Goodpasture's syndrome

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Goodpasture's syndrome
Classification and external resources
Crescentic glomerulonephritis - high mag.jpg
Micrograph of a crescentic glomerulonephritis that was shown to be anti-glomerular basement membrane disease. PAS stain.
ICD-10M31.0 (ILDS M31.010)
ICD-9446.21
OMIM233450
DiseasesDB5363
MedlinePlus000142
eMedicinemed/923 ped/888
MeSHD019867
 
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Goodpasture's syndrome
Classification and external resources
Crescentic glomerulonephritis - high mag.jpg
Micrograph of a crescentic glomerulonephritis that was shown to be anti-glomerular basement membrane disease. PAS stain.
ICD-10M31.0 (ILDS M31.010)
ICD-9446.21
OMIM233450
DiseasesDB5363
MedlinePlus000142
eMedicinemed/923 ped/888
MeSHD019867

Goodpasture’s syndrome (also known as Goodpasture’s disease and anti-glomerular basement antibody disease) is a rare autoimmune disease in which antibodies attack the lungs and kidneys, leading to bleeding from the lungs and to kidney failure. It may quickly result in permanent lung and kidney damage, often leading to death. It is treated with immunosuppressant drugs such as corticosteroids and cyclophosphamide, and with plasmapheresis, in which the antibodies are removed from the blood.

The specific target of the immune attack is the GBM antigen, which is found in the lungs and kidneys. The antigen is a component of the non-collagenous 1 (NC1) domain of the alpha-3 chain of type IV collagen in the glomerular basement membrane.

Goodpasture's syndrome is a type II hypersensitivity-like reaction.[1]

The disease was first reported by the American pathologist Ernest Goodpasture of Vanderbilt University, in 1919.[2][3]

Signs and symptoms[edit]

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.[4]

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[edit]

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 chemical fumes.

Kidney disease[edit]

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. Nephritic Syndrome in this disease will develop to another nephritic 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[edit]

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.

Differential diagnosis[edit]

Possible causes[edit]

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.[4]

Pathophysiology[edit]

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-like autoimmune 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. On an immunology stain Goodpasture's Syndrome usually presents with a linear staining pattern.

Renal failure is ultimately due to damage caused to the Glomerular Basement Membrane by immune system cells attacking in response to these antibodies. As the basement membrane is damaged, the ability of the kidneys to excrete waste and reabsorb nutrients is compromised.

Treatment[edit]

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[edit]

Goodpasture’s disease 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, men are surprisingly six times more affected than women.

Prognosis[edit]

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. In addition, the immunosuppressive treatment many patients are treated with increases their risk of infection with a number of serious or fatal secondary diseases.

See also[edit]

References[edit]

  1. ^ eMedicine: Goodpasture's syndrome
  2. ^ Goodpasture EW (1919). "The significance of certain pulmonary lesions in relation to the etiology of influenza". Am J Med Sci 158 (6): 863–870. doi:10.1097/00000441-191911000-00012. 
  3. ^ Salama AD, Levy JB, Lightstone L, Pusey CD (September 2001). "Goodpasture's disease". Lancet 358 (9285): 917–920. doi:10.1016/S0140-6736(01)06077-9. PMID 11567730. 
  4. ^ a b http://my.clevelandclinic.org/disorders/Goodpasture_Syndrome/hic_Goodpastures_Syndrome.aspx

External links[edit]