Download ppt - Goodpastures Syndrome and Anti- GBM disease. Goodpastures Syndrome Introduction Concurrence of pulmonary hemorrhage and focal necrotizing glomerulonephritis

Goodpasture’s Syndrome and Anti-GBM disease

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

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

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

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


• 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


• Renal– Nephritis– rbcs and rbc

casts– Proteinuria- <

5grams/day– Normal renal size on

US


• 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

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

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

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

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