Goodpasture

52Goodpasture Syndrome (Anti–Basement Membrane Antibody Disease)Nestor L. Müller and C. Isabela S. SilvaETIOLOGY, PREVALENCE,AND EPIDEMIOLOGYGoodpasture syndrome, also known as anti–basement membrane antibody disease, is an autoimmune disor-der characterized by repeated episodes of pulmonary hemorrhage usually associated with glomerulonephritis and the presence of anti–glomerular basement mem-brane (anti-GBM) antibodies. Goodpasture syndrome is rare, with an incidence of approximately one patient per million population per year.1 It has a bimodal distribution with respect to age, with peaks at 20 to 30 and 60 to 70 years of age, and a male-to-female ratio of approximately 3 : 2.2,3CLINICAL PRESENTATIONThe most common presenting symptom is hemoptysis, which occurs in about 80% to 95% of patients.3,4 The hemoptysis may range from mild to copious and life-threatening. I n more than 50% of patients, it precedes glomerulonephritis.3 On occasion, the hemoptysis may occur late in the course of the disease or be absent alto-gether. Other presenting symptoms include dyspnea, fatigue, weakness, pallor, cough, and (occasionally) frank hematuria.3 Although results of the initial urinalysis may be normal, proteinuria, hematuria, and cellular and granu-lar casts almost invariably develop at some stage.5 More than 90% of patients have anti-GBM antibodies, and approximately 80% have crescentic glomerulonephritis on renal biopsy.3 More than 90% of patients have iron deficiency anemia due to blood loss from pulmonary hemorrhage.3PATHOPHYSIOLOGYGoodpasture syndrome is an autoimmune disorder characterized by the presence of autoantibodies against the glomerular and alveolar basement membranes.3 I t has been suggested that environmental factors such as smoking, previous hydrocarbon exposure, and infection may play a role in triggering Goodpasture syndrome.2 In the kidney, complement activation and infl ammatory cell enzymes are responsible for glomerular damage. The precise pathogenesis of the pulmonary hemorrhage is unknown.The main histologic fi ndings of Goodpasture syndrome consist of pulmonary alveolar capillaritis, which results in diffuse pulmonary hemorrhage, and a segmental necrotizing glomerulonephritis, which progresses to a cres c entic nephritis.1 The capillaritis is identical to that of Wegener granulomatosis and microscopic polyangiitis and appears as a neutrophil infi ltrate intimately associated with alveolar septa with or without fi brin thrombi and necrosis. Other histologic changes depend on the duration and severity of the disease at the time of examina-tion but usually include hemosiderin-laden macro-phages in alveolar airspaces and interstitial tissue and mild to moderate interstitial fi brosis.5I mmunofl uorescence studies show characteristic linear staining most readily recognized in the glomerulus but also frequently evident in the alveolar capillary walls.1,6 IgG is the usual antibodyC H A P T E R52●Goodpasture Syndrome (Anti–Basement Membrane Antibody Disease) 829detected, although IgA and IgM are occasionally present as well.5MANIFESTATIONS OF THE DISEASE RadiographyIn the early stages of the disease, the radiographic pattern is one of patchy hazy areas of increased opacity (ground-glass opacities) scattered fairly evenly throughout the lungs (Fig. 52-1). With more severe hemorrhage, the pattern may progress to focal or confl uent areas of con-solidation often associated with air bronchograms (Fig. 52-2). The opacities usually are widespread but may be more prominent in the perihilar areas and in the mid and lower lung zones.7 The apices and costophrenic angles almost invariably are spared. Although parenchymal involvement usually is bilateral, it is commonly asymmet-ric and occasionally may be unilateral.7,8 The chest radio-graph may be normal in patients with diffuse pulmonary hemorrhage. In one review of 39 episodes of diffuse pul-monary hemorrhage in 23 patients, the radiograph was normal in 7 (18%) episodes.8 Serial radiographs show that within 2 to 3 days, the areas of consolidation are gradually replaced by a reticular or reticulonodular pattern, the dis-tribution of which is identical to that of the airspace disease (Fig. 52-3).7,9 This reticular pattern diminishes gradually during the next several days, and the appearance of the chest radiograph usually returns to normal about 10 to 12 days after the original episode.9 With repeated episodes of hemorrhage, increasing amounts of hemosid-erin are deposited within the interstitial tissue and areAB C■FIGURE 52-1Goodpasture syndrome with mild diffuse pulmonary hemorrhage: radiographic and CT fi ndings. Chest radiograph (A) shows bilateral subtle hazy increased opacity (ground-glass pattern). Also noted is a hemodialysis catheter in place. Coronal (B) and sagittal (C) reformatted images from volumetric