Clinical Features

  • Most common symptomatic primary immunodeficiency (1 in 25-50,000)
  • Usually diagnosed in adults 20-40 years old, with 6-8 year delay in diagnosis
  • Due to overlap with transient hypogammaglobulinemia of infancy, diagnosis of CVID in children is made at >4 years old

CVID complications.png


  • In a series of patients, features included
    • Infections (94%), typically bacterial sinopulmonary
      • B-cells inhibited in their ability to develop into class-switched memory and plasma cells
      • History of shingles, PCP pneumonia, severe zoster may be due to deficiencies in T-cell response (even with normal labs)
    • Increased risk for hematologic or organ-specific autoimmunity (29%), e.g. ITP and hemolytic anemia
    • Chronic lung disease (29%), bronchiectasis (11%)
    • GI inflammatory disease, e.g. IBD (15%), malabsorption (6%)
    • Systemic granulomatous disease (10%, or 8-22% of CVID patients)
    • Liver disease (9%)
    • Lymphoma, lymphoid hyperplasia (8%)
    • Other malignancies such as gastric cancer (7%)

  • Clinical phenotypes:
    • No disease related complications (~2/3)
    • Disease related complications (~1/3)
      • Cytopenias
      • Lymphoproliferation
      • Enteropathy




Evaluation (Cunningham-Rundles)

  • Diagnosis based on:
    1. Low IgG (generally <400 mg/dL), IgA, and/or IgM levels
      • Consider repeating to confirm accurate result
    2. Deficiency of antibody production (lack of protective vaccination titers)
      • To fully validate the immune defect, obtain antibody titers to:
        • Tetanus/diphtheria toxoids
        • H. influenzae (hib)
        • Measles, mumps, rubella
        • Varicella
        • Pneumococcus
      • Also consider titers to hepatitis A or B after vaccination, influenza virus, isohemagglutinins (if available, and the blood type is known)
      • Note that in primary hypogammaglobulinemia, there is typically a low IgG level and low vaccination titers, vs. secondary hypogammaglobulinemia where the vaccination titers are rarely low
    3. An absence of any other defined immunodeficiency state
      • Routes: consider CF and complement defects
  • Additional workup
    • CBC with differential
    • T, B, NK cell counts
    • Complete chemistries
    • If signs of lung disease, complete PFT and a chest CT
    • If signs of GI disease, other tests as needed

  • Note that chronic oral steroid use (usually >5 mg/day) can lead to reduced IgG levels, which may be reversed by steroid abstinence
  • Other medications linked to suppression of antibody responses include:
    • Antirheumatic agents
      • Azathioprine
      • Cyclophosphamide
      • D-penicillamine
      • Gold
      • Sulfasalazine
    • Anticonvulsants - have been associated with selective isotype deficiency or losses among all isotypes, and can require months to years of avoidance to return to normal immunoglobulin levels
      • Carbamazepine
      • Levetiracetam
      • Oxcarbazepine
      • Phenytoin

Management

  • IVIG
  • Monitoring CVID patients on IVIG
    • Immunoglobulin levels at 6 month intervals
    • CBC and complete chemistries yearly
    • Lung functions yearly
    • CT chest3-4 years, and only if lung disease suspected or lung functions not normal


References