(See also Overview of Immunodeficiency Disorders Overview of Immunodeficiency Disorders Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more and Approach to the Patient With an Immunodeficiency Disorder Approach to the Patient With Suspected Immunodeficiency Immunodeficiency typically manifests as recurrent infections. However, recurrent infections are more likely to have causes other than immunodeficiency (eg, inadequate treatment, resistant organisms... read more .)
Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder Primary Immunodeficiencies Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more that involves humoral immunity deficiencies Humoral immunity deficiencies Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies... read more . 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 X-linked Agammaglobulinemia X-linked agammaglobulinemia is characterized by low levels or absence of immunoglobulins and absence of B cells, leading to recurrent infections with encapsulated bacteria. (See also Overview... read more 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 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
, 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
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
, 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
, 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
, 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
) 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
, splenomegaly, and bronchiectasis. Gastric carcinoma or lymphoma occurs in 10% of patients.
Diagnosis of CVID
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
X-linked Agammaglobulinemia
X-linked agammaglobulinemia is characterized by low levels or absence of immunoglobulins and absence of B cells, leading to recurrent infections with encapsulated bacteria. (See also Overview...
read more
, multiple myeloma
Multiple Myeloma
Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones causing...
read more
, and chronic lymphocytic leukemia
Chronic Lymphocytic Leukemia (CLL)
Chronic lymphocytic leukemia (CLL) is characterized by progressive accumulation of phenotypically mature malignant B lymphocytes. Primary sites of disease include peripheral blood, bone marrow...
read more
; 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
Treatment of CVID consists of immune globulin Replacement of missing immune components Immunodeficiency typically manifests as recurrent infections. However, recurrent infections are more likely to have causes other than immunodeficiency (eg, inadequate treatment, resistant organisms... read more 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 Common variable immunodeficiency (acquired or adult-onset hypogammaglobulinemia) is characterized by low immunoglobulin (Ig) levels with phenotypically normal B cells that can proliferate but... read more ).
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
