ࡱ> QSP@ (bjbjFF "N,, $lrrrrrrrrRrrrr rr:,Frf Ul  0RFFDr0"rrr$Systemic Lupus Erythematosus Multi-system, autoimmune chronic inflammatory condition of unknown cause that can affect any tissue and organ of the body- Predominantly skin, joints, kidneys (MCC of death in SLE) Lethal lupus- MCC-kidney disease, CNS lupus Fluctuating course and variable pattern from mild to severe Exacerbating factors- Infection, sun, stress, drugs, trauma, diet, pregnancy Most follow course of remissions and exacerbations; may have spontaneous permanent remission Drug induced lupus is caused by procainamide, chlorpromazine, methyldopa, hydralazine, isoniazid, phenytoin, oral contraceptives- symptoms should gradually decrease upon discontinuation of the suspected agent Diagnosis: antihistamine antibodies (associated with DNA molecule) Can be in regular but mostly in drug induced Pathophysiology: Connective tissue disorder affecting skin, blood vessels (vasculitis), serous (pleura) and synovial membranes (joints) Infiltration of polymorphonuclear leukocytes, plasma cells, lymphocytes in walls of small vessels, arterioles of skin, spleen, glomeruli, endocardium pericardium, brain Hyperactivity especially of B and T cells Autoantibody and immune complex production leading to inflammatory changes, vasculitis, and immune complex deposition in multiple organ systems There are variants of lupus that involve: Discoid lupus erythematosus- only lupus on the skin; located to head; face, neck, neck, and scalp. Erythematous scarring plaques Subacute cutaneous lupus erythematosus- predominantly skin; on trunk and extremities Associated antiphospholipid syndrome- antibodies against cellular phospholipid components with tendency toward recurrent vascular thrombosis. Present with stroke, MI, DVT, PE Positive antibodies to cardiolipin, lupus anticoagulant (misnomer)- prolonged PTT but predisposed to clotting problems Associated with: thrombocytopenia, prolonged PTT, Thrombophlebitis Recurrent fetal abortions Risk factors: 90% patients are females of childbearing age 10:1 females to males Affects all ages, but peak onset between ages 15-40 Race-blacks, Hispanics, Asians, and native Americans have higher prevalence than whites Genetic markers- HLA-B8, HLA-DR2, HLA-DR3- increase our susceptibility to have an immune reaction Other autoimmune diseases- rheumatoid arthritis, DM I, Hashimotos thyroiditis, Sjogrens syndrome Oral contraceptives- twice the risk to get SLE Signs and symptoms Variable with no typical pattern of presentation; the symptoms result from small vessel vasculitis, causing renal, mucocutaneous and possibly CNS involvement and polyserositis with joint, peritoneal and pleuropericardial symptoms SystemicFever, anorexia, malaise, weight loss- 90% have fever in all SLE with decrease WBC so leukocytosis suggests infection Chills or leukocytosis should raise suspicion of an underlying infectionSkin and hairMalar rash-butterfly rash on face (42%) Discoid rash- raised red patches on head, arms, chest, back (scarring, disfiguring) Photosensitivity rash- exacerbated by light (30%); not diagnostic Subcutaneous nodulesJoints (95%)Muscle tenderness, aching and stiffness Arthralgia, arthritis- symmetric, non-erosive, migratory; involves hands, wrists, knees Defined as- 2 or more peripheral joints with warmth, tenderness, or effusionRenal (40%)Proteinuria, glomerulonephritis, nephrotic syndrome, renal failureHeart and VascularChest pain, pericarditis with friction rub, murmur Endocarditis, myocarditis, CHF, conduction abnormalities, MI, hemolytic anemia Libman-Sacks endocarditis- non-bacterial verrucous valvular lesions (mitral tricuspid); break off and go into periphery and get stroke Vasculitis, thrombosis, atherosclerosis, peripheral vascular disease, pallorLungsDyspnea, pleural effusion, pleuritis, friction rub, rales, pneumonitis, pulmonary hemorrhage or embolism, pneumonia, pulmonary edema, pulmonary hypertensionCNSPsychosis, delirium, depression, headache, seizures, peripheral neuropathies, stroke, headaches, CN defects, visual problems, eye pain/rednessGIPainless oral ulcers, abdominal