Disseminated infection due to Chrysosporium zonatum in a patient with chronic granulomatous disease and review of non-Aspergillus fungal infections in patients with this disease

Abstract

We report the first case of Chrysosporium zonatum infection in a 15-year-old male with chronic granulomatous disease who developed a lobar pneumonia and tibia osteomyelitis while on prophylaxis with gamma interferon. The fungus was isolated from sputum and affected bone, and hyphae were observed in the bone by histopathology. Therapy with amphotericin B eradicated the osteomyelitis and pneumonia, but pneumonia recurred in association with pericarditis and pleuritis during therapy with itraconazole. These manifestations subsided, and no recurrences occurred with liposomal amphotericin B therapy. Infections caused by Chrysosporium species are very rare, and C. zonatum has not previously been reported to cause mycosis in humans. This species, the anamorph of the heterothallic ascomycete Uncinocarpus orissi (family Onygenaceae), is distinguished by its thermotolerance, by colonies which darken from yellowish white to buff, and by club-shaped terminal aleurioconidia borne at the ends of short, typically curved stalks. The case isolate produced fertile ascomata in mating tests with representative isolates. The median (range) MICs for our isolate as well as those for two other human isolates and a nonhuman isolate determined by the National Committee for Clinical Laboratory Standards method adapted for moulds were </=0.06 microg/ml (</=0.06 to 0.25 microg/ml) for amphotericin B, 0. 687 microg/ml (0.25 to 2 microg/ml) for itraconazole, >128 microg/ml (>128 microg/ml) for flucytosine, and 48 microg/ml (32 to >128 microg/ml) for fluconazole.

FIG. 1

Chest CT. (A) Enlarged left hilar lymph nodes and lingular pneumonitis. (B) Right lower lobe mass.

FIG. 2

Histopathological findings from tibia osteomyelitis. (A) Silver methenamine stain. Magnification, ×680. Polymorphic fungal elements can be seen in the midst of inflammatory infiltrate of tibia lesion. (B) Hematoxylin-eosin stain. Magnification, ×1,600. In the midst of inflammatory cells, fungal elements (three of them in the lower part of the picture) with a thin capsule and a fine basophilic internal structure can be recognized.

FIG. 3

Colony of C. zonatum UAMH 8936 (case isolate) on PDA after 14 days at 37°C. Magnification, ×0.8.

FIG. 4

Microscopic appearance of C. zonatum in slide culture preparations showing aleurioconidia borne at the tips of short, typically curved stalks (curved arrow) or sessile (straight arrow). (A) Case isolate (UAMH 8936). Magnification, ×580. (B) Isolate with a single ascospore (UAMH 6635). Magnification, ×460.

FIG. 5

Oblate (appearing flattened in the side view and spherical in the face view) ascospores (straight arrow) of the sexual stage of U. orissi and detached conidia of the C. zonatum stage (curved arrow). Ascospores were formed in a mating between the case isolate (UAMH 8936) and an isolate with a single ascospore (UAMH 6635). Magnification, ×580.

FIG. 6

Scanning electron microscopic appearance of oblate ascospores of a cross of strains UAMH 6499 and UAMH 6500 reveals minute surface pits (puncta) and a shallow equatorial furrow (arrow). Bar, 4 μm.