Recalcitrant primary subcutaneous phaeohyphomycosis due to Phialophora verrucosa.

Phialophora verrucosa has rarely been reported for causing phaeohyphomycosis, which tends to occur in immunocompromised individuals. The case of primary subcutaneous phaeohyphomycosis due to P. verrucosa in an otherwise healthy Chinese female is presented. The girl presented with asymptomatic skin lesions when she was only 16 year old. Histological examinations revealed multiple dematiceous hyphael elements in the dermis and subcutaneous tissues. Fungal cultures were identified as P. verrucosa repeatedly based on the morphological features and confirmed by the internal transcribed spacer region nucleotide sequencing. The infection was so extremely recalcitrant that prolonged systemic antifungal regimens for 12 years revealed limited effect. The skin lesions slowly progressed and caused marked disfigurement despite the encouraging results of in vitro susceptibility. However, no relevant side effects have been reported in the course, and the patient gave birth to a healthy baby while under the maintenance treatment of itraconazole and terbinafine. This case is special in terms of the early onset, the rare clinical aspect of the pathogen, the discrepancy between in vitro and in vivo antifungal activities and especially the prolonged and recalcitrant course in such an otherwise healthy host.

Mycotic granuloma caused by Phialophora repens.

This is the first reported infection by the saprophytic fungus, Phialophora repens. The infection was a solitary granulomatous nodule in the scalp of a Zaïrian man with advanced lepromatous leprosy. The patient was being treated by long-term prednisolone therapy. In tissue sections there were nonpigmented microcolonies composed of irregularly branched septate hyphae. A darkly pigmented fungus was isolated on Sabouraud's medium. The mycologic features of the etiologic agent were typical of P. repens. The infection was treated successfully by excision of the nodule.

Phialophora mutabilis endocarditis.

This is the first reported case of fungal endocarditis due to vegetative growth of Phialophora mutabilis on a prosthetic mitral valve. The patient had rheumatic heart disease with mitral and aortic stenosis. Four months after the mitral and aortic valves had been replaced by prostheses the patient developed congestive failure. Because of increased left atrial pressure, the mitral prosthesis was replaced. A large matted obstructive fungal vegetation was found on the prosthesis. Culture of this vegetation grew Phialophora mutabilis. The patient died postoperatively, and at autopsy the fungus was not found in other tissues. Culturally and morphologically, P. mutabilis shows wide variation in pigmentation, colonial and microscopic appearance. Conidia formation from intercalary cells along the hyphae is somewhat similar to that of Aureobasidium spp. P. mutabilis was injected into mice. Mice pretreated with cortisone died 3 to 5 weeks after intraperitoneal inoculation, while the majority of untreated mice died within 20 weeks of inoculation.

Phaeohyphomycotic ulcer caused by Phialophora verrucosa: successful treatment with itraconazole.

We report the first well documented case of subcutaneous phaeohyphomycotic infection caused by Phialophora verrucosa in India. Examination of the biopsied tissue from an ulcerating lesion on the shin of the left leg of a 45-year-old woman from Bombay, India, showed numerous dematiaceous, septate, branching hyphal elements and thick-walled cells characteristic of phaeohyphomycosis. Cultures of the scrapings from the lesion and of the biopsied tissue yielded a pigmented fungus that was identified as P. verrucosa. Initial treatment with fluconazole followed by oral itraconazole for 30 days and local application of a copper sulphate solution resulted in complete resolution of the lesion. Treatment with itraconazole was continued for an additional 3 months after complete healing. No new lesions developed and the patient did not show jaundice, hepatosplenomegaly or any other signs of toxicity.

Invasive chromoblastomycosis and sinusitis due to Phialophora verrucosa in a child from northern Africa.

We report on a severe, verrucous facial mycosis and sinusitis in a 12-year-old Libyan girl. Her disease started with verrucous, hyperkeratotic plaques and subcutaneous violet nodules of unknown origin on her face and upper extremities. Despite topical antimycotic therapy she needed in-hospital treatment because of severely progressive tumorous cutaneous and nasal lesions. Microscopic examination of scale samples taken from the upper extremities and the face revealed brown, thick-walled fungal elements. Under the assumption of a chromoblastomycosis, an oral treatment with itraconazole and fluorocytosin was initiated, with significant improvement of the lesions. The aetiological agent was identified as Phialophora verrucosa.

Nuclear division in temperature-sensitive multicellular mutants of Wangiella dermatitidis.

