Goodpasture syndrome: what is it, symptoms, treatment, prognosis

What is Goodpasture Syndrome?

Goodpasture Syndrome (or anti-GBM disease) Is a rare autoimmune diseasecharacterized by inflammation of the filtering structures (glomeruli) of the kidneys (glomerulonephritis) and excessive bleeding into the lungs (pulmonary hemorrhage). Autoimmune syndromes occur when the body's natural defenses (antibodies) against invasion or "foreign" organisms begin to attack the body's own tissues, often for unknown reasons.

Symptoms of Goodpasture Syndrome include recurring episodes coughing up blood (hemoptysis), shortness of breath (dyspnea), fatigue, chest pain and / or an abnormally low level of circulating red blood cells (anemia). In many cases, anti-GBM disease can result in an inability of the kidneys to process waste products from the blood and excrete them in the urine (acute renal failure). In some cases of Goodpasture's syndrome, the sufferers had an upper respiratory infection before the disorder developed. The exact cause of anti-GBM disease is not known.

Signs and symptoms

The main symptoms of Goodpasture syndrome are excessive bleeding into the lungs (pulmonary bleeding) and inflammation of the filtering structures (glomeruli) or kidneys (glomerulonephritis). In some cases, an upper respiratory tract infection may precede the development of the disorder. Common symptoms associated with the syndrome may include:

• fever;
• nausea;
• fatigue.

Pulmonary bleeding can lead to episodes of people coughing up blood (hemoptysis). The severity of this symptom can range from a few spots to an excessive amount of blood. Those affected may also have difficulty breathing (dyspnea), apathy, chest pain, dry harsh sound from the throat, and / or frequent coughing. In rare cases, those affected may experience abnormal accumulation fluid (edema) in the lung tissue. Pulmonary abnormalities usually occur before or simultaneously with renal abnormalities in about 70 percent of cases.

Inflammation of the filtering structures (glomeruli) of the kidneys (glomerulonephritis) can make the kidneys unable to process waste products from the blood and excrete them in urine (acute renal failure). Kidney failure usually results in a decrease in the amount of urine produced by the body. Additional symptoms associated with kidney failure may include:

• pallor of the skin;
• drowsiness;
• nausea and / or vomiting.

Severe complications of kidney failure include bleeding into the stomach and / or a decrease in the number of circulating red blood cells (anemia).

In rare cases, people may have high blood pressure (arterial hypertension) and / or pain and swelling of the joints (arthritis). In some cases, symptoms of Goodpasture's syndrome may recur after treatment.

Causes and risk factors

Goodpasture syndrome develops due to unknown causes. Environmental factors such as chemical exposure to hydrocarbons, cigarette smoke, or infections such as flumay play a role in the development of the disorder. It is not known why simple infections can progress to anti-GBM disease in some people. When an infection occurs, the body's natural defenses (antibodies) fight off invading organisms (such as viruses or bacteria). At autoimmune diseases antibodies attack healthy tissue for no apparent reason. Pulmonary hemorrhage is often associated with smoking in individuals with Goodpasture's syndrome.

In Goodpasture syndrome, certain antibodies (antibodies against the glomerular membrane [anti-GBM]) can be produced and circulated in the blood. These antibodies can damage the thin membranes that line the lungs and kidneys, or tiny blood vessels (capillaries) in the lungs and kidneys.

In some cases, people with Goodpasture syndrome may have an association with human leukocyte antigens (LAS). LAC are proteins that play an important role in the body's immune system; they influence the outcome of organ transplantation and appear to influence a person's susceptibility to certain diseases. However, the implications of such conclusions are not fully understood.

Anti-GBM disease has been reported in more than one family member (e.g. siblings) in several cases, confirming the possibility of genetic susceptibility as a factor in some cases. A person who is genetically predisposed to the disorder carries the gene (or genes) for the disorder, but it cannot be expressed unless caused or "activated" under certain circumstances, such as due to certain environmental factors (multifactorial inheritance).

