A 15-month-old boy is brought to the emergency department due to fever and foot swelling. The patient first developed swelling of the right foot and fever 4 days ago. Today, swelling of the left foot also developed. Medical history is significant for a perianal abscess at 9 months of age. Imaging studies reveal osteomyelitis affecting the metatarsal bones of both feet. Intravenous antimicrobials are administered, but the patient still has fever and bilateral foot swelling 2 weeks later. Laboratory workup shows persistent neutrophilic leukocytosis. Bone biopsy culture grows Staphylococcus aureus. Evaluation for an underlying diagnosis is initiated; via use of a rhodamine derivative, the patient's peripheral blood is stimulated with phorbol myristate acetate (PMA) and compared with a control. Results of the test are shown in the image below: Which of the following processes is most likely impaired in this patient?

Question

A 15-month-old boy is brought to the emergency department due to fever and foot swelling.  The patient first developed swelling of the right foot and fever 4 days ago.  Today, swelling of the left foot also developed.  Medical history is significant for a perianal abscess at 9 months of age.  Imaging studies reveal osteomyelitis affecting the metatarsal bones of both feet.  Intravenous antimicrobials are administered, but the patient still has fever and bilateral foot swelling 2 weeks later.  Laboratory workup shows persistent neutrophilic leukocytosis.  Bone biopsy culture grows Staphylococcus aureus.  Evaluation for an underlying diagnosis is initiated; via use of a rhodamine derivative, the patient's peripheral blood is stimulated with phorbol myristate acetate (PMA) and compared with a control.  Results of the test are shown in the image below:  Which of the following processes is most likely impaired in this patient?

Quizplus · Accepted Answer

11ec160b_37a5_6471_9249_152ecb029701_MD0001_00 This young patient has multifocal osteomyelitis resistant to treatment, as well as a previous cutaneous (perianal) abscess. This history of multiple, invasive infections is worrisome for underlying immunodeficiency. Laboratory results show a normal white blood cell response to bacterial infection (ie, neutrophilic leukocytosis), but dihydrorhodamine (DHR) testing, which evaluates for phagocytic oxidative response, is abnormal. These findings are consistent with chronic granulomatous disease (CGD). CGD is a disorder of phagocytic metabolism characterized by defective NADPH oxidase, an enzyme in the respiratory burst pathway. Without this enzyme, neutrophils cannot form the reactive oxygen species required for intracellular killing of phagocytized organisms. Patients are predisposed to recurrent infections with certain catalase-positive organisms (eg, Staphylococcus aureus). The DHR assay detects the conversion of DHR (a colorless substance) to rhodamine (fluoresces green) by free radicals produced when the NADPH oxidase pathway is stimulated (eg, by a protein kinase C agonist such as phorbol myristate acetate). In unaffected patients, stimulated cells show increased intensity of fluorescence (ie, rightward shift along the x-axis), indicating appropriate NADPH activity, whereas unstimulated cells remain colorless. In patients with CGD, the stimulated cells show no increased fluorescence (ie, no oxidation of DHR). (Choice A) Leukocyte adhesion deficiency, or a defect in CD18-containing integrins, is characterized by impaired leukocyte migration (chemotaxis) to sites of inflammation, leading to recurrent mucosal infections and abscesses that lack pus. Neutrophilic leukocytosis is common, but DHR testing would be normal. (Choice B) Complement deficiencies often present with recurrent Neisseria infections, not S aureus osteomyelitis. Neutrophil respiratory burst on DHR testing would be normal. (Choice C) Opsonization is impaired in patients lacking IgG (eg, X-linked agammaglobulinemia). The typical presentation involves recurrent sinopulmonary infections by encapsulated bacteria, not S aureus. Moreover, this patient's DHR test is diagnostic of CGD. (Choice E) Impaired T-lymphocyte function (eg, HIV infection) predisposes patients to severe, recurrent bacterial, viral, and fungal opportunistic infections (eg, Pneumocystis jirovecii). Neutrophil respiratory burst would not be affected. Educational objective: Chronic granulomatous disease (CGD) is due to defective NADPH oxidase and is diagnosed by dihydrorhodamine testing, which measures neutrophil respiratory burst. When NADPH oxidase is stimulated, dihydrorhodamine is normally oxidized and fluoresces green (increased fluorescence intensity); it remains colorless (ie, no oxidation) in patients with CGD.

A 15-Month-Old Boy Is Brought to the Emergency Department Due