Common variable immunodeficiency

Common variable immunodeficiency
Classification and external resources
ICD-10	D83
ICD-9	279.06
OMIM	240500
DiseasesDB	3274
eMedicine	ped/444 derm/870
MeSH	D017074

Common variable immunodeficiency (CVID) (also known as Acquired hypogammaglobulinemia^[1]) is a group of approximately 150 primary immunodeficiencies (PIDs), which have a common set of symptoms (including hypogammaglobulinemia)^[2] but which have different underlying causes.

Common variable immunodeficiency is the most commonly encountered primary immunodeficiency.^[3]

Causes and types

CVID is believed to be a genetically determined primary immune defect; however, the underlying causes are different. The result of these defects is that the patient doesn't produce sufficient antibodies in response to exposure to pathogens. As a result, the patient's immune system fails to protect them against common bacterial and viral (and occasionally parasitic and protozoan) infections. The net result is that the patient is susceptible to illness.

In CVID, the B cells are affected. In severe combined immunodeficiency (SCID), a more severe condition than CVID, diagnosed in infancy, both parts of the immune system (the cellular and humoral system) are affected, hence its classified as combined immunodeficiency.

CVID appears to include a number of defects, some of which have been identified. For the majority, the genetic causes are still unknown.

ICOS, TACI and CD19 have been identified as candidates.^[4][5]

It is possible that environmental agents or a virus provoke the immune defect, due to genetic predisposition, but this has not been clarified.

Types include:

Type	OMIM	Gene
CVID1	607594	ICOS
CVID2	240500	TACI
CVID3	613943	CD19
CVID4	613494	TNFRSF13C
CVID5	613495	CD20
CVID6	613496	CD81

Clinical Features

Signs and Symptoms of CVID include:

• Hypogammaglobulinemia: low levels of immunoglobulin G (IgG), immunoglobulin A (IgA) and/or immunoglobulin M (IgM).
• Poor titer response to vaccination with polysaccharide and protein antigens (e.g. pneumococci, tetanus, and diphtheria).
• Recurring infections involving the ears, eyes, sinuses, nose, bronchi, lungs, skin, GI tract, joints, bones, CNS, parotid glands, etc. These infections respond to antibiotics but recur upon discontinuation of the medications. Bronchiectasis can occur from severe and recurrent lung infections.
• Viral infections that usually respond to antivirals.
• Enlarged lymph nodes, Enlarged spleen.
• Fatigue.
• Abdominal pain, Bloating, Nausea, Vomiting, Diarrhea, Weight loss.
• Malabsorption.
• Helicobacter pylori, Giardiasis, Cryptosporidiosis, Small bowel bacterial overgrowth syndrome, etc.
• Atrophic gastritis with pernicious anemia and achlorhydria.
• Nodular lymphoid hyperplasia of the GI tract.
• Villous atrophy of the small intestine, which can resemble celiac disease.
• Inflammatory bowel disease.
• Aphthous stomatitis.
• Increased intestinal permeability.
• Polyarthritis, or joint pain, spread across most joints, but specifically fingers, wrists, elbows, toes, ankles and knees. In some cases, Mycoplasma can be the cause.
• Children may show a "failure to thrive" - they may be underweight and underdeveloped compared with "normal" peers.
• Candida infection of the lungs.
• Anxiety and depression, usually as a result of dealing with the other symptoms.^[6]

Diagnosis

Diagnosis of CVID is usually made by demonstrating low levels of immunoglobulins in the serum. Diagnosis may be made rapidly, but is often delayed; it is usually made in the second or third decade of life after referral to an immunologist.

Diagnosis of CVID is a diagnosis of exclusion.^[7]

It presents similar to X-linked agammaglobulinemia, but the conditions can be distinguished with flow cytometry.^[8]

Associated conditions

As with several other immune cell disorders, CVID may predispose to lymphoma or possibly stomach cancer.^[9] There also appears to be a predilection for autoimmune diseases, with a risk of up to 25%. Autoimmune destruction of platelets or red blood cells are the most common of these.

Treatment

Treatment usually consists of immunoglobulin therapy, which is an injection of human antibodies harvested from plasma donations:

• intravenous immunoglobulin (IVIG, most common treatment in the US)^[10]
• subcutaneous immunoglobulin G (SCIG, relatively new treatment in the US and UK)
• intramuscular immunglobulin (IMIG, less effective, painful)

This is not a cure, but it strengthens immunity by ensuring that the patient has "normal" levels of antibodies, which helps to prevent recurrent upper respiratory infections.

IG therapy can't be used if the patient has anti-IgA antibodies but in this case, products low in IgA can be used; subcutaneous delivery also is a means of permitting such patients to have adequate antibody replacement.

IVIG treatment can be received by patients with a complete IgA deficiency if the IgA is completely removed from the treatment.

