Goodpasture's Syndrome

It is also known as anti-glomerular basement membrane disease and anti-GBM disease.

This is an autoimmune disease which is characterised by:

• Deposition of antibodies to the glomerular basement membrane along with compliment
• A progressive glomerulonephritis and often renal failure
• Cross reaction with the basement membrane in the lungs causing pulmonary haemorrhage

It is a type II Gel and Coombs reaction.

It is uncommon. In the USA it represents 1 to 2% of all cases of rapidly progressive glomerulonephritis. In England 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 women¹ and tends to affect just the kidneys. A male preponderance in an autoimmune disease is unusual. It affects both sexes equally in children. Classification can be difficult in that sometimes either the lungs or the kidneys are affected but not both. However, the presence of autoantibodies to the glomerular basement membrane is the diagnostic feature.

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

• Genetic predisposition², ³ with possession of HLA-DRw2
• Exposure to organic solvents or hydrocarbons⁴
• Smoking⁵
• Infection (eg, influenza)
• A case in a heavy smoker who had taken to using crack cocaine is described⁶
• Exposure to metal dusts
• Goodpasture's syndrome can occur after renal transplantation in Alport's syndrome⁷

Symptoms

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.

• Chills and fever present in about 25% of patients
• There is nausea and vomiting in 40%
• Weight loss occurs in about 15%
• Chest pain is present in approximately 40% of patients
• 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
• Inspiratory crackles over lung bases
• Cyanosis
• Hepatosplenomegaly (sometimes)
• Hypertension in 20%
• Skin rash

Dyspnoea can be severe. Death is often due to respiratory failure. There may be gross haematuria and pallor from anaemia.

Pulmonary haemorrhage with renal failure can also occur in collagen vascular diseases like SLE and RA, idiopathic rapidly progressive glomerulonephritis, microscopic polyarteritis, Wegener's granulomatosis, and essential mixed cryoglobulinemia. All these diseases have specific laboratory features. In Goodpasture's syndrome the essential feature is antibody to the glomerular basement membrane.

Blood tests

• FBC. Iron-deficiency anaemia from intrapulmonary bleeding. Leukocytosis.
• U&E and creatinine: Watch for renal failure.
• ESR is raised in vasculitis but not in this disorder.
• 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.

Imaging

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

Other Tests

Pulmonary function tests are not helpful. 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 plasmapheresis⁸ 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. The IV steroids are 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 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.⁹

In the past, the disease was almost invariably fatal, and sometimes rapidly so. Now the mortality rate is about 10%,

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.⁴

Ernest William Goodpasture¹⁰ was born in Tennessee in 1866 and died in Nashville in 1960. He obtained his doctorate at the Johns Hopkins University in 1912. He is most famous for his paper of 1919¹¹ that first described the syndrome that bears his name, linking it to influenza. His original patient was a man of 19 who died of pulmonary haemorrhage. However, his most notable achievement was his study of viruses in chicken embryos and fertilized chicken eggs. In 1931 he succeeded in finding a method for cultivating viruses and rickettsiae in fertilized chicken eggs. This made possible the production of vaccines against chicken pox, smallpox, yellow fever typhus, Rocky mountain fever and other diseases caused by pathogenic agents that can propagate in living tissue. He also developed several staining methods and techniques. McCullum-Goodpasture stain is a stain for Gram negative bacteria.