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Immunodeficiency is a physiologic state in which the immune system succumbs to microbiologic exposures typically controlled by members of the nonimmunodeficient population. This state can be transient or persistent, in-born or acquired, and it can result from dysfunction of one or multiple components of the immune system. The infectious manifestations of immunodeficiency arise from a failure to prevent, clear, limit the spread, or suppress a microorganism that would typically be controlled in one of the modes of defense. Clinical manifestations therefore include infection with an unusual microorganism, greater extent of spread of an infection, persistent infection, recurrent infection, and the associated inflammatory consequences of these scenarios. Since infections in immunodeficiency are dependent on a relevant microbiologic exposure, it is possible that immunodeficiency can remain undiagnosed; however, careful consideration of associated features, family history, immunosuppressive medications, and laboratory findings can hasten the diagnosis and possibly prevent a severe infection or other complication. As a result, it is important that physicians be aware of clues that could lead to a prompt diagnosis.
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The human immune system consists of the phylogenetically more primitive innate immune system and the adaptive immune system (Figure 33–1). To assist clinical categorization, immunodeficiencies are commonly divided into four main groups: antibody deficiencies, combined T- and B-cell immunodeficiencies, phagocyte disorders, and other deficiencies of innate immunity, which include complement deficiencies. Understanding the role each part of the immune system plays in host defense allows critical evaluation for possible immunodeficiency as the cause of recurrent infections and immune dysregulation, which can lead to associated autoimmunity and chronic inflammation.
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The prevalence of primary immunodeficiency (PID) is currently unknown, particularly in the pediatric population; however, significant advances have provided a more accurate understanding of parts of the PID picture. With the implementation of T-cell receptor rearrangement excision circle (TREC) newborn screening, the incidence of severe combined immunodeficiency disease (SCID) in newborns is estimated to be 1 in 50,000 births (Table 33–1). Likewise, the incidence of severely impaired or absent thymus activity is 1 in 50,000 births. Thus, the anticipated frequencies of two separate etiologies of severe T-cell deficiency are now more precisely known. The remainder of pediatric PID incidence or prevalence remains much less well understood. The scope of PID includes neutrophil, complement, B-cell, and T-cell deficiencies. In addition, several common chromosomal syndromes include a subset of patients with varying degrees of PID severity, including 10% of 22q11 deletion and most with trisomy 21. Including such patients, the landscape of PID includes many patients with syndromic immunodeficiency as well as rarer genetic defects that result in specific inborn errors of immunity. Combining all such patients, the prevalence in children is likely between 1 in 1000 and 1 in 10,000. PID patients are therefore not infrequently seen in the pediatric practice; although, any ...