Disease Profile

Common variable immunodeficiency

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 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

46,215 - 5,135

Europe Estimated

Age of Onset

All ages

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ICD-10

D83.0 D83.1 D83.2 D83.8 D83.9

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.

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)

CVID; Common variable hypogamma-globulinemia; Hypogamma-globulinemia, acquired;

Categories

Congenital and Genetic Diseases; Immune System Diseases; Rare Cancers

Summary

Common variable immunodeficiency (CVID) is a group of disorders characterized by low levels of a type of protein known as immunoglobulins (Ig). Because of low level of Ig, the immune system cannot make antibodies that fight bacteria, viruses or other toxins in the body.[1] This leads to frequent infections, particularly in the sinuses, lungs, and digestive tract.[2][3] Symptoms most commonly begin in early adulthood but can occur at any age. While in most cases the cause of CVID is unknown, a genetic change has been found in about one-third of cases.[4] This condition is diagnosed based on the symptoms, specific laboratory testings, and exclusion of other disorders. Treatment for CVID includes Ig replacement therapy, which stops the cycle of recurrent infections.[2][3] The long term outlook for people with CVID varies depending on the severity of the symptoms and any underlying conditions.[2]

Symptoms

The symptoms of common variable immunodeficiency (CVID) may be different from person to person. Some people may be more severely affected than others, even people who have the same form. Not everyone with common variable immunodeficiency will have the same symptoms.

The most common signs and symptoms of CVID include [2][3]:

Low levels of proteins that help the immune system work (immunoglobulins)
Recurrent infections especially of the lungs and digestive systems
Autoimmunity (body attacks healthy organs and tissues)
Liver involvement 
Increased risk for malignancy

About 20-30% of people with CVID will develop autoimmunity, and about 10% of people with CVID will have liver involvement.[2]

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
Autoimmune thrombocytopenia
0001973
Brachycephaly
Short and broad skull
0000248
Chronic otitis media
Chronic infections of the middle ear
0000389
Decreased circulating antibody level
0004313
Immunodeficiency
Decreased immune function
0002721
Lymphopenia
Decreased blood lymphocyte number
Low lymphocyte number

[ more ]

0001888
Pneumonia
0002090
Recurrent bronchitis
0002837
30%-79% of people have these symptoms
Abnormality of the liver
Abnormal liver
Liver abnormality

[ more ]

0001392
Anal atresia
Absent anus
0002023
Bronchiectasis
Permanent enlargement of the airways of the lungs
0002110
Elevated hepatic transaminase
High liver enzymes
0002910
Hemolytic anemia
0001878
Lymphadenopathy
Swollen lymph nodes
0002716
Purpura
Red or purple spots on the skin
0000979
Splenomegaly
Increased spleen size
0001744
5%-29% of people have these symptoms
Arthralgia
Joint pain
0002829
Emphysema
0002097
Failure to thrive in infancy
Faltering weight in infancy
Weight faltering in infancy

[ more ]

0001531
Gastrointestinal stroma tumor
0100723
Lymphoma
Cancer of lymphatic system
0002665
Neutropenia in presence of anti-neutropil antibodies
0001904
Posterior pharyngeal cleft
0006783
Restrictive ventilatory defect
Stiff lung or chest wall causing decreased lung volume
0002091
Vasculitis
Inflammation of blood vessel
0002633
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
B lymphocytopenia
Low B cell count
0010976
Conjunctivitis
Pink eye
0000509
Decreased circulating IgA level
0002720
Decreased circulating IgG level
0004315
Decreased circulating total IgM
0002850
Diarrhea
Watery stool
0002014
Hepatomegaly
Enlarged liver
0002240
Impaired T cell function
T-cell dysfunction
0005435
Recurrent bacterial infections
Bacterial infections, recurrent
Frequent bacterial infections
Increased susceptibility to bacterial infections
Recurrent major bacterial infections

[ more ]

0002718
Recurrent otitis media
Recurrent middle ear infection
0000403
Recurrent pneumonia
0006532
Recurrent sinusitis
0011108

Cause

Common variable immunodeficiency (CVID) is thought to be the result of a combination of genetic and environmental factors. In most cases, the exact cause of CVID is unknown.[1][4]

At least 20 different genes have been associated with CVID.[4] Some families with this condition have a gene mutation that has not yet been found in any other family. Genes associated with CVID are generally involved in the development and function of immune system cells (B cells) which help protect against infection.

Diagnosis

Common variable immunodeficiency is diagnosed based on symptoms (chronic, recurrent infections) and laboratory tests that look for decreased levels of specific immunoglobulins.[4] Because there are many causes of immune deficiency, other conditions must be ruled out. Several groups have published criteria for diagnosing CVID and other immune deficiencies.[5][6]

Treatment

The main treatment for common variable immunodeficiency (CVID) is Ig replacement therapy, which stops the cycle of recurrent infections. Ig may be taken intravenously (through the vein) or subcutaneously (by injection). Adverse reactions to Ig must be monitored during therapy. In some people with CVID and severe autoimmune disease, steroids or other immunosuppressive drugs in addition to Ig therapy may be needed.[2]

There are multiple forms of Ig replacement therapy available and people with CVID should speak to their health care providers to determine which therapy may be best for their situation.

Detailed information about the management of CVID can be viewed on Medscape Reference's Web site.

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

    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

      • The Immune Deficiency Foundation has an information page on this topic. Click on the link above to view the information page.
      • Genetics Home Reference (GHR) contains information on Common variable immunodeficiency. This website is maintained by the National Library of Medicine.
      • 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.

        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 Common variable immunodeficiency. Click on the link to view a sample search on this topic.

          References

          1. Common variable immune deficiency. Genetics Home Reference. 2016; https://ghr.nlm.nih.gov/condition/common-variable-immune-deficiency.
          2. Song J. Lleo A, Yang GX, Zhang W, Bowlus CL, Gershwin ME, Leung PSC. Common variable immunodeficiency and liver involvement. Clin Rev Allergy Immunol. Dec 2018; 55(3): 340-51. Dec 2018; 55(3):340-51. https://www.ncbi.nlm.nih.gov/pubmed/28785926.
          3. Common variable immune deficiency. National Organization for Rare Disorders (NORD). Updated 2017; https://rarediseases.org/rare-diseases/common-variable-immune-deficiency/.
          4. Ameratunga R, Lehnert K, Woon ST, Gillis D, Bryant VL, Slade C, Steele R. Review: Diagnosing Common Variable Immunodeficiency Disorder in the Era of Genome Sequencing. Clin Rev Allergy Immunol. Apr 2018; 54(2):261-268. https://www.ncbi.nlm.nih.gov/pubmed/29030829.
          5. Ameratunga R1, Woon ST, Gillis D, Koopmans W, Steele R. New diagnostic criteria for common variable immune deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin. Clin Exp Immunol. 2013 Nov;174(2):203-11. Nov 2013; 174(2):203-11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828823/.
          6. Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol. 1999; 93:190-197. https://www.ncbi.nlm.nih.gov/pubmed/10600329.
          7. Karin Engelhardt, Bodo Grimbacher, P Herholz. Common Variable immunodeficiency. Orphanet. June, 2010; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=1572.