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, requiring prompt diagnosis and treatment with immunoglobulin replacement therapy to improve quality of life and reduce infection-related complications.

Diagnosis and Presentation

The condition typically presents with recurrent bacterial infections, particularly of the respiratory and gastrointestinal tracts, and is diagnosed based on hypogammaglobulinemia (significant reduction in >2 isotypes of serum immunoglobulin) and defective antibody production, as well as abnormalities in B cells, such as alterations in memory B cells or isotype switched B cells, as noted in the study by 1.

Treatment and Management

Treatment primarily consists of immunoglobulin replacement therapy, usually administered intravenously (IVIG) at doses of 400-600 mg/kg every 3-4 weeks or subcutaneously (SCIG) at 100-200 mg/kg weekly, as recommended by 1.

• Patients should also receive prompt antibiotic treatment for infections, with choices guided by culture results when possible.
• Prophylactic antibiotics may be considered for those with frequent infections.
• Vaccination with killed or inactivated vaccines is recommended, though live vaccines should be avoided.
• Regular monitoring of immunoglobulin levels and clinical response is essential.

Complications and Associated Conditions

CVID results from defects in B-cell differentiation, leading to impaired antibody production despite normal B-cell numbers, and has variable presentation and severity, with some patients also experiencing autoimmune disorders, granulomatous disease, or malignancies, particularly lymphoma, as discussed in 1 and 1.

• Approximately 20% to 25% of patients with CVID have gastrointestinal complications, including chronic gastritis, lymphoid nodular hyperplasia, and inflammatory bowel disease.
• Autoimmune diseases, such as autoimmune cytopenias, occur in approximately 20% of patients with CVID.
• Nonmalignant and malignant lymphoproliferative diseases can also occur in patients with CVID, and stem cell transplantation may be considered in severe cases, as noted in 1. Early diagnosis and consistent immunoglobulin replacement therapy significantly improve quality of life and reduce infection-related complications in patients with CVID, as supported by the studies 1, 1, and 1.

From the Research

Definition and Characteristics of Common Variable Immunodeficiency (CVID)

• Common Variable Immunodeficiency (CVID) is a primary immunodeficiency caused by the lack of B cell differentiation into plasma cells, leading to decreased serum immunoglobulins 2.
• It is characterized by hypogammaglobulinemia due to an unknown molecular defect in immune regulation 3.
• CVID is a heterogeneous disorder with variable severity, ranging from mild forms of infections to chronic progressive complications 3, 4.

Clinical Manifestations of CVID

• The primary clinical manifestations of CVID are recurrent infections that may lead to structural damage of affected organs 3.
• Patients with CVID are predisposed to recurrent infections, and are more likely to develop certain cancers and autoimmune diseases 2.
• Noninfectious systemic manifestations, such as granulomatous inflammation, interstitial lung disease, inflammatory bowel disease, lymphoproliferation, and developing malignancies, can also occur 3, 4, 5.

Diagnosis and Treatment of CVID

• Diagnosis of CVID can be challenging due to its heterogeneous and unspecific symptoms 6.
• Treatment of CVID typically involves immunoglobulin replacement therapy, antibiotics, immunosuppressants, and hematopoietic stem cell transplantation 6.
• Intravenous immunoglobulin (IVIG) therapy has dramatically changed the prognosis of CVID, and home subcutaneous Ig therapy has further improved the quality of life of patients 3.
• Noninfectious complications of CVID can affect different organs and progress despite advanced therapies, and single or multiorgan transplantation may be a treatment option for patients with end-stage organ involvement refractory to medical therapy 5.