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DEFINITIONS AND EPIDEMIOLOGY

There are two basic types of immunodeficiency (also termed immune deficiency): (1) primary and (2) acquired or secondary. Primary immuno­deficiencies are a class of disorders in which there is an intrinsic defect in the immune system. In contrast, acquired or secondary immunodeficiency states occur as a consequence of external agents such as infection or chemotherapy. Over 300 distinct primary immunodeficiency syndromes have been recognized.

The prevalence of most primary immunodeficiencies remains unknown, as routine screening for these defects is rarely performed. One well-conducted telephone survey of 10,000 households found that the population rate for the diagnosis of primary immunodeficiency was 1 in 1200.1

Children with primary immunodeficiency diseases most commonly present with recurrent infections. When evaluating a child with recurrent infections, it is important to remember the normal pattern of infections for different ages and situations. For example, a normal child may have 6–12 infections per year if exposures occur only at home, and up to 18 infections per year when cared for at a daycare center. These frequent infections in normal children are most often uncomplicated upper respiratory infections, including acute otitis media. A thorough physical examination may reveal subtle scarring from previous infections, eczema, lymphadenopathy, or prior surgery. A history suggestive of childhood immunodeficiency usually contains one or more red flags. Situations that warrant consideration of a primary immune deficiency include frequent infections without any other explanation, severe or opportunistic infections without obvious cause and unusual autoimmunity.2–4

PATHOGENESIS

The components of the immune response are exceedingly complex and require the close cooperation and orchestration of a variety of cellular elements. Immunodeficiencies occur as a result of blocks in development, compromised function of a cell or pathway, and the increasingly recognized category of gain-of-function mutations that disrupt the careful balance of host defense. For clinical utility, however, the functional categories of immunodeficiency can be categorized as follows: (1) defects in T cells, (2) defects in B cells and antibody production, (3) defects in phagocytes (including neutrophils and macrophages), and (4) defects in complement. Combined B- and T-cell defects also occur. Among these functional categories of immune deficiency, about 50% are B-cell defects (Table 63-1). Severe combined immunodeficiencies tend to manifest in the neonatal period. B-cell defects tend to manifest after 4–6 months of life, when the maternally derived antibody titers have decreased.5

TABLE 63-1Distribution of Primary Immunodeficiencies by Category

Each of these functional categories of the immune response provides protection against specific classes of microorganisms. Deficiencies in a particular function of the immune response can lead to infections with specific types of infectious ...

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