A 2-year-old boy is brought to the office due to fever, cough, and irritability lasting 3 days. Medical history is significant for a perirectal abscess that was drained at age 9 months. Temperature is 38.9 C (102 F), blood pressure is 100/70 mm Hg, pulse is 124/min, and respirations are 24/min. Eyes, ears, nose, and throat examinations are normal. Bilateral patchy crackles are auscultated in the lower lobes. Chest x-ray confirms bilateral focal pneumonia. The patient receives empiric antibiotic therapy; however, he is persistently febrile after 3 days. CT scan of the chest reveals a small, left pleural effusion and enlarged paratracheal and hilar lymphadenopathy, in addition to the bilateral pneumonia. Fine-needle biopsy of the lymph nodes and lung tissue shows an inflammatory reaction with granuloma formation. Biopsy cultures grow Burkholderia (Pseudomonas) cepacia. What is the mechanism most likely responsible for this patient's current infection?
A)Decreased immunoglobulin production
B)Decreased superoxide production
C)Defective opsonization
D)Impaired clearing of airway secretions
E)Impaired neutrophil chemotaxis

Question

A 2-year-old boy is brought to the office due to fever, cough, and irritability lasting 3 days.  Medical history is significant for a perirectal abscess that was drained at age 9 months.  Temperature is 38.9 C (102 F), blood pressure is 100/70 mm Hg, pulse is 124/min, and respirations are 24/min.  Eyes, ears, nose, and throat examinations are normal.  Bilateral patchy crackles are auscultated in the lower lobes.  Chest x-ray confirms bilateral focal pneumonia.  The patient receives empiric antibiotic therapy; however, he is persistently febrile after 3 days.  CT scan of the chest reveals a small, left pleural effusion and enlarged paratracheal and hilar lymphadenopathy, in addition to the bilateral pneumonia.  Fine-needle biopsy of the lymph nodes and lung tissue shows an inflammatory reaction with granuloma formation.  Biopsy cultures grow Burkholderia (Pseudomonas) cepacia.  What is the mechanism most likely responsible for this patient's current infection?
A)Decreased immunoglobulin production
B)Decreased superoxide production
C)Defective opsonization
D)Impaired clearing of airway secretions
E)Impaired neutrophil chemotaxis

Quizplus · Accepted Answer

11ec25c8_d623_57ed_bc81_e9bbb893f458_MD0003_00 This patient with Burkholderia (Pseudomonas) cepacia pneumonia and granulomas on biopsy most likely has chronic granulomatous disease (CGD), an X-linked recessive immunodeficiency that typically occurs in boys. Patients are predisposed primarily to recurrent lung infections (eg, pneumonia, empyema, hilar lymphadenopathy) and abscesses (eg, skin, liver, lymph node); perirectal infection is common. The pathogenesis of CGD involves NADPH oxidase. This enzyme is normally responsible for the neutrophil respiratory burst, a process in which reactive oxygen species (eg, superoxide radicals, hydrogen peroxide) are formed and activate lysosomal proteases involved in pathogen destruction. Patients with CGD have mutations in NADPH oxidase and therefore decreased production of superoxide anions. Although neutrophils may use hydrogen peroxide produced by pathogens, organisms that produce catalase can degrade their own reactive oxygen species. Therefore, infections in CGD are typically due to catalase-positive bacteria and fungi (eg, Staphylococcus aureus, B cepacia, Nocardia, Aspergillus). Patients with CGD also develop characteristic granulomas, as seen in this boy, that can involve many organ systems (eg, gastrointestinal tract, genitourinary tract, lungs). The pathogenesis likely involves migration of phagocytes to infection sites but inability to degrade inflammatory signals and invading organisms; this leads to a chronic and focal aggregation of inflammatory cells, or granulomas. (Choices A and C) Decreased immunoglobulin production, as seen in X-linked agammaglobulinemia, generally presents with recurrent sinopulmonary infections. Typical pathogens include encapsulated bacteria (eg, Streptococcus pneumoniae) due to lack of opsonizing IgG. Similarly, complement dysfunction (eg, C3 deficiency) also causes defective opsonization and infection due to encapsulated bacteria. Perirectal abscess, granulomas, and B cepacia infection are not expected with either condition. (Choice D) Impaired airway clearance is a feature of cystic fibrosis (CF), which can predispose to B cepacia pneumonia, but granuloma formation does not occur. In addition, infections in CF are limited to the sinopulmonary tract, so perirectal abscesses would not be seen. (Choice E) Impaired neutrophil chemotaxis is seen in leukocyte adhesion deficiency. Patients are susceptible to recurrent skin and mucosal infections; however, pneumonia with granuloma formation does not occur. Educational objective: Chronic granulomatous disease is due to a defect in NADPH oxidase, resulting in decreased formation of superoxide anions and inability of phagocytes to kill certain bacterial and fungal pathogens. The presentation includes recurrent abscesses and pulmonary infections caused by catalase-positive organisms (eg, Burkholderia [Pseudomonas] cepacia) and granuloma formation. References: Clinical and laboratory profiles of 17 cases of chronic granulomatous disease in North India. (http://www.ncbi.nlm.nih.gov/pubmed/33707834)

A 2-Year-Old Boy Is Brought to the Office Due to Fever