Residual NADPH oxidase activity is significantly associated with disease severity and the chance of survival of the patient
About
- A Primary immunodeficiency disorder.
- Increases risk of infections due to fungi and bacteria
- Increased granuloma formation
- Also called Bridges–Good syndrome
Aetiology
- Defective function of the NADPH oxidase
- Mutations in one of five different genes can cause these defects.
Different manifestations
- X-linked CGD: Infections early childhood and may have discoid lupus like symptoms
- Autosomal recessive CGD: older children with milder disease.
Different Types
- X-linked chronic granulomatous disease (CGD)
- AR cytochrome b-negative CGD
- AR cytochrome b-positive CGD type I
- AR cytochrome b-positive CGD type II
- atypical granulomatous disease
Clinical
- Aspergillus: pneumonia, lymphadenitis, osteomyelitis, brain abscess
- Candida: sepsis, soft tissue infection, liver abscess
- Nocardia: pneumonia, osteomyelitis, brain abscess
- Serratia marcescens: osteomyelitis, soft tissue infections; pneumonia, sepsis
- Burkholderia (pseudomonas) pneumonia, sepsis
- Klebsiella: pneumonia, skin infections, lymphadenitis
- Staphylococcus aureus: soft tissue infections, lymphadenitis, liver abscess, perirectal abscess, osteomyelitis, pneumonia, sepsis
Severe infections: bacterial and fungal e.g. Aspergillus, Nocardia, Serratia, Burkholderia, Klebsiella, and Staphylococcus aureus are catalase-positive. Catalase-positive pathogens can neutralize the hydrogen peroxide produced by phagocytes other than those in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.
Investigations
- FBC: anaemia with iron deficiency is not unusual
- Nitroblue-tetrazolium (NBT) test is negative in CGD, meaning that it does not turn blue.
- Hypergammaglobulinaemia
- Genetic testing: p47phox defect
Management
- Lifelong regimens of antibiotics and antifungals to prevent infections.
- Interferon gamma can improve the activity of phagocytes and reduce infection,
- Abscesses need aggressive care that may include surgery.
- Psychological support, Genetic counselling.
- Granulomas may require steroid therapy.
- Some have responded to bone marrow transplantation but it has been associated with unacceptably high rates of morbidity, mortality and graft failure except in patients with an HLA-identical sibling donor
- Gene therapy using genome-editing technology such as CRISPR/Cas9 nucleases is a promising approach for patients with CGD in the future.
- Live bacterial vaccines such as Bacille Calmette–Guérin (BCG) should be avoided.
References