Common Variable Immunodeficiency: Diagnosis, Management, and Treatment

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Key points

  • Common variable immunodeficiency (CVID) is a grouping of heterogeneous diseases with the common finding of impaired antibody production.

  • Morbidity is not limited to infection; in fact, noninfectious complications can be the most threatening and difficult to treat.

  • Proper care of patients with CVID includes both replacement of immunoglobulin G and monitoring for CVID-associated disease on a regular basis.

Initial Evaluation

Historically, the definition of common variable immunodeficiency (CVID) focused on the predominant finding of antibody deficiency, but more recent definitions have focused on the associated clinical features frequently seen. The most cited definition of CVID was presented by the European Society for Immunodeficiency (ESID) and the Pan American Group for Immunodeficiency in 1999, and the following criteria for probable CVID were proposed: greater than 2 years of age, immunoglobulin G (IgG) and

Epidemiology

Because of the rarity of primary immunodeficiency in general, very large groups of patients with CVID have not been studied; however, there are several reports of CVID cohorts with substantial numbers of patients from which generalizations can be drawn (Table 2).13, 15, 17, 19, 20, 42, 43, 44, 45 CVID occurs equally in males and females, although, among children, boys predominate. CVID age of onset is variable, but more recent studies suggest peaks in early childhood and around the third decade

Cell Biology

Most patients with CVID have intrinsic B-cell defects. It has been known for some time that peripheral B cells from most patients with CVID produce subnormal amounts of IgG or IgM when subjected to B-cell receptor stimulation9; however, this finding may merely reflect the marked reduction of memory B cells in those patients with CVID.10 Taking into account the variability in B-cell subsets contained in peripheral blood, several groups still have identified intrinsic B-cell abnormalities,

Prognosis

The diagnosis of CVID carries a significantly increased mortality risk; however, the risk seems to be entirely contained within a subset of patients. The increased mortality risk was initially attributed to noninfectious complications in a large retrospective analysis of a European CVID registry.15 Confirming that finding, a large single-center study identified an 11-times higher risk of death among patients with CVID with noninfectious complications compared with patients with CVID with only

Concluding remarks

Over the past 60 years, CVID has emerged as the predominant class of primary antibody deficiencies. During this time period, important variation in both clinical features and underlying pathology have been identified. In fact, many patients with CVID have little in common other than meeting minimal diagnostic criteria. Nonetheless, grouping patients with antibody deficiency into this diagnostic category has allowed for the differentiation of multiple important endotypes, the study of which will

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