24. Common Variable Immunodeficiency (CVID)

  • This is the most frequent type of primary immunodeficiency and is characterized by defective antibody production; commonly occurs after the age of 18 months, with two incidence peaks between ages 1-5 years and 16-20 years, and often is not recognized until adulthood
  • CVID is heterogeneous. Serum IgG level is reduced usually to at least 2 SD below the mean for age. Most patients also have reduced IgA concentrations, and in 50% of patients, the IgM level is reduced
  • Most patients have a normal number of B cells but these B cells generally do not function and will not proliferate. T-cell dysfunction may also appear over time in patients with CVID
  • Mutations which disrupt B-cell development to cause antibody deficiency include Bruton's tyrosine kinase, Ig heavy chain and lambda 5/14.1 surrogate light chain loci, the latter being found in at least one human with CVID
  • Patients have recurrent sinopulmonary infections with H. influenzae, Moraxella catarrhalis, and S. pneumoniae, often leading to bronchiectasis
  • There is increased susceptibility to gastrointestinal infection with Giardia lamblia and Campylobacter jejuni, often causing chronic diarrhea and malabsorption
  • Autoimmune disorders, including ITP, autoimmune hemolytic anemia, neutropenia, and pernicious anemia are common in CIVD
  • Sarcoid-like (non-caseating) granulomata of the lungs, liver, spleen, and conjunctivae occur in CVID, as well as follicular hyperplasia of lymph nodes, diffuse nodular lymphoid hyperplasia of the intestine, and splenomegaly
  • There is an increased incidence of lymphoma (23x) and GI malignancies (50x).