Chronic granulomatous disease

Background

• Primary immunodeficiency of neutrophils leading to recurrent infections with catalase-positive organisms

Pathophysiology

• Defect in NADPH oxidase
• Therefore unable to generate superoxide radicals required by phagocytes to kill pathogens

Clinical Manifestations

• Recurrent infections
  • Catalase-positive organisms, including Staphylococcus aureus, Burkholderia cepacia, Serratia marcescens, Nocardia species, and Aspergillus species
  • CGD is the highest-risk group for invasive aspergillosis
• Granuloma formation, often in the GI and GU tracts and may precede other clinical symptoms

Differential Diagnosis

• Other primary immunodeficiencies
  • MPO deficiency, which will have an abnormal DHR test but largely asymptomatic unless concurrent diabetes mellitus
  • Hyper-IgE syndrome, though Aspergillus will be more typically pulmonary
  • IRAK4/MyD88 deficiency, which won't have fungal infections and improves with age
  • Humoral immunodeficiencies, such as CVID or Bruton tyrosine kinase deficiency, though they tend to have more infections with encapsulated organisms and will have abnormal quantitative immunoglobulins
• Inflammatory bowel disease
• Cystic fibrosis
• Sarcoidosis, which will cause granuloma formation but shouldn't increase risk of infection

Diagnosis

• The diagnosis is confirmed with the dihydrohodamine-123 (DHR-123) test

Management

• Treat intercurrent infections
• Prophylaxis with:
  • TMP-SMX
  • Itraconazole
  • Possibly also interferon-γ

Further Reading

• Considerations in the Diagnosis of Chronic Granulomatous Disease. J Pediatric Infect Dis Soc. 2018;7(S1):S6-S11. doi: 10.1093/jpids/piy007