- Incidence: 0.10 cases per 100,000 person-years
- Peak incidence: 30-40 years
- Sex ratio: more common in males 2:1
|Granulomatosis with polyangiitis||10.00|
|Eosinophilic granulomatosis with polyangiitis||2.00|
- Genetic component:
- People with the human leukocyte antigen (HLA) serotype of HLA-DR15 and -DR4 are more likely to develop anti-GBM disease.
- Environmental factors:
- Cigarette smoke
- Organic solvents, hydrocarbons and metal dust
- Following infection (especially viruses like influenza)
- Anti-GBM antibodies
- These attack the basement membranes of alveoli and glomeruli by binding to them and activating the complement cascade, leading to their death.
- Auto-reactive T cells
- These contribute to anti-GBM disease. Circulating T cells that are specific to epitopes in the alpha-3 chain of type IV collagen contribute to the formation of crescent formation.
- Genetic component
- There have also been rare cases of familial anti-GBM disease where patients with HLA-DR15 and -DR4 are at increased risk.
- The majority of patients (90%) present with rapidly progressing glomerulonephritis with accompanying alveolar haemorrhage (25-60%).
- Very few patients present with isolated lung findings (10%).
- Haemoptysis (65%)
- Cough (30%)
- Shortness of breath (30%)
- Nausea and vomiting (20%)
- Chest pain (20%)
- Decreased urine output (15%)
- Fatigue and malaise
- Haematuria (5%)
- Lung crackles (45%)
- Fever (30%)
- Lower extremity oedema (15%)
- Men to women ratio 3:2
- Bimodal age distribution (at 20-30 years and 60-70 years)
- Renal biopsy - should be performed for definitive diagnosis
- Crescentic glomerulonephritis
- Linear IgG staining on immunofluorescence
- Anti-GBM antibody titre - useful confirmatory diagnostic test in addition to the renal biopsy.
- Anti-neutrophil cytoplasmic antibodies (ANCA) - positive in up to 30% of patients with anti-GBM disease.
- Urea & electrolytes - high urea and creatinine
- Urinalysis - proteinuria, hematuria and casts
- Chest imaging
- X-ray may show diffuse opacities
- CT characteristically shows ground glass or consolidative opacities in a diffuse and bilateral distribution
- ANCA vasculitides. Main examples include granulomatosis with polyangiitis (Wegener’s), microscopic polyangiitis and Churg-Strauss syndrome.
- Similarities: blood tests may show positive ANCA
- Differences: renal biopsy shows no immune complex deposition.
- Post-streptococcal glomerulonephritis
- Similarities: presents only with glomerulonephritis
- Differences: renal biopsy shows immune complex deposition in a granular pattern but no immune complex deposition.
There are no NICE guidelines on Goodpasture's syndrome and all BMJ recommendations are based on the 2012 KDIGO (Kidney Disease: Improving Global Outcomes) guidelines which recommend the following management of Goodpasture's syndrome:
- Intensive plasmapheresis
- Removes the pathogenic antibody and inflammatory mediators
- 4 litres per day for 10-14 days, or until anti-GBM is undetectable
- The dose is tapered over the course of 3 months
- Suppresses the immune system
Long term management
- Optimal duration of treatment is unknown but the cessation of autoantibody formation can take at least 6 to 9 months.
- Maintenance therapy should include less toxic drugs such as azathioprine and low dose prednisolone.
- Smoking cessation as this causes glomerular and alveolar damage leading to the release of increased amounts of auto-antigen.
- Pulmonary haemorrhage
- High likelihood in smokers.
- Plasmapheresis related bleeding
- This removes clotting factors from the blood which may need to be replaced with fresh frozen plasma.
- Cyclophosphamide-related neutropenia
- This drug can cause dose-related leukopenia, therefore should be stopped and recommenced at a lower dose.
- Immunosuppression related infection
- May need antibiotic prophylaxis for Pneumocystis jirovecii pneumonia infection
- Chronic kidney disease requiring dialysis
- Most patients are left with a degree of renal impairment which may need dialysis.
- Long term prednisolone complications
- Requires prophylactic proton pump inhibitor for prevention of gastric ulcers
- Requires prophylactic bisphosphonates for prevention of osteoporosis
- Cyclophosphamide complications
- Can cause sterility if used for over 2-3 months. Gamete preservation should be considered.
- At high doses cyclophosphamide increases the risk of bladder cancer or haemorrhagic cystitis.
- Early treatment is associated with good chances of recovery with a five-year survival rate of over 80%.
- With aggressive treatment, out of the patients with mild to moderate kidney failure who do not need dialysis at arrival, 82-95% do not require dialysis at one year.
- In patients with more severe disease, the chance of renal recovery is 8%.
- Patients with end-stage renal disease and undetectable anti-GBM may undergo transplantation.
- Reports of recurrence is low.