An 11 year old boy was admitted to hospital with right upper lobe pneumonia. Two weeks earlier he presented to his general practitioner with several days’ history of fever, cough, and malaise. He was prescribed amoxicillin, followed after a week by erythromycin.
Previous to this he had been healthy, except for an unusual, butterfly shaped, pigmented, indolent palatal lesion present for many years (fig 1). Because of this his dentist referred him at the age of 6 years to the oral surgeons who had noticed “somewhat hyperplastic palatal tissue that looked like a chronic candidiasis but with peculiar distribution”. However, no swabs were taken and no biopsy was performed at the time.
Figure 1 The unusual, butterfly shaped, pigmented, indolent palatal lesion that was present for many years in our patient.
After admission to hospital, he was started on intravenous penicillin and erythromycin but remained febrile and unwell. By day 4 he became lethargic, developed diarrhoea, progressive liver failure, leucopenia, and thrombocytopenia. Repeat chest radiography showed extension of pneumonia to the entire right lung, and ultrasound demonstrated pleural and pericardial effusions. Antibiotics were changed to ciprofloxacin and cefuroxime and he was transferred to a paediatric intensive care unit. Despite aggressive supportive care he died within 12 hours of transfer from overwhelming septic shock and multiorgan failure. Antemortem sputum and blood cultures had been negative.
The patient’s deterioration while on appropriate treatment for community acquired pneumonia suggested the involvement of an unusual organism.1
Indeed, postmortem cultures (blood, lungs, liver, and spleen) grew Burkholderia cepacia
. The presence of this well known, opportunistic pathogen found in individuals with pre-existing respiratory epithelial damage (such as patients with cystic fibrosis) suggested an underlying neutrophil disorder.2
The granulomatous inflammation of the lungs, liver, and spleen seen on postmortem histopathology further supported this possibility.
Unfortunately, because of the fulminant disease course, no immunological investigations were performed before death. However, 20% of the mother’s neutrophils had reduced oxidative burst activity, suggesting a carrier state for X linked chronic granulomatous disease (CGD) (fig 2C). Consequently, the mother’s sister’s 4 year old son, who was being investigated at the time for the cause of recurrent ear infections, intermittent colitis, and reduced energy levels, came to our attention. His neutrophil oxidative burst activity was absent (fig 2B). A C189G mutation in the CYBB
gene on the X chromosome, predicting Asn63Lys substitution in the gp-91phox
component of leucocyte NADPH oxidase, confirmed the diagnosis of X linked CGD and a heterozygous state in both mothers.3
He has since successfully undergone bone marrow transplantation from a human leucocyte antigen matched sibling.
Figure 2 Neutrophil oxidative burst activity; neutrophil counts (y axis) and log scale of arbitrary units of fluorescence (x axis). (A–C) Before (shaded) and (more ...)