Review Question - QID 217201

This pediatric patient with a history of recurrent sinopulmonary infections and an abscess growing S. aureus and S. marcescens likely has chronic granulomatous disease (CGD), a diagnosis which is confirmed using dihydrorhodamine flow cytometry.

CGD is a primary immunodeficiency of phagocytes that is inherited in an X-linked recessive manner. The immunodeficiency results from a defect in NADPH oxidase, which is a vital enzyme in the respiratory burst pathway. Defects in the respiratory burst lead to an inability to produce peroxide which is a reactive oxygen species, leading to susceptibility to catalase-positive organisms such as S. aureus, Burkholderia cepacia complex, and Aspergillus. Due to impaired phagocytosis and dysregulated inflammation, granulomas form in patients affected by CGD when infected by catalase-positive organisms as the immune system attempts to isolate the pathogen but is unable to phagocytose it. Patients with CGD present with recurrent pyogenic infections, pneumonia, skin abscesses, and pulmonary abscesses. Infection with unusual organisms such as S. marcescens and Nocardia may also be seen. Diagnosis of CGD is confirmed using flow cytometry reduction of dihydrorhodamine, though the nitroblue tetrazolium dye reduction test may also be used. Dihydrorhodamine flow cytometry directly measures the function of NADPH oxidase in neutrophils, evaluating whether cells turn blue following addition of a colorless chemical called nitroblue tetrazolium, indicating functional NADPH oxidase. Treatment of CGD includes antibacterial and antifungal prophylaxis and interferon-gamma. Curative treatment for CGD requires stem cell transplant.

Yu et al. reviewed considerations in the diagnosis of CGD. The authors found that the most common organisms causing infection in CGD are Staphylococcus aureus, Burkholderia cepacia complex, Serratia marcescens, Nocardia species, and Aspergillus species. They recommended that the dihydrorhodamine neutrophil respiratory burst assay is the preferred test to evaluate the function of NADPH oxidase.

Incorrect Answers:
Answer 2: Lymph node biopsy may be used to diagnose Hodgkin lymphoma. Hodgkin lymphoma presents with lymphadenopathy and "B" symptoms such as fever, night sweats, and chills. Though this patient has lymphadenopathy, it is likely reactive lymphadenopathy secondary to his axillary abscess. Recurrent sinopulmonary infections is more suggestive of an immunodeficiency syndrome rather than Hodgkin lymphoma.

Answer 3: Measurement of B and T cell counts may be beneficial in the diagnosis of immunodeficiencies caused by impaired cellular immunity, such as severe combined immunodeficiency (SCID). SCID is caused by defects in the development of B and T cells, leading to failure to thrive, recurrent infections, and chronic diarrhea. It is usually apparent before 3 months of age. SCID is universally fatal without stem cell transplant before age 2.

Answer 4: Measurement of serum complement levels may be used to help diagnose immunodeficiency caused by defects in the complement pathway. Inherited defects in the complement pathway would present with recurrent infections with Neisseria meningitidis or Streptococcus pneumoniae, which are encapsulated organisms that require complement-assisted lysis.

Answer 5: Measurement of serum immunoglobulin levels is used to diagnose X-linked agammaglobulinemia. X-linked agammaglobulinemia results from defective B cell development, leading to recurrent infections due to defective humoral immunity. X-linked agammaglobulinemia usually presents after 6 months of age after levels of maternal antibodies decrease. Infections would be localized to the skin and lungs. Infection with S. marcescens would be atypical.

Bullet Summary:
Chronic granulomatous disease causes recurrent pulmonary and cutaneous infections from catalase-positive organisms and is diagnosed using dihydrorhodamine flow cytometry.