Common variable immunodeficiency

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

Causes and types

CVID's underlying causes are different, but the result of these are 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 protozoal) infections. The net result is that the patient is prone to illness. Both parts of the immune system (the cellular and humoral system) are affected, hence its classification as a combined immunodeficiency.

Because CVID is a catch-all diagnosis, which encompasses a number of as-yet undifferentiated disorders, the cause of each specific disorder is different so one can't identify a single common theme. Some cases appear to be genetic, similarly to severe combined immunodeficiency (SCID), some appear to be environmental in some way, some may be pathogenic (with Epstein-Barr virus implicated by some informal research). Most of the diagnoses are probably a combination of genetic predisposition along with a pathogenic or envirogenic trigger.

Symptomology

Symptoms of CVID are:

hypogammaglobulinemia, or low levels of immunoglobulin G (IgG)
many patients have low levels of immunoglobulin A (IgA) and immunoglobulin M (IgM)
polyarthritis, or joint pain, spread across most joints, but specifically fingers, wrists, elbows, toes, ankles and knees
repeated incidence of infections which respond to antibiotics or antivirals, specifically: upper respiratory tract infections (URTIs), sinusitis, tonsilitis, epiglottitis, dermatological abscesses/boils (often, but not exclusively, facial and axillary), pneumonia, bronchitis, pleurisy, stomach/intestinal infections, colds, influenza, shingles, conjunctivitis
Tiredness
atrophic gastritis with pernicious anemia
nodular lymphoid hyperplasia of the intestine. This finding can be mistaken for intestinal lymphoma
bacterial overgrowth of the intestine.
villous atrophy in the small intestine, which can resemble coeliac disease and cause diarrhoea and malabsorption
diarrhoea (often arises as a result of "minor" intestinal infections, including protozoal 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 normally takes in excess of two years, and diagnosis is often made in the second or third decade of life after referral to an immunologist.

As with several other immune cell disorders, CVID can predispose for some skin cancers and lymphoma. There also appears to be a predilection for autoimmune diseases. However, these appear to be relatively rare, with a risk of about 7%.

Treatment

Treatment usually consists of immunoglobulin therapy, either intravenous immunoglobulin (IVIG), subcutaneous immunoglobulin G (SCIG) or (less frequently) intramuscular immunglobulin (IMIG). This is not a cure, but does help to ensure the patient has "normal" levels of antibodies, which helps to prevent recurrent infections. IG therapy may be inappropriate if the patient has anti-IgA antibodies.

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

anaphylactic shock (very rare)
hives (rare)
headache (relatively common, relieved by an antihistamine and paracetamol/acetaminophen)

Patients should not receive therapy if they are fighting an active infection as this increases the risk of reaction.

Reactions can be minimised by taking an antihistamine and/or hydrocortisone and some paracetamol/acetaminophen 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. 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 a prevalence is about 1:50,000, meaning that approximately 1,200 patients in the UK probably have this diagnosis. The typical patient is middle-aged, and males and females are equally affected.

History

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

Reference

Janeway CA, Apt L, Gitlin D. Agammaglobulinemia. Trans Assoc Am Physicians 1953;66:200-2. PMID 13136263.

External links

Hypogammaglobulinemia

Immunology

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