Cutaneous Phaeohyphomycosis of the Right Hand Caused by Exophiala jeanselmei: A Case Report and Literature Review.

Exophiala spp. is increasingly reported as a pathogen causing the cutaneous, subcutaneous or invasive infection. In this report, we present a case of cutaneous phaeohyphomycosis due to E. jeanselmei on the right hand of a farmer, who suffered from this disease three years ago which had not been definitely diagnosed until he was admitted to our hospital. In our hospital, a potential fungal pathogen was observed by histopathological examination, and then was recovered and identified as E. jeanselmei by sequencing its internal transcribed spacer region. After 4 weeks of antifungal treatment, his hand recovered very well. To investigate the in vitro susceptibility of E. jeanselmei isolates to antifungal agents and compare the characteristics of their related infections among immunocompetent and immunocompromised patients, we reviewed 84 cases published in PubMed database between 1980 and 2020.

Empiric antifungal therapy in patients with cutaneous and subcutaneous phaeohyphomycosis.

We encountered two cases of phaeohyphomycosis caused by Exophiala jeanselmei and E. oligosperma that were treated with fosravuconazole and terbinafine, respectively. Our cases were successfully treated with empiric therapy before the pathogen's species or antifungal sensitivity had been determined. We summarized 32 cases of cutaneous and subcutaneous phaeohyphomycosis caused by Exophiala species in Japan. The patients received antifungals, including itraconazole, terbinafine, voriconazole, and fosravuconazole, and the treatment success rates of these monotherapies were 77% (17/22), 67% (8/12), 100% (5/5), and 50% (1/2), respectively. Although the broad-spectrum azole antifungal itraconazole is the first choice for treatment, terbinafine at 125 mg/day might exert the same efficacy. Fosravuconazole is a novel broad-spectrum azole and a moderate inhibitor of Cyp3A4 that causes fewer drug interactions than itraconazole and voriconazole, indicating a promising drug for this disease.

A Case of Recalcitrant Phaeohyphomycosis of the Face Caused by Exophiala lecanii-corni.

We describe a case of recalcitrant phaeohyphomycosis caused by Exophiala lecanii-corni, which was previously reported as Exophiala jeanselmei, infection. A 63-year-old Japanese woman presented with a 15-year history of multiple pruritic erythematous patches and plaques on the face. Histopathological examination and fungal culture revealed phaeohyphomycosis by E. jeanselmei. The attempted treatments included 6 g/day 5-flucytosine (5-FC), 100 mg/day itraconazole (ITCZ), and local hyperthermia. 5-FC was effective initially, but the patient deteriorated after discontinuation. Subsequently, she was referred to our hospital. Histopathological examination showed granuloma with multinucleated giant cells with infiltrating fungal hyphae in the dermis. The causative fungus was finally identified as E. lecanii-corni by ribosomal RNA gene analysis. The patient improved after receiving 200 mg/day ITCZ orally for 15 months with local hyperthermia. In the present case, we confirmed the identification of E. lecanii-corni as the causative agent by molecular methods. We also emphasize the importance of combination therapy with antimycotic agents and local hyperthermia in phaeohyphomycosis.

Cloning, expression, and characterization of Baeyer-Villiger monooxygenases from eukaryotic Exophiala jeanselmei strain KUFI-6N.

The fungus Exophiala jeanselmei strain KUFI-6N produces a unique cycloalkanone monooxygenase (ExCAMO) that displays an uncommon substrate spectrum of Baeyer-Villiger oxidation of 4-10-membered ring ketones. In this study, we aimed to identify and sequence the gene encoding ExCAMO from KUFI-6N and overexpress the gene in Escherichia coli. We found that the primary structure of ExCAMO is most closely related to the cycloalkanone monooxygenase from Cylindrocarpon radicicola ATCC 11011, with 54.2% amino acid identity. ExCAMO was functionally expressed in E. coli and its substrate spectrum and kinetic parameters were investigated. Substrate profiling indicated that ExCAMO is unusual among known Baeyer-Villiger monooxygenases owing to its ability to accept a variety of substrates, including C4-C12 membered ring ketones. ExCAMO has high affinity and catalytic efficiency toward cycloalkanones, the highest being toward cyclohexanone. Five other genes encoding Baeyer-Villiger monooxygenases were also cloned and expressed in E. coli.

