Goodpasture's syndrome

Goodpasture’s syndrome (also known as Goodpasture’s disease and anti-glomerular basement antibody disease) is a rare disease characterized by glomerulonephritis and hemorrhaging of the lungs. Although many diseases can present with these symptoms, the name Goodpasture’s syndrome is usually reserved for the autoimmune disease triggered when the patient’s immune system attacks Goodpasture antigen (a type II hypersensitivity reaction ), which is found in the kidney and lung, and in time, causing damage to these organs. The disease bears the name of the American pathologist Dr. Ernest Goodpasture of Vanderbilt University, whose 1919 description is regarded as the first report on the existence of the condition.

The GBM antigen responsible for this disease is a component of the non-collagenous domain (NC1) of the alpha-3 chain of collagen type IV.

Signs and symptoms
Goodpasture’s syndrome can cause people to cough up blood or feel a burning sensation when urinating. But its first signs may be vague, such as fatigue, nausea, difficulty breathing, or skin pallor. These signs are followed by kidney involvement, represented first by small amounts of blood in the urine, protein in the urine, and other clinical and laboratory findings.

Other patients present with both lung and kidney disease; however, some patients present with one of these diseases alone. The first lung symptoms usually develop days to months before kidney damage is evident.

Lung disease
Lung symptoms may present as nothing more serious than a dry cough and minor breathlessness; and such mild symptoms may last for many years before more severe ones develop. At its most serious, however, lung damage may cause severe impairment of oxygenation so that intensive care is required. Deterioration between the two extremes may occur very rapidly, often at the same time as rapid deterioration occurs in the kidney. The patient often does not seek medical attention until he or she begins coughing up blood (hemoptysis). The patient may be anemic due to loss of blood through lung hemorrhaging over a long period. In Goodpasture’s syndrome, unlike many other conditions that cause similar symptoms, lung hemorrhaging most often occurs in smokers and those with damage from lung infection or exposure to fumes.

Kidney disease
The kidney portion of the disease mostly affects the glomeruli causing a form of nephritis. It is usually not detected until a rapid advance of the disease occurs and kidney function can be completely lost in a matter of days, a condition known as rapidly progressive (Crescentic) glomerulonephritis, or RPGN. Blood spills into the urine causing hematuria, the volume of urine output decreases and urea and other products usually excreted by the kidney are retained and build up in the blood. This is acute renal failure. Renal failure does not cause symptoms until more than 80% of kidney function has been lost. Symptoms include loss of appetite and malaise at first and then, when the damage is more advanced, breathlessness, high blood pressure and edema (swelling caused by fluid retention). The kidney involvement usually presents as nephritic syndrome, i.e. hematuria, a reduced glomerular filtration rate, and high blood pressure. This is in contrast to nephrotic syndrome, a rarer outcome of Goodpasture's, characterized by an abnormally large amount of protein in the urine (proteinuria), coupled with severe edema.

Diagnosis
Because of the vagueness of early symptoms and rapid progression of the disease, diagnosis is often not reached until very late in the course of the disease. A Kidney biopsy (linear IgG deposits along basement membrane) is often the fastest way to secure the diagnosis and gain information about the extent of the disease and likely effect of treatment. Tests for anti-GBM antibodies may also be useful, combined with tests for antibodies to neutrophil cytoplasmic antigens, which are also directed against the patient’s own proteins.

Possible causes
Viral infections, especially influenza, and kidney surgery are generally regarded as proven causes.

Other possible causes include the presence of an inherited component and exposure to certain chemicals, including hydrocarbon solvents and the weed killer Paraquat.

Pathophysiology
As with many autoimmune conditions, the precise cause of Goodpasture’s Syndrome is not yet known. It is believed to be a type II hypersensitivity reaction to Goodpasture’s antigens on the basement membrane of the glomerulus of the kidneys and the pulmonary alveolus, specifically the non-collagenous domain of the alpha-3 chain of Type IV collagen. The immune system wrongly recognizes these motifs as foreign and produces antibodies (IgG) toward them, eliciting an immune response.

Renal failure is due to anti-glomerular basement membrane (anti-GBM).

Treatment
Like many autoimmune diseases, Goodpasture’s syndrome responds well to treatment with corticosteroids and immunosuppressants. These drugs dampen the body's normal immune response and the patient may become more susceptible to infections. The concentration of anti-GBM antibodies in the blood may be reduced by apheresis to remove blood plasma and replace a portion of the plasma with an isotonic salt and protein solution. This course of treatment usually lasts between three and six months.

Unfortunately, none of these treatments can reverse permanent kidney damage and for patients who have suffered from the syndrome, renal transplant may be needed once the disease has subsided.

Epidemiology
Goodpasture’s syndrome is rare. In European populations, the incidence is between 1 in 1,000,000 and 1 in 2,000,000. It is less likely to be found in non-European populations. While cases have occurred in patients between the ages of 4 and 80, it is most common between ages 18 and 30 and again between 50 and 65. Unlike many other autoimmune diseases, males are surprisingly six times more affected than females.

Prognosis
In the 1970s, Goodpasture’s syndrome was most often fatal, but due to advances in diagnosis and treatment, deaths are less common now. Death from lung hemorrhage may occur before the diagnosis has been made, or in the initial stages of treatment before it has been properly controlled. With treatment, however, the patient can usually recover completely from lung damage. Kidneys, on the other hand, are less able to repair themselves and patients with kidney damage must often resort to a life on dialysis or kidney transplantation. Even with the best management there is still significant mortality from renal failure, particularly if the patient is otherwise in poor health. It must also be remembered that the immunosuppressive treatment many patients are treated with increases their risk of infection with a number of serious or fatal secondary diseases.