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PubMedDate not supplied

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↗
PubMed2003

Phosphatase activity on the cell wall of Fonsecaea pedrosoi.

The activity of a phosphatase was characterized in intact mycelial forms of Fonsecaea pedrosoi, a pathogenic fungus that causes chromoblastomycosis. At pH 5.5, this fungus hydrolyzed p-nitrophenylphosphate (p-NPP) to p-nitrophenol (p-NP) at a rate of 12.78 +/- 0.53 nmol p-NP per h per mg hyphal dry weight. The values of Vmax and apparent Km for p-NPP hydrolyses were measured as 17.89 +/- 0.92 nmol p-NP per h per mg hyphal dry weight and 1.57 +/- 0.26 mmol/l, respectively. This activity was inhibited at increased pH, a finding compatible with an acid phosphatase. The enzymatic activity was strongly inhibited by classical inhibitors of acid phosphatases such as sodium orthovanadate (Ki = 4.23 micromol/l), sodium molybdate (Ki = 7.53 micromol/l) and sodium fluoride (Ki = 126.78 micromol/l) in a dose-dependent manner. Levamizole (1 mmol/l) and sodium tartrate (10 mmol/l), had no effect on the enzyme activity. Cytochemical localization of the acid phosphatase showed electrondense cerium phosphate deposits on the cell wall, as visualized by transmission electron microscopy. Phosphatase activity in F. pedrosoi seems to be associated with parasitism, as sclerotic cells, which are the fungal forms mainly detected in chromoblastomycosis lesions, showed much higher activities than conidia and mycelia did. A strain of F. pedrosoi recently isolated from a human case of chromoblastomycosis also showed increased enzyme activity, suggesting that the expression of surface phosphatases may be stimulated by interaction with the host.

Ascomycota↗
PubMed1992

Saperconazole in the treatment of systemic and subcutaneous mycoses.

In a 2-year period, 30 patients with culture-proven mycoses (chromoblastomycosis, sporotrichosis, and paracoccidioidomycosis) were treated with the new orally administered triazole, saperconazole (SPZ) (R66905). The daily dose varied from 100 to 200 mg. All patients responded to treatment; the mean time required to heal the lesions and convert the cultures to negative was 3.5 months for sporotrichosis, 4.6 for paracoccidioidomycosis, and 9.0 for chromoblastomycosis. Evaluation by a scoring system indicated that 36.6% of the patients achieved complete resolution of the pretherapy abnormalities, while the remaining (63.3%) experienced major improvement. No collateral effects were reported; there were no bone-marrow or liver toxicities. SPZ is an effective drug for the treatment of the above-mentioned mycoses and appears to be suitable for the control of chromoblastomycosis.

Administration, Oral↗
PubMed2000

Black fungi: clinical and pathogenic approaches.

Data are presented on the clinically relevant black yeasts and their relatives, i.e., members of the Ascomycete order Chaetothyriales. In order to understand the pathology of these fungi it is essential to know their natural ecological niche. From a relatively low degree of molecular variability of the black yeast Exophiala dermatitidis, potential agent of brain infections in patients from East Asia, it is concluded that this species is an emerging pathogen, currently going through a process of active speciation. It is found to be an oligotrophic fungus in hot, moist environments, such as steambaths. Cladophialophora-, Fonsecaea- and Ramichloridium-like strains, known in humans as agents of chromoblastomycosis, are frequently found on rotten plant material, but the fungal molecular diversity in the environment is much higher than that on the human patient, so that it is difficult to trace the etiological agents of the disease with precision. This approach has been successful with Cladophialophora carrionii, of which cells resembling muriform cells, the tissue form of chromoblastomycosis, were found to occur in drying spines of cacti. Phagocytosis assays provide a method to distinguish between pathogens and non-pathogens, as the killing rates of strict saprobes proved to be consistently higher than of those species frequently known as agents of disease. The therapeutic possibilities for patients with chromoblastomycosis are reviewed.

Antifungal Agents↗
PubMed2006

Delayed-type hypersensitivity response to crude and fractionated antigens from Fonsecaea pedrosoi CMMI 1 grown in different culture media.

