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A Symptoms and Signs
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The systemic features include fever, anorexia, malaise, and weight loss Most patients have skin lesions at some time; the characteristic butterfly (malar) rash affects less than half of
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Arthritis & Musculoskeletal Disorders
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patients Other cutaneous manifestations are discoid lupus, typical fingertip lesions, periungual erythema, nail fold infarcts, and splinter hemorrhages Alopecia is common Mucous membrane lesions tend to occur during periods of exacerbation Raynaud s phenomenon, present in about 20% of patients, often antedates other features of the disease Joint symptoms, with or without active synovitis, occur in over 90% of patients and are often the earliest manifestation The arthritis is seldom deforming; erosive changes are almost never noted on radiographs Subcutaneous nodules are rare Ocular manifestations include conjunctivitis, photophobia, transient or permanent monocular blindness, and blurring of vision Cotton-wool spots on the retina (cytoid bodies) represent degeneration of nerve fibers due to occlusion of retinal blood vessels Pleurisy, pleural effusion, bronchopneumonia, and pneumonitis are frequent Restrictive lung disease can develop Alveolar hemorrhage is rare, but potentially life-threatening The pericardium is affected in the majority of patients Cardiac failure may result from myocarditis and hypertension Cardiac arrhythmias are common Atypical verrucous endocarditis of Libman-Sacks is usually clinically silent but occasionally can produce acute or chronic valvular incompetence most commonly mitral regurgitation and can serve as a source of emboli Mesenteric vasculitis occasionally occurs in SLE and may closely resemble polyarteritis nodosa, including the presence of aneurysms in medium-sized blood vessels Abdominal
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pain (particularly postprandial), ileus, peritonitis, and perforation may result Neurologic complications of SLE include psychosis, cognitive impairment, seizures, peripheral and cranial neuropathies, transverse myelitis, and strokes Severe depression and psychosis are sometimes exacerbated by the administration of large doses of corticosteroids Several forms of glomerulonephritis may occur, including mesangial, focal proliferative, diffuse proliferative, and membranous (see 22) Some patients may also have interstitial nephritis With appropriate therapy, the survival rate even for patients with serious renal disease (proliferative glomerulonephritis) is favorable, albeit a substantial portion of patients with severe lupus nephritis still eventually require renal replacement therapy
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B Laboratory Findings
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(Tables 20 10, 20 11, and 19 2) SLE is characterized by the production of many different autoantibodies, some of which produce specific laboratory abnormalities (eg, hemolytic anemia) Antinuclear antibody tests are sensitive but not specific for SLE ie, they are positive in virtually all patients with lupus but are positive also in many patients with nonlupus conditions such as rheumatoid arthritis, various forms of hepatitis, and interstitial lung disease Antibodies to double-stranded DNA and to Sm are specific for SLE but not sensitive, since they are present in only 60% and 30% of patients, respectively Depressed serum complement a
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Table 20 10 Frequency (%) of autoantibodies in rheumatic diseases1
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AntiNative DNA 0 5 60 Rheumatoid Factor 80 20 AntiSm 0 10 25 AntiSS-A 0 5 15 20 AntiSS-B 0 2 5 20 AntiSCL-70 0 0 AntiCentromere 0 0 AntiJo-1 0 0
ANA Rheumatoid arthritis Systemic lupus erythematosus Sj gren s syndrome Diffuse scleroderma Limited scleroderma (CREST syndrome) Polymyositis/ dermatomyositis Wegener s granulomatosis
ANCA 0 0 1
30 60 95 100
95 80 95 80 95
0 0 0
75 30 30
0 0 0
65 0 0
65 0 0
0 33 20
0 1 50
0 0 0
0 0 0
80 95
20 30
0 15
93 961
Frequency for generalized, active disease ANA, antinuclear antibodies; Anti-Sm, anti-Smith antibody; anti-SCHL-70, anti-scleroderma antibody; ANCA, antineutrophil cytoplasmic antibody; CREST, calcinosis cutis, Raynaud s phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia
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local administration of corticosteroids Minor joint symptoms can usually be alleviated by rest and NSAIDs Antimalarials (hydroxychloroquine) may be helpful in treating lupus rashes or joint symptoms that do not respond to NSAIDs When these are used, the dose should not exceed 400 mg/d ( 65 mg/kg/d), and annual monitoring for retinal changes is recommended Drug-induced neuropathy and myopathy may be erroneously ascribed to the underlying disease The androgenic corticosteroid danazol may be effective therapy for thrombocytopenia not responsive to corticosteroids Dehydroepiandrosterone (DHEA) has a therapeutic role comparable to that of the antimalarial agents in the treatment of SLE, but its side effects (particularly acne) are troubling to some patients Corticosteroids are required for the control of certain complications (Systemic corticosteroids are not usually given for minor arthritis, skin rash, leukopenia, or the anemia associated with chronic disease) Glomerulonephritis, hemolytic anemia, pericarditis or myocarditis, alveolar hemorrhage, central nervous system involvement, and thrombotic thrombocytopenic purpura all require corticosteroid treatment and often other interventions as well Forty to 60 mg of oral prednisone is often needed initially; however, the lowest dose of corticosteroid that controls the condition should be used Central nervous system lupus may require higher doses of corticosteroids than are usually given; however, corticosteroid psychosis may mimic lupus cerebritis, in which case reduced doses are appropriate Immunosuppressive agents such as cyclophosphamide, mycophenolate mofetil, and azathioprine are used in cases resistant to corticosteroids Treatment of severe lupus nephritis includes an induction phase and a maintenance phase Cyclophosphamide, which improves renal survival but not patient survival, was for many years the standard treatment for both phases of lupus nephritis More recently, mycophenolate mofetil, which may be more effective and is less toxic than cyclophosphamide, is emerging as the treatment of choice for many patients with lupus nephritis Very close follow-up is needed to watch for potential side effects when immunosuppressants are given; these agents should be administered by clinicians experienced in their use When cyclophosphamide is required, gonadotropin-releasing hormone analogs can be given to protect a woman against the risk of premature ovarian failure For patients with the antiphospholipid syndrome the presence of antiphospholipid antibodies and compatible clinical events anticoagulation is the treatment of choice (see Antiphospholipid Antibody Syndrome, below) Moderate intensive anticoagulation with warfarin to achieve an INR of 20 30 is as effective as more intensive regimens Pregnant patients with recurrent fetal loss associated with antiphospholipid antibodies should be treated with low-molecular-weight heparin plus aspirin
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