Goodpasture's Disease

Synonyms: anti-glomerular basement membrane disease, anti-GBM disease.

Goodpasture's syndrome (GS) is the co-existence of acute glomerulonephritis and pulmonary alveolar haemorrhage, of which Goodpasture's disease is one cause.¹ Goodpasture's disease 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 anti–glomerular basement membrane (anti-GBM) antibodies.

• It is uncommon. It represents 1 to 2% of all cases of rapidly progressive glomerulonephritis and the incidence is about 1 in 2 million. Wegener's granulomatosis is about 10 times as common.
• A survey of the British Isles found that it affects mostly young, white men aged 15 to 35 with a further peak after 55 when it is more common in women² and tends to affect just the kidneys.
• It affects both sexes equally in children.
• Between 60 and 80% have both renal and pulmonary disease. The kidneys alone are affected in 20 to 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-DRw2^3,4
• Exposure to organic solvents or hydrocarbons⁵
• Smoking⁶
• Infection, e.g. influenza
• A case in a heavy smoker who had taken to using crack cocaine is described⁷
• Exposure to metal dusts
• It can occur after renal transplantation in Alport's syndrome⁸

Symptoms

• Chills and fever
• Nausea and vomiting
• Weight loss
• Chest pain
• Anaemia may result from persistent intrapulmonary bleeding
• Massive pulmonary haemorrhage can cause respiratory failure
• 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 can be severe
• Inspiratory crackles over lung bases
• Cyanosis
• Hepatosplenomegaly (sometimes)
• Hypertension
• Skin rash
• There may be gross haematuria and pallor from anaemia

• 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.

Blood tests

• Full blood count: iron-deficiency anaemia from intrapulmonary bleeding, leucocytosis.
• Renal function and electrolytes: watch for renal failure.
• 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.
• Anti-GBM antibodies are diagnostic: assays for antibodies are valuable for confirming the diagnosis and monitoring therapy. Radioimmunoassays or enzyme-linked immunosorbent assays:
  • (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 (ANCA): at sometime 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 chest x-ray.
• 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.

Non-drug

• Intubation, assisted ventilation, and haemodialysis are often required in the acute phase.
• Repeated plasmapheresis⁹ removes anti-glomerular basement membrane antibodies from the circulation.
• End-stage renal disease can be managed by long-term haemodialysis or renal transplantation.

Drugs

• High-dose corticosteroids (methylprednisolone 7 to 15 mg/kg/day IV in divided doses) with cyclophosphamide or azathioprine are of benefit. IV 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 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.

• Pulmonary haemorrhage with respiratory failure is the commonest 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 jiroveci (carinii) 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 retardation requiring premature delivery. Both mother and baby are at risk.¹⁰

• In the past, the disease was almost invariably fatal, and sometimes rapidly so. Now the mortality rate is about 10%.
• Death is often due to respiratory failure.
• Most progress to end stage renal failure within months. Early, energetic treatment may delay or prevent this. It can last from a couple of weeks to 2 years.
• Some people get recurrent disease.

There is no known prevention, but avoid sniffing glue and siphoning petrol!⁵