Goodpasture Syndrome

What is Goodpasture Syndrome?

Goodpasture syndrome is a medical condition characterized by the body’s immune system attacking both the kidneys and lungs. It commonly shows up as bleeding in the lungs and an inflammatory kidney condition known as glomerulonephritis. This syndrome is among the top three causes for crescentic glomerulonephritis – a severe form of kidney inflammation. Goodpasture syndrome can have severe outcomes, especially if not treated promptly.

The syndrome may also be referred to as anti-glomerular basement membrane disease, Goodpasture’s disease, or simply as anti-GBM disease. Though all these terms are used intermittently, they slightly differ. Anti-GBM disease is when only the kidneys are affected, whereas Goodpasture’s disease or syndrome always involves the lungs as well. Some doctors call any disease affecting both lungs and kidneys as Goodpasture Syndrome. Generally, Goodpasture Syndrome is most often used when anti-GBM antibodies, the proteins that attack the kidneys and lungs, are present.

About 40% to 60% of Goodpasture Syndrome cases are associated with bleeding in the lungs, while less than 10% cases of anti-GBM diseases involve just the lungs. The syndrome was named after Ernest Goodpasture, who first described it in 1919. The development of testing methods for antibodies in the 1960s improved our understanding of the cause of Goodpasture Syndrome.

What Causes Goodpasture Syndrome?

Goodpasture syndrome is a disease that seems to be caused by a combination of genetic vulnerability and exposure to certain environmental or infectious factors. So far, no single cause has been pinpointed for producing specific antibodies that contribute to this disease, but it seems to be more common in certain places and seasons.

Research has shown strong evidence for genetic factors. People with particular genetic markers (known as human leukocyte antigens or HLA types) are more likely to develop the disease and often experience more severe symptoms. Specifically, the HLA-DR2 marker is found in up to 80% of patients with anti-GBM (glomerular basement membrane) disease, a key part of Goodpasture syndrome.

Other genetic markers, HLA-DRB1*01 and HLA-DRB1*07, appear to protect against the disease, while HLA-DRB1*1501 makes it more likely, especially in Asian populations. However, these markers are also found in people with other autoimmune diseases and even in healthy individuals. That’s why doctors don’t often do HLA testing – for example, the DRB1*1501 marker shows up in up to one third of all white people. Other factors also have to be present to cause Goodpasture syndrome.

The disease involves the body’s immune system attacking small blood vessels in the lungs and kidneys. This is likely started by some factor damaging lung or kidney tissues, causing local inflammation and exposure of usually hidden tissue components (antigens). Several potential triggers have been linked to this disease:

– Smoking
– Exposure to metal dust, organic solvents, or hydrocarbons (chemical compounds found in many places, including petrol)
– Bacterial blood infections
– Endotoxemia (having toxins in the blood)
– Exposure to volatile hydrocarbons (easily evaporated chemical compounds)
– Infections, such as influenza A
– Certain drugs, such as alemtuzumab, that reduce a specific type of immune cell
– Snorting cocaine
– Medical procedures like extracorporeal shockwave lithotripsy (breaking down kidney stones using sound waves)

High levels of inhaled oxygen are also associated with the syndrome.

Risk Factors and Frequency for Goodpasture Syndrome

Goodpasture syndrome is a rare health condition which occurs more frequently in Asian and European populations at a rate of between 0.5 to 1.8 cases per million people every year. It is responsible for 1% to 5% of all types of a kidney disease called glomerulonephritis and accounts for 10% to 15% of a specific type of this disease called crescentic glomerulonephritis.

• Goodpasture syndrome is seen more commonly in white people as compared to black people.
• However, it appears to be more common among certain ethnic groups, like the Maori people of New Zealand.
• The condition typically shows up in individuals either in their 30s or those in their 60s.
• Younger patients tend to have more complications that affect the lungs, whereas, older patients usually have a less severe form of the disease that only affects the kidneys.

Signs and Symptoms of Goodpasture Syndrome

Goodpasture syndrome is a condition that usually begins similarly to other diseases causing quick and serious kidney failure. There aren’t any specific symptoms that set it apart from these other diseases. Lung symptoms are often seen when first meeting with the patient, or soon after. Coughing up blood, in varying amounts, is a common sign of this disease. This can range from severe, life-threatening bleeding to a more subtle widespread bleed that might need closer examination to notice.

