What Is Goodpasture Syndrome?

Goodpasture syndrome also often referred to as Goodpasture disease, was named after the American pathologist, Ernest Goodpasture, who first described the disease in 1919¹. In this article, we will describe the disease including its causes and manifestations. 

The syndrome is an autoimmune disease referred to as an anti-glomerular basement membrane (anti-GBM) disease.¹ This means that the immune system that normally protects the body starts reacting abnormally and attacks normal tissues in the lungs and kidneys. It manifests as pulmonary haemorrhage in the lungs or glomerulonephritis in the kidneys. In some cases, only the kidneys are affected.¹ 

In the subsequent headings, you will be able to understand how the disease presents, how it is prevented and managed and other important information about the disease.

Overview

Goodpasture syndrome is a rare disease, estimated to have an incidence of less than 1 per million population per year in Europe and even rarer in Africa.³ It has two peaks, one in the third decade in which case both kidney and lung involvement is seen; and the second in the sixth to seventh decade where the proportion of those with kidney involvement predominates.³

The glomerulus is the filtering unit of the kidney made up of a bundle of capillaries.¹ The basement membrane in the glomerulus is a sheet-like structure that lies between the two filtration barriers - the podocytes (foot-like cells) and endothelial cells.² The basement membrane is mainly made up of laminin, type IV collagen, nidogen and heparan sulfate proteoglycan.² The alveolar basement membrane in the lungs share some similarities with the glomerular basement membrane in the kidneys.¹ 

In anti-GBM disease, molecules of the immune system known as antibodies that circulate in the body to provide immunity, wrongly recognize the basement membrane as a foreign body resulting in its destruction in the form of glomerulonephritis or alveolar haemorrhage.  

Causes of goodpasture syndrome

A combination of genetic predisposition and environmental factors have been identified to result in anti-GBM disease. Certain human leukocyte antigens (HLA) such as the HLA-DR15 have been associated with increased vulnerability to Goodpasture syndrome.¹ The environmental insults especially associated with alveolar involvement include

1. Smoking
2. Infections such as influenza
3. Cocaine
4. Exposure to toxins such as some hydrocarbons
5. Drugs such as alemtuzumab
6. A five-fold increase in anti-GBM disease has been found in association with COVID-19⁴

Signs and symptoms of goodpasture syndrome

The presentation of anti-GBM disease widely varies with 60-80% manifesting features of kidney and lung disease, 20-40% have renal disease alone while less than 10% have only lung involvement.³

Fever, chills and joint pains may precede the symptoms of the disease or occur concurrently.⁵ 

Initial symptoms may present with fatigue, weakness, nausea and vomiting. Lung involvement may present with varying degrees of hemoptysis (coughing up of blood or blood-stained sputum)^1,6 while kidney involvement manifests as glomerulonephritis in which patients have haematuria (passing of blood in urine), generalised body swelling, elevated blood pressure and elevated blood urea levels.⁵

Physical examination may reveal tachypnoea (fast breathing), crackles over the lung bases, hypertension and oedema.^5,6 Cyanosis can be seen in severe cases and purpuric rashes may appear in those with associated angitis.¹ 

Management and treatment for goodpasture syndrome

After developing a clinical impression through the identification of suggestive signs and symptoms, the next step in the management is to conduct tests leading to a diagnosis. This is made by the detection of circulating anti-GBM antibodies.³ 

Detection of anti-GBM antibodies can be made by radioimmunoassays or enzyme-linked immunosorbent assays (ELISAs), which are highly sensitive and specific.^1,7 Once circulating antibodies are detected,  a kidney biopsy may not be needed. However, a kidney biopsy may be necessary when the diagnosis has not been confirmed. In addition, in cases where alveolar haemorrhage is suspected, a diagnostic bronchoscopy can be helpful.

Urinalysis is important to detect the presence of glomerulonephritis which is determined by the presence of some protein in the urine, blood and red blood cell casts.³ Renal function may be deranged and might be detected by elevated serum creatinine levels and high blood urea nitrogen (BUN). Full blood count (FBC) may reveal anaemia due to pulmonary haemorrhage and the erythrocyte sedimentation rate (ESR) might be raised. 

Management usually involves different teams such as nephrologists, pulmonologists and vascular surgeons, who might be needed to secure a good vascular access for dialysis or plasmapheresis. 

Treatment options are aimed to achieve three basic goals; quickly neutralise circulating anti-GBM antibodies, use medications to halt the further production of the antibodies and lastly, eliminate the instigating factor that triggered the production of such antibodies.³ These treatments include

1. Plasmapheresis: In this intervention, the plasma is filtered to remove the circulating anti-GBM antibodies.⁸ The procedure can be done daily or on alternate days for 2-3 weeks till improvement occurs or anti-GBM becomes absent in the serum
2. Immunosuppressants: Drugs such as prednisolone, cyclophosphamide and rituximab inhibit antibody production and rebound production following plasmapheresis^3,5,9 
3. Kidney transplant: In cases of end-stage kidney disease

FAQs

How is Goodpasture syndrome diagnosed?

The Goodpasture syndrome can be diagnosed through a combination of clinical features and investigations. Investigations include serologies such as ELISA and radioimmunoassays. A urinalysis, complete blood count including ESR and a kidney function test are also important in guiding diagnosis.

How can I prevent goodpasture syndrome?

Although anti-GBM disease has a genetic predisposition, susceptible individuals can protect themselves by avoiding environmental factors such:

1. Avoiding smoking
2. Protection against infections like influenza, through vaccinations
3. Avoid cocaine and harmful compounds including certain hydrocarbons

Who are at risk of goodpasture syndrome

Those at risk of Goodpasture syndrome include those with inherited abnormalities in their HLA antigens such as HLA-DR15.

How common is goodpasture syndrome?

Goodpasture syndrome is rare with a frequency of about 1 in 1 million population in Europe.

When should I see a doctor?

Symptoms such as haemoptysis, haematuria or difficulty in breathing should prompt urgent medical attention.  

Summary

Goodpasture disease although rare, is an important cause of kidney damage. Those with genetic susceptibility are encouraged to observe extra protection from certain factors such as smoking, influenza infections and toxins. The disease usually present with features of glomerulonephritis or pulmonary haemorrhage. Management is multidisciplinary and involves options such as plasmapheresis, immunosuppressants or renal transplant.