Systemic lupus erythematosus (SLE or lupus) is a chronic, potentially debilitating or fatal autoimmune disease in which the immune system attacks the body’s cells and tissue, resulting in inflammation and tissue damage. SLE can affect any part of the body, but often harms the heart, joints (rheumatological), skin, lungs, blood vessels and brain/nervous system. Lupus is treatable, mainly with immunosuppression, though there is currently no cure for it.
The standard treatment, for decades, has been a limited group of drugs (primarily corticosteroids and chemotherapy drugs). Research into more modern treatments has recently begun and is accelerated by genetic discoveries, especially mapping of the human genome. SLE is known as "the great imitator", as its symptoms often mimic other illnesses and because they come and go unpredictably. Diagnosis can be elusive, with patients sometimes suffering unexplained symptoms and untreated SLE for years. Increased awareness and education about lupus since the 1960s has helped many more patients get an accurate diagnosis and made it possible to estimate the number of people with lupus. Lupus was previously believed to be a rare disease. In the United States alone, an estimated 270,000 to 1.5 million people have lupus, making it more common than cystic fibrosis or cerebral palsy. The disease primarily affects young women, although men can be diagnosed with lupus. World-wide, a conservative estimate states that over 5 million people have lupus.
SLE was called lupus (Latin for "wolf"), perhaps due to a crude similarity between the facial rash that some lupus patients develop, and a wolf's face, although various explanations have been proposed.
Common initial and chronic complaints are fever, malaise, joint pains, myalgias and fatigue. Because they are so often seen with other diseases, these signs and symptoms are not part of the diagnostic criteria for SLE. When occurring in conjunction with other signs and symptoms, however, they are considered suggestive.
Dermatological manifestations
As many as 30% of patients present with some dermatological symptoms (and 65% suffer such symptoms at some point), with 30% to 50% suffering from the classic malar rash (or butterfly) rash associated with the disease. Patients may present with discoid lupus (thick, red scaly patches on the skin). Alopecia, mouth, nasal, and vaginal ulcers, and lesions on the skin are also possible manifestations.
Musculoskeletal manifestations
Patients most often seek medical attention for joint pain, with small joints of the hand and wrist usually affected, although any joint is at risk. Unlike rheumatoid arthritis, SLE arthropathy is not usually destructive of bone, however, deformities caused by the disease may become irreversible in as many as 20% of patients.
Hematological manifestations
Anemia and iron deficiency may develop in as many as half of patients. Low platelet and white blood cell counts may be due to the disease or a side-effect of pharmacological treatment. Patients may have an association with antiphospholipid antibody syndrome (a thrombotic disorder) where autoantibodies to phospholipids are present in the patient's serum. Abnormalities associated with antiphospholipid antibody syndrome include a paradoxical prolonged PTT (which usually occurs in hemorrhagic disorders) and a positive test for antiphospholipid antibodies, the combination of such findings have earned the term "lupus anticoagulant positive". Another autoantibody finding in lupus is the anticardiolipin antibody which can cause a false positive test for syphillis.
Cardiac manifestations
Patients may present with inflammation of various parts of the heart: pericarditis, myocarditis and endocarditis. The endocarditis of SLE is characteristically non-infective (Libman-Sacks endocarditis), and involves either the mitral valve or the tricuspid valve. Atherosclerosis also tends to occur more often and advance more rapidly in SLE patients than in the general population. (Asanuma et al 2003, Bevra 2003, Roman et al 2003).
Pulmonary manifestations
Lung and plura inflammation can cause pleuritis, pleural effusion, lupus pneumonitis, chronic diffuse interstitial lung disease, pulmonary hypertension, pulmonary emboli, pulmonary hemorrhage.
Renal involvement
Painless hematuria or proteinuria may often be the only presenting renal symptom. Acute or chronic renal impairment may develop with lupus nephritis, leading to acute or end stage renal failure. Because of early recognition and management of SLE, end stage renal failure occurs in less than 5% of patients.
Histologically, a hallmark of SLE is membranous glomerulonephritis with "wire loop" abnormalities. This finding is due to immune complex deposition along the glomerular basement membrane leading to a typical granular appearance in immunofluorescence testing.
Neurological manifestations
About 10% of patients may present with seizures or psychosis. A third may test positive for abnormalities in the cerebrospinal fluid.
T-cell abnormalities
Abnormalities in T cell signaling are associated with SLE, including deficiency in CD45 {phosphatase, increased expression of CD40 ligand.
Also associated with SLE is increased expression of FcεRIγ, which replaces the TCR ζ chain, which is deficient in some SLE patients.
Other abnormalities include:
increased and sustained calcium levels in T cells
moderate increase of inositol triphosphate
reduction in PKC phosphorylation
reduction in Ras-MAP kinase signalling
And deficiencies in:
protein kinase A I activity
SLE is a chronic disease with no cure. There are, however, some medications, such as corticosteroids and immunosuppressants which can control the disease and prevent flares. Flares are typically treated with steroids, with DMARDs (disease-modifying antirheumatic drugs) to suppress the disease process, reduce steroid needs and prevent flares. DMARDs commonly in use are the antimalarials (e.g. hydroxychloroquine or methotrexate) and azathioprine. Cyclophosphamide is used for severe nephritis or other organ-damaging complications.
Patients who require steroids frequently may develop obesity, diabetes and osteoporosis. Hence, steroids are avoided where possible.
Measures such as avoiding sunlight (to prevent problems due to photosensitivity) may also have some effect.
2006-06-13 11:54:13
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answer #1
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answered by Drewy-D 4
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