Both X-linked and autosomal recessive forms of CGD are complicated by invasive aspergillosis and there is approximately a 40% lifetime incidence of this complication in CGD. A few even rarer cases of neutrophil dysfunction complicated by invasive aspergillosis are described. Occasional instances of 2 children from one family developing invasive aspergillosis, usually related to farm exposures have been reported. Most cases present in children, 56% at #5 years and 89% at #10 years.
The clinical presentation of invasive aspergillosis in CGD is distinctive. Pneumonia is most common but osteomyelitis is much more frequent, proportionately, than in other host groups (Table). Pneumonia tends to be bilateral, slowly progressive, with little or no fever. Radiologically it usually presents with a fine nodular pattern, widespread patchy shadowing or with a chest wall abscess with underlying consolidation. If a chest wall abscess is present (Table), rib osteomyelitis is invariably present as well. Extension from the lung may be posteriorly into the vertebral column giving rise to Aspergillus osteomyelitis and spinal cord compression. Often several vertebrae are involved.
Less commonly, long bone aspergillosis is the presenting feature, with localised pain and a subcutaneous abscess. This presentation of invasive aspergillosis is virtually unheard of in other clinical contexts. The same is true for lymph node aspergillosis, which may be in the mediastinum, which is exceptionally rare otherwise.
Disseminated aspergillosis, usually involving the brain, is the presenting feature of CGD occasionally but more commonly manifests as general ill health for a few days or weeks prior to focal disease becoming clinically apparent. Involvement of the brain is usually manifest as a fit or with features of a space occupying lesion. One unusual complication of pulmonary aspergillosis in CGD has been described – namely bronchopulmonary arterial malformation.
Treatment of amphotericin B 1mg/kg is of value but as treatment usually has to be continued for months or years, oral itraconazole is preferable. Short courses of amphotericin B (e.g. 4-8 weeks) are associated with unacceptably high relapse rates. Low serum concentrations of itraconazole are associated with clinical failure and therefore these should be monitored. Concentrations of at least1mg/l (HPLC) are necessary.
Prophylaxis against Aspergillus infection in chronic granulomatous disease patients can be achieved with itraconazole (Mouy et al,1994; Petropoulou et al, 1994). The dose used in studies was 5-10mg/kg daily. Units that have adopted itraconazole prophylaxis have seen a fall in the incidence of Aspergillus infections, although not to zero. This implies that patients may be non-compliant, especially during adolescence, that absorption may be inadequate, the dose used was too low for the patients weight or that the patients with infection were infected with itraconazole resistant isolates. A multicentre study is on-going in the USA to establish whether prophylaxis is useful. At present, it is not clear whether it should be used routinely, especially with the emergence of itraconazole resistant isolates of Aspergillus, but this would seem appropriate if serum concentrations are monitored.
Aspergillus infection in chronic granulomatous disease (Mouy, 1989)
|Pneumonia and extrapulmonary extension||9||(21%)|
|Visit the Chronic Granulomatous Disorder website