Rare Hematology News

Disease Profile

Goodpasture syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Elderly

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ICD-10

M31.0+ N08.5*

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Rapidly progressive glomerulonephritis with pulmonary hemorrhage; Anti-glomerular basement membrane antibody disease; Glomerulonephritis pulmonary hemorrhage;

Categories

Blood Diseases; Kidney and Urinary Diseases; Lung Diseases

Summary

Goodpasture syndrome is an autoimmune disease that affects the lungs and kidneys and is characterized by pulmonary alveolar hemorrhage (bleeding in the lungs) and a kidney disease known as glomerulonephritis. Some use the term "Goodpasture syndrome" for the findings of glomerulonephritis and pulmonary hemorrhage and the term "Goodpasture disease" for those patients with glomerulonephritis, pulmonary hemorrhage, and anti-GBM antibodies.[1][2] Currently, the preferred term for both conditions is “anti-GBM antibody disease”.[3] Circulating antibodies are directed against the collagen of the part of the kidney known as the glomerular basement membrane (GBM), resulting in acute or rapidly progressive glomerulonephritis. Antibodies also attack the collagen of the air sacs of the lung (alveoli) resulting in bleeding of the lung (pulmonary hemorrhage). Symptoms may include general body discomfort or pain, bleeding from the nose and/or blood in the urine, respiratory problems, anemia, chest pain, and kidney failure. Anti-GBM disease is thought to result from an environmental insult (smoking, infections, exposure to certain drugs) in a person with genetic susceptibility, such as a specific human leukocyte antigen (HLA) type. Diagnosis is confirmed with the presence of anti-GBM antibody in the blood or in the kidney. The treatment of choice is plasmapheresis in conjunction with prednisone and cyclophosphamide.[1][2][3][4]

Symptoms

The signs and symptoms related to the lung disease may include:[2]

  • Bleeding from the nose (hemoptysis), which occur before the kidney disease in about two thirds of cases and is present in 82%-90% of the adults
  • Cough (40%-60% of the cases)
  • Breathing difficulty (dyspnea) in about 57%-72% of the cases
  • Pallor (the most common clinical sign)
  • Crackles and rhonchi (low-pitched, rattling sound)
  • Heart murmur (20-25% of the cases)
  • Enlarged liver (hepatomegaly)
  • Edema

Prompt diagnosis of pulmonary hemorrhage is vital because it is the principal cause of early death in patients with anti-GBM antibody disease.

The signs and symptoms related to the kidney disease may include:[2]

  • Blood in urine (hematuria)
  • Protein in urine (proteinuria)
  • Abnormal kidney function
  • Hypertension (high blood pressure) can be present but is not very common (reported in 4-17% of adult patients and very rare in children)

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Anemia
Low number of red blood cells or hemoglobin
0001903
Autoimmunity
Autoimmune disease
Autoimmune disorder

[ more ]

0002960
Chest pain
0100749
Cough
Coughing
0012735
Glomerulopathy
0100820
Hemoptysis
Coughing up blood
0002105
Persistence of primary teeth
Delayed loss of baby teeth
Failure to lose baby teeth
Retained baby teeth

[ more ]

0006335
Proteinuria
High urine protein levels
Protein in urine

[ more ]

0000093
Pulmonary infiltrates
Lung infiltrates
0002113
Respiratory insufficiency
Respiratory impairment
0002093
Vasculitis
Inflammation of blood vessel
0002633
30%-79% of people have these symptoms
Hematuria
Blood in urine
0000790
5%-29% of people have these symptoms
Arthralgia
Joint pain
0002829
Arthritis
Joint inflammation
0001369
Fever
0001945
Myalgia
Muscle ache
Muscle pain

[ more ]

0003326
Purpura
Red or purple spots on the skin
0000979
Renal insufficiency
Renal failure
Renal failure in adulthood

[ more ]

0000083
Retinal detachment
Detached retina
0000541
1%-4% of people have these symptoms
Cytoplasmic antineutrophil antibody positivity
0032230
Pulmonary hemorrhage
0040223
Percent of people who have these symptoms is not available through HPO
Anti-glomerular basement membrane-antibody positivity
0033030
Autosomal recessive inheritance
0000007
Dyspnea
Trouble breathing
0002094
Glomerulonephritis
0000099

Cause

There is still much to learn about the cause of Goodpasture syndrome. It is thought that a combination of genetic and environmental factors, such as cigarette smoke, inhaled hydrocarbons, and viruses play a role in the development of this autoimmune condition.[1]

In autoimmune disorders, the body makes antibodies that attacks its own tissues. In the case of Goodpasture syndrome, antibodies form against a certain type of protein called collagen. Collagen is present in many tissues in the body. In Goodpasture syndrome, collagen in the alveoli (tiny air sacs in the lungs) and in the glomeruli (the filtering units of the kidney) is attacked. This leads to bleeding in the air sacs and inflammation in the glomeruli of the kidney. Symptoms of the antibody attack may include shortness of breath, cough, bloody sputum, blood and protein in the urine, and kidney failure.[5]