Temperature-sensitive morphological mutants of Wangiella dermatitidis were stained with mithramycin, a fluorescent nuclear stain. Multicellular forms of the mutants each contained two or more nuclei, documenting that nuclear division accompanied the yeast-to-multicellular form conversion.

Budding in the dimorphic fungus Phialophora dermatitidis.

Ultrastructural comparisons of yeast and hyphal bud formation in Phialophora dermatitidis reveal that bud initiation is characterized by a blastic rupture of the outer portion of the yeast or hyphal wall and the emergence of a bud protuberance through the resulting opening. The wall of the emerging bud is continuous, with only an inner wall layer of the parental yeast or hypha. The outer, ruptured portion of the parental wall typically forms a collar around the constricted emergence region of the developing bud. The cytoplasm within the very young emerging bud invariably contains a small number of membrane-bound vesicles. The septum formed between the daughter bud and the parental yeast or hypha is a complete septum devoid of a septal pore, septal pore plug, or any associated Woronin bodies characteristic of simple septa of the moniliform or true hyphae. These observations suggest that yeast bud formation and lateral hyphal bud formation in the dimorphic fungus P. dermatitidis involve a growth process which occurs identically in both the yeast and mold phase of this human pathogenic organism.

Conjugation in the dimorphic chromomycosis fungus Phialophora dermatitidis.

Phase-contrast microscope observations of the dimorphic fungus Phialophora dermatitidis revealed that thick-walled yeasts often tended to form aggregates and then to conjugate. Fusions were also observed among hyphae derived from the thick-walled yeasts.

The relationship of Phialophora verrucosa to Phialophora americana.

Phialophora verrucosa and P. americana, two dematiaceous hyphomycetes, are known to cause chromoblastomycosis. Even though most medical mycologists consider P. americana as synonymous with P. verrucosa, others maintain them as two distinct species on the basis that the phialides of P. americana have deeper collarettes than those of P. verrucosa. Thirty-two isolates, identified either as P. americana or P. verrucosa, were studied for their morphologic, physiologic, and antigenic characteristics to evaluate their taxonomic status. Collarette morphology was found to be a variable character in 12 of the 32 isolates. Those 12 produced phialides with both shallow and deep collarettes. All of the isolates hydrolysed urea within 7 days at 25 degrees C, and failed to liquefy gelatin after 3 weeks at 25 degrees C. None of the isolates decomposed casein, xanthine, or hypoxanthine at the end of 3 weeks at 25 degrees C. All decomposed tyrosine. They grew at 25 degrees C and 37 degrees C, but failed to grow at 40 degrees C. The antigenic relationship between the two species was studied by the exoantigen procedure. The 32 isolates showed close antigenic relatedness. Adsorptions of antisera with homologous and heterologous antigens rendered the antisera free of precipitin bands when studied by the microimmunodiffusion test. The depth of phialide collarettes produced by the two species, being found to be variable character, and the identical nature of the two species with respect to their physiologic and antigenic characteristics, led us to conclude that P. americana should be considered as a synonym of P. verrucosa.

Chromoblastomycosis. Report of a case from Tripoli, Libya.

A case of chromoblastomycosis which showed typical clinical and pathological features is presented from Tripoli, Libya, for record, as no cases seem to have been reported from that region.

Phialophora cyanescens sp. nov. with Phaeosclera-like synanamorph, causing white-grain mycetoma in man.

The human-pathogenic fungus, Phialophora cyanescens sp. nov. is characterized by the abundant production of chlamydospore-like cell aggregates resembling the form-genus Phaeosclera Sigler et al., and by elongate phialides with ellipsoidal conidia. A brown pigment and a blue, acid-labile pigment may be present.

Morphologica and structural changes during the yeast-to mold conversion of Phialophora dermatitidis.

The details of the morphological and structural events occurring during yeast-to-mold conversion of the human pathogenic fungus Phialophora dermatitidis as seen by phase-contrast microscopy and electron microscopy are described and illustrated. Budding yeasts growing exponentially were observed to have thin walls and a cytoplasm exhibiting the characteristics of rapidly growing cells including numerous mitochondria, abundant ribosomes, few vacuoles, and little accumulation of storage material. In contrast, thick-walled yeasts were characterized by less apparent or significantly fewer mitochondria and ribosomes and the presence of considerable amounts of storage materials. Microscope observations of yeast-to-mold conversion revealed that only thick-walled yeasts having prominent lipid bodies in their cytoplasm converted to hyphal forms. Typically, the thick-walled yeast formed two to a number of moniliform hyphal cells which in turn often produced true hyphae. The results indicated that yeasts of P. dermatitidis must acquire spore-like characteristics by becoming thick-walled and by accumulating considerable endogenous substrate reserves before they convert and produce hyphae.

