Common variable immunodeficiency
|Common variable immunodeficiency|
|Classification and external resources|
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.
Causes and types
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.
It is possible that environmental agents or a virus provoke the immune defect, due to genetic predisposition, but this has not been clarified.
Signs and symptoms of CVID include:
- Hypogammaglobulinemia: low levels of immunoglobulin A (IgA), immunoglobulin G (IgG), and/or occasionally 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.
- Abdominal pain, Bloating, Nausea, Vomiting, Diarrhea, Weight loss.
- Helicobacter pylori, Giardiasis, Cryptosporidiosis, Small intestinal bacterial overgrowth, 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.
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. 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.
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 most common of these.
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)
- 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 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.
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) (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 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, and funding is raised through the annual Jeans for Genes campaign.
CVID has an estimated prevalence of 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.
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- 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
- Support and Discussion Forum for Primary Immunodeficiency including CVID, XLA, SCID, IgA Deficiency, Neutropenia, Goods Syndrome and Other Primary Immunodeficiencies