Makindo Medical Notes.com

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

• Chronic Granulomatous Disease