(See also Overview of Immunodeficiency Disorders and Approach to the Patient With an Immunodeficiency Disorder.)
Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder that involves humoral immunity deficiencies. It includes several different molecular defects, but in most patients, the molecular defect is unknown. Mutations are sporadic in > 90% of cases. CVID is clinically similar to X-linked agammaglobulinemia in the types of infections that develop, but onset tends to be later (typically between ages 20 and 40). T-cell immunity may be impaired in some patients.
Symptoms and Signs
Patients with CVID have recurrent sinopulmonary infections.
Autoimmune disorders (eg, autoimmune thrombocytopenia, autoimmune hemolytic anemia or pernicious anemia, systemic lupus erythematosus, Addison disease, thyroiditis, rheumatoid arthritis, alopecia areata) can occur, as can malabsorption, nodular lymphoid hyperplasia of the gastrointestinal tract, systemic granulomatous inflammation, lymphocytic interstitial pneumonia, splenomegaly, and bronchiectasis. Gastric carcinoma and lymphoma occur in 10% of patients.
Diagnosis
Diagnosis of common variable immunodeficiency is suggested by recurrent sinopulmonary infections and requires all of the following:
Antibody levels should not be measured if patients have been treated with IV immune globulin (IVIG) within the previous 6 months because any detected antibodies are from the IVIG.
B-cell and T-cell quantification by flow cytometry is done to exclude other immunodeficiency disorders and to distinguish CVID from X-linked agammaglobulinemia, multiple myeloma, and chronic lymphocytic leukemia; findings may include low numbers of class-switched memory B cells or CD21+ cells. Serum protein electrophoresis is done to screen for monoclonal gammopathies (eg, myeloma), which may be associated with reduced levels of other immunoglobulin isotypes.
Spirometry, complete blood count, liver tests, and a basic metabolic panel are recommended yearly to check for associated disorders. If lung function changes, CT should be done.
Because mutations are usually sporadic, screening relatives is not recommended unless there is a significant family history of CVID.
Treatment
Treatment of CVID consists of immune globulin and antibiotics as needed to treat infection.
Rituximab, tumor necrosis factor (TNF)-alpha inhibitors (eg, etanercept, infliximab), corticosteroids, and/or other treatments may be required to treat complications such as autoimmune disorders, lymphoid interstitial pneumonia, and granulomatous inflammation.
Recent trials have confirmed the benefit of prophylactic antibiotics in select patients with antibody deficiency (1).
Treatment reference
-
1. Milito C, Pulvirenti F, Cinetto F, et al: Double-blind, placebo-controlled, randomized trial on low-dose azithromycin prophylaxis in patients with primary antibody deficiencies. J Allergy Clin Immunol 144:584–593. e7, 2019. doi: 10.1016/j.jaci.2019.01.051
