Goodpasture's syndrome

Infobox_Disease
Name = PAGENAME


Caption =
DiseasesDB = 5363
ICD10 = ICD10|M|31|0|m|30 (ILDS M31.010)
ICD9 = ICD9|446.21
ICDO =
OMIM = 233450
MedlinePlus =
eMedicineSubj = med
eMedicineTopic = 923
eMedicine_mult = eMedicine2|ped|888
MeshID = D019867

Goodpasture’s syndrome (also known as Goodpasture’s disease and anti-glomerular basement membrane disease) is a rare condition characterised by rapid destruction of the kidneys and haemorrhaging of the lungs. Although many diseases can present with these symptoms, the name Goodpasture’s syndrome is usually reserved for the autoimmune disease produced when the patient’s immune system attacks cells presenting the Goodpasture antigen (a type II hypersensitivity reaction), which are found in the kidney and lung, causing damage to these organs. The disease bears the name of the American pathologist Dr Ernest Goodpasture, whose 1919 description is regarded as the first report on the existence of the condition. [cite journal | author=Goodpasture EW | title=The significance of certain pulmonary lesions in relation to the etiology of influenza | journal=Am J Med Sci | year=1919 | volume=158 | pages=863–70 | doi=10.1097/00000441-191911000-00012] [cite journal |author=Salama AD, Levy JB, Lightstone L, Pusey CD |title=Goodpasture's disease |journal=Lancet |volume=358 |issue=9285 |pages=917–20 |year=2001 |month=September |pmid=11567730 |doi=10.1016/S0140-6736(01)06077-9]

igns and symptoms

Most 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. There is an increased incidence of syndactyly.

Lung disease

Lung damage may cause 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 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 haemorrhaging 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 disease mostly affects the glomeruli causing a form of nephritis. It is usually not detected until a rapid advance of the disease occurs so that kidney function can be completely lost in a matter of days, a condition known as rapidly progressive (Crescentic) glomerulonephritis, or RPGN. Blood leaks into the urine causing hematuria, the volume urinated 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 sickness 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 more rare outcome of Goodpasture's, characterized by an abnormally large amount 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. Kidney biopsy 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.

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, elliciting an immune response.

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. A serious side effect of this is that 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 its replacement with an isotonic salt and protein solution. This course of treatment usually lasts between three and six months.

Antibiotic treatment of lung infection and stopping smoking may also help to reduce lung haemorrhaging.

However, none of these can reverse permanent kidney damage and so for patients who have suffered this, renal transplant once the disease has subsided may be the only option.

Epidemiology

Goodpasture’s syndrome is rare. In European populations between half and one case presents per million people per year. It is rarer than this 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. Males are 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 haemorrhage 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 put on increases their risk of infection with a number of serious or fatal diseases.

ee also

* HLA-DR#DR2

References

External links

* [http://www.antibodypatterns.com/gbm.php GBM antibodies: immunofluorescence image]