pain, nausea, vomiting, diarrhea Mesenteric ischemia, peritonitis, pancreatitisHemeHepatosplenomegaly, lymphadenopathy, anemia (normochromic normocytic, bleeding (thrombocytopenia) Prolonged PTT- lupus anticoagulant Leukopenia (<4,000), lymphopenia (<1,500), thrombocytopenia (<100,000)ImmuneProduction of ANA (90%-95%), anti-cytoplasmic antibodies, immune complexes Diagnosis American rheumatology association (ARA) criteria- combination of any 4 manifestations of 11 listed: Malar rash (butterfly) Discoid rash Photosensitivity ANA Arthritis/arthralgia Serositis (pleuritis or pericarditis) Painless oral ulcers Renal Disorder- protein, RBC, RBC casts, lipids Neurological disorder- dementia, headache, seizure Hematologic disorder, anemia, leukopenia, thrombocytopenia Immunologic disorder- anti-dsDNA, anti-Smith antibody, anti-phospholipid antibody In practical situations, combination of a multi system inflammatory illness, +ANA and absence of a better diagnosis often represents the most practical way to make a clinical diagnosis Diagnostic Work-up Antibodies to nuclear antigens (ANA) are almost always positive- Best screening test for SLE Antibodies to double stranded DNA (anti-dsDNA) and Smith antigen (anti-smith)- Best confirmatory tests Decreased levels of complement proteins- consumed by the antibody responses False positive VDRL and positive Rheumatoid factor (20%) Coagulation (antiphospholipid antibody, lupus anticoagulant)- prolonged PTT but a state of hypercoaguability Biopsy of skin, kidney, and peripheral nerves may reveal typical histopathology- infiltration of our immune systems and immune complex deposition Cerebral angiography or MRI in CNS lupus- headache, seizures, AMS Chest X-ray- may show pleural effusion or pulmonary edema Echocardiogram- for pericardial effusion; pleural infiltration Urinalysis (protein, casts, hematuria, WBCs), BUN, creatinine ESR- draw during acute exacerbations and to monitor progress of treatment CBC- pancytopenia Electrolytes EKG and pulse oximetry- heart block in fetus Treatment Patient educations Avoidance of or protection from ultraviolet light by using sunscreens, hats, etc Topical steroids and sunscreens for cutaneous manifestations Early intervention when infection occur- because of pancytopenia Energy conservation, stress avoidance/management Medications- No one drug of choice available; treatment is symptomatic with certain exceptions NSAIDs Skin and mild systemic manifestations treated with local steroids hydroxychloroqine (anti-malaria) Immunosuppresants are indicated for renal disease and severe disease in other organs Prednisone, cyclophosphamide, methotrexate Treatment of renal lupus (most serious form)- immunosuppresants, renal dialysis, renal transplantation, and control of HTN Immunoglobulin IV pulse effective in temporary treatment of SLE thrombocytopenia Most patients with hematologic manifestations respond well to steroid treatments Heparin and Warfarin in obvious thrombotic disease and/or CNS symptoms, when associated with a positive lupus anticoagulant test or anticardiolipin antibody Complications: fever, vasculitis, myositis, avascular necrosis of bone, endocarditis, pulmonary fibrosis, renal failure, organic brain syndromes, peripheral neuropathy, stroke syndromes, pancreatitis, and elevated liver enzymes, infertility, ascites, venous thrombosis, seizures Death usually occurs from: (1)renal failure, (2)CNS disease,(3) infection, (4)GI hemorrhage Pregnancy Onset of lupus and lupus flares are more common during pregnancy Give heparin, aspirin, and steroids Fetal loss is increased for mothers with lupus- occur in abortions, treat with heparin Newborns of mothers with lupus more likely to have cardiac arrhythmias Complete heart block Differential Diagnosis SLE mimics numerous systemic conditions, especially those involving inflammation Many other disorders mimic SLE-rheumatoid arthritis, mixed connective tissue disease (MCTD), scleroderma, metastatic malignancy, fever of unknown origin, psychogenic rheumatism and many cutaneous rashes. 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