high-resolution CT demonstrate extensive bilateral ground-glass opacities and poorly defi ned small centrilobular nodules. The patient was a 41-year-old man with Goodpasture syndrome, diffuse pulmonary hemorrhage, and renal failure.830P A R T T E N●Vasculitis and Granulomatosisassociated with progressive fibrosis. I n most cases, the chest radiograph shows only partial clearing after each hemorrhagic episode, revealing persistence of a fi ne retic-ulonodular pattern indicative of the irreversible interstitial disease.9 Once these changes have developed, new epi-sodes of pulmonary hemorrhage usually result in the typical pattern of airspace consolidation superimposed on the diffuse interstitial disease.Computed TomographyThe CT manifestations of acute pulmonary hemorrhage consist of bilateral ground-glass opacities and, less com-monly, areas of consolidation (see Figs. 52-1 and 52-2).7,10 The ground-glass opacities may have a patchy distribution or be diffuse. CT scans performed 2 to 3 days after the acute episode show decrease in the ground-glass opacities and consolidation and presence of small, poorly defi ned centrilobular nodules and, less commonly, interlobular septal thickening.10 These findings are presumably sec-ondary to the lymphatic resorption of the blood and grad-ually resolve during the next 1 to 2 weeks.Imaging AlgorithmThe chest radiograph is usually the initial imaging modal-ity used in the evaluation of patients with diffuse pulmo-nary hemorrhage and Goodpasture syndrome. n the proper clinical setting, when the radiograph demonstrates bilateral ground-glass opacities or consolidation, no furtherABC ■FIGURE 52-2Goodpasture syndrome with severe diffuse pulmonary hemorrhage: radiographic and CT fi ndings. A, Chest radiograph shows dense consolidation in the lung apices and hazy opacifi cation of the remaining lungs. B, High-resolution CT at the level of the upper lobes demonstrates extensive ground-glass opacities and areas of consolidation. C, High-resolution CT at the level of the middle and lower lobes shows diffuse bilateral ground-glass opacities. The patient was a 78-year-old woman with Goodpasture syndrome and severe acute pulmonary hemorrhage.C H A P T E R52●Goodpasture Syndrome (Anti–Basement Membrane Antibody Disease)831■FIGURE 52-3Goodpasture syndrome: changes on sequential radiographs. Posteroanterior radiograph (A) shows extensive consolidation of both lungs. A well-defi ned air bronchogram is visualized. Three days later (B), the pattern was somewhat more granular, and 10 days after the initial episode (C), the pattern had become distinctly reticular. Six days later (D), only a fi ne reticular pattern remains in an anatomic distribution identical to the original involvement. The sequence of changes illustrated by this 49-year-old patient with Goodpasture syndrome is typical of massive pulmonary hemorrhage. (From Müller NL, Fraser RS, Colman NC, Paré PD. Radiologic Diagnosis of Diseases of the Chest. Philadelphia, WB Saunders, 2001.)imaging is required. In some patients with diffuse pulmo-nary hemorrhage, the radiograph may be normal or show only questionable abnormalities. High-resolution CT is indicated in patients with clinically suspected diffuse pul-monary hemorrhage and questionable or nonspecifi c radiographic fi ndings. High-resolution CT is also indicated in patients with hemoptysis in whom the clinical presenta-tion is not characteristic of Goodpasture syndrome. I n these cases, high-resolution CT performed continuously through the chest on a multidetector spiral CT scanner is helpful to rule out other causes of hemoptysis, such as bronchiectasis and bronchogenic carcinoma.11 DIFFERENTIAL DIAGNOSISApproximately 20% of patients with glomerulonephritis and pulmonary hemorrhage have Goodpasture syndrome, 50% have some form of systemic vasculitis, and most of832 P A R T T E N ● Vasculitis and Granulomatosisthe remainder have diffuse alveolar hemorrhage in associa-tion with other forms of glomerulonephritis.12 The diag-nosis of Goodpasture syndrome should be suspected when an adult patient has hemoptysis and bilateral air-space consolidation on the chest radiograph, particularly when manifestations of renal disease are also present. Confi rmation can be obtained by demonstration of circu-lating or tissue-bound anti-GBM antibodies by enzyme-linked immunosorbent assay or immunofl uorescentexamination.13I f the diagnosis remains uncertain, it can be confi rmed by demonstration of autoantibodies on kidney biopsy. Most other conditions characterized by hemoptysis and renal dysfunction can be recognized by associated clinical and laboratory manifestations of vascu-litis or by the observation of immunoglobulin and comple-ment deposition in a granular pattern on immunofl uorescentexamination of a kidney biopsy specimen.5Because renal involvement in Goodpasture