A 3-year-old boy is brought to the clinic due to 3 days of fever and painful swelling in his right groin. His medical history includes 4 episodes of cutaneous abscesses and a lung abscess due to Staphylococcus aureus, all of which required drainage and prolonged antimicrobial therapy. The patient's maternal uncle died in childhood from recurrent infections. Temperature is 38.5 C (101.3 F). Physical examination shows an enlarged, tender, and fluctuant lymph node in the right inguinal area. There are several areas of scarring over previous drainage sites. The remainder of the physical examination is normal. Laboratory results are as follows: Gram stain of fluid aspirated from the affected lymph node reveals numerous organism-filled, segmented neutrophils. Cultures grow Aspergillus niger. Which of the following tests would most likely confirm this patient's diagnosis?

Question

A 3-year-old boy is brought to the clinic due to 3 days of fever and painful swelling in his right groin.  His medical history includes 4 episodes of cutaneous abscesses and a lung abscess due to Staphylococcus aureus, all of which required drainage and prolonged antimicrobial therapy.  The patient's maternal uncle died in childhood from recurrent infections.  Temperature is 38.5 C (101.3 F).  Physical examination shows an enlarged, tender, and fluctuant lymph node in the right inguinal area.  There are several areas of scarring over previous drainage sites.  The remainder of the physical examination is normal.  Laboratory results are as follows:  Gram stain of fluid aspirated from the affected lymph node reveals numerous organism-filled, segmented neutrophils.  Cultures grow Aspergillus niger.  Which of the following tests would most likely confirm this patient's diagnosis?

Quizplus · Accepted Answer

11ec25c8_d622_949c_bc81_77d557d3d9e4_MD0003_00 This patient's family history and recurrent pulmonary and cutaneous abscesses are concerning for a primary immunodeficiency syndrome. Specifically, his Gram stain showing organism-filled neutrophils is suggestive of chronic granulomatous disease (CGD). CGD is caused by a mutation that prevents phagocytic respiratory burst, or the formation of reactive oxygen species (ROS) such as hydrogen peroxide (H₂O₂). This results in impaired intracellular killing by phagocytes. CGD is most commonly inherited in an X-linked recessive manner, as seen in this male patient with a maternal uncle who had similar symptoms. Patients with CGD experience recurrent infections starting in early childhood and are classically susceptible to catalase-positive organisms (eg, Staphylococcus aureus, Aspergillus). Catalase is an enzyme that can destroy H₂O₂ produced by the pathogen itself, thereby limiting any pathogen-produced ROS for neutrophil use. Infections of the lungs (eg, pneumonia, empyema), skin/soft tissue, and lymph nodes (eg, suppurative adenitis) are most common. Leukocyte and absolute neutrophil counts typically are normal or elevated, and phagocytic cells filled with bacteria (due to ineffective intracellular killing) are a frequent finding on Gram stain. The diagnosis of CGD is made by testing neutrophil oxidative burst on dihydrorhodamine (DHR) 123 or nitroblue tetrazolium test. DHR flow cytometry is preferred and uses a rhodamine derivative that fluoresces green when oxidized (normal) but remains colorless when oxidative burst is impaired (CGD). (Choices A and D) Low B cell concentrations and immunoglobulin levels are characteristic of X-linked agammaglobulinemia (XLA). Patients have recurrent sinopulmonary infections caused by encapsulated bacteria, not Aspergillus. Aspergillus and S aureus infections can occur in hyper-IgE syndrome; however, unlike this case, abscesses are "cold" (ie, nontender, nonfluctuant) because the pathophysiology of hyper-IgE syndrome involves impaired neutrophil chemotaxis. Moreover, bacteria-filled phagocytes are inconsistent with both XLA and hyper-IgE syndrome. (Choice B) CH50 assays are used to determine total complement concentration. Complement deficiencies present with recurrent infections from encapsulated bacteria, particularly Neisseria. S aureus and Aspergillus infections are inconsistent with complement deficiency. (Choice E) T cell concentrations are markedly low in severe combined immunodeficiency and 22q11.2 deletion (DiGeorge syndrome). T cell defects cause severe, recurrent bacterial, viral, and fungal infection from early infancy. Low absolute leukocyte count with lymphopenia would be expected, and organism-filled neutrophils do not occur. Educational objective: Chronic granulomatous disease is caused by impaired intracellular killing by phagocytes. Pneumonia, cutaneous abscesses, and suppurative adenitis are common. Diagnosis is made by abnormal neutrophil respiratory burst testing (eg, dihydrorhodamine 123, nitroblue tetrazolium). References: Chronic granulomatous disease: clinical, molecular, and therapeutic aspects. (http://www.ncbi.nlm.nih.gov/pubmed/26680691)

A 3-Year-Old Boy Is Brought to the Clinic Due to 3