Common Variable Immunodeficiency (CVID)
Common Variable Immunodeficiency (CVID) is a primary immunodeficiency characterized by low immunoglobulin levels, impaired antibody production, and increased susceptibility to recurrent infections, with additional complications including autoimmune disorders, gastrointestinal disease, and malignancies. 1, 2
Definition and Diagnostic Criteria
CVID is defined by:
- Low serum IgG levels (below normal range for age)
- Low IgA and/or IgM levels
- Impaired specific antibody production to vaccines or infections
- Exclusion of other causes of hypogammaglobulinemia
- Age >4 years (diagnosis not appropriate before this age) 1
- Normal or reduced B cell numbers in peripheral blood 1
Laboratory findings typically show:
- Reduced levels of at least 2 immunoglobulin isotypes
- Poor antibody response to vaccines (particularly polysaccharide antigens)
- B-cell abnormalities on flow cytometry 2
Epidemiology
- Prevalence: 1 in 25,000 to 1 in 50,000 individuals worldwide 3
- Most common symptomatic primary antibody deficiency 4
- Typically presents in young adulthood (20s-30s), but can occur at any age 3
- Only 10% of cases have an identified genetic cause 3
Clinical Manifestations
Infectious Complications
- Recurrent sinopulmonary infections (most common presentation)
- Bronchitis and pneumonia (can lead to bronchiectasis in 10-20% of patients) 1
- Otitis media
- Gastrointestinal infections (Giardiasis, Campylobacter jejuni, Salmonella) 1
- Viral enteritis (CMV, norovirus, parechovirus) 1
Non-infectious Complications
Pulmonary:
- Bronchiectasis (10-20% of patients)
- Granulomatous and lymphocytic interstitial lung disease (GLILD) (10% of patients)
- Asthma-like presentation (10-15% of patients) 1
Gastrointestinal (20-25% of patients):
- Chronic gastritis
- Pernicious anemia
- Lymphoid nodular hyperplasia
- Villous atrophy
- Inflammatory bowel disease
- Enteropathy 1
Autoimmune disorders (20% of patients):
Liver abnormalities (40% of patients):
- Elevated alkaline phosphatase
- Nodular regenerative hyperplasia (can lead to portal hypertension) 1
Lymphoproliferative disorders:
- Lymphadenopathy
- Splenomegaly
- Increased risk of lymphoma 1
Classification
B-cell subset analysis by flow cytometry can help classify CVID patients (EUROclass):
- Decreased switched memory B cells correlates with granulomatous disease and splenomegaly
- Expansion of CD21low B cells correlates with splenomegaly and autoimmunity
- Expansion of transitional B cells correlates with lymphadenopathy 1
Management
Immunoglobulin Replacement Therapy
- Primary treatment: IgG replacement therapy (400-600 mg/kg every 3-4 weeks)
- Higher doses (600 mg/kg/month) for patients with bronchiectasis or pulmonary complications 2
- Available as intravenous (IVIG) or subcutaneous (SCIG) formulations 2
- Regular monitoring of IgG trough levels every 6-12 months 2
Antimicrobial Therapy
- Aggressive antimicrobial treatment for infections
- Prophylactic antibiotics for patients with recurrent infections despite adequate IgG replacement 1
Monitoring and Follow-up
- Regular pulmonary function testing
- Monitoring of liver function tests
- Gastrointestinal evaluation when symptoms present
- Vigilance for autoimmune diseases and malignancies 1, 2
Special Considerations
- Good syndrome: CVID with thymoma requires thymoma excision 1
- Stem cell transplantation: May be considered for patients with malignancy or severe organ damage 1
- Joint care: Patients with bronchiectasis should be under joint care of immunologist and respiratory specialist 2
Prognosis
Prognosis depends on:
- Early diagnosis and treatment
- Presence and severity of complications
- Non-infectious complications (particularly GLILD, enteropathy, and malignancy) associated with increased mortality 1
Early diagnosis and prompt initiation of immunoglobulin replacement therapy are crucial to prevent permanent organ damage and improve quality of life 2.