Comparison of Aspergillus nidulans and Aspergillus fumigatus as causes of osteomyelitis in patients with chronic granulomatous disease

J Dotis, Filioti, E. Farmaki, R. Winn, E. Roilides

Author address: 

3rd Department of Paediatrics, Aristotle University, Thessaloniki, Greece


Chronic granulomatous disease (CGD) is a rare inherited disorder of the NADPH oxidase complex in which neutrophils and monocytes fail to generate reactive oxidants such as superoxide anion and hydrogen peroxide, key elements in host defense against a variety of bacterial and fungal pathogens. The overall incidence of fungal infections in CGD has been reported at least 20%, with Aspergillus spp. being responsible for 78% of all fungal infections. Aspergillosis is the most common cause of mortality in these patients being responsible for over one third of deaths. Although Aspergillus fumigatus is by far the most frequent fungus causing infections in immunocompromised patients, A. nidulans has also been recognized as a human pathogen. Osteomyelitis has occurred in 25% of patients with CGD. Aspergillus spp. are the second most common cause accounting for approximately 22% of all osteomyelitis cases as recorded in the USA registry. We recently treated a CGD patient with femoral osteomyelitis due to A. nidulans who had a favorable outcome. We review the reported cases of osteomyelitis in CGD patients due to this organism and we compare them with those due to A. fumigatus. Twenty cases of A. nidulans infections have been reported in CGD patients to date. In the great majority, lungs have been involved, whereas in some patients, expansion to neighboring tissues or to remote areas has taken place. Fifteen cases of osteomyelitis due to A. nidulans have been described in patients with CGD. All of them have been males and associated with simultaneous pulmonary infection except for our case. Vertebrae and ribs have been found as the sites most commonly affected mainly as a result of rapid contiguous spread from a pulmonary focus. The outcome has been generally poor with a mortality rate approaching 50%. The commonest genetic pattern has been Xlinked CGD gp91-phox-deficient (60% of 15 cases). The management of these cases has been problematic. Treatment has required a combined approach with surgical debridement, because of the persistent nature of the organism, and administration of intensive and prolonged antifungal therapy with amphotericin-B (AMB) in the great majority of cases. The addition of a colonystimulating factor or interferon-gamma has appeared to have catalytic role in the treatment of these infections. By comparison, osteomyelitis due to A. fumigatus has been reported in 8 male CGD patients to date.There has been no predilection for particular bones; tibia, femur, spine and cranium have been some examples. At least two multifocal osteomyelitis cases have been described. In all cases the outcome has been favourable. However, in most of them treatment has required a combined approach with surgical debridement and AMB. In some cases, interferon-gamma has also been used. In conclusion, overall A. fumigatus has been a more common pathogen compared with A. nidulans in CGD, but A. nidulans has been more virulent and significantly more likely to result in death, to involve adjacent bones and to cause disseminated disease compared to A. fumigatus. Patients with A. nidulans osteomyelitis have received longer courses of AMB therapy compared to patients with A. fumigatus osteomyelitis. Surgical debridement appears to be necessary, but especially in A. nidulans osteomyelitis early surgery is imperative. Adjunctive use of cytokines in both A. nidulans and A. fimigatus osteomyelitis seems to be successful. This comparison shows that A. nidulans osteomyelitis carries more severe implications than that of A. fumigatus and needs more aggressive therapy.

abstract No: 


Full conference title: 

12th International Symposium on Infections in the Immunocompromised Host
    • ISIIH 12th