Common variable immunodefiency

Common variable immunodefiency
ICD-10	D83
ICD-9	279.06
OMIM	240500
DiseasesDB	3274
eMedicine	ped/444  derm/870
MeSH	D017074

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Common variable immunodeficiency (CVID) is a group of 20-30 primary immunodeficiencies (PIDs) which have a common set of symptoms (including hypogammaglobulinemia) but with different underlying causes.

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. Both parts of the immune system (the cellular and humoral system) are affected, hence its classification as a 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.

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

Symptoms

Symptoms of CVID are:

• hypogammaglobulinemia, or low levels of immunoglobulin G (IgG), immunoglobulin A (IgA) and/or immunoglobulin M (IgM).
• lack of normal levels of antibody in the serum is part of the diagnosis
• polyarthritis, or joint pain, spread across most joints, but specifically fingers, wrists, elbows, toes, ankles and knees
• chronic infections. (most common symptom) Specifically: upper respiratory tract infection - e.g. bronchitis, sinusitis which respond to antibiotics but return or recur.
• Viral infections that usually respond to antivirals, sinusitis, tonsilitis, epiglottitis, dermatological abscesses/boils (often, but not exclusively, facial and axillary), pneumonia, bronchitis, pleurisy, stomach/intestinal infections, colds, influenza, shingles, conjunctivitis
• Tiredness
• 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
• bacterial overgrowth of the intestine.
• increased intestinal permeability (i.e. leaky gut)
• villous atrophy in the small intestine, which can resemble coeliac disease and cause diarrhoea and malabsorption
• chronic diarrhoea (often arises as a result of "minor" intestinal infections, including protozoan and parasitic infections)
• 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)
• children may show a "failure to thrive" - they may be underweight and underdeveloped compared with "normal" peers
• patients may lose weight

Diagnosis

Diagnosis is often delayed; and diagnosis is often made in the second or third decade of life after referral to an immunologist.

It is a diagnosis of exclusion, and sometimes considered a wastebasket diagnosis.

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

Associated conditions

As with several other immune cell disorders, CVID may predispose to lymphoma or possibly stomach cancer. 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 commonest of these.

Treatment

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

• intravenous immunoglobulin (IVIG, most common treatment)
• subcutaneous immunoglobulin G (SCIG, relatively new therapy)
• 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.

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)
• fever (common)
• aseptic meningitis (rare)
• severe fatigue
• muscle aches and pain, or joint pain
• thrombotic events (rare)

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).

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 is about 1:50,000. The typical patient is between 20 and 40, and males and females are equally affected. About 20% of patients are diagnosed in childhood.

History

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

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)