Goodpasture's syndrome
Encyclopedia
Goodpasture’s syndrome is a rare disease
characterized by glomerulonephritis
and hemorrhaging of the lung
s. 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.
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.
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.
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.
may also be useful, combined with tests for antibodies to neutrophil cytoplasmic antigens, which are also directed against the patient’s own proteins.
, 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
.
Renal failure is due to anti-glomerular basement membrane (anti-GBM).
s and immunosuppressant
s. 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.
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.
Rare disease
A rare disease, also referred to as an orphan disease, is any disease that affects a small percentage of the population.Most rare diseases are genetic, and thus are present throughout the person's entire life, even if symptoms do not immediately appear...
characterized by glomerulonephritis
Glomerulonephritis
Glomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease characterized by inflammation of the glomeruli, or small blood vessels in the kidneys...
and hemorrhaging of the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
s. Although many diseases can present with these symptoms, the name Goodpasture’s syndrome is usually reserved for the autoimmune disease
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
triggered when the patient’s immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
attacks Goodpasture antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
(a type II hypersensitivity
Type II hypersensitivity
In type II hypersensitivity the antibodies produced by the immune response bind to antigens on the patient's own cell surfaces...
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
Vanderbilt University
Vanderbilt University is a private research university located in Nashville, Tennessee, United States. Founded in 1873, the university is named for shipping and rail magnate "Commodore" Cornelius Vanderbilt, who provided Vanderbilt its initial $1 million endowment despite having never been to the...
, 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 coughCough
A cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes...
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
Hemoptysis
Hemoptysis or haemoptysis is the expectoration of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis is the expectoration (coughing up) of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis ...
). The patient may be anemic
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
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
Tobacco smoking
Tobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...
and those with damage from lung infection
Infectious disease
Infectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...
or exposure to fumes.
Kidney disease
The kidney portion of the disease mostly affects the glomeruliGlomerulus
A glomerulus is a capillary tuft that is involved in the first step of filtering blood to form urine.A glomerulus is surrounded by Bowman's capsule, the beginning component of nephrons in the vertebrate kidney. A glomerulus receives its blood supply from an afferent arteriole of the renal...
causing a form of nephritis
Nephritis
Nephritis is inflammation of the nephrons in the kidneys. The word "nephritis" was imported from Latin, which took it from Greek: νεφρίτιδα. The word comes from the Greek νεφρός - nephro- meaning "of the kidney" and -itis meaning "inflammation"....
. 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
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
spills into the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
causing hematuria
Hematuria
In medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...
, the volume of urine output decreases and urea
Urea
Urea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....
and other products usually excreted by the kidney are retained and build up in the blood. This is acute renal failure
Acute renal failure
Acute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...
. 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
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
and edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
(swelling caused by fluid retention). The kidney involvement usually presents as nephritic syndrome
Nephritic syndrome
Nephritic syndrome is a collection of signs associated with disorders affecting the kidneys, more specifically glomerular disorders. It is characterized by having small pores in the podocytes of the glomerulus, large enough to permit proteins and red blood cells to pass into the urine...
, i.e. hematuria, a reduced glomerular filtration rate, and high blood pressure. This is in contrast to nephrotic syndrome
Nephrotic syndrome
Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
, a rarer outcome of Goodpasture's, characterized by an abnormally large amount of protein in the urine (proteinuria
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
), 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 antibodiesAntibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
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 influenzaInfluenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
, 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
Paraquat
Paraquat is the trade name for N,N′-dimethyl-4,4′-bipyridinium dichloride, one of the most widely used herbicides in the world. Paraquat, a viologen, is quick-acting and non-selective, killing green plant tissue on contact. It is also toxic to human beings and animals...
.
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 corticosteroidCorticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s and immunosuppressant
Immunosuppressant
An immunosuppressant is any substance that performs immunosuppression of the immune system. They may be either exogenous, as immunosuppressive drugs, or endogenous, as ,e. g., testosterone...
s. 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
Apheresis
Apheresis is a medical technology in which the blood of a donor or patient is passed through an apparatus that separates out one particular constituent and returns the remainder to the circulation...
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
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
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 dialysisDialysis
In medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
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.