Rare Hematology News

Disease Profile

Autoimmune pulmonary alveolar proteinosis

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.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Adult

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ICD-10

J84.0

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)

PAP; Pulmonary alveolar lipoproteinosis acquired; PAP acquired;

Categories

Lung Diseases

Summary

Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare autoimmune lung disorder. It is the most common form (90% of the cases) of pulmonary alveolar proteinosis (PAP). Most cases affect adults between the ages of 20-50 years. Some people may not show symptoms, while others may have progressive difficulty breathing and shortness of breath upon exertion. Other signs and symptoms may include a dry, chronic cough; fatigue; weight loss; chest pain; and a general feeling of ill health. In rare cases, coughing up of blood, rounding and swelling of the tips of the fingers, and cyanosis may be present.[1] Autoimmune PAP is caused by an immune system malfunction, due to IgG antibodies that block the granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) effect. GM-CSF is a protein that regulates clearance of surfactant (a mix of protein and fat) by alveolar macrophages. The surfactant pile up in the air sacs of the lungs (alveoli), and eventually lead to an inability to breath.[1][2] The standard treatment is a procedure called lung lavage. A drug called GM-CSF might effectively treat aPAP.[2]

Other PAP forms include congenital PAP, a very rare form that occurs in some newborns, caused by disorders of surfactant production; hereditary PAP, where people are born with genetic mutations that destroy the function of the proteins (receptors) on alveolar macrophages that interact with GM-CSF; and, secondary PAP, which occur in people with another disease or dust exposure.[1][2]

Symptoms

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
Intraalveolar phospholipid accumulation
0006517
30%-79% of people have these symptoms
Abnormal circulating protein level
0010876
Abnormality of the upper respiratory tract
Upper respiratory tract issues
0002087
Autoimmune antibody positivity
0030057
Clubbing
Clubbing of fingers and toes
0001217
Cyanosis
Blue discoloration of the skin
0000961
Decreased DLCO
0045051
Dyspnea
Trouble breathing
0002094
Foam cells
0003651
Hypoxemia
Low blood oxygen level
0012418
Increased lactate dehydrogenase level
0025435
Restrictive ventilatory defect
Stiff lung or chest wall causing decreased lung volume
0002091
5%-29% of people have these symptoms
Cough
Coughing
0012735
Crackles
0030830
Crazy paving pattern on pulmonary HRCT
0025391
1%-4% of people have these symptoms
Anti-granulocyte-macrophage colony stimulating factor antibody positivity
0020050
Brain abscess
0030049
Chest pain
0100749
Fatigue
Tired
Tiredness

[ more ]

0012378
Fever
0001945
Hemoptysis
Coughing up blood
0002105
Inspiratory crackles
0031996
Lung abscess
0025044
Weight loss
0001824
Percent of people who have these symptoms is not available through HPO
Insidious onset
Gradual onset
0003587
Pneumonia
0002090
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

0002205
Sporadic
No previous family history
0003745

Treatment

The treatment of PAP varies from case to case depending upon the form of PAP and the age of an affected individual and severity of the disease. About one-third of individuals with idiopathic PAP (of unknown cause) will improve without treatment (spontaneous remission). 

Patients with moderate or severe respiratory problems due to autoimmune PAP can be treated by a whole lung lavage, a procedure in which one lung is cleansed with a salt solution while the other is pumped with pure oxygen. In some cases, the procedure may need to be performed once; in others it may need to be repeated many times over several years.[1] Generally, one lung is lavaged in the first procedure, followed by lavage of the opposite lung one to two weeks later.[1][3]

A treatment using recombinant granulocyte macrophage-colony stimulating factor (GM-CSF) given by nose, or with a subcutaneous injection is not approved for use in autoimmune PAP yet, but soon may be an effective option.[1][3][4] 

Lung transplantation has been used to treat adults with PAP as a last resort. According to the medical literature, in some cases, PAP has recurred in adults who have received lung transplantation.[1]

Treatment options for patients with secondary and hereditary PAP are less clear and depend in part on the specific cause. In secondary PAP, removal and avoidance of the causative agent (e.g., silica exposure) or treatment of the underlying disorder may improve symptoms.[1] For neonates with severe congenital PAP, lung transplantation is the only treatment that appears to improve outcome.[4][5]

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 Supporting this Disease

    Social Networking Websites

    • Yahoo Group is available for pulmonary alveolar proteinosis. You can connect with others through this forum. GARD does not monitor their messages, so please use your own discretion when using this group.

      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

      • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
      • The Merck Manuals Online Medical Library provides information on this condition for patients and caregivers.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
      • A page For Individuals with PAP is available from the PAP Foundation. This page covers frequently asked questions about the condition. Please note: this organization appears to be inactive, so the page may not be kept up-to-date.

        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 Autoimmune pulmonary alveolar proteinosis. Click on the link to view a sample search on this topic.

          References

          1. Pulmonary Alveolar Proteinosis. NORD. May 6, 2008; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/594/viewAbstract. Accessed 7/3/2011.
          2. Chang ED & King Jr. Talmadge. Causes, clinical manifestations, and diagnosis of pulmonary alveolar proteinosis in adults. UpToDate. January 3, 2017; https://www.uptodate.com/contents/causes-clinical-manifestations-and-diagnosis-of-pulmonary-alveolar-proteinosis-in-adults.
          3. Allen J. Blaivas. Pulmonary Alveolar Proteinosis. MedlinePlus. May 21, 2009; https://www.nlm.nih.gov/medlineplus/ency/article/000114.htm. Accessed 7/3/2011.
          4. Chan ED & King Jr TE. Treatment and prognosis of pulmonary alveolar proteinosis in adults. UpToDate. May, 2017; https://www.uptodate.com/contents/treatment-and-prognosis-of-pulmonary-alveolar-proteinosis-in-adults.
          5. Vece TJ. Pulmonary alveolar proteinosis in children. UpToDate. October 31, 2016; https://www.uptodate.com/contents/pulmonary-alveolar-proteinosis-in-children.

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