Common variable immunodeficiency
| Common variable immunodeficiency | |
| ICD-10 | D83 |
|---|---|
| ICD-9 | 279.06 |
| OMIM | 240500 |
| DiseasesDB | 3274 |
| MeSH | D017074 |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]
Synonyms and keywords: CVID; common variable hypogammaglobulinaemia; non-familial hypogammaglobulinaemia; acquired hypogammaglobulinemia; immunodeficiency, common variable; late-onset immunoglobulin deficiency
Overview
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.
Historical Perspective
Charles Janeway et al (1953) is generally credited with the description of the first case of CVID.[1]
Classification
Types of CVID include:
| Type | Gene |
|---|---|
| CVID1 | ICOS |
| CVID2 | TACI |
| CVID3 | CD19 |
| CVID4 | TNFRSF13C |
| CVID5 | CD20 |
| CVID6 | CD81 |
Pathophysiology
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. It is possible that environmental agents provoke the immune defect, due to genetic predisposition, but this has not been clarified.
Causes
Differentiating Common Variable Immunodeficiency from other Diseases
CVID should be differentiated from the following diseases:
Epidemiology and Demographics
Prevalence
CVID has an estimated prevalence ranging from a low of 2 per 100,000 to a high of 4 per 100,000 with an average of 3 per 100,000.
Age
- The typical patient is between 20 and 40 years age.
- About 20% of patients are diagnosed in childhood.
Gender
Gender is not associated with an increased risk of common variable immunodeficiency.
Race
Race is not associated with an increased risk of common variable immunodeficiency.
Natural History, Complications and Prognosis
Natural History
All patients have acute and recurrent infections because of the level of immunodeficiency in CVID.
Complications
3 complications are possible in CVID. They include:
- Recurrent infections
- Autoimmune phenomena - Vitiligo, autoimmune hepatitis, primary biliary cirrhosis, hemolytic anemia
- Malignancy - Lymphomas, gastric cancer, malignant melanoma
- Rheumatoid arthritis
- Vitiligo
- Thrombocytopenia
- Neutropenia
- Hemolytic anemia
- Pernicious anemia
- Malabsorption
- Autoimmune hepatitis
- Primary biliary cirrhosis
- Atrophic gastritis
- Inflammatory bowel disease
Prognosis
Diagnosis
History and Symptoms
Symptoms of CVID are:
- 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 reoccur. Common infective organisms include:
- Viral infections that usually respond to antivirals, (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
- Shortness of breath - due to bronchiectasis (lung tissue damage as a result of repeated chest infections)
- Patients may lose weight
- Children may show a "failure to thrive" - they may be underweight and underdeveloped compared with "normal" peers
- Diarrhoea and malabsorption - due to villous atrophy in the small intestine, which can resemble coeliac disease, intestinal infections, including protozoan and parasitic infections, bacterial overgrowth of the intestine
- Increased incidence of inflammatory bowel disease
- Abdominal pain, bloating, nausea, vomiting, diarrhea, weight loss.
Physical Examination
Head
Abdomen
Laboratory Findings
- Complete blood count and differential count - lymphocytopenia
- Blood culture
- Hypogammaglobulinemia, or low levels of immunoglobulin G (IgG), IgA and/or IgM. Lack of normal levels of antibody in the serum is part of the diagnosis
- 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)
Diagnosis is often delayed; 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 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.
Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
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.
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)
- 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).
Surgery
Primary Prevention
Secondary Prevention
References
- ↑ Janeway CA, Apt L, Gitlin D. Agammaglobulinemia. Trans Assoc Am Physicians 1953;66:200-2. PMID 13136263
External links
- Primary Immunodeficiency Association (UK)
- Immune Deficiency 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)