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) (also known as Acquired hypogammaglobulinemia^[1]) is a group of 20–30 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]

Contents 1 Causes and types 2 Clinical Features 3 Diagnosis 4 Associated conditions 5 Treatment 5.1 Reactions 6 Research 7 Epidemiology 8 History 9 References 10 External links

[edit] 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 provoke the immune defect, due to genetic predisposition, but this has not been clarified.

[edit] Clinical Features

Signs and Symptoms of CVID include:

• Hypogammaglobulinemia: low levels of immunoglobulin G (IgG), immunoglobulin A (IgA) and/or immunoglobulin M (IgM).
• Recurrent and chronic infections, particularly intestinal infections with Giardia lamblia. Other infections include upper respiratory tract infection such as bronchitis and sinusitis. These infections respond to antibiotics but recur upon discontinuation of the medications.
• Bacterial overgrowth in the intestines.
• Viral infections that usually respond to antivirals. These viral infections may manifest as sinusitis, tonsilitis, epiglottitis, dermatological abscesses/boils (often, but not exclusively, facial and axillary), pneumonia, bronchitis, pleurisy, stomach/intestinal infections, colds, influenza, shingles or conjunctivitis.
• Chronic diarrhoea (often arises as a result of "minor" intestinal infections, including protozoan and parasitic infections).
• Chronic swelling of the lymph glands.
• Enlarged spleen.
• Atrophic gastritis with pernicious anemia.
• Nodular lymphoid hyperplasia of the intestine. This finding can be mistaken for intestinal lymphoma.
• Increased intestinal permeability (i.e. leaky gut).
• Villous atrophy in the small intestine, which can resemble coeliac disease and cause diarrhoea and malabsorption.
• Increased incidence of inflammatory bowel disease.
• Bronchiectasis (lung tissue damage as a result of repeated chest infections) leading to shortness of breath.
• Poor titer levels in response to vaccination. Responsiveness may be tested after administration of polysaccharide and non-polysaccharide coated pathogens (e.g. streptococci and tetanus respectively).
• Polyarthritis, or joint pain, spread across most joints, but specifically fingers, wrists, elbows, toes, ankles and knees.
• Fatigue.
• Children may show a "failure to thrive" - they may be underweight and underdeveloped compared with "normal" peers.
• Malabsorption.
• Weight loss.

[edit] 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,^[6] and sometimes considered a wastebasket diagnosis.^[7]

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

[edit] 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.

[edit] Treatment

Treatment usually consists of immunoglobulin therapy, which is an injection of human antibodies harvested from blood 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.

[edit] Reactions

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

• anaphylactic shock (very rare)
• hives (rare)
• 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 minimised 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).

[edit] 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.

[edit] 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.

[edit] History

Janeway et al. (1953) is generally credited with the description of the first case of CVID.^[12]

[edit] References

[edit] 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)
• Maker of SCIG product

v • d • e Immune disorders: Lymphoid and complement immunodeficiency (D80-D85, 279) Primary Antibody/humoral (B) Hypogammaglobulinemia X-linked agammaglobulinemia · Transient hypogammaglobulinemia of infancy Dysgammaglobulinemia IgA deficiency · IgG deficiency · IgM deficiency · Hyper IgM syndrome (2, 3, 4, 5) · Wiskott-Aldrich syndrome · Hyper-IgE syndrome Other Common variable immunodeficiency · ICF syndrome Cell-mediated (T) thymic hypoplasia: hypoparathyroid (Di George's syndrome) · euparathyroid (Nezelof syndrome, Ataxia telangiectasia) peripheral: Purine nucleoside phosphorylase deficiency · Hyper IgM syndrome (1) Severe combined (B+T) x-linked: X-SCID autosomal: Adenosine deaminase deficiency · Omenn syndrome · ZAP70 deficiency · Bare lymphocyte syndrome Acquired AIDS Lymphocytopenia Idiopathic CD4+ lymphocytopenia Complement deficiency C1-inhibitor (Angioedema/Hereditary angioedema) · Complement 2 deficiency lymphocyte navs: cells/physio, immunodeficiency/immunoproliferative immunoglobulin/neoplasia, proc