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Phaeohyphomycosis due to Phialophora richardsiae.

Phaeohyphomycosis, an infection characterised by dematiaceous yeast-like cells, hyphae and pseudohyphae in tissue, is an uncommon condition, often affecting immunosuppressed patients. A sixty four year old boat-builder, receiving treatment with prednisone and azathioprine developed multiple cutaneous nodules on the extremities. Histology showed a mixed dermal inflammatory infiltrate with scattered spores and hyphae. Culture revealed two organisms, Phialophora richardsiae and Exophiala jeanselmei. Fluorocytosine was initially given but the organism was found to be resistant. Since side effects have been associated with long term ketoconazole therapy, a less toxic and more potent triazole compound, itraconazole, was used. After three months, the lesions had completely resolved without adverse clinical or biochemical changes.

Antifungal Agents↗

Phialophora corneal ulcer.

BACKGROUND: A corneal fungal ulcer which appeared to be quite superficial clinically, was found by histologic examination to unexpectedly involve the full thickness of the cornea. METHODS: A patient with an apparent superficial corneal fungal ulcer due to Phialophora species was resistant to topical and intravenous antifungal therapy. RESULTS: Penetrating keratoplasty cured the condition with retention of normal vision with a follow-up of two years. CONCLUSIONS: If keratomycosis is unresponsive to topical and intravenous antifungal therapy, penetrating keratoplasty may be required to eliminate the infection. Resistance to medical therapy might suggest presence of fungus far deeper in the cornea than suspected clinically.

Adult↗

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.

Cell Wall↗

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.

Cell Wall↗

Gluteal abscess caused by Phialophora hoffmannii and review of the role of this organism in human mycoses.

Infections caused by members of the Phialophora hoffmannii (Beyma) Schol-Schwarz fungal aggregate (a group of related taxa, especially species of uncertain circumscription) are not reported frequently. This case report concerns the development of a gluteal abscess after multiple intramuscular injections of antimicrobial agents. Microbiological examination of the abscess material yielded a pure growth of the mold P. hoffmannii. Hyphal elements in the purulent exudate were only demonstrated when the specimen was digested by an N-acetyl cysteine-NaOH digestion-decontamination procedure or in stained paraffin block sections of the exudate. Other cases of disease caused by members of this fungal aggregate and the status of the mycology of this organism are reviewed.

Abscess↗

Phialophora repens, an emerging agent of subcutaneous phaeohyphomycosis in humans.

A 63-year-old Japanese man had phaeohyphomycosis that occurred as a solitary subcutaneous nodule on the dorsal aspect of his left hand. In the nodule there were foci of mixed granulomatous and suppurative infiltrations circumscribed by thick fibrous tissue reaction. The foci contained short septate hyphae and occasionally small rounded aggregates of irregularly branched septate hyphae, both of which were nonpigmented or rarely weakly pale brown. Fungal culture from the nodule was positive for a dematiaceous mold. The mycologic features of the mold were typical of Phialophora repens. The infection was successfully treated by excision of the nodule. This is the second reported case of infection due to P. repens.

Dermatomycoses↗

Molecular identification of Phialophora oxyspora as the cause of mycetoma in a horse.

CASE DESCRIPTION: An 18-year-old mare was evaluated for an oral mass that developed after extraction of a broken incisor. CLINICAL FINDINGS: An ulcerated, firm, darkly pigmented, approximately 5-cm-diameter spherical mass involved the gingiva lateral and dorsal to the right first to third maxillary incisors. Osteolysis of the roots of the first and second right maxillary incisors and periosteal proliferation of the adjacent premaxilla margins were apparent on radiographs. Histologic examination of the mass revealed multiple coalescing and ramifying foci of abscess formation, each containing a well-defined, discrete, black mass (2 to 7 mm in diameter). Myriad fungal hyphae enmeshed in a black, granular, cementlike material were within each of the black structures. Mycetoma was the histologic diagnosis. The causative agent could not be identified via culture because of lack of distinguishing characteristics. Fungal DNA was isolated from frozen fungal cultures and paraffin sections. The D1/D2 domains of the large subunit P gene rDNA were amplified and sequenced. The sequences of the D1/D2 domains of both isolates were 96% homologous with those of Phialophora oxyspora. TREATMENT AND OUTCOME: The mass was surgically excised, the local area curetted, and the wound allowed to heal by second intention. Postoperative treatment consisted of administration of phenylbutazone and IV administration of sodium iodide followed by oral administration of potassium iodide. There was no evidence of recurrence 1 year later. CLINICAL RELEVANCE: Mycetomata should be a differential diagnosis for equine gingival masses. Identification of the fungal agent can be critical for selection of optimal treatments. Molecular methods may permit definitive identification when standard phenotypic-based identification criteria are inconclusive.

Animals↗

Multifocal subcutaneous phaeohyphomycosis caused by Phialophora verrucosa.

