Chronic granulomatous disease (CGD), also known as Bridges–Good syndrome and Quie syndrome is a diverse group of hereditary primary immunodeficiency disorders characterized by recurrent, life-threatening bacterial and fungal infections of the skin, the airways, the lymph nodes, the liver, the brain and the bones.
- Leads to the formation of granulomata (collection of histiocytes/macrophages) in many organs
- Type of primary immunodeficiency
History:
Chronic granulomatous disease (CGD) was first identified in the 1950s in a 12-month-old Minnesotan child who presented with a constellation of findings, including chronic suppurative lymphadenitis, hepatosplenomegaly, pulmonary infiltrates, and eczematoid dermatitis. In the classic 1959 description of “fatal granulomatous disease of childhood,” Bridges et al reported that “no satisfactory therapy has been found, however, and the disease has relentlessly progressed through severe debilitation to ultimate death over a period of several years.”
Etiopathogenesis
Inheritance patterns:
- X-linked CGD
- Autosomal recessive cytochrome b-negative CGD
- Autosomal recessive cytochrome b-positive CGD type I
- Autosomal recessive cytochrome b-positive CGD type II
- Atypical granulomatous disease
Defective phagocyte NADPH oxidase:
Disruption in the formation of reactive oxygen compounds (most importantly superoxide radical due to defective phagocyte NADPH oxidase) used to kill certain ingested pathogens leding to a dysregulated inflammatory response resulting in granuloma formation and other inflammatory disorders such as colitis.
Presentation
Specific recurrent infections:
- In decreasing order of frequency:
- Pneumonia
- Abscesses of the skin, tissues, and organs
- Suppurative arthritis
- Osteomyelitis
- Bacteremia/fungemia
- Superficial skin infections such as cellulitis or impetigo
Diagnosis
Screening tests:
- Nitroblue tetrazolium dye reduction test (NBT)
- Negative in CGD, meaning that it does not turn blue.
- The higher the blue score, the better the cell is at producing reactive oxygen species
Confirmatory tests:
- Flow cytometry
Management
Supportive management:
- Bacterial infections: Trimethoprim-sulfamethoxazole (TMP-SMX)
- Fungal infections: Itraconazole or voriconazole
- Interferon: Interferon gamma-1b (Actimmune)
Definitive treatment: Hematopoietic stem cell transplantation (HSCT)
Summary:
