Goodpasture’s Syndrome and Anti- GBM disease

Goodpasture’s Syndrome Introduction Concurrence of pulmonary hemorrhage and focal necrotizing glomerulonephritis –Short hand for pulmonary renal syndrome Better to refer to as Goodpasture’s disease to specifically describe the pulmonary renal syndrome associated with anti-GBM antibodies

Goodpasture’s Syndrome Precipitating 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 Syndrome Pulmonary 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 Syndrome Clinical and Pathologic Features Peak incidence 3-6 th decades, with a 2 nd peak in the 6-7 th decade Males –Tend to have the full blown lung and renal disease ? 2 nd 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

Goodpasture’s Syndrome Clinical 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

Goodpasture’s Syndrome Clinical and Pathologic Features Renal –Nephritis– rbcs and rbc casts –Proteinuria- < 5grams/day –Normal renal size on US

Goodpasture’s Syndrome Clinical 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

Goodpasture’s Syndrome Diagnosis 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 Syndrome Differential 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 Syndrome Concurrence 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 2 nd 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 Syndrome Therapy 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