syndrome may not be appar-ent initially, the diagnosis must be considered in any patient who has radiologic and clinical fi ndings consistent with diffuse alveolar hemorrhage and no evidence of kidney disease.5 The differential diagnosis in this situation is large and includes various connective tissue diseases (especially systemic lupus erythematosus), systemic vas-culitis (e.g., Wegener granulomatosis), aspirated blood after vascular disruption, and occasionally certain meta-static neoplasms such as choriocarcinoma.14,15SYNOPSIS OF TREATMENT OPTIONSThe treatment of Goodpasture syndrome is aimed at removal of circulating autoantibodies, which is accom-plished by plasmapheresis, and stopping of the pro-duction of the anti-GBM antibodies with use of immunosuppressive medications, typically corticosteroids and cyclophosphamide.3With treatment, the 5-year survival ranges from 63% to 94%, depending on the initial renal function.16 I n one study, approximately 20% of patients had normal recov-ery, 39% were receiving maintenance hemodialysis, 12% received transplants and were doing well, 5% were await-ing transplants, and 24% died.3 The prognosis is closely associated with the degree of initial renal impairment. Predictors of poor prognosis include initial creatinineS U G G E S T E D R E A D I N G S(R E V I E W A R T I C L E S O N L Y )Bruzzi JF, Remy-Jardin M, Delhaye D, et al. Multi-detector row CT of hemoptysis. RadioGraphics 2006; 26:3-22.Erlich JH, Sevastos J, Pussell BA. Goodpasture’s disease: antiglomerular basement membrane disease. Nephrology (Carlton) 2004; 9:49-51.Hansell DM. Small-vessel diseases of the lung: CT-pathologic correlates. Radiology 2002; 225:639-653.Mayberry JP, Primack SL, Müller NL. Thoracic manifestations of systemic autoimmune diseases: radiographic and high-resolution CT fi ndings. RadioGraphics 2000; 20:1623-1635.Shah MK, Hugghins SY. Characteristics and outcomes of patients with Goodpasture’s syndrome. South Med J 2002; 95:1411-1418.R E F E R E N C E S3. Shah MK, Hugghins SY. Characteristics and outcomes of patientswith Goodpasture’s syndrome. South Med J 2002; 95:1411-1418. 4. Kelly PT, Haponik EF. Goodpasture syndrome: molecular and clini-cal advances. Medicine (Baltimore) 1994; 73:171-185.levels above 5 mg/dL, crescent formation in more than 50% of glomeruli, and oligoanuria.3On occasion, Good-pasture syndrome may recur years later in patients whose disease remits spontaneously or as a result of therapy.171. Davies DJ. Small vessel vasculitis. Cardiovasc Pathol 2005; 14:335-346.2. Erlich JH, Sevastos J, Pussell BA. Goodpasture’s disease: antiglomerularbasement membrane disease. Nephrology (Carlton) 2004; 9:49-51.What the Referring Physician Needs to KnowC H A P T E R52●Goodpasture Syndrome (Anti–Basement Membrane Antibody Disease) 8335. Fraser RS, Colman N, Müller NL, Paré PD. Immunologic lung disease.In Fraser RS, Colman N, Müller NL, Paré PD, eds. Synopsis of Diseases of the Chest. Philadelphia, Elsevier Saunders, 2005, pp 481-524. 6. Beechler CR, Enquist RW, Hunt KK, et al. Immunofl uorescence oftransbronchial biopsies in Goodpasture’s syndrome. Am Rev Respir Dis 1980; 121:869-872.7. Primack SL, Miller RR, Müller NL. Diffuse pulmonary hemorrhage:clinical, pathologic, and imaging features. AJR Am J Roentgenol 1995; 164:295-300.8. Bowley NB, Steiner RE, Chin WS. The chest X-ray in antiglomerularbasement membrane antibody disease (Goodpasture’s syndrome).Clin Radiol 1979; 30:419-429.9. Müller NL, Miller RR. Diffuse pulmonary hemorrhage. Radiol ClinNorth Am 1991; 29:965-971.10. Hansell DM. Small-vessel diseases of the lung: CT-pathologic corre-lates. Radiology 2002; 225:639-653.11. Bruzzi JF, Remy-Jardin M, Delhaye D, et al. Multi-detector row CTof hemoptysis. RadioGraphics 2006; 26:3-22.12. Boyce NW, Holdsworth SR. Pulmonary manifestations of the clinicalsyndrome of acute glomerulonephritis and lung hemorrhage. Am J Kidney Dis 1986; 8:31-36.13. Salama AD, Dougan T, Levy JB, et al. Goodpasture’s disease in theabsence of circulating anti–glomerular basement membrane anti-bodies as detected by standard techniques. Am J Kidney Dis 2002;39:1162-1167.14. Hughson MD, He Z, Henegar J, McMurray R. Alveolar hemorrhageand renal microangiopathy in systemic lupus erythematosus. Arch Pathol Lab Med 2001; 125:475-483.15. Benditt JO, Farber HW, Wright J, Karnad AB. Pulmonary hemorrhagewith diffuse alveolar infi ltrates in men with high-volume choriocar-cinoma. Ann Intern Med 1988; 109:674-675.16. Levy JB, Turner AN, Rees AJ, Pusey CD. Long-term outcome ofanti–glomerular basement membrane antibody disease treated with plasma exchange and immunosuppression. Ann I ntern Med 2001;134:1033-1042.17. Klasa RJ, Abboud RT, Ballon HS, Grossman L. Goodpasture’s syn-drome: recurrence after a five-year remission. Case report and review of the literature. Am J Med 1988; 84:751-755.。