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Clinical Findings
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A Symptoms and Signs
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Symptoms of a systemic inflammatory disease, including fever, malaise, and weight loss, may be present In addition to hematuria and proteinuria from glomerular inflammation, some patients exhibit purpura from dermal capillary involvement and mononeuritis multiplex from nerve arteriolar involvement Ninety percent of patients with Wegener s granulomatosis will have upper or lower respiratory tract symptoms with nodular lesions that can cavitate and bleed
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B Laboratory Findings
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Serologically, ANCA subtype analysis can be done A cytoplasmic pattern (C-ANCA) is specific for antiproteinase-3 antibodies, while a perinuclear pattern (P-ANCA) is specific for antimyeloperoxidase antibodies Over 90% of patients with Wegener s syndrome will have C-ANCA; the remainder can have a P-ANCA pattern Microscopic angiitis will have either a P-ANCA or C-ANCA pattern about 80% of the time Pathologically, the small vessels and glomeruli will lack immune deposits (pauci-immune); however, a cell-mediated immune response is often seen Necrotizing lesions and crescents signify a rapidly progressive glomerulonephritis
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2 Henoch-Sch nlein Purpura (Anaphylactoid Purpura)
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This disease is a leukocytoclastic vasculitis of unknown cause It is most common in children and has a male predominance It classically presents with palpable purpura, arthralgias, and abdominal symptoms such as nausea, colic, and melena Purpuric skin lesions are most often found on the lower extremities Renal insufficiency is common with a nephritic presentation The renal lesions are identical to those found in IgA nephropathy Most patients will recover fully over several weeks Further details about Henoch-Sch nlein purpura are provided in 20
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Donadio JV et al IgA nephropathy N Engl J Med 2002 Sep 5;347(10):738 48 [PMID: 12213946] Gedalia A Henoch-Sch nlein purpura Curr Rheumatol Rep 2004 Jun;6(3):195 202 [PMID: 15134598] Julian BA et al IgA nephropathy: an update Curr Opin Nephrol Hypertens 2004 Mar;13(2):171 9 [PMID: 15202611]
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Treatment
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Treatment should be instituted early if aggressive disease is suspected High doses of corticosteroids (methylprednisolone, 1 2 g/d for 3 days, followed by prednisone, 1 mg/kg for 1 month, with a slow taper over the next 6 months) and cytotoxic agents (cyclophosphamide, 05 10 g/m2 intravenously or 15 2 mg/kg orally for 3 6 months with potential conversion to less toxic agents such as azathioprine or mycophenolate mofetil for 12 18 months) are recommended for controlling end-organ damage Intravenous cyclophosphamide is likely associated with fewer side effects and is just as efficacious as corticosteroids Without treatment, prognosis is extremely poor, but with the above regimen, complete remission can be achieved in about 75% of patients The addition of plasmapheresis does not
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Kidney Disease
seem to improve outcomes Prognosis depends mainly on the extent of glomerular involvement before treatment is started ANCA levels can be monitored to help determine the efficacy of treatment
Booth AD et al; Pan-Thames Renal Research Group Outcome of ANCA-associated renal vasculitis: a 5-year retrospective study Am J Kidney Dis 2003 Apr;41(4):776 84 [PMID: 12666064] Harper L et al ANCA-associated renal vasculitis at the end of the twentieth century a disease of older patients Rheumatology (Oxford) 2005 Apr;44(4):495 501 [PMID: 15613403] Jara LJ et al Pulmonary-renal vasculitic disorders: differential diagnosis and management Curr Rheumatol Rep 2003 Apr;5 (2):107 15 [PMID: 12628041] Jennette JC et al Microscopic polyangiitis (microscopic polyarteritis) Semin Diagn Pathol 2001 Feb;18(1):3 13 [PMID: 11296991]
CMDT 2008
of prednisone or methylprednisolone, 1 2 g/d for 3 days, then 1 mg/kg/d Cyclophosphamide is administered intravenously at a dose of 05 10 g/m2 or orally at a dosage of 2 3 mg/kg/d Daily plasmapheresis is performed for up to 2 weeks A poorer prognosis exists in patients with oliguria and a serum creatinine greater than 6 7 mg/dL Anti-GBM antibody levels should decrease as the clinical course improves
Hudson BG et al Alport s syndrome, Goodpasture s syndrome, and type IV collagen N Engl J Med 2003 Jun 19;348(25): 2543 56 [PMID: 12815141] Levy JB et al Long-term outcome of anti-glomerular basement membrane antibody disease treated with plasma exchange and immunosuppression Ann Intern Med 2001 Jun 5;134 (11):1033 42 [PMID: 11388816]
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