Common variable immunodeficiency (CVID) is a primary humoral immunodeficiency disorder, characterized by impaired B cell differentiation and deficiencies in some or all classes of immunoglobulins. It is not a diagnosis in itself but rather incorporates several disorders, characterized by impaired antibody production.
Diagnostic criteria for CVID are as follows:
Probable CVID
- ≥2 standard deviations (SD) below mean for age in serum IgG & IgA and
- onset of immunodeficiency >2 years of age and
- absent isohemagglutinins and/or poor response to vaccinations and
- no other cause of hypogammaglobulinemia
Possible CVID
- ≥2 SD below mean for age in one of the major immunoglobulin isotypes (IgM, IgG & IgA) and
- onset of immunodeficiency >2 years of age and
- absent isohemagglutinins and/or poor response to vaccinations and
- no other cause of hypogammaglobulinemia1
Epidemiology
CVID is rare, affecting only 1:50,000 to 1:25,000 people. However, it is the most common symptomatic primary antibody disorder.2 It has no gender predilection.2 CVID has a bimodal distribution, with peaks during childhood and between 30-40 years.2
Pathology
Most cases of CVID are sporadic. Only approximately 20% are inherited.3 Although patients may have normal amounts of B cells, the number of switched memory B cells may be severely reduced. These cells are crucial in recall antibody responses.4 T cell abnormalities are also common.
Clinical presentation
Symptoms and signs in patients with CVID are highly variable. Patients are at increased risk of both infectious and non-infectious diseases within multiple organ systems.
Recurrent infections, typically bacterial, are very common, especially within the upper and lower respiratory tracts. Otitis, conjunctivitis, meningitis, hepatitis, enteritis/colitis and osteomyelitis/septic arthritis have also been described.5
Non-infectious diseases associated with CVID include autoimmune disorders, polyclonal lymphocytic infiltration and malignancy – both lymphoid and other. Cytopenias, i.e. autoimmune thrombocytopenia purpura, haemolytic anaemia and other autoimmune diseases, i.e. pernicious anaemia, atrophic gastritis, thyroiditis and vitiligo are commonly associated with CVID. Polyclonal lymphocytic infiltration associated with CVID can result in enteropathy, granulomata, hepatosplenomegaly and lymphadenopathy. Malignancy especially non-Hodgkin’s lymphoma but also breast and gastric cancer are seen with increased incidence in this popoulation.3, 5, 6
The most common thoracic findings in patients with CVID are, in order of decreasing frequency:
1. Infection
2. Bronchiectasis
3. Granulomatous disease
Clinical significance
Pulmonary infections, i.e. pneumonia and bronchitis and chronic lung disease result in recurrent hospitalizations and are associated with significant morbidity and mortality among patients with CVID.7