PEDBASE.org - The Pediatric Database - Detailed information of GOODPASTURE'S DISEASE

GOODPASTURE'S DISEASE

DEFINITION:

An autoimmune disorder characterized by glomerulonephritis, lung hemorrhage, and anti-glomerular basement membrane (GBM) antibody formation.

EPIDEMIOLOGY:

incidence: extremely rare in childhood
age of onset:
- 3rd decade
risk factors:
- HLA-B8, DR2 - associated with poorer outcome

PATHOGENESIS:

1. Background

disorder is considered to result in a secondary glomerulopathy
etiology of anti-GBM autoantibody production is unknown but may be related to exposure to environmental agents that are inspired, damage alveolar walls, and release autoantigens:
- cigarette smoke
- cocaine
- inhaled hydrocarbons
- products in hair permanents
- viruses

2. Autoimmune

IgG autoantibodies react with well-defined epitopes on the noncollagenous glycoprotein domain (NG-1) of Type IV collagen - binding results in activation of the complement cascade -> infiltration of PMN's and monocytes -> glomerular injury (crescent formation)
the anti-GBM antibody may also react with non-GBM antigens in:
- Bowman's capsule
- renal tubules
- pulmonary alveoli
lung injury may be mediated by autoantibody and nonantibody factors

3. Goodpasture's Syndrome

glomerulonephritis and lung hemmorhage may occur in association with other disorders (Goodpasture's Syndrome):
- SLE
- Henoch-Schoenlein Purpura
- Polyarteritis Nodosa
- Wegener's Granulomatosis

CLINICAL FEATURES:

1. Renal Manifestations

1. Hematuria

microscopic and gross

2. Proteinuria

can progress to the nephrotic range

3. Complications

1. Azotemia

decreased GFR with elevated BUN and creatinine
presents at or near to onset of hemoptysis or renal disease in 50-70% of cases
ESRD occurs within a year (mean = 3.5 months) in 81% of cases

2. Hypertension

mild to moderate diastolic hypertension

2. Pulmonary Manifestations

1. Hemoptysis

usually the presenting complaint
precedes or occurs coincident with renal lesion in 70% of cases
most common extrarenal symptom
mild and evanescent, recurrent
occurs in some degree in most patients and ranges from a few flecks -> massive intra-alveolar hemorrhage -> massive exsanguination

2. Others

cough, crackles, dyspnea
URTI may precede onset in 10-30% of cases

3. Other Manifestations

anemia with pallor
arthritis

INVESTIGATIONS:

1. Urinalysis

hematuria, proteinuria (minimal -> nephrotic)
microscope - glomerular pattern - damaged RBC's & RBC casts

2. Serum

1. Anti-GBM IgG Antibody

found in 90% of cases at onset
titre does not correlate with clinical severity
usually peak then decline (therapy -> accelerated decline)
usually does not persist for more than 6 months
recrudesence of circulating antibody -> recurrence of symptoms

2. Anemia

microscopic, hypochromic
low iron levels (elevated intrapulmonary lung sequestration)

3. Others

hypoxia
- increased a-A gradient due to pulmonary bleeding
azotemia (elevated BUN and creatinine)
normal C3

3. Renal Biopsy

LM - range from normal -> focal and segmental glomerular hyper-cellularity -> crescentric GN
tubulointerstitial changes
EM - lucent widening of subendothelial space of the capillaries (at site of antibody attachment)
IFM - linear, ribbon-like deposits of IgG along glomerular capillary walls (rarely IgM and IgA)
frequently accompanied by C3 (in 70-80% of cases)
lung tissue reveals a similar linear deposits of IgG along the alveolar capillary membrane

MANAGEMENT:

1. Supportive

no treatment for underlying disorder
multidisciplinary approach
- Paediatrics, Nephrology, Respirology

2. Renal Manifestations

1. Acute Phase

plasmapheresis (3-4 L daily)
cytotoxic drugs
- azathioprine and cyclophosphamide
prednisone (1 mg/kg/d)
moniter renal function, anti-GBM antibody, and pulmonary function

2. Nephritic Syndrome

fluid restriction, control hypertension, manage hyper-kalemia, manage pulmonary edema

3. Nephrotic Syndrome

fluid restriction, salt-free diet, diuretics, albumin transfusion, prednisone, alkylating agents
see file on "Idiopathic Nephrotic Syndrome"

4. Chronic Renal Failure

dialysis or renal transplant

5. Recurrence

may be as high as 30%
may be related to intercurrent infections

2. Hemoptysis

1. Steroids

high dose parenteral (pulse therapy) or oral prednisone

Pediatric Database - GOODPASTURE'S DISEASE

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