Chromoblastomycosis is a subcutaneous fungal disease caused by dematiaceous fungi, especially by Fonsecaea pedrosoi, regarded as its major causative agent in Brazil. In recent years there has been a decline in the use of skin testing for delayed-type hypersensitivity (DTH) in epidemiological surveys of fungal infections, mainly because of the unpredictability of positive reactions and lack of specificity of the antigens used. The aim of the present study was to assess delayed-type skin tests in guinea pigs experimentally infected with F. pedrosoi using exoantigens prepared from two culture filtrates. Sixteen adult male guinea pigs were inoculated intratesticularly with fungal cells and submitted to sensitivity assays 4 weeks after inoculation. They received an intradermal injection with crude and fractionated antigens from Alviano's and Smith's cultures, and were assessed 24 and 48 h thereafter. Except for one animal, all of them had positive indurations after 48 h. There were no statistical differences between the measurements at 24 and 48 h for each exoantigen used, neither among the induration measurements at 48 h when different preparations were compared. Our results suggest that a delayed-type skin test using antigens produced in synthetic media may be useful for the assessment of primary exposure to chromoblastomycosis.

Animals↗
PubMed2026

Simultaneous determination of imiquimod and terbinafine in skin permeation studies: Validation of a liquid chromatography method with fluorescence detection.

Chromoblastomycosis is a chronic, neglected subcutaneous mycosis posing significant therapeutic challenges. A topical strategy combining terbinafine (TBF), an antifungal, with imiquimod (IMQ), a TLR-7/8 agonist immunomodulator, has emerged a promising alternative. However, no validated analytical method is currently available to simultaneously quantify both drugs in skin, which is crucial for novel formulation development. This study reports the development and validation of a simple HPLC method with fluorescence detection (excitation 236 nm, emission 340 nm) for the simultaneous determination of TBF and IMQ extracted from porcine skin. Separation was achieved on a C8 reversed-phase column (125 × 4.0 mm, 5 μm) using a mobile phase of methanol and water (60,40, v/v), both containing 0.1% formic acid at a flow rate of 0.8 mL/min. The method showed excellent linearity (r > 0.999) over 0.01-1.0 μg/mL for IMQ and 0.1-2.0 μg/mL for TBF. Intra- and inter-day precision demonstrated coefficients of variation below 5%, and recovery rates from skin (79-105%) confirmed accuracy. Limits of detection were 0.001 μg/mL for IMQ and 0.004 μg/mL for TBF, with quantification limits of 0.02 μg/mL and 0.16 μg/mL, respectively. This selective, sensitive, and reproducible method represents a valuable analytical tool for supporting the development and quality control of topical formulations for chromoblastomycosis and other fungal skin diseases.

Animals↗
PubMed1994

Treatment of tropical mycoses.

Several subcutaneous and deep-seated mycoses are either observed more frequently in the tropical areas or are restricted to certain regions within the tropics. These mycoses include sporotichosis, chromoblastomycosis, entomophthoromycosis, eumycetoma, lobomycosis, and paracoccidioidomycosis. In sporotrichosis and paracoccidioidomycosis, therapy often results in either complete resolution or marked improvement. For decades sporotrichosis has been treated successfully with potassium iodide, but recently the triazole compounds, especially itraconazole, have proved effective and free of major side effects. The usual therapy for paracoccidioidomycosis is sulfonamides or amphotericin B; the former requires prolonged treatment, whereas the latter causes a significant degree of toxicity. Various azole derivatives (ketoconazole, fluconazole, saperconazole, and itraconazole) allow shorter treatment courses, can be given orally, and are more effective. Presently, itraconazole is the drug of choice. Chromoblastomycosis is a difficult condition to treat, especially if it is caused by Fonsecaea pedrosoi. Several therapeutic approaches have been used, including heat, surgery, cryotherapy, thiabendazole, amphotericin B combined with flucytosine, and azole derivatives, but their success has been modest. A 65% response rate has been obtained with itraconazole given for periods of 6 to 19 months; in limited trials, saperconazole appears to be more effective and requires shorter treatment courses. Only a few patients with eumycetoma respond to therapy; 70% of patients with Madurella mycetomatis respond to prolonged treatment with ketoconazole. Griseofulvin has been tried in nonresponders with partial success. Limited data in patients with Fusarium species eumycetoma indicate good responses to itraconazole. Eumycetoma caused by Pseudallescheria boydii or Acremonium species has been refractory to therapy. Therapy of entomophthoromycosis is also difficult because the diagnosis is usually established late and not all patients respond to therapy; this situation applies to infection caused by either Basidiobolus haptosporus or Conidiobolus coronatus. Although there is no consensus, African physicians prefer to use potassium iodide or trimethoprim-sulfamethoxazole. Isolated reports indicate that the azole derivatives, including the triazoles, may be effective. As for lobomycosis, all attempts at medical treatment have failed. Surgery is successful only when the lesion is small and can be fully resected; repeated cryotherapy appears to be more successful.

Antifungal Agents↗
PubMed2006

Absence of CD4+ T cells impairs host defence of mice infected with Fonsecaea pedrosoi.

