78: Common Variable Immune Deficiency

Key Points

• Disease summary:

  • Common variable immune deficiency (CVID) is a heterogeneous immunodeficiency disease characterized by low serum levels of the immunoglobulin isotypes IgG and IgA, impaired ability to produce specific antibodies after immunization and recurrent infections of the sinopulmonary or gastrointestinal tract.

  • First described in 1953 and later coined in 1973, CVID may present in childhood, adolescence, or adulthood and is the most common primary immunodeficiency syndrome that comes to medical attention.

  • In addition to being more susceptible to infections, CVID also can manifest aspects of immune dysregulation with noninfectious complications including autoimmunity (most typically autoimmune cytopenias), noninfectious gastrointestinal disease, granulomatous inflammation, lymphoid disease, and an increased risk of malignancy.

  • Although most cases of CVID are sporadic mutations, seven disease-causing or contributing genes have been identified that give rise to a CVID phenotype in the past 10 years.

• Prevalence:

  • The prevalence of CVID has been estimated at between 1:10000 and 1:100000 depending on geographic location.

• Differential diagnosis:

  • Because CVID is a diagnosis of exclusion, other causes of hypogammaglobulinemia must be ruled out. These include

  • X-linked agammaglobulinemia; X-linked lymphoproliferative disease; hyper-IgM syndromes; IgG subclass deficiency; selective antibody deficiency; secondary hypogammaglobulinemia; decreased production due to malignancy, drugs such as gold salts, penicillamine, antimalarial drugs, corticosteroids, phenytoin, carbamazapine, viral infections, and systemic illnesses causing bone marrow suppression are associated with the decreased production of immunoglobulins; increased loss due to protein-losing enteropathies, such as intestinal lymphangiectasia, nephrotic syndrome, burns, and other traumas leading to loss of fluids.

Diagnostic Criteria and Clinical Characteristics

Diagnostic Criteria for CVID

CVID is defined as a diagnosis of exclusion.

The current PAGID diagnostic criteria state that CVID is probable in a male or female patient who has a marked decrease of IgG (at least 2 SD below the mean for age) and a marked decrease in at least one of the isotypes IgM or IgA, and fulfills all of the following criteria:

1. Onset of immunodeficiency at greater than 2 years of age.

2. Absent isohemagglutinins and/or poor response to vaccines.

3. Defined causes of hypogammaglobulinemia have been excluded.

Clinical Characteristics

Most patients with CVID are recognized to have a clinically significant immunodeficiency in the second, third, or fourth decades of life, after they have had several infections. Viral, fungal, and parasitic infections as well as bacterial infections may be causative.

The serum concentration of IgM is normal in about half of the patients. Abnormalities in T-cell numbers or function are common. The majority of patients have normal numbers of B cells; however, some have low or absent B cells with a unique subset being deficient in class switched memory B cells.

Clinical Complications

Infections

Acute and chronic infections account for a large part of morbidity in patients with CVID. ...