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Goodpasture's syndrome

Glomerulonephritis associated with anti-glomerular basement membrane (GBM) antibodies. Antibodies to collagen 4 alpha-3. Epidemiology: 1) male:female ratio 6-7:1 2) 5-40 years of age: average 27 years 3) separate group of patients with primarily renal manifestations a) peak incidence in 6th decade of life b) no sex predilection Pathology: 1) anti-glomerular basement membrane (GBM) antibody with specificity for collagen 4 alpha-3 2) the alveolar basement membrane is affected by cross- reactivity with the glomerular basement membrane (GBM) 3) linear deposition of IgG & complement along glomerular & alveolar basement membranes Genetics: association with HLA-DRw2 Clinical manifestations: 1) recurrent hemoptysis 2) glomerulonephritis a) hematuria b) rapidly progressive renal failure - death secondary to acute renal failure 3) anemia 4) pulmonary alveolar hemorrhage a) almost always precedes renal manifestations b) risk increased by active smoking 5) symptoms may be exacerbated by: a) exposure to hydrocarbons b) administration of penicillamine Laboratory: 1) serum chemistries a) creatinine is increased with renal faulure b) urea nitrogen 2) urinalysis: a) hematuria b) proteinuria c) red cell casts 3) serology for anti-GBM a) present in 90% of patients b) used to monitor response to therapy c) non-specific 4) serum complement levels are normal 5) 1/3 are positive for p-ANCA - these patients more prone to develop fulminant pulmonary hemorrhage 6) antinuclear antibodies (ANA) are negative 7) serum cryoglobulins are negative 6) renal biopsy (gold standard for diagnosis) 7) lung biopsy 8) see ARUP consult [7] Special laboratory: Pulmonary function testing: 1) history pulmonary hemorrhage is associated with decreasedDLCO 2) other pulmonary function tests not adversely affected Radiology: -> chest X-ray - diffuse alveolar process with sparing of costophrenic angles Management: 1) combination of - plasmapheresis QD or QOD for 1-2 weeks - prednisone 1 mg/kg/day - cyclophosphamide 2-3 mg/kg/day or azathioprine 1-2 mg/kg/day - rituximab 375 mg/m2/dose slow IV infusion (over 4 h) weekly for 6 doses has been used in severe cases [6] 2) prognosis - timeliness of therapy is a critical aspect of outcome - one year kidney salvage is > 90% if therapy is initiated before serum creatinine reaches 5 mg/dL - patients who require dialysis seldom regain renal function 3) response to therapy monitored by serial anti-GBM 4) renal tranplantation - recurrence of anti-GBM in the graft is rare if anti-GBM titers have been negative for 2-3 months prior to transplantation

Interactions

disease interactions

Related

anti-neutrophil cytoplasmic antibody (ANCA) collagen 4 alpha-3; Goodpasture antigen; contains: tumstatin (COL4A3)

General

anti-glomerular basement membrane [GBM] disease

Properties

PATHOLOGY: crescentic glomerulonephritis pulmonary hemorrhage

Database Correlations

OMIM correlations

References

  1. Stedman's Medical Dictionary 26th ed, Williams & Wilkins, Baltimore, 1995
  2. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 1539
  3. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 784-85
  4. Medical Knowledge Self Assessment Program (MKSAP) 11, 17, 18 American College of Physicians, Philadelphia 1998, 2015, 2018
  5. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1307
  6. eMedicine: Goodpasture's syndrome http://emedicine.medscape.com/article/1001872-overview
  7. ARUP Consult: Antiglomerular Basement Membrane Disease - Goodpasture Syndrome https://arupconsult.com/content/antiglomerular-basement-membrane-disease
  8. Hellmark T, Segelmark M. Diagnosis and classification of Goodpasture's disease (anti-GBM). J Autoimmun. 2014 Feb-Mar;48-49:108-12. Review. PMID: 24456936
  9. Goodpasture's Syndrome http://kidney.niddk.nih.gov/kudiseases/pubs/goodpasture/index.htm