Younger people suffering from Goodpasture syndrome often show both kidney and lung symptoms at the same time, which can make them very sick. People over the age of 50 usually only exhibit symptoms related to glomerulonephritis, a type of kidney disease, and their condition tends to be less severe.

During a physical exam, there might be several other signs to look out for in a person with Goodpasture syndrome. These can include:

• A higher than normal breathing rate
• Crackling sounds at the base of the lungs when breathing in
• Blue discoloration of the skin due to low oxygen (cyanosis)
• Enlarged liver and spleen (hepatosplenomegaly)
• High blood pressure (found in about 20% of cases)
• Purple or red-colored spots on the skin (purpuric rash)
• Swelling caused by excess fluid in the body’s tissues (edema)

Testing for Goodpasture Syndrome

In order to diagnose certain kidney conditions, a kidney biopsy is the gold standard, or best method. However, you can start treatment even if a biopsy can’t be performed. When a biopsy is taken, it gives crucial information about the condition and stage of the disease. This info can help guide the treatment plan. A kidney biopsy is generally preferred over a lung biopsy as it provides more useful results, but if for some reason a kidney biopsy can’t be done, a lung biopsy can be performed.

The biopsy sample is studied under various microscopes for a detailed analysis. This can show signs like changes in the kidney’s filtering units or scarred kidney tissue. These signs can point towards disease progression.

Another way to diagnose is through blood tests. Doctors use techniques called ELISA or bead-based fluorescence assays to detect certain harmful antibodies. These specific antibodies attack a certain area of type IV collagen, one of the key structural proteins in our body. However, these tests can sometimes give false results. There are even cases when patients tested negative for these antibodies but were confirmed to have the disease through a biopsy. To avoid this, researchers are studying a potentially more sensitive test, the chemiluminescence immunoassay. The amount of these antibodies in the blood can help determine what treatment is needed.

There are additional tests that can be performed for diagnosis:

• Analysis of urine can show signs of kidney problems such as protein or blood in the urine.
• A blood test can indicate anemia due to bleeding in the lungs, and an increased number of white blood cells, which usually indicates inflammation or infection.
• Tests of kidney function can show abnormal results due to kidney dysfunction.
• A chest X-ray may show abnormalities in the lung tissue, often in both lungs and near the base. The tops and outer corners of the lungs are usually unaffected.
• Pulmonary function tests measure how well your lungs work. These tests can show increased absorption of carbon monoxide due to its binding with hemoglobin, a protein in your blood.

Treatment Options for Goodpasture Syndrome

Goodpasture syndrome is a serious disease which affects your kidneys and lungs. It can even be life-threatening, often requiring emergency procedures like dialysis, which is a treatment to filter your blood when the kidneys fail, and breathing assistance through a machine (intubation) in case of respiratory failure. If your doctor suspects you have Goodpasture syndrome, they will likely order a kidney biopsy, which is an examination of your kidney to confirm the diagnosis as soon as it is medically sensible.

Treatment ideally needs to start as soon as possible to prevent your kidneys and lungs from getting worse. The common treatment method involves a procedure called plasmapheresis and the use of immunosuppressive drugs (medications that reduce body’s immune response). Plasmapheresis is a process that cleans the blood similar to dialysis, but it specifically removes the harmful autoantibodies, which are proteins that mistakenly target your own cells causing the disease.

The guidance for treating Goodpasture syndrome suggests using a specific combination of medications unless the patient is already dependent on dialysis and does not have lung bleeding. Those medications include cyclophosphamide and corticosteroids. Another drug called rituximab can be used as an alternative to cyclophosphamide especially for those who have side effects or concerns about reproduction.

