Goodpasture syndrome

Overview

Goodpasture syndrome, also known as anti-glomerular basement membrane (anti-GBM) disease, is a rare autoimmune disorder in which the immune system mistakenly produces antibodies that attack the basement membranes in the kidneys and lungs. This leads to rapidly progressive glomerulonephritis (kidney inflammation) and pulmonary hemorrhage (bleeding in the lungs). The syndrome is most common in young men in their 20s and older adults in their 60s, and it requires urgent medical attention to prevent irreversible kidney damage or life-threatening respiratory failure.

Causes

Goodpasture syndrome is caused by the production of autoantibodies that target the alpha-3 chain of type IV collagen, a key component of the basement membrane in the glomeruli of the kidneys and the alveoli of the lungs. The exact trigger for this autoimmune response is unknown, but several environmental and genetic factors have been implicated:

• Genetic predisposition: Certain HLA types, such as HLA-DR15, increase susceptibility

• Environmental triggers: Exposure to tobacco smoke, hydrocarbons, or certain medications

• Viral infections: Such as influenza or other upper respiratory infections

These factors may disrupt the immune system’s tolerance and expose hidden antigens in the basement membranes, leading to autoantibody formation.

Symptoms

The symptoms of Goodpasture syndrome primarily affect the kidneys and lungs. They may appear suddenly and progress rapidly over days to weeks. Common symptoms include:

Renal Symptoms:

• Hematuria (blood in the urine)

• Proteinuria (protein in the urine)

• Reduced urine output

• Swelling in the legs and ankles (edema)

• Fatigue due to kidney failure

Pulmonary Symptoms:

• Shortness of breath

• Dry cough or cough with blood (hemoptysis)

• Chest pain

• Fatigue and pallor due to anemia from blood loss

In some patients, symptoms may be isolated to either the kidneys or the lungs initially, but most eventually develop involvement of both organs.

Diagnosis

Early diagnosis of Goodpasture syndrome is critical for effective treatment. Diagnostic steps include:

• Blood tests: Detection of circulating anti-GBM antibodies confirms the diagnosis

• Urinalysis: Shows blood, protein, and cellular casts indicating kidney inflammation

• Renal function tests: Elevated serum creatinine and blood urea nitrogen (BUN) levels

• Chest X-ray or CT scan: To identify pulmonary infiltrates or bleeding

• Kidney biopsy: Reveals linear deposition of immunoglobulin G (IgG) along the glomerular basement membrane, confirming the autoimmune nature of the disease

Treatment

Goodpasture syndrome is a medical emergency that requires aggressive immunosuppressive therapy and supportive care. Treatment strategies include:

• Plasmapheresis (plasma exchange): Removes circulating anti-GBM antibodies from the bloodstream

• Corticosteroids: Such as prednisone to suppress the immune response and reduce inflammation

• Cytotoxic drugs: Like cyclophosphamide to further inhibit antibody production

• Supportive care: Includes oxygen therapy, dialysis for kidney failure, and blood transfusions if needed

Early and aggressive treatment can significantly reduce the severity of the disease and improve survival outcomes.

Prognosis

The prognosis of Goodpasture syndrome depends on the extent of kidney and lung involvement and the timing of diagnosis and treatment. If identified and treated early, many patients recover lung function and can stabilize or partially recover kidney function. However, if kidney damage is advanced at the time of diagnosis, patients may progress to end-stage renal disease and require long-term dialysis or a kidney transplant. Pulmonary symptoms usually resolve with treatment, but recurrent bleeding can be life-threatening. Long-term follow-up and monitoring for disease recurrence are essential, although relapses are relatively uncommon.