Chromoblastomycosis by Exophiala jeanselmei associated with squamous cell carcinoma.

Chromoblastomycosis is a subcutaneous, chronic, granulomatous mycosis that occurs more frequently in tropical and subtropical countries. Herein, we describe a case of a 90-year-old female patient with diagnosis of chromoblastomycosis by Exophiala jeanselmei with a 22-year evolution who developed a squamous cell carcinoma. In the meantime, She underwent two misdiagnoses and an unnecessary operation. This case is also the fifth case of E. jeanselmei caused CBM in history.

Subcutaneous phaeohyphomycosis due to Exophiala jeanselmei following renal transplantation: A case report with a published work review of phaeohyphomycosis in Japan.

We describe a case of cutaneous phaeohyphomycosis following renal transplantation and include a review of the previously published Japanese cases. A 40-year-old Japanese woman taking immunosuppressants following renal transplantation 6 years prior presented to our hospital with a subcutaneous lesion on her right leg. Skin biopsy revealed an abscess, and culture confirmed Exophiala jeanselmei to be the causative agent. Treatment with itraconazole combined with surgical drainage was effective, and the lesion disappeared after 15 months. Upon review of 128 Japanese phaeohyphomycosis cases, it was found that more than 80% of the cases occurred in patients aged more than 60 years, and most cases involved underlying diseases associated with immunodeficiency. E. jeanselmei was the most common etiologic fungus. Recently, however, the Exophiala species has been reclassified based on molecular identification, and cases due to E. jeanselmei decreased with the concomitant increase of cases due to Exophiala oligosperma and Exophiala xenobiotica. In approximately half of the cases, lesions were treated by surgical removal, with or without concomitant antifungal drugs. Itraconazole was the antifungal agent most frequently used. In many cases, the disease course was reported as either healing or improving. There was no difference in either treatment or prognosis based on the etiologic species of fungus.

Exploiting the Advantages of Molecular Tools for the Monitoring of Fungal Indoor Air Contamination: First Detection of Exophiala jeanselmei in Indoor Air of Air-Conditioned Offices.

Today, indoor air pollution is considered a public health issue. Among the impacting pollutants, indoor airborne fungi are increasingly highlighted. Most of the monitoring protocols are culture-based, but these are unable to detect the uncultivable and/or dead fraction or species suppressed by fast-growing fungi, even though this fraction could impact health. Among the contaminants suspected to be part of this fraction, Exophiala jeanselmei is an interesting case study. Known to be pathogenic, this black yeast grows in humid environments such as air-conditioning systems, where it has been previously detected using classical culture-based methods. However, until now, this fungus was never detected in indoor air in contact with these air-conditioning systems. This study shows the first detection of E. jeanselmei in indoor air collected from offices in contact with contaminated air-conditioning reservoirs. While its presence in indoor air could not be demonstrated with culture-based methods, it was found by real-time PCR and massive parallel sequencing. The latter also allowed obtaining a broader view on the fungal diversity in the tested samples. Similar approaches were applied on water samples collected from the conditioning reservoirs to trace the source of contamination. The comparison of results obtained with both methods confirmed that the molecular tools could improve indoor air monitoring, especially of dead and/or uncultivable contaminants or when competition between species could occur.

"A fine needle aspiration cytology in time saves nine" - cutaneous phaeohyphomycosis caused by Exophiala jeanselmei in a renal transplant patient: Diagnosis by fine needle aspiration cytology.

Infections by dematiaceous fungi are an emerging group of infectious diseases worldwide with a variety of clinical presentations. Though generally localized, they can disseminate in immunocompromised settings, therefore, early diagnosis and prompt therapy can prevent significant morbidity and mortality in these patients. Fungi of genus Exophiala are common causative organisms; however, Exophiala jeanselmei (E. jeanselmei) has not yet been reported from environmental sources in India. We present here the case of a renal transplant recipient who presented with an innocuous lesion on the foot, diagnosed on fine needle aspiration cytology (FNAC) as phaeohyphomycosis, and promptly treated with excision and antifungal therapy. To the best of our knowledge, this is the first case report from India of E. jeanselmei causing phaeohyphomycosis in a transplant recipient and highlights the role a cytopathologist can play in the timely management of such cases.

