CVID

Common variable immunodeficiency (CVID) is the most frequently diagnosed clinically significant primary immunodeficiency in adults and children. It is a heterogeneous condition with defective antibody production, resulting in low serum immunoglobulins and poor responses to vaccines. Onset is typically in adolescence or early adulthood but may occur at any age. Diagnosis requires evidence of hypogammaglobulinemia with impaired antibody responses after excluding secondary causes.

CVID features recurrent infections, especially of the sinopulmonary tract, including otitis, sinusitis, and pneumonia. Gastrointestinal issues and malabsorption occur in some patients. Autoimmune and inflammatory complications, lymphoproliferation, and bronchiectasis may develop; there is an increased risk of lymphoma and other malignancies.

The condition reflects defective B cell differentiation and antibody production. B cell numbers are often normal or reduced, with impaired class switching and reduced switched memory B cells. Genetic causes are diverse; several genes have been implicated (eg, TACI, BAFFR, CD19, ICOS, LRBA, PIK3CD, PIK3R1, NFKB1), but many cases lack an identifiable mutation and appear sporadic; familial forms may be autosomal dominant or recessive.

Diagnosis relies on low IgG with low IgA and/or IgM, poor or absent vaccine responses, and exclusion of secondary causes. Immunophenotyping and assessment of antibody responses support the diagnosis. Management centers on immunoglobulin replacement therapy (IVIG or SCIG), plus prompt treatment of infections and complications. Non-live vaccines are recommended, with monitoring of antibody responses.

CVID affects about 1 in 25,000 to 50,000 people. Immunoglobulin replacement reduces infections and improves survival, but morbidity from chronic lung disease, autoimmunity, and cancer remains. Early diagnosis and ongoing specialist care are important for favorable outcomes.