Goodpasture's syndrome
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Introduction
Glomerulonephritis associated with anti-glomerular basement membrane (GBM) antibodies. Antibodies to collagen 4 alpha-3.
Epidemiology
- male:female ratio 6-7:1
- 5-40 years of age: average 27 years
- separate group of patients with primarily renal manifestations
- peak incidence in 6th decade of life
- no sex predilection
Pathology
- anti-glomerular basement membrane (GBM) antibody with specificity for collagen 4 alpha-3
- the alveolar basement membrane is affected by cross- reactivity with the glomerular basement membrane (GBM)
- linear deposition of IgG & complement along glomerular & alveolar basement membranes
Genetics
association with HLA-DRw2
Clinical manifestations
- recurrent hemoptysis
- glomerulonephritis
- hematuria
- rapidly progressive renal failure
- death secondary to acute renal failure
- anemia
- pulmonary alveolar hemorrhage
- almost always precedes renal manifestations
- risk increased by active smoking
- symptoms may be exacerbated by:
- exposure to hydrocarbons
- administration of penicillamine
Laboratory
- serum chemistries
- creatinine is increased with renal faulure
- urea nitrogen
- urinalysis:
- serology for anti-GBM
- present in 90% of patients
- used to monitor response to therapy
- non-specific
- serum complement levels are normal
- 1/3 are positive for p-ANCA
- these patients more prone to develop fulminant pulmonary hemorrhage
- antinuclear antibodies (ANA) are negative
- serum cryoglobulins are negative
- renal biopsy (gold standard for diagnosis)
- lung biopsy
- see ARUP consult[7]
Diagnostic procedures
- history pulmonary hemorrhage is associated with decreasedDLCO
- other pulmonary function tests not adversely affected
Radiology
- chest X-ray
- diffuse alveolar process with sparing of costophrenic angles
Management
- 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]
- 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
- response to therapy monitored by serial anti-GBM
- 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
More general terms
Additional terms
- anti-neutrophil cytoplasmic antibody (ANCA)
- collagen 4 alpha-3; Goodpasture antigen; contains: tumstatin (COL4A3)
References
- ↑ Stedman's Medical Dictionary 26th ed, Williams & Wilkins, Baltimore, 1995
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 1539
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 784-85
- ↑ Medical Knowledge Self Assessment Program (MKSAP) 11, 17, 18 American College of Physicians, Philadelphia 1998, 2015, 2018
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1307
- ↑ 6.0 6.1 eMedicine: Goodpasture's syndrome http://emedicine.medscape.com/article/1001872-overview
- ↑ 7.0 7.1 ARUP Consult: Antiglomerular Basement Membrane Disease - Goodpasture Syndrome https://arupconsult.com/content/antiglomerular-basement-membrane-disease
- ↑ Hellmark T, Segelmark M. Diagnosis and classification of Goodpasture's disease (anti-GBM). J Autoimmun. 2014 Feb-Mar;48-49:108-12. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24456936
- ↑ Goodpasture's Syndrome http://kidney.niddk.nih.gov/kudiseases/pubs/goodpasture/index.htm
Patient information
Goodpasture's Syndrome patient information