What is Common Variable Immunodeficiency (CVID)?

From the Guidelines

Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by low levels of immunoglobulins (antibodies) and an increased susceptibility to infections, typically presenting with recurrent bacterial infections, particularly of the respiratory tract, sinuses, and gastrointestinal system, and is diagnosed based on hypogammaglobulinemia, defective antibody production, and abnormalities in B cells, such as alterations in memory B cells or isotype switched B cells, as noted in studies 1.

Key Characteristics of CVID

• Low levels of immunoglobulins (antibodies)
• Increased susceptibility to infections
• Recurrent bacterial infections, particularly of the respiratory tract, sinuses, and gastrointestinal system
• Hypogammaglobulinemia (significant reduction in >2 isotypes of serum immunoglobulin)
• Defective antibody production
• Abnormalities in B cells, such as alterations in memory B cells or isotype switched B cells

Diagnosis and Management

• Diagnosis is based on clinical presentation, laboratory findings, and exclusion of other primary and secondary causes of antibody deficiency
• Management centers on immunoglobulin replacement therapy, which is administered either intravenously (IVIG) at doses of 400-600 mg/kg every 3-4 weeks or subcutaneously (SCIG) at 100-200 mg/kg weekly, as recommended in studies 1
• Prompt antibiotic treatment for infections is essential, often requiring longer courses or prophylactic antibiotics in patients with bronchiectasis or chronic sinusitis
• Patients should receive all non-live vaccines according to schedule, though live vaccines are contraindicated
• Regular monitoring includes immunoglobulin levels, complete blood counts, and screening for complications like autoimmune disorders, granulomatous disease, and malignancies, particularly lymphoma, as noted in studies 1

Quality of Life and Prognosis

• Early diagnosis and consistent treatment significantly improve quality of life and prevent complications
• CVID has a genetic basis in about 10-20% of cases, with mutations affecting B-cell development and antibody production
• The condition varies widely in severity, and prognosis is generally good with appropriate treatment, although some patients may experience significant morbidity and mortality due to complications, as reported in studies 1

From the Research

Definition and Characteristics of Common Variable Immunodeficiency (CVID)

• CVID is a primary immunological disease with variable severity, ranging from mild forms of infections to chronic progressive complications 2.
• It is characterized by humoral immunodeficiency resulting in increased susceptibility to infections and diminished responses to protein and polysaccharide vaccines 3.
• The hallmark of this disorder is hypogammaglobulinemia due to an unknown molecular defect in immune regulation 2.

Clinical Manifestations and Complications

• The primary clinical manifestations are recurrent infections that may lead to structural damage of affected organs 2.
• CVID patients may develop additional autoimmune, inflammatory or lymphoproliferative complications, such as thrombocytopenia, granulomatous inflammation, interstitial lung disease, inflammatory bowel disease, lymphoproliferation, and malignancies 4, 5.
• Any organ can be involved, and therefore a multidisciplinary approach to the management of this disorder is essential 2.

Diagnosis and Treatment

• Diagnosis of CVID is based on hypogammaglobulinemia, low production of specific antibodies, and disorders of cellular immunity 6.
• The standard therapy includes replacement of specific antibodies with human immunoglobulin, prophylaxis, and symptomatic therapy of infections 6.
• Immunoglobulin replacement therapy, antibiotics, immunosuppressants, and hematopoietic stem cell transplantation are used to treat CVID 4.
• Regular immunoglobulin substitution has a supportive role in patients with CVID and chronic thrombocytopenia, but does not prevent the occurrence of autoimmune thrombocytopenia episodes or exacerbations of chronic form 6.