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 Burkholderia 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.

Macrophage activation syndrome/haemophagocytic lymphohistiocytosis secondary toBurkholderia cepaciacomplex septicaemia in an elderly female carrier of X-linked chronic granulomatous disease with extreme lyonisation: ‘cepacia syndrome’ revisited

“…There have been 14 cases to date describing MAS/HLH in CGD patients,7 18–21 with four of them appearing to be triggered by a member of the B. cepacia complex. Case reports of female X-linked carriers with a mutated CYBB gene, who have become immunodeficient through skewed lyonisation, have also previously been described,6 22–24 although our case is the first documented case of an elderly female carrier of X-linked CGD with profound skewing of lyonisation resulting in susceptibility to B. cepacia with triggering of MAS/HLH.…”

Recent advances in understanding and treating chronic granulomatous disease

“…An immunological assessment demonstrated reduced neutrophil function due to extreme lyonisation with only 3% normally functioning neutrophils. A pathogenic mutation in CYBB was found on sequencing, confirming her status as a symptomatic carrier of X-linked CGD; a positive family history was subsequently elicited 44 .…”

Late Onset of Chronic Granulomatous Disease Revealed by Paecilomyces lilacinus Cutaneous Infection

“…Three other cases of late-onset CGD have been described in the literature, all three patients being women aged 45, 53, and 64 [6][7][8]. These cases were diagnosed after infection by opportunistic pathogens (Aspergillus spp.…”

“…These cases were diagnosed after infection by opportunistic pathogens ( Aspergillus spp. [ 6 ], pulmonary infection with Burkholderia cepacia [ 7 ], and Serratia marcescens [ 8 ]). Invasive fungal diseases due to molds other than Aspergillus spp.…”