Phaeohyphomycosis Due to Exophiala jeanselmei: An Emerging Pathogen in India--Case Report and Review.

We present a rare case of a 30-year-old woman who presented with a swelling on the lateral aspect of her left forearm, present since 6 months, adjacent to a 16-year-old burn scar. X-ray of elbow joint and forearm revealed the subcutaneous nature of the swelling. Giemsa and periodic acid-Schiff-stained smears and potassium hydroxide mount of fine-needle aspirate of the swelling revealed dematiaceous, branching, and septate fungal hyphae. Fungal culture of the aspirated pus showed growth of Exophiala jeanselmei. Histopathological examination revealed brown-coloured hyphae with foreign body giant cell reaction and palisading granulomas in the surrounding tissue. The patient was successfully treated with surgical excision of the swelling. All the cases of phaeohyphomycosis due to Exophiala spp. in India are also reviewed.

A molecular approach for the rapid, selective and sensitive detection of Exophiala jeanselmei in environmental samples: development and performance assessment of a real-time PCR assay.

Exophiala jeanselmei is an opportunistic pathogenic black yeast growing in humid environments such as water reservoirs of air-conditioning systems. Because this fungal contaminant could be vaporized into the air and subsequently cause health problems, its monitoring is recommended. Currently, this monitoring is based on culture and microscopic identification which are complex, sometimes ambiguous and time-demanding, i.e., up to 21 days. Therefore, molecular, culture-independent methods could be more advantageous for the monitoring of E. jeanselmei. In this study, we developed a SYBR®green real-time PCR assay based on the internal transcribed spacer 2 from the 18S ribosomal DNA complex for the specific detection of E. jeanselmei. The selectivity (100 %), PCR efficiency (95.5 %), dynamic range and repeatability of this qPCR assay were subsequently evaluated. The limit of detection for this qPCR assay was determined to be 1 copy of genomic DNA of E. jeanselmei. Finally, water samples collected from cooling reservoirs were analyzed using this qPCR assay to deliver a proof of concept for the molecular detection of E. jeanselmei in environmental samples. The results obtained by molecular analysis were compared with those of classical methods (i.e., culture and microscopic identification) used in routine analysis and were 100 % matching. This comparison demonstrated that this SYBR®green qPCR assay can be used as a molecular alternative for monitoring and routine investigation of samples contaminated by E. jeanselmei, while eliminating the need for culturing and thereby considerably decreasing the required analysis time to 2 days.

Subcutaneous phaeohyphomycosis caused by Exophiala jeanselmei.

Exophiala jeanselmei, a saprobe in the environment, is an opportunistic pathogen. We present a rare case of subcutaneous phaeohyphomycosis caused by E jeanselmei in a man aged 66 years with a 3-month history of a tender swelling on the dorsal area of the left middle finger. Purulent fluid was aspirated from the area, and the culture yielded black colonies composed of conidiophores, phialides, and yeast cells. After sequencing of the rDNA ITS1-5.8S-ITS2 gene, the pathogen was confirmed as E jeanselmei. The patient was cured by surgical excision without any antifungal agents.

Pulmonary phaeohyphomycosis due to Exophiala jeanselmei：a case report and review of literature / 中国感染与化疗杂志

