Anti-GBM Disease

(Goodpasture Syndrome )

Presentation by:
Dr Muhammad Burhan Pasha
FCPS
Senior registrar MU III
• Clinical entity of

– Diffuse pulmonary hemorrhage

– Glomerulonephritis
– Presence of anti–glomerular basement
membrane (anti-GBM) antibodies
Pathophysiology
• Ernest Goodpasture first described this
disorder in 1919

• In 1967, Lerner, Glassock, and

Dixon confirmed that the antibodies
taken from the diseased kidneys
produced nephritis in experimental
animals
• Autoantibodies directed against the
glomerular/alveolar basement membrane

• Autoantibodies bind to their reactive epitopes

in the basement membranes and activate the
complement cascade

• Type II hypersensitivity, Ag-Ab reaction

• Autoantibody is directed against a 28-kd

subunit present within the noncollagenous
domain of the alpha3 chain of type IV collagen
(alpha3[IV]NC1)
• Environmental insult in a person with genetic
susceptibility.
• HLA-DR15
• Exposure to organic solvents or hydrocarbons
• Smoking
• Infection (eg, influenza A2)
• Cocaine inhalation
• Exposure to metal dusts
• Extracorporeal shock wave lithotripsy
Clinical Features
• Constitutional symptoms (eg, malaise, chills
and fever, arthralgias)

• Hemoptysis is the presenting symptom when

the disease affects the lungs

• Massive pulmonary hemorrhage leading to

respiratory failure may occur

• Renal manifestations include hematuria,

edema, high blood pressure and eventually
uremia
• Tachypnea

• Cyanosis

• Hypertension (present in 20% of cases)

• Edema

• Inspiratory crackles over lung bases

Differential Diagnosis
• Acute Glomerulonephritis

• Eosinophilic Granulomatosis with Polyangiitis

(Churg-Strauss Syndrome)

• Community-Acquired Pneumonia (CAP)

• Granulomatosis with Polyangiitis (Wegener

Granulomatosis)
Laboratory Workup
• Urinalysis: low-grade proteinuria, gross
or microscopic hematuria, and red blood
cell casts
• Anemia
• Leukocytosis
• ESR raised
• Blood urea and creatinine and
electrolytes
• Anti GBM antibody

• One third of patients have

antineutrophilic cytoplasmic antibodies
(ANCAs) in addition to anti-GBM
antibody.
• Chest Radiograph

– patchy parenchymal consolidations, which

are usually bilateral, symmetric perihilar,
and bibasilar
– apices and costophrenic angles are usually
spared
• Pulmonary Function Testing
– not helpful
– Spirometry and lung volume tests may
reveal evidence of restriction.
– The diffusing capacity for carbon monoxide
(DLCO) is elevated secondary to binding of
carbon monoxide to intra-alveolar
hemoglobin.
– Recurrent pulmonary hemorrhage may be
diagnosed with new opacities observed on
chest radiographs and a 30% rise in
DLCO.
BIOPSY

• Renal biopsy provides a significantly higher

yield than lung biopsy, but transbronchial or
open lung biopsy may be performed in cases
where renal biopsy cannot be performed.
• Light microscopy demonstrates nonspecific
features of a proliferative or necrotizing
glomerulonephritis with cellular crescents in
Bowman space
• Over time, the crescents become
fibrotic, and frank glomerulosclerosis,
interstitial fibrosis, and tubular atrophy
may be observed.
• Immunofluorescence stains show bright
linear deposits of immunoglobulin G
(IgG) along the glomerular basement
membrane and the alveolar basement
membrane
• Lung biopsy shows extensive
hemorrhage with accumulation of
hemosiderin-laden macrophages within
alveolar spaces
Treatment
• The three principles of therapy :

– Rapidly remove circulating antibody,

primarily by plasmapheresis
– Stop further production of antibodies using
immunosuppression with medications
– Remove offending agents that may have
initiated the antibody production
Plasmaphresis
• 4-liter plasma exchanges daily or every
other day is usually performed. The
plasmapheresis is continued for 2-3
weeks or until the patient's clinical
course has improved and serum anti-
GBM antibodies are not detected
Immunosuppressive therapy

• Cyclophosphamide at 2 mg/kg orally, and

corticosteroids (eg, prednisone at 1-1.5
mg/kg)

• Treatment of acute life-threatening alveolar

hemorrhage is with pulse methylprednisolone
at 1g/day for 3 days, followed by a gradual
corticosteroid taper
• Cyclophosphamide is continued for 2-3
months and steroids for 6 months
• Patients with clinically or serologically active
disease at 3-4 months need longer
immunosuppression (6-9 mo)
• Rituximab, a monoclonal antibody,
effectively depletes CD20-positive B
cells over 6-9 months and has been
used in several case reports as an
alternative approach in the treatment of
anti-GBM antibody disease.
• Renal transplant
Prognosis
• 5-year survival rate exceeds 80% and
fewer than 30% of patients require long-
term dialysis
Patients presenting with

– serum creatinine levels greater than 4 mg/dL,

– oliguria, and
– more than 50% crescents on renal biopsy
rarely recover. They usually progress to end-
stage renal failure that requires long-term
dialysis.
• Goodpasture syndrome. Close-up view
of gross pathology in a 45-year-old man
admitted to the intensive care unit with
respiratory failure secondary to massive
hemoptysis and acute renal failure. The
antiglomerular basement membrane
antibodies were strongly positive. The
autopsy showed consolidated lung from
extensive bleeding, which led to
asphyxiation.