multiple problems, including depression, sleep deprivation, and fibromyalgia. Fever and weight loss, if mild, can be managed with the conservative approaches outlined in the preceding paragraphs. When severe, systemic glucocorticoid therapy is necessary.

Serositis

Episodes of chest and abdominal pain may be secondary to lupus serositis. In some patients, complaints respond to salicylates, NSAIDs (indomethacin may be best), or antimalarial therapies, or to low doses of systemic glucocorticoids, such as 15 mg/day In others, systemic glucocorticoids must be given in high doses to achieve disease remission.

RECENT ADVANCES

TABLE 1 -- APPROACHES IN THE MANAGEMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS

Agent Target Anti-CD40L (gp 39) mAbs T-cell activation/T-cell-B-cell collaboration CTLA-4Ig   3E10 mAb vaccine Inhibition of Ab production LJP 394: B-cell toleragen Inhibition of Ab production rHuDNAse Inhibition of Ab production Anti-C5 mAb Complement activation/immune complex deposition Anti-IL-10 mAbs Cytokine activation/modulation AS101 (anti-IL-10) Cytokine activation/modulation Gene therapy Cytokine activation/modulation Thalidomide (anti-tumor necrosis factor-alpha) Cytokine activation/modulation IVIg Immunomodulation Bindarit Immunomodulation Plasmapheresis Immunomodulation *Mycophenolate mofetil Immunomodulation Immunoadsorption Immunomodulation 2CdA Immunomodulation Fludaribine Immunomodulation Methimazole Immunomodulation Stem cell transplantation Stem cells Immunoablative treatment   DHEA Sex hormones Selective estrogen receptor modulators Sex hormone

*Mycophenolate mofetil has been tried as a treatment for several autoimmune diseases, on the basis of the positive experience with this drug in recipients of solid-organ transplants. The parent compound is hydrolyzed to mycophenolic acid, an inhibitor of inosine monophosphate dehydrogenase, which blocks several steps in the effector arm of the immune system. In mice with lupus, mycophenolate mofetil prolonged overall survival and delayed the onset and severity of nephritis.7 In small studies of patients with lupus nephritis that was resistant to cyclophosphamide, mycophenolate mofetil appeared to be effective in controlling renal disease. Treatment of Lupus Nephritis The standard of care for the treatment of aggressive forms of the disorder is the administration of intravenous cyclophosphamide.3 In addition to oral glucocorticoids, cyclophosphamide is given in monthly intravenous pulses for at least six consecutive months. In one study, exacerbations of lupus nephritis were reduced when intravenous cyclophosphamide was given every three months for an additional two years. Chan et al. present the results of a study in Hong Kong in which patients with diffuse proliferative lupus nephritis were treated with prednisolone and mycophenolate mofetil or with prednisolone and cyclophosphamide followed by prednisolone and azathioprine.The study provides evidence that treatment with mycophenolate mofetil is as effective as and has fewer side effects than sequential treatment with cyclophosphamide and azathioprine. There are several reasons for caution in generalizing these findings to other patients with diffuse proliferative lupus glomerulonephritis. *Prophylactic anticoagulation therapy is not justified in patients with high titer anticardiolipin antibodies with no history of thrombosis. *However, if a history of recurrent deep vein thrombosis or pulmonary embolism is established, long-term anticoagulant therapy with international normalized ratio (INR) of approximately 3 is needed. Antiphospholipid syndrome The syndrome occurs most commonly in young to middle-aged adults; however, it also can occur in children and the elderly. Among patients with SLE, the prevalence of antiphospholipid antibodies is high, ranging from 12% to 30% for anticardiolipin antibodies, and 15% to 34% for lupus anticoagulant antibodies. In general, anticardiolipin antibodies occur approximately five times more often then lupus anticoagulant in patients with antiphospholipid syndrome. This syndrome is the most common cause of acquired thrombophilia, associated with either venous or arterial thrombosis or both. It is characterized by the presence of antiphospholipid antibodies, recurrent arterial and venous thrombosis, and spontaneous abortion. Rarely, patients with antiphospholipid syndrome may have fulminate multiple organ failure, or catastrophic antiphospholipid syndrome. This is caused by widespread microthrombi in multiple vascular beds, and can be devastating. Patients with catastrophic antiphospholipid syndrome may have massive venous thromboembolism, along with respiratory failure, stroke, abnormal liver enzyme concentrations, renal impairment, adrenal insufficiency, and areas of cutaneous infarction. According to the international consensus statement, at least one clinical criterion (vascular thrombosis, pregnancy complications) and one laboratory criterion (lupus anticoagulant, antipcardiolipin antibodies) should be present for a diagnosis of antiphospholipid syndrome. The hallmark result from laboratory tests that defines antiphospholipid syndrome is the presence of antibodies or abnormalities in phospholipid-dependent tests of coagulation, such as dilute Russell viper venom time. There is no consensus for treatment among physicians. Overall, there is general agreement that patients with recurrent thrombotic episodes require life-long anticoagulation therapy and that those with recurrent spontaneous abortion require anticoagulation therapy and low- dose aspirin therapy during most of gestation.

CONCLUSIONS

An appreciation of the many facets of SLE is essential, including a recognition of the current limit of our knowledge about the disease and its management. A better understanding of the pathogenesis of SLE promises to provide much information about the nature and the role of the immune response in this and other diseases.