Chromoblastomycosis is a human chronic, often debilitating, suppurative, granulomatus mycosis of the skin and subcutaneous tissues beginning after inoculation trauma. It occurs worldwide, but is more frequently observed in tropical countries such as Brazil. Some studies have focused on fungus-host interaction, showing a predominantly cell-mediated immune response, with the activation of macrophages involved in fungus phagocytosis. Immunization with live conidia produced a high influx of CD4 T cells into the draining lymph node. The sensitized T cells proliferate in vitro when restimulated with specific antigen and preferentially produce IFN- gamma. To better characterize the role played by T cells on the chromoblastomycosis infection we used mice deficient for CD4 and CD8. Data determined by CFU counts associated with decreased DTH and IFN-gamma production of infected mice clearly demonstrated that, during experimental F. pedrosoi infection, absence of CD4(+) cells induces a more severe disease.

Animals↗
PubMed2002

Comparison of Fonsecaea pedrosoi sclerotic cells obtained in vivo and in vitro: ultrastructure and antigenicity.

The parasitic form of Fonsecaea pedrosoi from the hyperkeratotic layer of the skin was obtained from four patients with chromoblastomycosis. Primary cultures containing hyphae and conidia were successfully converted into sclerotic cells in the presence of 800 microM propranolol and low pH as described before. The morphology of sclerotic cells of F. pedrosoi obtained in vivo and in vitro was analyzed by light and electron microscopy. Their antigenicity was also compared by immunofluorescence microscopy and ELISA assays, using serum samples from untreated patients infected with F. pedrosoi. Due to the similarity of the sclerotic cells obtained in vivo and in vitro, the latter can be more adequately in studies of host-parasite interactions in chromoblastomycosis.

Adult↗
PubMed2005

Clinical treatment of corneal infection due to Fonsecaea pedrosoi--case report.

UNLABELLED: To report an unusual case of fungus keratitis due to Fonsecaea pedrosoi that developed after corneal trauma. CASE REPORT: A 18-year-old male presented with a corneal ulcer in the right eye, 28 days after a trauma with glass fragments. Corneal scrapings were collected for smears and culture. Dematiaceous hyphae were seen on wet mounts of the scrapings and dark pigmented colonies grew repetitively on the culture media; all colonies were identical, and were subsequently identified as Fonsecaea pedrosoi. Treatment was initiated with topical natamycin at one hour intervals, 200 mg oral ketoconazole per day and later changed to a combination of 200 mg ketoconazole and amphotericin B. In humid tropical regions Fonsecaea pedrosoi is one of the primary causes of human chronic cutaneous mycosis, chromoblastomycosis. Combination of systemic and topical antifungal medications may provide the best option for cure in corneal chromoblastomycosis.

Adolescent↗
PubMed2006

Isolation of Fonsecaea pedrosoi from the shell of the babassu coconut (Orbignya phalerata Martius) in the Amazon region of Maranhão Brazil.

Fonsecaea pedrosoi, a dematiaceous fungus and the main causative agent of chromoblastomycosis, has been isolated in worldwide from different natural sources in regions where the disease is endemic. In the Amazon region of Maranhão, Brazil, where the disease is prevalent, the breaking of the babassu coconut (Orbignya phalerata Martius) represents an important agricultural activity. In order to determine the presence of this fungus on this plant and on other natural substrates, material was collected in the Fortaleza Village Municipality of Pinheiro, Maranhão, in April and September 2002. A total of 68 samples, including 18 (26.5%) obtained from the shell of the babassu coconut, were analyzed. Samples were cultured using a standard method. Isolates were identified based on macromorphological aspects of the colonies on Sabouraud dextrose agar and based on the micromorphology of the conidia after growth on potato dextrose agar. Exophiala sp. was the most prevalent fungus isolated from the different natural substrates analyzed, while Cladophialophora sp. was only isolated from decomposing wood. Fonsecaea pedrosoi was isolated from one sample of babassu coconut shell suggesting that this coconut represents an important source of infection of chromoblastomycosis during extraction of the plant product in this region.

Ascomycota↗
PubMed1995

Successful treatment of subcutaneous mycoses with fluconazole: a report of two cases.

Lymphocutaneous sporotrichosis and chromoblastomycosis are subcutaneous mycoses caused by traumatic implantation of the fungus into the skin. Medical treatments for chromoblastomycosis has been disappointing, while lymphocutaneous sporotrichosis usually responds well to iodides. Here we present a case of chromomycosis and a case of lymphocutaneous sporotrichosis. Both patients were treated successfully with fluconazole.

Adult↗