|ECR 2019 / C-2011|
|Chronic Granulomatous disease: pictorial assay of infectious and inflammatory complications|
Chronic granulomatous disease (CGD) is a rare (1:200,000 live births) and inherited disorder. It is mostly diagnosed before 5 years old, with slightly male predominance.
Mutation in CYBB gene is transmitted in a X-linked pattern (65-70%), while the other four gene mutations (CYBA, NCF1, NCF2, NCF3) are transmitted in a autosomal recessive pattern (35%).
Dysfunction of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase limits
the generation of free radical superoxide by the normal respiratory burst in human phagocytes (neutrophils, mononuclear cells, macrophages and eosinophils), leading to the formation of inflammatory granulomas.
Disease manifests as recurrent and severe bacterial and fungal infections in a variety of organs such as lungs, brain, liver and spleen, but patients also have greater risk of inflammatory and autoimmune diseases, growth deficiency and abnormal wound healing.
Most common agents isolated are Staphylococcus aureus, gram-negative enterobacteria (e.g., Salmonella spp., Klebsiella spp., Aerobacter spp., Serratia spp., Pseudomonas spp.), Nocardia spp. and Aspergillus fumigatus. Aspergillosis is the most common cause of death (18%)
Differential diagnosis should included other causes of recurrent infections in paediatric population, such as cystic fibrosis and immunodeficiencies like hyperimmunoglobulin E syndrome, glucose-6-phosphate dehydrogenase and glutathione synthetase deficiencies. Crohn's disease should also include in differential diagnosis since it shares various clinical features with granulomatous colitis.
Antibiotic and antifungal prophylaxis and treatment with allogeneic hematopoietic stem cell transplantation have improved its prognosis and most patients will survive into adulthood. Interferon-γ is additionally administered in an effort to boost the phagocytic oxidative metabolism in some forms of CGD.