Goodpasture syndrome

There is still much to learn about the cause of Goodpasture syndrome. It is thought that a combination of genetic and environmental factors, such as cigarette smoke, inhaled hydrocarbons, and viruses play a role in the development of this autoimmune condition.

In autoimmune disorders, the body makes antibodies that attacks its own tissues. In the case of Goodpasture syndrome, antibodies form against a certain type of protein called collagen. Collagen is present in many tissues in the body. In Goodpasture syndrome, collagen in the alveoli (tiny air sacs in the lungs) and in the glomeruli (the filtering units of the kidney) is attacked. This leads to bleeding in the air sacs and inflammation in the glomeruli of the kidney. Symptoms of the antibody attack may include shortness of breath, cough, bloody sputum, blood and protein in the urine, and kidney failure.

Genetic predisposition to Goodpasture syndrome involves the human leukocyte antigen (HLA) system. The HLA system is involved in helping our immune system know the difference between "self" and "non-self." Human leukocyte antigens determine a person's tissue type. Each person has 3 pairs of major HLA antigens. We inherit one set from each of our parents (and pass one of our two sets on to each of our children).

Below we have provided some facts regarding HLA antigens and Goodpasture syndrome:

1. A certain HLA antigen, HLA-DR15 (previously known as HLA-DR2), is found in 88% of patients with Goodpasture syndrome, as compared to 25-32% of those without it.
2. People with Goodpasture syndrome who have two types of HLA antigens: HLA-B8 and HLA-DR2 tend to have a worse prognosis.
3. HLA antigen types HLA-DR7 and HLA-DR1 are thought to confer some protection against developing Goodpasture syndrome.

A diagnosis of anti-GBM antibody disease is made when a patient presents with lung hemorrhage, urinary findings such as proteinuria (protein in the urine) and hematuria (blood in the urine), and circulating anti–glomerular basement membrane (anti-GBM) antibodies.

A kidney biopsy is the best method for detecting anti-GBM antibodies in tissues. Some recommend doing a kidney biopsy in all cases while others suggest only doing the biopsy when the diagnosis is still in doubt. Light microscopy usually shows a feature known as crescentic glomerulonephritis, whereas immunofluorescence microscopy demonstrates a finding that is characteristic of this disease, of “linear deposition of IgG along the glomerular capillaries”. Patients in whom the diagnosis of lung hemorrhage is still unclear should have bronchoscopy.

In children, the most consistent feature is ‘crescentic glomerulonephritis’ with either circulating anti-GBM antibodies or linear staining of IgG on the immunofluorescence. Clinical features include severe kidney malfunction in all patients and lung hemorrhage in half of them.

It is essential to promptly diagnose pulmonary hemorrhage because this is the principal cause of early death when untreated.

Conditions that affect the lung and kidney (pulmonary-renal syndromes) are important to consider and need to be ruled out when the diagnosis is not confirmed. These include granulomatosis with polyangiitis (Wegener granulomatosis), Churg-Strauss syndrome, systemic lupus erythematosus, microscopic polyangiitis, rheumathoid arthritis, IgA-mediated disorders (eg, IgA nephropathy or Henoch-Schönlein purpura) and of immune complex–mediated renal disease (eg, essential mixed cryoglobulinemia), community-acquired pneumonia and undifferentiated connective-tissue disease. In children, other diseases that also need to be ruled out are Behcet Syndrome, hemosiderosis (bleeding into the lung and iron accumulation) and Legionella infection.

See an image of the kidney and glomerulus.

The treatment of choice is plasmapheresis in conjunction with prednisone and cyclophosphamide. The three main goals for the treatment are:

1. Rapidly remove circulating antibody, primarily by plasmapheresis.
2. Stop further production of antibodies using immunosuppression with medications, namely, corticosteroids (e.g., prednisone) and cyclophosphamide. In children, plasmapheresis is done together with corticosteroids and cyclophosphamide. The duration of the immunosuppressive treatment varies but is typically 6 months for corticosteroids and 3 months for cyclophosphamide.
3. Remove offending agents that may have initiated the antibody production.

After hospital discharge, patients require long-term regular visits for monitoring kidney function and for immunosuppressive therapy. If kidney function does not return, dialysis is continued indefinitely and the patient should be referred for kidney transplantation.

If the person smokes, it is recommended he or she stop. Also, if the patient is exposed to hydrocarbon in his or her occupation, he or she should consider changing jobs, as exposure to hydrocarbon has been shown to increase a person's chances of disease recurrence.