Reactions

Some CVID patients may experience reactions to IG therapies; reactions may include:

• anaphylactic shock (very rare)
• hives (rare)
• chills
• difficulty breathing
• headache (relatively common, may be relieved by an antihistamine, paracetamol/acetaminophen, or an anti-inflammatory (naproxen, advil, aspirin)
• nausea (common in IVIG)
• fever (common in IVIG and rare in SCIG)
• aseptic meningitis (rare)
• severe fatigue (common in IVIG)
• muscle aches and pain, or joint pain
• thrombotic events (rare)
• swelling at the insertion site (common in SCIG)

Patients should not receive therapy if they are fighting an active infection as this increases the risk of reaction. Also, patients changing from one brand of product to another may be at higher risk of reaction for the first couple of treatments on the new brand.

Reactions can be minimized by taking an antihistamine and/or hydrocortisone and some paracetamol/acetaminophen/anti-inflammatory (naproxen, advil, aspirin) prior to treatment; patients should also be thoroughly hydrated and continue to drink water before, after and during treatment (if possible). IVIG should be prepared soon before IVIG infusion. Patient using a heating pad or warm blanket can help alleviate chills.

Research

Research is currently focussing on genetic analysis, and in differentiating between the various different disorders in order to allow a cure to be developed. Cures are likely to be genetic in nature, repairing faulty genes and allowing the individual to start producing antibodies. Funding for research in the US is provided by the National Institutes of Health. Key research in the UK is funded by the Primary Immunodeficiency Association (PiA), and funding is raised through the annual Jeans for Genes campaign.

Epidemiology

CVID has an estimated prevalence of about 1:50,000.^[11] The typical patient is between 20 and 40, and males and females are equally affected. About 20% of patients are diagnosed in childhood.

History

Charles Janeway, Sr. is generally credited with the first description of a case of CVID in 1953.^[12]

References

1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. ^:84
2. ^ "common variable immunodeficiency" at Dorland's Medical Dictionary
3. ^ Park MA, Li JT, Hagan JB, Maddox DE, Abraham RS (August 2008). "Common variable immunodeficiency: a new look at an old disease". Lancet 372 (9637): 489–502. doi:10.1016/S0140-6736(08)61199-X. PMID 18692715. http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)61199-X. 
4. ^ Salzer U, Neumann C, Thiel J, et al. (2008). "Screening of functional and positional candidate genes in families with common variable immunodeficiency". BMC Immunol. 9: 3. doi:10.1186/1471-2172-9-3. PMC 2268914. PMID 18254984. http://www.biomedcentral.com/1471-2172/9/3. 
5. ^ Blanco-Quirós A, Solís-Sánchez P, Garrote-Adrados JA, Arranz-Sanz E (2006). "Common variable immunodeficiency. Old questions are getting clearer". Allergol Immunopathol (Madr) 34 (6): 263–75. doi:10.1157/13095875. PMID 17173844. http://db.doyma.es/cgi-bin/wdbcgi.exe/doyma/mrevista.pubmed_full?inctrl=05ZI0102&rev=105&vol=34&num=6&pag=263. 
6. ^ Sanger, David E. [http://www.pia.org.uk/psychosocialstudysummary.htm "An Investigation of Coping and Psychosocial Functioning in Persons with Common Variable Immunodeficiency (CVID)"], Barts and The London NHS Trust, 2003, accessed August 7, 2011.
7. ^ Common Variable Immunodeficiency : Article by C Lucy Park at eMedicine
8. ^ Common Variable Immunodeficiency at Merck Manual of Diagnosis and Therapy Professional Edition
9. ^ Mellemkjaer L, Hammarstrom L, Andersen V, et al. (2002). "Cancer risk among patients with IgA deficiency or common variable immunodeficiency and their relatives: a combined Danish and Swedish study". Clin. Exp. Immunol. 130 (3): 495–500. doi:10.1046/j.1365-2249.2002.02004.x. PMC 1906562. PMID 12452841. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1906562. 
10. ^ Pourpak Z, Aghamohammadi A, Sedighipour L, et al. (2006). "Effect of regular intravenous immunoglobulin therapy on prevention of pneumonia in patients with common variable immunodeficiency" (abstract). J Microbiol Immunol Infect 39 (2): 114–20. PMID 16604243. http://www.jmii.org/content/abstracts/v39n2p114.php. 
11. ^ Common Variable Immunodeficiency : Article by Robert A Schwartz at eMedicine
12. ^ Janeway CA, Apt L, Gitlin D. Agammaglobulinemia. Trans Assoc Am Physicians 1953;66:200-2. PMID 13136263

External links

• Primary Immunodeficiency Association (UK)
• Immune Deficiency Foundation (US)
• Michigan Immunodeficiency Foundation (US)
• Immune Deficiencies Foundation of Australia
• Immune Deficiencies Foundation of New Zealand
• IPOPI (International Patient Organisation for Patients with Primary Immunodeficiency)
• Canadian Immunodeficiencies Patient Organization (Canada)
• Dutch Patient Organisation for Primary Immunodeficiencies (SAS)
• GeneReviews/NCBI/NIH/UW entry on Common Variable Immune Deficiency Overview
• Maker of SCIG product