Genetic predisposition to Goodpasture syndrome involves the human leukocyte antigen (HLA) system. The HLA system is involved in helping our immune system know the difference between "self" and "non-self." Human leukocyte antigens determine a person's tissue type. Each person has 3 pairs of major HLA antigens. We inherit one set from each of our parents (and pass one of our two sets on to each of our children).[6]

Below we have provided some facts regarding HLA antigens and Goodpasture syndrome:[1]

  1. A certain HLA antigen, HLA-DR15 (previously known as HLA-DR2), is found in 88% of patients with Goodpasture syndrome, as compared to 25-32% of those without it.
  2. People with Goodpasture syndrome who have two types of HLA antigens: HLA-B8 and HLA-DR2 tend to have a worse prognosis.
  3. HLA antigen types HLA-DR7 and HLA-DR1 are thought to confer some protection against developing Goodpasture syndrome.

Diagnosis

A diagnosis of anti-GBM antibody disease is made when a patient presents with lung hemorrhage, urinary findings such as proteinuria (protein in the urine) and hematuria (blood in the urine), and circulating anti–glomerular basement membrane (anti-GBM) antibodies.[1]

A kidney biopsy is the best method for detecting anti-GBM antibodies in tissues. Some recommend doing a kidney biopsy in all cases while others suggest only doing the biopsy when the diagnosis is still in doubt. Light microscopy usually shows a feature known as crescentic glomerulonephritis, whereas immunofluorescence microscopy demonstrates a finding that is characteristic of this disease, of “linear deposition of IgG along the glomerular capillaries”. Patients in whom the diagnosis of lung hemorrhage is still unclear should have bronchoscopy.[1]

In children, the most consistent feature is ‘crescentic glomerulonephritis’ with either circulating anti-GBM antibodies or linear staining of IgG on the immunofluorescence. Clinical features include severe kidney malfunction in all patients and lung hemorrhage in half of them.[2]

It is essential to promptly diagnose pulmonary hemorrhage because this is the principal cause of early death when untreated.[1][2]

Conditions that affect the lung and kidney (pulmonary-renal syndromes) are important to consider and need to be ruled out when the diagnosis is not confirmed. These include granulomatosis with polyangiitis (Wegener granulomatosis), Churg-Strauss syndrome, systemic lupus erythematosus, microscopic polyangiitis, rheumathoid arthritis, IgA-mediated disorders (eg, IgA nephropathy or Henoch-Schönlein purpura) and of immune complex–mediated renal disease (eg, essential mixed cryoglobulinemia), community-acquired pneumonia and undifferentiated connective-tissue disease.[2] In children, other diseases that also need to be ruled out are Behcet Syndrome, hemosiderosis (bleeding into the lung and iron accumulation) and Legionella infection.[2]

See an image of the kidney and glomerulus.

Treatment

The treatment of choice is plasmapheresis in conjunction with prednisone and cyclophosphamide. The three main goals for the treatment are:[1][2][3] 

  1. Rapidly remove circulating antibody, primarily by plasmapheresis.
  2. Stop further production of antibodies using immunosuppression with medications, namely, corticosteroids (e.g., prednisone) and cyclophosphamide. In children, plasmapheresis is done together with corticosteroids and cyclophosphamide. The duration of the immunosuppressive treatment varies but is typically 6 months for corticosteroids and 3 months for cyclophosphamide.
  3. Remove offending agents that may have initiated the antibody production.

After hospital discharge, patients require long-term regular visits for monitoring kidney function and for immunosuppressive therapy. If kidney function does not return, dialysis is continued indefinitely and the patient should be referred for kidney transplantation.

If the person smokes, it is recommended he or she stop. Also, if the patient is exposed to hydrocarbon in his or her occupation, he or she should consider changing jobs, as exposure to hydrocarbon has been shown to increase a person's chances of disease recurrence.[2]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Providing General Support

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    Where to Start

      In-Depth Information

      • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss Goodpasture syndrome. Click on the link to view a sample search on this topic.

        References

        1. Valentini RP. Pediatric Anti-GBM Disease (Goodpasture Syndrome). Medscape Reference. March 5, 2015; https://www.emedicine.com/ped/TOPIC888.HTM.
        2. Kathuria P. Goodpasture Syndrome. Mescape Reference. 2016; https://emedicine.medscape.com/article/240556-overview.
        3. Anti-Glomerular Basement Membrane Disease. Medical Subject Headings. 2008; https://id.nlm.nih.gov/mesh/D019867.html.
        4. Pusey CD & Kalluri R. Pathogenesis and diagnosis of anti-GBM antibody (Goodpasture's) disease. UpToDate. January 13, 2016; https://www.uptodate.com/contents/pathogenesis-and-diagnosis-of-anti-gbm-antibody-goodpastures-disease.
        5. Goodpasture syndrome. MedlinePlus. 9/22/2015; https://www.nlm.nih.gov/medlineplus/ency/article/000142.htm.
        6. Stem Cell Transplant for Cancer. American Cancer Society. 5/11/2016; https://www.cancer.org/acs/groups/cid/documents/webcontent/003215-pdf.pdf.

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