Synonyms: antiglomerular basement membrane disease, anti-GBM disease

Goodpasture's syndrome is the co-existence of acute glomerulonephritis and pulmonary alveolar haemorrhage, of which Goodpasture's syndrome is one cause.¹ Goodpasture's syndrome is a specific autoimmune disease caused by a type II antigen-antibody reaction leading to diffuse pulmonary haemorrhage, glomerulonephritis (and often renal failure). There are circulating antiglomerular basement membrane (anti-GBM) antibodies.

Epidemiology

• Goodpasture's syndrome is uncommon. It represents 1 to 2% of all cases of rapidly progressive glomerulonephritis and the incidence is about 1 in 2 million.²
• In adults, Goodpasture's syndrome is more common in men.²
• It affects both sexes equally in children.³
• Between 60-80% have both renal and pulmonary disease. The kidneys alone are affected in 20-40% and in about 10% only the lungs are affected.

Risk factors

Insults to the lungs are probably required to produce both the renal and pulmonary disease.

• Genetic predisposition with possession of HLA-DRw2.^4,5
• HLA-B7 is found more frequently and is associated with more severe anti-GBM nephritis.²
• Exposure to organic solvents or hydrocarbons.⁶
• Smoking.⁷
• Infection, e.g. influenza.
• A case in a heavy smoker who had taken to using crack cocaine is described.⁸
• Exposure to metal dusts.
• It can occur after renal transplantation in Alport's syndrome.⁹

Presentation

Symptoms

• Chills and fever.
• Nausea and vomiting.
• Weight loss.
• Chest pain.
• Anaemia, which may result from persistent intrapulmonary bleeding.
• Massive pulmonary haemorrhage, which can cause respiratory failure.
• Haematuria.
• There is a rapidly progressive glomerulonephritis that may lead to acute renal failure and volume overload.
• Arthralgia.

Sometimes the pulmonary haemorrhage may precede the renal disease by weeks or months.

Signs

• Tachypnoea.
• Dyspnoea, which can be severe.
• Inspiratory crackles over lung bases.
• Cyanosis.
• Hepatosplenomegaly (sometimes).
• Hypertension.
• Skin rash.
• There may be gross haematuria and pallor from anaemia.

Differential diagnosis

• Pulmonary haemorrhage with renal failure can also occur in collagen vascular diseases like systemic lupus erythematosus and rheumatoid arthritis, idiopathic rapidly progressive glomerulonephritis, microscopic polyarteritis, Wegener's granulomatosis, and essential mixed cryoglobulinaemia.
• All these diseases have specific laboratory features. In Goodpasture's syndrome the essential feature is antibody to the glomerular basement membrane (GBM).

Investigations

Blood tests

• FBC: iron-deficiency anaemia from intrapulmonary bleeding, leukocytosis.
• Renal function and electrolytes: watch for renal failure. Azotemia (abnormally high blood levels of nitrogen-containing compounds, such as urea, creatinine and other nitrogen-rich compounds) is often present.²
• Erythrocyte sedimentation rate (ESR) is raised in vasculitis but not in Goodpasture's syndrome.
• Urinalysis is typical of acute glomerulonephritis, with low-grade albuminuria, gross or microscopic haematuria, and red blood cell casts.
• Assess antinuclear antibodies and complement levels.²
• Antiglomerular basement membrane (anti-GBM) antibodies are diagnostic: assays for antibodies are valuable for confirming the diagnosis and monitoring therapy. Radioimmunoassays or enzyme-linked immunosorbent assays (ELISAs):
  • ELISAs for anti-GBM antibodies are highly sensitive (>95%) and specific (>97%) but are performed only in a few laboratories. Although the peak of serum anti-GBM antibody titre does not correlate with the severity of disease, changes in titre over time may be a guide to the efficacy of treatment.
  • Antineutrophilic cytoplasmic antibodies (ANCAs): at some point during the illness, one third of patients with Goodpasture's syndrome have circulating ANCA in addition to anti-GBM antibody.

Chest X-ray

• Patchy consolidation, usually bilateral, symmetrical, perihilar, and bibasilar.
• The apices and costophrenic angles are usually spared.
• 18% may have a normal CXR.
• Recurrent pulmonary haemorrhage causes new opacities.

Other tests

Pulmonary function tests are not usually helpful but spirometry may show some restriction.

Procedures

• Percutaneous kidney biopsy is the preferred invasive procedure to substantiate the diagnosis.
• Sometimes transjugular renal biopsy is performed. Renal biopsy is not required if anti-GBM antibodies are present.
• Lung biopsy: either transbronchial or open lung biopsy may be performed in cases where renal biopsy cannot be performed.

Management

The three main principles of management are to:²

• Remove circulating antibodies rapidly by plasmapheresis (plasma exchange).
• Stop further production of antibodies using immunosuppressant medications.
• Remove any identifiable cause of the antibody production.