An otherwise healthy 85-year-old woman presented with purulent multifocal subcutaneous nodules on the dorsal side of the right forearm and hand. Histopathologic examination of the biopsied specimen showed a subcutaneous granuloma with central abscess and necrosis, consistent with phaeomycotic cyst. Faint brown septate hyphae and moniliform fungal elements were found in the granuloma. Culture of the discharge grew Phialophora verrucosa. This fungus has rarely been reported as a pathogen of subcutaneous phaeohyphomycosis. Subcutaneous phaeohyphomycosis usually presents as a single lesion. In this case of multifocal lesions, initial imperfect excision seems to have caused satellite lesions. To our knowledge, this is the first report of multifocal subcutaneous phaeohyphomycosis caused by P verrucosa. The disease responded to oral itraconazole administration.

Aged↗

Mycetoma and phaeohyphomycosis caused by Phialophora parasitica in Thailand.

Phaeohyphomycosis caused by Phialophora parasitica is rare and it has never been documented in Thailand. The first two Thai cases of phaeohyphomycosis caused by P. parasitica were recognized in early 1990 at Ramathibodi Hospital, Bangkok, Thailand. Both patients had underlying diseases. The fungus developed in abscesses with pigmented mycelium at the lower extremity. Cultures from pus and tissue biopsies were positive for dematiaceous fungi. Light microscopic features suggested P. parasitica and which was illustrated by both scanning and transmission electron microscope. The first case was treated with itraconazole with a satisfactory initial response. The second case was successfully treated by surgical removal of the entire lesion.

Adult↗

Details of the fungistatic effect of Phialophora cinerescens.

We have previously isolated two chlorinated antibiotics from Phialophora asteris and P. asteris f. sp. helianthi, vascular pathogens on plants. P. cinerescens, pathogen on carnation, also presents a fungitoxic activity but the nature of the antibiotic compound is still unknown. We point out that this activity can be lost by sectorial variations on the growing margin and that the antibiotic product shows a striking photolability.

Antifungal Agents↗

A case of disseminated Phialophora parasitica infection.

The numbers and kinds of fungi that are known to cause human mycoses have increased greatly in the past decade. We report the first case (to our knowledge) of disseminated Phialophora parasitica infection. The patient, a 92-year-old woman, had known chronic subcutaneous infection with P parasitica. The systemic nature of her disease was diagnosed at autopsy, when the organism was identified in cultures obtained from a thrombus within an abdominal aortic aneurysm and was also histologically demonstrated within sections obtained from the aneurysm wall.

Aged↗

Phialophora verrucosa-induced subcutaneous phaeohyphomycosis. Fine needle aspiration findings.

A 34-year-old woman on immunosuppressive therapy presented with a subcutaneous, cystic lesion on the dorsum of the right foot. Cytologic examination of material obtained by fine needle aspiration (FNA) revealed a mixture of acute and granulomatous inflammation as well as brown-pigmented fungi in the form of budding yeast, pseudohyphae and septate hyphae. The findings suggested subcutaneous phaeohyphomycosis (phaeomycotic cyst). Culture grew Phialophora verrucosa. The cytologic, histologic and cultural findings are given. This case demonstrates that phaeohyphomycosis can be diagnosed by FNA but that fungal culture is necessary to establish the identity of the etiologic agent. This appears to be the first case of P. verrucosa-induced subcutaneous phaeohyphomycosis reported in the Western Hemisphere.

Adrenal Cortex Hormones↗

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.

Adult↗

Sex hormone effects on Phialophora verrucosa in vitro and characterization of progesterone receptors.

To determine the effects of sex steroid hormones on the growth of an aetiologic agent of chromoblastomycosis, we studied the dematiaceous fungus Phialophora verrucosa. The in vitro growth of this species on culture media containing either progesterone, testosterone or oestradiol at various concentrations was assessed. Both progesterone and testosterone inhibited the growth of P. verrucosa, whereas oestradiol did not. In other experiments, fungal cytosolic fractions were obtained and steroid binding assays were performed. These studies showed that the presence of progesterone receptors possessed two binding sites as determined by Scatchard analysis, one of which has a high affinity to progesterone (Kd = 6.02 x 10(-8) M) with total binding sites of 120 fmol micrograms-1 protein. These findings suggest that the growth of P. verrucosa is regulated by steroid hormones and that the effect of progesterone could be mediated through fungal intracellular progesterone receptors.

Antifungal Agents↗

Atypical eumycetoma caused by Phialophora parasitica successfully treated with itraconazole and flucytosine.

Phialophora species are occasional pathogens causing subcutaneous and invasive disease. We report the first case of eumycetoma caused by P. parasitica in an otherwise healthy U.K. resident who visited India. She failed to respond to surgical excision and itraconazole, 400 mg daily, but responded to itraconazole, 400 mg daily, and flucytosine, 1 g three times daily, for 12 months. In vitro susceptibility testing predicted a response.

Adult↗

A case of chromoblastomycosis due to Phialophora verrucosa responding to treatment with fluconazole.

We report the case of a 40-year-old Filippino woman, with a 5-year history of a slowly spreading, painful skin lesion on her left foot. Histological examination showed a dermal, granulomatous infiltrate consisting of neutrophils, histiocytes and lymphocytes, with "sclerotic bodies" in the cytoplasm of phagocytic cells. Mycological culture revealed the presence of Phialophora verrucosa and confirmed the histopathological diagnosis of chromo-blastomycosis. Association of surgical curettage of the exuberant, infected tissue with systemic fluconazole administration gave good therapeutic results with no relevant side effects.

Adult↗