Objective To better understanding the clinical presentations of phaeohyphomycosis,and improve the diagnosis and management of the disease.Methods We reported a case of pulmonary phaeohyphomycosis caused by Exophiala jeanselmei at the First Affiliated Hospital of Guangzhou Medical University in 2008,and reviewed the relevant literature.The clinical,radio-logical and etiological features were summarized based on this case and the other 23 phaeohyphomycosis patients reported in China from January 1995 to August 2013.Results 24 Chinese cases of phaeohyphomycosis have been reported to date,including 15 males and 9 females.The age of these patients ranged from 4 to 76 (mean 40.0±21 .8)years old.Seventeen patients were otherwise healthy.The other 7 patients had complications.Clinical presentations of phaeohyphomycosis vary widely,including cutaneous and subcutaneous infection in 18 cases,pulmonary and central nervous system involvement in two cases each,para-nasal sinus and palpebral conjunctiva infection one case each.The diagnosis of 18 cases were confirmed both microbiologically and histologically.One case was confirmed histologically alone.Five cases were identified microbiologically alone.The samples for culture were collected from skin abscess (1/5 ),pulmonary tissue (2/5 ),and cervical spinal fluid (2/5 ),respectively. Twenty-two strains of causative organisms were identified,7 of which were Exophiala jeanselmei .Twenty-three patients received treatment.They were cured by antifungal agents alone (18)or in conjunction with surgical resection (4 ),or assisted with XD-635AB-based photodynamic laser therapy (1).Specifically,10 pa-tients were cured by itraconazole alone.Conclusions In China, most patients of phaeohyphomycosis have concurrent conditions or have previously received immunosuppressive agents and cor-ticosteroids.Cutaneous and subcutaneous infection were most common,located mainly on limbs,face,chest and abdominal skin.The most frequently isolated pathogen is Exophiala jeanselmei ,followed by Phialophora verrucosa and Exophiala spinifera .Itraconazole therapy would be very effective.Susceptibility testing is very useful in case of refractory infection.

Eumycetoma of the foot caused by Exophiala jeanselmei in a Guinean woman.

Eumycetomas are chronic infectious entities characterized by presence of mycotic grains in (sub-)cutaneous tissues, after accidental inoculation of an exogenous filamentous fungus in the skin. The lesions evolve towards painless pseudotumor of the soft parts. We report the original case of a Guinean woman exhibiting eumycetoma of the right foot. Both laboratory tests identified a dematiaceous fungus, Exophiala jeanselmei, as the responsible infectious agent. A medical treatment with voriconazole alone was sufficient to notice a substantial clinical improvement. This finding is unusual as E. jeanselmei is uncommon in Guinea-Conakry, and as optimal treatment rather associate antifungal azoles and surgical excision.

Case of phaeohyphomycosis producing sporotrichoid lesions.

A 90-year-old Japanese woman, taking prednisolone (5-10 mg/day) for polyarthritis, presented to our hospital with multiple subcutaneous lesions on her left arm in 2009. Her history included excision of a phaeomycotic cyst on the left middle finger in 2007. There were three subcutaneous nodules approximately 15 mm in diameter around her left wrist and a large soft cystic lesion measuring 80 mm × 60 mm on her left elbow. A granuloma with neutrophilic infiltration was detected in the deep dermis of a biopsy specimen. Chains composed of round brown cells and short pseudomycelia were found in the granuloma. Fungal cultures from the samples confirmed Exophiala sp. to be the causative agent. Treatment with terbinafine and local hyperthermia seemed effective as all the lesions tended to subside. However, the patient died due to pneumonia approximately 1 month after commencement of therapy.

Phaeohyphomycosis: a clinical-epidemiological and diagnostic study of eighteen cases in Rio Grande do Sul, Brazil

The goal of this study was to review 18 cases of phaeohyphomycosis in Rio Grande do Sul. The records of all of the patients with a diagnosis of phaeohyphomycosis between 1995-2010 were reviewed. Twelve of the 18 patients (66.6%) were male. The average age of the patients was 50 years old (range: 16-74 years). Eleven patients (61%) presented with subcutaneous lesions. Seven patients (38.8%) had received a solid organ transplant. In all of the cases, the presence of melanin in the fungal cells was determined by Fontana-Masson staining of tissue sections and documented. Among the 18 patients, a total of 11 different fungal species were isolated. The causative organisms included Exophiala jeanselmei, Alternaria, Curvularia, Cladophialophora and Colletotrichum gloeosporioides. To our knowledge, this review reports the first case of subcutaneous phaeohyphomycosis caused by C. gloeosporioides in a lung transplant patient. The number of reported cases of phaeohyphomycosis has increased in the last decade. In a number of cases, this increased incidence may be primarily attributed to iatrogenic immunodeficiency.