Non-drug

• Intubation, assisted ventilation, and haemodialysis are often required in the acute phase.
• Repeated plasma exchange removes anti-glomerular basement membrane (anti-GBM) antibodies from the circulation.¹⁰
• End-stage renal disease can be managed by long-term haemodialysis or renal transplantation.

Drugs

• High-dose corticosteroids (intravenous methylprednisolone 7 to 15 mg/kg/day in divided doses) with cyclophosphamide or azathioprine are of benefit. Intravenous steroids are then converted to oral prednisolone.
• Duration of immunosuppressive therapy varies considerably and may be necessary for longer than 12 to 18 months in some patients.
• Usually, cyclophosphamide is given for 3 months and then the prednisolone is tailed off. Early use of these measures in combination may preserve renal function.

Surgical

• Cessation of pulmonary haemorrhage has been described after bilateral nephrectomy.
• Renal transplantation has been used and, although there are immunoglobulin G (IgG) deposits in the graft, it does not appear to damage the kidney. Most centres still like to wait 6 to 12 months before transplantation.

Complications

Acute respiratory failure, acute renal failure and chronic renal failure are the most common complications.²

• Pulmonary haemorrhage with respiratory failure is the most common cause of death.
• Renal failure in 90%.
• The circulating antibodies clear within 8 weeks, but an early relapse within 2 months may occur when circulating antibodies are still present. This typically presents as alveolar haemorrhage.
• The risk factors for relapse include infection, volume overload, and cigarette smoking.
• Pneumocystis jirovecii pneumonia has an annual incidence of 1% but is a potentially deadly complication of immunosuppressive therapy in patients with Goodpasture's syndrome. Prophylaxis with co-trimoxazole may be useful.
• If Goodpasture's syndrome occurs in pregnancy it may produce hypertension and associated intrauterine growth restriction requiring premature delivery. Both mother and baby are at risk.¹¹

Prognosis²

• In the past, the disease was almost invariably fatal, and sometimes rapidly so.
• Aggressive therapy with plasma exchange, corticosteroids, and immunosuppressant drugs has dramatically improved prognosis, with the 5-year survival rate above 80% and fewer than 30% of patients requiring long-term dialysis.
• Circulating antibodies clear within 8 weeks, but a relapse (usually presenting as alveolar haemorrhage) within the first 2 months may occur when circulating antibodies are still present. Risk factors for relapse include infection, volume overload and cigarette smoking.
• Some people may suffer from recurrent disease. Goodpasture's syndrome can recur in a transplanted kidney.

Prevention

There is no known prevention, but avoid associated environmental risk factors such as cigarette smoking and hydrocarbon exposure, e.g. sniffing glue and siphoning petrol.^2,6

Document references

1. Valentini RP; Goodpasture syndrome (Paediatric perspective), eMedicine, Mar 2009
2. Stevenson FT et al; Goodpasture Syndrome, eMedicine, Oct 2009
3. Savage CO, Pusey CD, Bowman C, et al; Antiglomerular basement membrane antibody mediated disease in the British Isles 1980-4. Br Med J (Clin Res Ed). 1986 Feb 1;292(6516):301-4. [abstract]
4. D'Apice AJ, Kincaid-Smith P, Becker GH, et al; Goodpasture's syndrome in identical twins. Ann Intern Med. 1978 Jan;88(1):61-2.
5. Gossain VV, Gerstein AR, Janes AW; Goodpasture's syndrome: a familial occurrence. Am Rev Respir Dis. 1972 Apr;105(4):621-4.
6. Bombassei GJ, Kaplan AA; The association between hydrocarbon exposure and anti-glomerular basement membrane antibody-mediated disease (Goodpasture's syndrome). Am J Ind Med. 1992;21(2):141-53. [abstract]
7. Murin S, Bilello KS, Matthay R; Other smoking-affected pulmonary diseases. Clin Chest Med. 2000 Mar;21(1):121-37, ix. [abstract]
8. Garcia-Rostan y Perez GM, Garcia Bragado F, Puras Gil AM; Pulmonary hemorrhage and antiglomerular basement membrane antibody-mediated glomerulonephritis after exposure to smoked cocaine (crack): a case report and review of the literature. Pathol Int. 1997 Oct;47(10):692-7. [abstract]
9. Hudson BG, Tryggvason K, Sundaramoorthy M, et al; Alport's syndrome, Goodpasture's syndrome, and type IV collagen. N Engl J Med. 2003 Jun 19;348(25):2543-56.
10. Lockwood CM, Rees AJ, Pearson TA, et al; Immunosuppression and plasma-exchange in the treatment of Goodpasture's syndrome. Lancet. 1976 Apr 3;1(7962):711-5. [abstract]
11. Vasiliou DM, Maxwell C, Shah P, et al; Goodpasture syndrome in a pregnant woman. Obstet Gynecol. 2005 Nov;106(5 Pt 2):1196-9. [abstract]

Acknowledgements