A 56-year-old woman on insulin therapy for diabetes visited our clinic due to whitish discoloration on the right index finger. Despite topical application of 1% lanoconazole solution, the lesion ...grew, causing paronychia. Direct microscopy revealed non-dermatophyte molds. Based on the morphological features and genetic analysis of the isolate, the pathogen was identified as Aspergillus flavus. The patient was diagnosed with proximal subungual onychomycosis due to A. flavus. Following itraconazole pulse therapy, she was cured in 6 months. To our knowledge, this is the first reported case of fingernail onychomycosis due to A. flavus in Japan.
Fusarium onychomycosis is uncommon in the temperate climate zone of Japan. Based on the morphological characteristics and a gene analysis, we diagnosed a patient with ungual hyalohyphomycosis caused ...by Fusarium cugenangense belonging to the F oxysporum complex. This intractable disease was cured by 6‐month treatment with efinaconazole 10% solution.
Fusarium onychomycosis is uncommon in the temperate climate zone of Japan. Based on the morphological characteristics and a gene analysis, we diagnosed a patient with ungual hyalohyphomycosis caused by Fusarium cugenangense belonging to the F oxysporum complex. This intractable disease was cured by 6‐month treatment with efinaconazole 10% solution.
A 68-year-old male plasterer with no history of trauma presented to our clinic in March 2012 with a 16×14-mm ulcer that developed following a crushed small papule on the right anterior chest. In ...April 2012, the patient was referred to another hospital, where cutaneous cryptococcosis was diagnosed based on discharge culture results. The patient was treated with oral itraconazole at a dose of 150 mg/day for 10 weeks; however, the ulcer remained unchanged and he discontinued the treatment. In May 2014, when he revisited our clinic, the ulcer with crust had grown to 29×13 mm. No regional lymph node swelling was noted. India ink staining showed a yeast-like fungus with a thick, clear capsule. A cream-colored, viscous yeast-like colony was observed on Sabouraud dextrose agar. Genetic testing identified the isolate as Cryptococcus neoformans serotype A. The patient was negative for serum cryptococcal antigen. Neither chest radiography nor computed tomography revealed any abnormalities. The patient had no underlying disease. Oral fluconazole (400 mg/day for 12 weeks) was prescribed, resulting in scar formation. The patient has remained free of relapse for one year to date, since the end of treatment. Localized cutaneous cryptococcosis is not a commonly used disease name overseas. However, 36 cases of this disease have been reported in Japan (since in 1968). We herein report a new case with localized cutaneous cryptococcosis and summarize previously reported cases in Japan.
From March 2008 through February 2014, 80 patients aged 1-95 years (43 men and 37 women) were diagnosed with tinea faciei by a rural Japanese clinic. The affected sites were the cheek in 42 patients ...(52.5%), the auricles and area surrounding the auricles in 16 (20.0%), and the mandible in 12 (15.0%); 33 patients (41.2%) had concurrent ringworm in areas other than the face. Twenty-one patients (26.3%) had applied topical steroids to treat a rash. The pathogen responsible for tinea faciei was Trichophyton rubrum in 35 patients (43.7%), T. tonsurans in 19 (23.8%), T. mentagrophytes in 3 (3.8%), T. verrucosum in 2 (2.5%), T. violaceum in 2 (2.5%), Microsporum canis in 17 (21.3%), and M. gypseum in 2 (2.5%). Clinical symptoms were divided into three groups based on the severity of inflammation and the extent of lesions and scored in points. Anthropophilic dermatophytes resulted in a score of 1.82 points for the severity of inflammation and a score of 1.84 points for the extent of lesions while zoophilic dermatophytes resulted in a score of 2.14 points for the severity of inflammation and a score of 1.50 points for the extent of lesions. This indicates that anthropophilic fungi resulted in less inflammation and broader lesions, whereas zoophilic fungi resulted in more intense inflammation and smaller lesions. Patients who had applied topical steroids had a mean score of 1.90 points for the severity of inflammation and a mean score of 2.10 points for the extent of lesions. Patients who had not applied topical steroids had a mean score of 1.95 points for the severity of inflammation and a mean score of 1.59 points for the extent of lesions. The severity of inflammation did not differ significantly. However, lesions were significantly broader in patients who had applied topical steroids than in those who had not applied topical steroids (p < 0.04). The severity of tinea faciei is a useful index for the clinical diagnosis of tinea faciei.
