Screening for Humoral Immunodeficiency in Patients with Community-Acquired Pneumonia
BACKGROUND: Immunodeficiency is an underrecognized risk factor for infections, such as community-acquired pneumonia (CAP).
OBJECTIVE: We evaluated patients admitted with CAP for humoral immunodeficiency.
DESIGN: Prospective cohort study.
SETTING: Inpatients
PATIENTS, INTERVENTION, AND MEASUREMENTS: We enrolled 100 consecutive patients admitted with a diagnosis of CAP from February 2017 to April 2017. Serum IgG, IgM, IgA, and IgE levels were obtained within the first 24 hours of admission. CURB-65 score and length of hospital stay were calculated. The Wilcoxon rank-sum test, Kruskal-Wallis test, and simple linear regression analysis were used in data analysis.
RESULTS: The prevalence of hypogammaglobinemia in patients with CAP was 38% (95% CI: 28.47% to 48.25%). Twenty-seven of 100 patients had IgG hypogammaglobinemia (median: 598 mg/dL, IQ range: 459-654), 23 of 100 had IgM hypogammaglobinemia (median: 38 mg/dL, IQ range: 25-43), and 6 of 100 had IgA hypogammaglobinemia (median: 36 mg/dL, IQ range: 18-50). The median hospital length of stay for patients with IgG hypogammaglobinemia was significantly higher when compared to patients with normal IgG levels (five days, IQ range [3-10] vs three days, IQ range [2-5], P = .0085). Fourteen patients underwent further immune evaluation, resulting in one diagnosis of multiple myeloma, three patients diagnosed with specific antibody deficiency, and one patient diagnosed with selective IgA deficiency.
CONCLUSION: There is a high prevalence of hypogammaglobinemia in patients hospitalized with CAP, with IgG and IgM being the most commonly affected classes. IgG hypogammaglobinemia was associated with an increased length of hospitalization. Screening immunoglobulin levels in CAP patients may also uncover underlying humoral immunodeficiency or immuno-proliferative disorders.
© 2018 Society of Hospital Medicine
Community-acquired pneumonia (CAP) is the most common infection in hospitalized patients and the eighth most common cause of death in the United States.1 Mortality from CAP is estimated to be 5.1% in the outpatient population,13.6% in hospitalized patients, and 35.1% in patients admitted to the intensive care unit.2,3 CAP accounts for more than 50,000 deaths annually in the United States.2 There are multiple risk factors for CAP, including tobacco use, malnutrition, chronic obstructive pulmonary disease (COPD), bronchiectasis, cystic fibrosis, and mechanical bronchial obstruction. Underlying immunodeficiency, specifically humoral immunodeficiency, is also a risk factor for CAP.
Primary immunodeficiency (PIDD) is estimated to affect one in 1,800 individuals in the United States.4 The National Institutes of Health (NIH) estimates that only one out of three individuals with PIDD are appropriately diagnosed. Based on probability calculations on known PIDD patients versus incidence of disease, the NIH estimates that more than 500,000 individuals with PIDD remain undiagnosed in the United States.4 Further, there exists an average diagnostic delay of at least five years. This delay increases both morbidity and mortality and leads to increased healthcare utilization.5,6
The most common form of primary immunodeficiency is due to humoral immunodeficiency, including selective IgA deficiency, specific antibody deficiency, and common variable immunodeficiency. Specific antibody deficiency is defined as a lack of response to polysaccharide antigens in the setting of low to normal Ig levels and an intact response to peptide antigens.7 Selective IgA deficiency is defined as the isolated deficiency of serum IgA in the setting of normal serum levels of IgG and IgM in an individual older than four years in whom other causes of hypogammaglobinemia have been excluded.8 Common variable immunodeficiency (CVID) is defined as a decreased serum concentration of IgG in combination with low levels of IgA and/or IgM with a poor or absent response to immunization in the absence of other defined immunodeficiency state.9 In addition to experiencing recurrent infections—namely bronchitis, sinusitis, otitis, and pneumonia—patients with CVID are also at increased risk of autoimmunity and malignancy. In adults, secondary immunodeficiency is more common than primary immunodeficiency. Secondary immunodeficiency occurs commonly with disease states like HIV infection, diabetes, cirrhosis, malnutrition, and autoimmune conditions.10 Additional causes of secondary immune defects due to humoral immunodeficiency include immune-modulating drugs—such as rituximab and ibrutinib—and hematologic malignancies, including chronic lymphocytic leukemia and multiple myeloma. Recurrent infections remain the leading cause of morbidity and mortality in patients with both primary and secondary immunodeficiency.11,12
Evaluation of the humoral immune system begins with measurement of serum immunoglobulin (Ig) levels. Although abnormal Ig levels are not diagnostic of immunodeficiency, abnormal results may prompt additional evaluation. Screening strategies may assist in making an earlier diagnoses, potentially decreasing morbidity and mortality in patients with immunodeficiency.13-15 To date, there have been no studies evaluating the utility of screening Ig levels to evaluate for underlying humoral immunodeficiency in patients hospitalized for CAP.
