Common variable immunodeficiency (acquired or adult-onset hypogammaglobulinemia) is characterized by low immunoglobulin (Ig) levels with phenotypically normal B cells that can proliferate but do not develop into Ig-producing cells. Patients have recurrent sinopulmonary infections. Diagnosis is based mainly on serum Ig levels. Treatment includes prophylactic IgG replacement therapy and antibiotics for infection.
(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 known 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). Impaired T-cell immunity also may be present in some patients.
Autoimmune disorders can occur, including autoimmune thrombocytopenia, autoimmune hemolytic anemia or pernicious anemia, systemic lupus erythematosus, Addison disease, thyroiditis, rheumatoid arthritis, and alopecia areata. Patients also may develop malabsorption, nodular lymphoid hyperplasia of the gastrointestinal tract, systemic granulomatous inflammation, lymphocytic interstitial pneumonia, splenomegaly, and/or bronchiectasis. Gastric carcinoma or lymphoma occurs in 10% of patients.
Symptoms and Signs of CVID
Patients with CVID have recurrent sinopulmonary infections causing sinus congestion and pressure, cough, shortness of breath, chest pain, mucus production, fevers, chills, and/or lymphadenopathy.
Diagnosis of CVID
Measurement of serum immunoglobulin (Ig) and antibody titers
Flow cytometry for T-cell and B-cell subsets
Serum protein electrophoresis
Diagnosis of common variable immunodeficiency is suggested by recurrent sinopulmonary infections and requires all of the following:
Low (at least 2 standard deviations below the mean) levels of IgG
Low levels of IgA, IgM, or both
Impaired response to immunizations (usually both protein and polysaccharide vaccines)
Exclusion of other immunodeficiency disorders
Antibody or autoantibody levels should not be measured if patients have been treated with IV immune globulin (IVIG) within the previous 6 months because any detected antibodies may be 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 of CVID
Prophylactic immune globulin (IgG) replacement therapy
Antibiotics for infections
Disease-specific treatment for comorbid immunodeficiency disorders such as granulomatous lung disease or associated autoimmune disease
Treatment of CVID consists of immune globulin and antibiotics as needed to treat infection.
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