Affected populations

Goodpasture's syndrome is a rare autoimmune disorder that appears to affect men more often than women. The age of onset is usually between 20 and 30 years, but people of any age can be affected.

The disease was first identified in 1919. Since then, about 600 cases have been reported in the medical literature.

In Russia, anti-GBM disease is a rare disease; approximately 1-2% of all cases of rapidly progressive glomerulonephritis are secondary to this disorder.

Symptomatic disorders

Symptoms of the following disorders may be similar to those of Goodpasture's syndrome. Comparisons can be useful for differential diagnosis:

• Wegener's granulomatosis (granulomatosis with polyangiitis) is a rare disease characterized by inflammation of the blood vessels (vasculitis), which leads to damage to various body systems, most often the respiratory tract and kidneys. Symptoms may include ulceration of the mucous membranes in the nose with a secondary bacterial infection, persistent runny nose, sinus pain, and chronic middle ear infection (otitis media), potentially leading to hearing loss. In some cases, renal impairment can progress to renal failure, a serious complication. If the lungs are affected, coughing, coughing up blood (hemoptysis), and inflammation of the thin membrane that lines the outside of the lungs and the inside of the lung may be present. The exact cause of Wegener's granulomatosis is unknown.
• Idiopathic pulmonary hemosiderosis — lung disease, similar to Goodpasture's syndrome. Victims may also have secondary iron deficiency anemia. It appears to occur primarily in young children and lack the antibody response found in Goodpasture's syndrome. The exact cause of this disorder is unknown (idiopathic).
• Bacterial endocarditis Is a disease of the lungs and kidneys with clinical similarities to Goodpasture's syndrome, but also affecting the heart. Bacterial endocarditis caused by a bacterial infection. Those affected may develop heart murmuras well as blockage of the arteries (embolism). Skin lesions enlargement of the spleen and intermittent high fever are other symptoms associated with this disorder.

Diagnostics

The diagnosis of anti-GBM disease can be suspected based on identifying characteristic physical signs (eg, pulmonary hemorrhage and glomerulonephritis). The diagnosis can be confirmed by detecting the presence of antiglomerular basement membrane antibodies in the body. In some cases, affected people may have blood (hematuria) and / or protein (proteinuria) in the urine.

Standard treatments

Mild forms of Goodpasture Syndrome can be treated with drugs that suppress or interfere with the effectiveness of the body's immune system (immunosuppressants). Corticosteroids, such as prednisone, may be given to control bleeding in the lungs (pulmonary bleeding).

Many patients can be treated with plasmapheresis. This procedure is a method of removing unwanted substances (toxins, harmful antibodies and metabolic substances) from the blood. The blood is removed from the patient and the blood cells are separated from the plasma. The patient's plasma is then replaced with another human plasma, and the blood is transfused into the patient. Plasmapheresis is often given in combination with corticosteroids.

In severe and recurring cases of Goodpasture Syndrome, those affected may be treated with a procedure that removes waste from the blood (dialysis). In the most severe cases, a kidney transplant may be required.

Forecast

In the past, anti-GBM disease was usually fatal. Aggressive therapy with plasmapheresis, corticosteroids and immunosuppressants significantly improved the prognosis. With this approach, the 5-year survival rate exceeds 80%, and less than 30% of patients require long-term dialysis.

Patients with serum creatinine levels greater than 4 mg / dL, oliguria, and more than 50% of crescents on kidney biopsy rarely recover. They usually progress to end-stage renal disease, which requires prolonged dialysis. In a retrospective analysis of patients with anti-GBM disease who began renal replacement therapy for end-stage renal disease (ESRD) in Australia and New Zealand (ANZDATA register), median survival was 5.93 years, with mortality predicted in older ages and a history of pulmonary hemorrhage.

Lilia Khabibulina/ article author