Usually in plasmapheresis, they’ll replace your blood with a substance called albumin, however, if you have ongoing lung bleeding or are about to have an invasive procedure, fresh frozen plasma is used instead. The treatment continues daily until the harmful antibodies in your blood are reduced or for about 2 weeks. But if your lung disease is active or antibodies are still high, the treatment may go on for longer. Plasmapheresis is always followed by immunosuppressive therapy, typically glucocorticoids and cyclophosphamide. Some recent studies indicate that other substances may also be beneficial in the treatment. This process is usually continued for 3 to 6 months until full recovery is achieved.

If you can’t tolerate cyclophosphamide, rituximab or another drug mycophenolate mofetil could be used. Another agent called alemtuzumab is currently being studied for its ability to stop the disease from getting worse. Additionally, imlifidase, a protein that breaks down antibodies, is showing promise for severe cases of this disease, although more research is needed. After the remission phase, a maintenance treatment is usually considered to ensure complete recovery. This maintenance phase includes medications with fewer potential side effects.

For a specific type of Goodpasture syndrome known as double-positive antibody crescentic glomerulonephritis, the treatment approach is somewhat similar but includes the addition of plasmapheresis. This form of the disease can have relapses and requires long term monitoring. Just as in the general form of the disease, a long-term medication is often used following the treatment phase to minimize chances of a recurrence. More information about this specific type of Goodpasture syndrome can be found in the section titled “Double-Positive Antibody Crescentic Glomerulonephritis” in StatPearls’ reference material “Rapidly Progressive Glomerulonephritis”.

What else can Goodpasture Syndrome be?

If a person has symptoms that affect both their lungs and kidneys, doctors may need to consider several health conditions called “pulmonary-renal syndromes”. Some of these conditions are:

• Granulomatosis with polyangiitis (used to be called Wegener granulomatosis)
• Microscopic polyangiitis
• Eosinophilic granulomatosis with polyangiitis (also known as Churg-Strauss syndrome)
• Systemic lupus erythematosus

There are also some health conditions related to a type of antibody known as IgA. These conditions also present with lung and kidney symptoms. They include:

• IgA nephropathy
• IgA vasculitis (previously known as Henoch-Schönlein purpura)

Additionally, the doctor may need to consider other health conditions as potential causes. These include:

• Acute glomerulonephritis
• Community-acquired pneumonia with a type of kidney disease called infection-related glomerulonephritis
• Cryoglobulinemia, a condition that involves abnormal proteins in the blood
• Endocarditis, an inflammation of the heart valves
• Drug-induced vasculitis, which is inflammation of blood vessels caused by medication
• Alport syndrome, which is a genetic condition that is rarely associated with lung symptoms

What to expect with Goodpasture Syndrome

Some indicators of a poor prognosis, or outcome, include having a low amount or absence of urine (oligo- or anuria), globally hardened crescents in the kidneys, and the need for dialysis due to kidney failure. However, it’s worth noting that the reoccurrence of the disease after a kidney transplant is quite rare, happening in fewer than 3% of cases.

In a long-term study, it was found that among patients who showed a creatinine level of less than 5.7 mg/dL (a waste product in the blood that the kidneys filter out), 95% survived after one year and 94% after five years. However, the outlook isn’t as positive for patients who needed dialysis – only 8% regained their kidney function after one year.

Possible Complications When Diagnosed with Goodpasture Syndrome

: Complications from a disease can come in two types: those that are caused by the disease itself and those that are a result of the treatment.

Disease-Related Complications:

• Lung bleeding, often seen in anti-GBM disease, can require artificial breathing assistance and cause related problems.
• Kidney failure can require dialysis and lead to problems such as infections or bleeding associated with the dialysis catheter.

Treatment-Related Complications:

• Main complications linked to therapy that reduces the immune system are numerous infections that can even be fatal.
• Cyclophosphamide, a specific drug, can cause other complications including bladder inflammation and blood in urine. Older patients are especially at risk for infections and problems arising from taking this drug.
• Plasmapheresis, a procedure that filters the blood, can increase a patient’s risk of bleeding by removing clotting agents.

Preventing Goodpasture Syndrome

Doctors need to inform patients about the different treatment options and any potential negative side effects from medications. It’s crucial for patients and those caring for them to know when they should seek medical attention. Signs that their condition may be worsening could include blood in their urine (hematuria), swelling in body parts (edema), or high blood pressure (hypertension).