A Case of Subcutaneous Phaeohyphomycosis Caused by Exophiala jeanselmei / 대한피부과학회지

We report a case of subcutaneous phaeohyphomycosis caused by Exophiala (E.) jeanselmei in a 75-year-old female, who showed subcutaneous abscesses on the both forearms for 8 months. Histopathologically, suppurative granulomatous inflammation and short hyphae & spores were observed. Fungal culture grew out the typical black-gray velvety colonies of E. jeanselmei after 3 weeks. The isolate grew well at 25degrees C, but very poorly at 37degrees C. No growth could be observed at 40degrees C. We confirmed E. jeanselmei by colony & microscopic morphology and temperature tolerance test. The patient had been treated with fluconazole for 3 months.

A Case of Subcutaneous Phaeohyphomycosis Caused by Exophiala Jeanselmei / 대한피부과학회지

We report a case of subcutaneous phaeohyphomycosis caused by Exophiala(E,) jeanselmei in a 66-year-old female, who showed a mild tender, 4.5x3.5cm sized, erythematous cystic mass with satellite lesions on the left forearm for 4 months. Histopathologically, suppurative granulomatous inflammation, brownish conidia in a chain and hyphae were observed. Fungal culture grew out the typical black-gray velvety colonies of E. jeanselmei after 2 weeks. The isolate grow well at 25 C, but very poorly at 37 C. No growth could be observed at 40 C. Sporulation adequate for evaluation was present on the malt extract agar. We confirmed E. jeanselmei by colony and microscopic morphology, temperature tolerance and sugar assimilation tests. The patient had been treated with itraconazole for 6 momths. Complete remission was observed.

The Biodegradation of Low-molecular-weight Urethane Compounds by a Strain of Exophiala jeanselmei.

To further analyze the biodegradation of polyurethane polymers, we investigated the biodegradation of low-molecular-weight N-tolylcarbamate model compounds with structures closely resembling the urethane linkages found in polyurethanes based on tolylene-diisocyanate (TDI). Soil microflora were screened for microorganisms that were able to utilize toluene-2,4-dicarbamic acid, diethyl ester (compound 1) as the sole source of carbon, and the soil fungus Exophiala jeanselmei strain REN-11A was selected as the most effective strain. Several N-tolylcarhamate compounds were used, and it was found that REN-11A was able to degrade compound 1, as well as the related compound toluene-2,6-dicarbamic acid, diethyl ester, very efficiently. Further investigation showed that compound 1 was biodegraded to tolylene-2,4-diamine via the aromatic amine intermediates carbamic acid, (3-amino-4-methylphenyl)-, ethyl ester and carbamic acid, (5-amino-2-methylphenyl)-, ethyl ester.

Isolation of Fungi from Heterodera glycines and in vitro Bioassays for Their Antagonism to Eggs.

Twenty fungi were assayed in vitro for antagonism to eggs of Heterodera glycines. Eight of the fungi were isolated from cysts or eggs of H. glycines during the current study, one was isolated from Panagrellus redivivus, and eleven were obtained from other researchers or collections. The bioassays were conducted on eggs from nematodes that had been grown monoxenically on excised root tips. Phoma chrysanthemicola, one strain of Verticillium chlamydosporium, and one strain of V. lecanii caused a decrease (P < 0.01, P < 0.05, P < 0.05, respectively) in the number of viable eggs, although no hyphae were observed colonizing live eggs. Trichoderma polysporum infected live eggs but enhanced (P < 0.05) egg survival. Acremonium bacillisporum, Chaetomium sp., Drechmeria coniospora (two strains), Epicoccum sp., Exophiala jeanselmei, Fusarium sp., Neocosmospora vasinfecta, Scytalidium fulvum, Trichoderma harzianum (two strains), V. chlamydosporium (one strain), V. lecanii (three strains), and an unidentified fungus did not measurably affect egg viability, even though hyphae of five of these fungi were seen in live eggs. The bioassay provides a useful step in the selection of a biological control agent for this major nematode pest.