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Essentials of Diagnosis
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Frequent sinopulmonary infections secondary to humoral immune deficiency
Two or more low serum immunoglobulin levels (IgG, IgA, or IgM) and deficient functional antibody responses to vaccination
Secondary causes for hypogammaglobulinemia and recurrent sinopulmonary infections have been ruled out
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General Considerations
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Most common symptomatic primary immunodeficiency disorder
Heterogeneous immunodeficiency disorder clinically characterized by an increased incidence of recurrent severe sinopulmonary infections with hypogammaglobulinemia
Approximately half of patients will also have autoimmune phenomena with or without neoplastic disease
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Onset is generally in adolescence or early adulthood but can occur at any age
The prevalence is about 1 in 25,000 in the United States
Most cases are sporadic; about 10–20% are familial
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Increased susceptibility to serious infections, especially with encapsulated organisms is the hallmark
Recurrent
Infections may be prolonged or associated with unusual complications such as meningitis, empyema, or sepsis
Bronchiectasis occurs in > 25% of patients who are not treated with IgG-RT and is a leading cause of morbidity
Recurrent viral infections: not prototypic of common variable immunodeficiency, but varicella zoster reactivation, cytomegalovirus reactivation, and increased symptomatic disease from other herpes viruses and candida can occur
Gastrointestinal infections and dysfunction
Many patients develop an inflammatory sprue-like syndrome, with diarrhea, steatorrhea, malabsorption, protein-losing enteropathy, and hepatosplenomegaly
Norovirus and giardia can be problematic
Increased incidence of autoimmune disease (20%)
Patients often do not display the usual serologic markers as they are hypogammaglobulinemic
Autoimmune cytopenias are most common
Autoimmune endocrinopathies and seronegative rheumatic disease also common
Lymph nodes may be enlarged, yet biopsies show marked reduction in plasma cells
Noncaseating granulomas mimicking sarcoidosis can be found in the spleen, liver, lungs, or skin
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Diagnosis is made when there are reduced serum immunoglobulins and poor antibody response to vaccines
Poor antibody response to vaccines
Check antibody response to polysaccharide (Pneumovax-23, H influenzae type b) and protein (tetanus, diphtheria) antigens
Demonstrates functional or quantitative defects in antibody production
Exclude secondary causes of hypogammaglobulinemia, such as
Proteinuria
Protein-losing enteropathy
Drug effects (eg, rituximab, antiepileptics)
Hematologic malignancies
Absolute B-cell count in peripheral blood can be normal; a subset of patients, however, have concomitant T-cell immunodeficiency with
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