A 4-month-old boy is brought to the emergency department due to 5 days of fever, cough, and shortness of breath. The patient was born at 38 weeks gestation via uncomplicated vaginal delivery. At age 2 months, he was diagnosed with cervical lymphadenitis that required prolonged oral antibiotics. Temperature is 38.5 C (101.3 F), blood pressure is 80/40 mm Hg, pulse is 120/min, and respirations are 40/min. Oxygen saturation is 95% on room air. The patient is alert and responsive. Oropharyngeal examination shows no abnormalities. Mild chest retraction and bilateral rales are present. Chest x-ray reveals bilateral pulmonary infiltrates. The patient is given appropriate empiric antibiotic therapy for pneumonia; however, after 3 days, he continues to be febrile and laboratory assessment shows increased leukocyte count. CT scan of the chest shows multifocal pneumonia with areas of cavitation. Cultures obtained via bronchoalveolar lavage grow a filamentous, gram-positive rod consistent with Nocardia infection. Immunodeficiency is suspected. Which of the following tests would most likely identify the underlying immune disorder in this patient?

Question

A 4-month-old boy is brought to the emergency department due to 5 days of fever, cough, and shortness of breath.  The patient was born at 38 weeks gestation via uncomplicated vaginal delivery.  At age 2 months, he was diagnosed with cervical lymphadenitis that required prolonged oral antibiotics.  Temperature is 38.5 C (101.3 F), blood pressure is 80/40 mm Hg, pulse is 120/min, and respirations are 40/min.  Oxygen saturation is 95% on room air.  The patient is alert and responsive.  Oropharyngeal examination shows no abnormalities.  Mild chest retraction and bilateral rales are present.  Chest x-ray reveals bilateral pulmonary infiltrates.  The patient is given appropriate empiric antibiotic therapy for pneumonia; however, after 3 days, he continues to be febrile and laboratory assessment shows increased leukocyte count.  CT scan of the chest shows multifocal pneumonia with areas of cavitation.  Cultures obtained via bronchoalveolar lavage grow a filamentous, gram-positive rod consistent with Nocardia infection.  Immunodeficiency is suspected.  Which of the following tests would most likely identify the underlying immune disorder in this patient?

Quizplus · Accepted Answer

11ec25c8_d624_1b3e_bc81_efd0ecbb969e_MD0003_00 The presence of cervical lymphadenitis and Nocardia pulmonary infection within the first few months of this boy's life suggests chronic granulomatous disease (CGD), a typically X-linked recessive disorder characterized by impaired NADPH oxidase function. NADPH oxidase generates superoxide free radicals in the phagolysosome of neutrophils as part of the oxidative burst. oxidative burst Impaired NADPH oxidase activity allows invading bacteria and fungi to escape destruction following phagocytosis. Therefore, patients are at high risk for recurrent bacterial (eg, Staphylococcus aureus, Nocardia, Burkholderia cepacia, Serratia marcescens) and fungal (eg, Aspergillus) infections. Risk is greatest with pathogens containing catalase, an enzyme that breaks down hydrogen peroxide (a free radical). CGD is diagnosed by measuring oxidative burst with dihydrorhodamine 123 testing, a flow cytometry assay that uses a rhodamine derivative that fluoresces green when oxidation occurs (normal) and is colorless when respiratory burst is absent (CGD). Nocardia, a partially acid-fast, filamentous, gram-positive rod, is one of the most common pathogens in patients with CGD and should be suspected in the setting of cavitary pneumonia. Patients are also at risk for recurrent abscesses (eg, liver, skin), adenitis, and granulomas (eg, gastrointestinal, genitourinary). (Choices A and D) X-linked agammaglobulinemia is marked by abnormal B-cell development, leading to reduced mature B cells and very low levels of serum immunoglobulin. It typically presents with recurrent sinopulmonary infections with encapsulated bacteria (eg, Streptococcus pneumoniae) due to lack of opsonizing IgG. Because humoral immunity does not play a major role in control of Nocardia, Nocardia infections typically are not seen. (Choice C) Natural killer (NK) cells primarily destroy viral-infected and tumor cells. Primary immunodeficiency in NK cells usually manifests as severe herpes virus infections in infancy. NK cells are not a major component of defense against bacteria; therefore, Nocardia infection and lymphadenitis typically are not seen. (Choice E) Complement helps control infections by generating membrane attack complexes and the opsonizing protein C3ba. Early complement disorders (eg, C1 complex) are marked by recurrent sinopulmonary bacterial infection and childhood systemic lupus erythematosus. Late complement disorders (eg, C5-9) are marked by recurrent encapsulated bacterial infection, particularly with Neisseria. Complement does not play a major role in the control of Nocardia infections. Complement Educational objective: Patients with chronic granulomatous disease (CGD) are susceptible to cavitary pneumonia caused by Nocardia due to impaired respiratory burst and defective intracellular killing by neutrophils. Diagnosis of CGD is established by measuring the phagocytic oxidative response via flow cytometry. References: Chronic granulomatous disease. (http://www.ncbi.nlm.nih.gov/pubmed/29630223)

A 4-Month-Old Boy Is Brought to the Emergency Department Due