Phialophora verrucosa infection in an AIDS patient.

Phialophora verrucosa is one of several pathogenic dematiaceous fungi associated with chromomycosis and occasionally phaeohyphomycosis. Infection appears to be increasing in frequency in both immunocompromised and presumably healthy patients. Medical therapy is often difficult, and a wide variety of antifungal agents have been tried with varying degrees of success. We report a patient with acquired immunodeficiency syndrome (AIDS) and extensive cutaneous fungal infection due to Phialophora verrucosa. The disease failed to respond to ketoconazole, but regression of the lesions was obtained with itraconazole.

Isolation of Lecythophora mutabilis and Wangiella dermatitidis from the fruit eating bat, Eidolon helvum.

Lecythophora mutabilis was isolated from the lungs of 3 and from the liver of 2 bats, Eidolon helvum a fruit eating species. Wangiella dermatitidis was recovered from the liver of 2 bats of the same species. The isolates were pathogenic for laboratory mice when injected by subcutaneous, intraperitoneal and intravenous routes. W. dermatitidis was neurotropic in the mice injected intravenously.

Studies on the phylogenesis of pathogenic 'black yeasts'.

This paper deals mainly with the conidium ontogenesis and phylogenesis of black yeasts such as E. jeanselmei, E. gougerotii, E. dermatitidis and E. spinifera. The conidium ontogenesis of E. jeanselmei, E. gougerotii and E. dermatitidis was almost the same. One to five annellated tips were observed through a scanning microscope at the apices of conidiogenous cells, which were bottle- or jar-shaped. Annellations on the tips looked like fringes and the conidiogenous cells of these three species were annellides. Annellated projections occurred on hyphae and annelloconidia were also produced from them. Occasionally, secondary annellides occurred from primary ones. They looked like moniliform hyphae. Daughter conidia sometimes budded directly from mother cells. The shapes and sizes of the conidia of these species were very similar to each other. The conidium ontogenesis of E. spinifera was annellidic as well. However, a single annellated tip usually occurred on an annellide. The annellated tips of the fungus were long and more than 20 annellations were observed on their walls. The conidiogenesis of the four species of Exophiala is only annellidic. There were no differences in the biological examinations except KNO3 assimilation among these four species. The growth of E. jeanselmei and E. gougerotii was poor at 37 degrees C. The GC contents of E. jeanselmei 1171, E. gougerotii B-1800, E. dermatitidis MM-7 and E. spinifera DU-3342 were 54.6, 54.6, 56.6 and 59.7%, respectively.

Subcutaneous infection with phialophora richardsiae and its susceptibility to 5-fluorocytosine, amphotericin B and miconazole.

Two patients are described with subcutaneous infections due to Phialophora richardsiae. Both were diabetics and originally came from subtropical areas. One of the patients had a cystic lesion which was well encapsulated while the other had a large ulcerating lesion with draining sinus tracts. The organisms were found to be susceptible to cycloheximide but resistant to 5-fluorocytosine, miconazole and amphotericin B. There was some variability in the degree of resistance depending upon whether the primary or secondary phialoconidia were tested. While simple excision appears curative for the solitary cystic type of lesion, therapy of the ulcerating form of the disease remains problematic.

Calcium regulates in vitro dimorphism in chromoblastomycotic fungi.

Cladosporium carrionii, Fonsecaea pedrosoi and Phialophora verrucosa, the three most important agents of chromoblastomycosis, produced large numbers of sclerotic bodies at 25 degrees C, and greater numbers at 37 degrees C, after inoculation into a defined pH 2.5 medium containing 0.1 mmol l-1 Ca2+. Higher concentrations of Ca2+ reversed this tendency and promoted maintenance of hyphal growth. Addition of the Ca2+ chelator EGTA to the same medium buffered at pH 6.5 also induced sclerotic bodies, but in a more concentration-dependent fashion. EGTA at 0.5-1.0 mmol l-1 induced maximum numbers of sclerotic bodies in Cl. carrionii, whereas 2 and 8 mmol l-1 concentrations were required for the same results with F. pedrosoi and P. verrucosa, respectively. These findings suggest that Ca2+ concentrations in human tissue may play a paramount role in the dimorphic switching between hyphae and sclerotic bodies among chromoblastomycotic agents during infection.