(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 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 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). Impaired T-cell immunity Cellular 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 also may be present in some patients.
Autoimmune disorders can occur, including 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 is a chronic systemic autoimmune disease that primarily involves the joints. Rheumatoid arthritis causes damage mediated by cytokines, chemokines, and metalloproteases.... read more 
, and alopecia areata Alopecia Areata Alopecia areata is typically sudden patchy nonscarring hair loss in people with no obvious skin or systemic disorder. Diagnosis is typically by inspection, although sometimes a skin biopsy is... read more 
. Patients also may develop malabsorption Overview of Malabsorption Malabsorption is inadequate assimilation of dietary substances due to defects in digestion, absorption, or transport. Malabsorption can affect macronutrients (eg, proteins, carbohydrates, fats)... read more , 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/or bronchiectasis Bronchiectasis Bronchiectasis is dilation and destruction of larger bronchi caused by chronic infection and inflammation. Common causes are cystic fibrosis, immune defects, and recurrent infections, though... read more 
. Gastric carcinoma Stomach Cancer Etiology of stomach cancer is multifactorial, but Helicobacter pylori plays a significant role. Symptoms include early satiety, obstruction, and bleeding but tend to occur late in the... read more 
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 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
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 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, vedolizumab, tumor necrosis factor (TNF)-alpha inhibitors (eg, etanercept, infliximab), corticosteroids, and/or other treatments may be required to treat complications such as autoimmune disorders, immune enteropathy, 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
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
rituximab |
RIABNI, Rituxan, RUXIENCE, truxima |
vedolizumab |
Entyvio |
etanercept |
Enbrel |
infliximab |
AVSOLA, INFLECTRA, Remicade, RENFLEXIS |