In this study, we induced terbinafine (TRF) resistance in a
T. rubrum
strain in vitro for 18 months then compared the genomes of the TRF-resistant (N42-3) and TRF-susceptible wild-type (N42WT) ...strains to identify mutations
.
In the
SQLE
gene, N42WT had no mutation while N42-3 had a F397L mutation. We sequenced approximately 22.53 Mb of the genomes of the N43WT and N42-3 strains. Other than the F397L mutation in
SQLE
, there were three other genetic mutations in three different genes that were found in N42-3, but not in N43WT; however, these three mutations were not detected in other TRF-resistant
T. rubrum
strains. From this genome sequencing analysis, the only variation that was confirmed to be associated with drug resistance in the genome of the TRF-resistant
T. rubrum
was a hotspot mutation in
SQLE
.
Trichophyton rubrum is an anthropophilic dermatophyte that is most frequently isolated from onychomycosis (tinea unguium) worldwide. T. rubrum strains showing resistance to the anti-fungal drug ...terbinafine (TRF) have also been isolated from human patients worldwide.
In this study, we isolated a TRF-resistant strain (N99-2) of T. rubrum from a patient with recurrent tinea unguium. In vitro susceptibility of the clinical isolate to TRF, itraconazole (ITZ), ravuconazole (RVZ), and luliconazole (LCZ) was investigated using the Clinical & Laboratory Standards Institute M38-A2 test. To identify mutations, we compared the gene sequence of N99-2 to that of a TRF-susceptible strain of T. rubrum. Results; In N99-2, the minimum inhibitory concentrations were 32 mg/L for TRF, <0.03 mg/L for ITZ, <0.03 mg/L for RVZ, and <0.03 mg/L for LCZ. The squalene epoxidase (SQLE) gene sequence in N99-2 was determined to be 1467 bp in length, and it encoded a protein of 488 amino acids, beginning with a putative initiating methionine (ATG). The following mutations were identified from the SQLE of N99-2: L393F and Y394del.
This is the first report of the detection of a deletion mutation in SQLE in a TRF-resistant strain. The protein of SQLE is the target of TRF, and it is essential for cell membrane synthesis in dermatophytes. However, dermatophyte cells were found to undergo gene mutations to escape the effects of antifungal agents.
A 28-year-old man undergoing treatment for hemophagocytic syndrome developed Paecilomyces lilacinus infection in skin ulcers on the face and in the tracheotomy stoma. While his bone marrow was ...suppressed by chemotherapy with dexamethasone, cyclosporin and etoposide for hemophagocytic syndrome, dental infection led to subacute necrotizing fasciitis caused by Pseudomonas aeruginosa on the right side of the face, resulting in a large area of soft tissue defects. Etoposide was discontinued, and prophylactic treatment with itraconazole was initiated. The ulcers resulting from necrotizing fasciitis were treated conservatively using trafermin and alprostadil alfadex ointment 0.003 %, and near-complete re-epithelialization occurred, except on the right lower eyelid, right buccal mucosa and perioral area. However, 6 weeks later, pustules/crusts started to form and break down repeatedly, leading to expansion of tissue defects on the face. Direct microscopic examination revealed fungal elements, and fungal culture identified Paecilomyces lilacinus suspicious twice some other day. Based on DNA extraction from the isolated fungus, this fungal strain was identified as Paecilomyces lilacinus. Cyclosporin and itraconazole were discontinued, and treatment with liposomal amphotericin B and a tapering dose of steroids was initiated. Cure was achieved in approximately 2.5 months after treatment initiation, and no relapse has been observed. The most important factor that ultimately contributed to the resolution of fungal infection might have been release of immunosuppression by discontinuing cyclosporin and tapering steroids.
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