Goodpastures Syndrome and Anti- GBM disease. Goodpastures Syndrome Introduction Concurrence of...
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Transcript of Goodpastures Syndrome and Anti- GBM disease. Goodpastures Syndrome Introduction Concurrence of...
![Page 1: Goodpastures Syndrome and Anti- GBM disease. Goodpastures Syndrome Introduction Concurrence of pulmonary hemorrhage and focal necrotizing glomerulonephritis.](https://reader035.fdocuments.us/reader035/viewer/2022081514/5a4d1bb57f8b9ab0599ce547/html5/thumbnails/1.jpg)
Goodpasture’s Syndrome and Anti-GBM disease
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Goodpasture’s SyndromeIntroduction
• Concurrence of pulmonary hemorrhage and focal necrotizing glomerulonephritis– Short hand for pulmonary renal
syndrome
• Better to refer to as Goodpasture’s diseaseto specifically describe the pulmonary renal syndrome associated with anti-GBM antibodies
![Page 3: Goodpastures Syndrome and Anti- GBM disease. Goodpastures Syndrome Introduction Concurrence of pulmonary hemorrhage and focal necrotizing glomerulonephritis.](https://reader035.fdocuments.us/reader035/viewer/2022081514/5a4d1bb57f8b9ab0599ce547/html5/thumbnails/3.jpg)
Goodpasture’s SyndromePrecipitating factors
• Hydrocarbon exposure & Smoking– May simply trigger
pulmonary hemorrhage in patients who already have the disease
• Several instances where renal trauma or inflammation precipitates– Lithotripsy– Urinary obstruction– Membranous– thickened
GBM associated with increased antigen exposure
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Goodpasture’s SyndromePulmonary hemorrhage
• Only occurs if there is additional insults to the lung– Infection, fluid overload,
cigarette smoke, inhaled vapors
• Why do the lungs require an additional insult?– Because alveolar GBM
protected from circulating antibodies, the slit pores in the GBM means it is already “disrupted” and exposed
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Goodpasture’s SyndromeClinical and Pathologic Features
• Peak incidence 3-6th decades, with a 2nd peak in the 6-7th decade
• Males– Tend to have the full blown lung and renal disease
• ? 2nd smoking or occupational lung exposures– Pulmonary hemorrhage tends to lead to earlier
presentation/diagnosis• Females
– Tend to have nephritis alone– results in late diagnosis– often presenting at ESRD
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Goodpasture’s SyndromeClinical and Pathologic Features
• Pulmonary– Continuous or episodic
dyspnea and hemoptysis• 1/3 of patients have NO
pulmonary manifestations– CXR with patchy or diffuse
infiltrates in the central lung fields
• Findings usually unimpressive so must check DLCO
– Increased DLCO• The most sensitive marker
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Goodpasture’s SyndromeClinical and Pathologic Features
• Renal– Nephritis– rbcs and rbc
casts– Proteinuria- <
5grams/day– Normal renal size on
US
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Goodpasture’s SyndromeClinical and Pathologic Features
• Renal Biopsy– Preferred over lung biopsy,
given difficulty of performing IF on pulmonary tissue
– Linear IgG staining along GBM
• Diff dx- SLE, NIDDM, nl autopsy kidney, cadaveric kidney after perfusion, and renal transplants with Alport’s
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Goodpasture’s SyndromeDiagnosis
• Confirmed by– Presence of linear IgG
along the GBM in renal biopsy tissue
– Detection of circulating anti-GBM antibodies
• False positives from inflammatory d/o
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Goodpasture’s SyndromeDifferential Diagnosis
• Microscopic polyangiitis• Wegener’s granulomatosis• Goodpasture’s disease• SLE• Churg-Strauss• HSP• Behcet’s disease• Rheumatoid vasculitis• Penicillamine• Hantavirus• Concurrent lung and renal diseases:
– Renal Cell carcinoma– Sarcoidosis– Pulmonary emboli/RVT
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Goodpasture’s SyndromeConcurrence with other diseases
• Membranous GN can evolve into Goodpasture’s– Probably due to increased antigen (GBM) with damage which
allows for antigen exposure• Occasionally have concurrent ANCAs
– “double positive”– usually Wegner’s with 2nd development of anti-GBM antibodies, tx as Wegners
• Associated with Alport’s syndrome s/p transplantation– Due to a genetic lack of the alpha 5 (IV) chains in Alport’s– Therefore when they are transplanted a normal kidney, the
immune system “sees” the GBM antibody for the first time
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Goodpasture’s SyndromeTherapy
• Remove anti-GBM antibodies ASAP– Via pheresis – 4L exchanges with albumin qd x 14 days, or until
antibodies are undetectable• May have to give back FFP if pulmonary hemorrhage
• Preventing further synthesis and reinstituting tolerance to NC1-alpha3IV– Steroids and cytotoxics
• Steroids- controls the pulmonary manifestations– 1mg/kg day, decrease weekly to 20mg qd, then taper over 1-2 years
• Cytoxan- 2.5mg/kg/day x 4 months, then switch to AZA for 1-2 years– Once on HD– don’t recover renal function– so don’t bother with
immunosuppressives