title: Chronic granulomatous disease presenting as refractory pneumonia in late adulthood.
abstract: We present a case of refractory pneumonia in an adult patient with underlying chronic granulomatous disease (CGD). Her lobectomy tissue grew B urkholderia cepacia and histopathology revealed diffuse severe pneumonic consolidation with suppurative/necrotizing granulomata. An initial attempt to find an underlying immune deficiency was unsuccessful. Following recurrent invasive infections, repeat immunological assessment revealed reduced neutrophil function, demonstrating skewed carrier status (lyonization) for X-linked CGD (only 3% normal cells). A pathogenic mutation in the CYBB gene was found on sequencing. CYBB gene encodes the gp91phox, a catalytic subunit of nicotinamide adenine dinucleotide phosphate-oxidase that produces reactive oxygen species in phagocytes. Lyonization increases with age, explaining the delayed clinical CGD. CGD is a rare neutrophil disorder that usually presents in early life with recurrent infections due to bacteria and fungi primarily involving lungs and skin. It is secondary to a defective NADPH oxidase system needed to kill intracellular organisms and activate the formation of neutrophil extracellular traps.
authors.affiliation: Department of Medicine, John Hunter Hospital New Lambton, New South Wales, Australia ; School of Medicine and Public Health, The University of Newcastle Newcastle, New South Wales, Australia.
authors.forename: Ghulam
authors.initials: G
authors.lastname: Sarwar
authors.affiliation: School of Medicine and Public Health, The University of Newcastle Newcastle, New South Wales, Australia ; Immunology, Hunter Area Pathology Service New Lambton, New South Wales, Australia.
authors.forename: Theo
authors.initials: T
authors.lastname: de Malmanche
authors.affiliation: School of Medicine and Public Health, The University of Newcastle Newcastle, New South Wales, Australia ; Pathology, Hunter Area Pathology Service New Lambton, New South Wales, Australia.
authors.forename: Loui
authors.initials: L
authors.lastname: Rassam
authors.affiliation: School of Medicine and Public Health, The University of Newcastle Newcastle, New South Wales, Australia ; Department of Respiratory Medicine, John Hunter Hospital New Lambton, New South Wales, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Grainge
authors.affiliation: Immunology Laboratory, The Children's Hospital at Westmead Sydney, New South Wales, Australia ; Central Clinical School, University of Sydney Sydney, New South Wales, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Williams
authors.affiliation: School of Medicine and Public Health, The University of Newcastle Newcastle, New South Wales, Australia ; Department of Respiratory Medicine, John Hunter Hospital New Lambton, New South Wales, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Arnold
keywords: CYBB mutations; Chronic granulomatous disease; refractory pneumonia; skewed lyonization