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Common Variable Immunodeficiency (CVID)

By

James Fernandez

, MD, PhD, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University

Last full review/revision Apr 2021| Content last modified Apr 2021
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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.

Symptoms and Signs of CVID

Patients with CVID have recurrent sinopulmonary infections.

Autoimmune disorders (eg, autoimmune thrombocytopenia Immune Thrombocytopenia (ITP) Immune thrombocytopenia (ITP) is a bleeding disorder usually without anemia or leukopenia. Typically, it is chronic in adults, but it is usually acute and self-limited in children. Spleen size... read more Immune Thrombocytopenia (ITP) , autoimmune hemolytic anemia Autoimmune Hemolytic Anemia Autoimmune hemolytic anemia is caused by autoantibodies that react with red blood cells at temperatures ≥ 37° C (warm antibody hemolytic anemia) or 37° C (cold agglutinin disease). Hemolysis... read more Autoimmune Hemolytic Anemia or pernicious anemia, systemic lupus erythematosus Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic, multisystem, inflammatory disorder of autoimmune etiology, occurring predominantly in young women. Common manifestations may include arthralgias and... read more Systemic Lupus Erythematosus (SLE) , Addison disease Addison Disease Addison disease is an insidious, usually progressive hypofunctioning of the adrenal cortex. It causes various symptoms, including hypotension and hyperpigmentation, and can lead to adrenal crisis... read more Addison Disease , thyroiditis, rheumatoid arthritis Rheumatoid Arthritis (RA) Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily involves the joints. RA causes damage mediated by cytokines, chemokines, and metalloproteases. Characteristically... read more Rheumatoid Arthritis (RA) , alopecia areata Alopecia Areata Alopecia areata is typically sudden patchy nonscarring hair loss in people with no obvious skin or systemic disorder. (See also Alopecia.) This photo shows patchy loss of scalp hair in alopecia... read more Alopecia Areata ) can occur, as can malabsorption, nodular lymphoid hyperplasia of the gastrointestinal tract, systemic granulomatous inflammation, lymphocytic interstitial pneumonia Lymphocytic Interstitial Pneumonia Lymphocytic interstitial pneumonia (LIP) is lymphocytic infiltration of the alveolar interstitium and air spaces. The cause is unknown. Symptoms and signs are cough, progressive dyspnea, and... read more Lymphocytic Interstitial Pneumonia , splenomegaly, and bronchiectasis. Gastric carcinoma or lymphoma occurs in 10% of patients.

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 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.

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

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.

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

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