Common variable immunodeficiency

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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) is one in a group of approximately 150 primary immunodeficiencies. Its main feature is hypogammaglobulinemia. CVID is the most commonly encountered primary immunodeficiency.[1]

Causes and types[edit]

CVID is shown to be a genetically determined primary immune defect; however, the underlying causes are different. The result of these defects is that the patient does not 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 in normal numbers but do not make an effective amount of immunoglobulins. In severe combined immunodeficiency (SCID), a more severe condition than CVID, diagnosed in infancy, B and T cells are affected. SCID patients have deficiencies in both parts of the immune system (the cellular and humoral system), and therefore, SCID is classified as a combined immunodeficiency. Approximately 10% CVID cases present with significant T cell involvement, with CD4 < 200 cells/mm3, in these cases CVID can be thought of as a combined immunodeficiency, and this is sometimes refereed to as late onset combined immunodeficiency (LOCID). The prognosis for LOCID tends to be poorer than classic CVID.

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.[2][3]

Mutation of the NFKB2 gene has been linked to Common variable immunodeficiency (CVID) as the cause. The frequency of NFKB2 mutation in CVID population is, however, yet to be established.[4]

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 613493 CD19
CVID4 613494 TNFRSF13C
CVID5 613495 CD20
CVID6 613496 CD81

Clinical features[edit]

Signs and symptoms of CVID include:

Diagnosis[edit]

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.[6] Diagnoses to exclude include loss of protein from the kidneys or reduced antibody production secondary to chronic lymphocytic leukemia or multiple myeloma. It presents similar to X-linked agammaglobulinemia, but the conditions can be distinguished with flow cytometry.[7]

Associated conditions[edit]

As with several other immune cell disorders, CVID may predispose to lymphoma or possibly stomach cancer.[8] 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[edit]

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)[9]
  • subcutaneous immunoglobulin G (SCIG, relatively new treatment in the US and UK)
  • intramuscular immunglobulin (IMIG, less effective, painful)
Intragam infusion (intravenous immunoglobulin) as treatment for Common Variable Immunodeficiency in Australia, 2013

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 cannot 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[edit]

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) (More common in patients with SLE)
  • 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[edit]

Research is currently focussing on genetic analysis, and in differentiating between the various 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 was previously funded by the Primary Immunodeficiency Association (PiA) until its closure in January 2012,[10] and funding is raised through the annual Jeans for Genes campaign.

Epidemiology[edit]

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[edit]

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

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ Chen, Karin; Emily M. Coonrod, Attila Kumánovics, Zechariah F. Franks, Jacob D. Durtschi, Rebecca L. Margraf, Wilfred Wu, Nahla M. Heikal, Nancy H. Augustine, Perry G. Ridge, Harry R. Hill, Lynn B. Jorde, Andrew S. Weyrich, Guy A. Zimmerman, Adi V. Gundlapalli, John F. Bohnsack, Karl V. Voelkerding (17 October 2013). "Germline Mutations in NFKB2 Implicate the Noncanonical NF-κB Pathway in the Pathogenesis of Common Variable Immunodeficiency.". The American Journal of Human Genetics. doi:10.1016/j.ajhg.2013.09.009. Retrieved 18 October 2013. 
  5. ^ Sanger, David E. "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.
  6. ^ Common Variable Immunodeficiency : Article by C Lucy Park at eMedicine
  7. ^ Common Variable Immunodeficiency at Merck Manual of Diagnosis and Therapy Professional Edition
  8. ^ 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. 
  9. ^ 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. 
  10. ^ http://www.ukpin.org.uk/home/PIA-archive/index.htm
  11. ^ Common Variable Immunodeficiency : Article by Robert A Schwartz at eMedicine
  12. ^ Janeway CA, Apt L, Gitlin D (1953). "Agammaglobulinemia". Trans Assoc Am Physicians 66: 200–2. PMID 13136263. 
  • Moris G., Garcia-Monco JC (1999). "The Challenge of Drug-Induced Aseptic Meningitis". Archives of Internal Medicine 159 (11): 1185–1194. doi:10.1001/archinte.159.11.1185. PMID 10371226.  (IVIG and Aseptic Meningitis, association with SLE)

External links[edit]