Possibly the first case of onychomycosis by Fusarium lactis: Case presentation and literature review of onychomycosis by Fusarium species.

Fusarium species (spp.) is frequently found in soil and plant residues and on plant bodies in all climatic zones worldwide. Although there have been few reports of onychomycosis caused by Fusarium spp., it is characterized by drug sensitivity and other characteristics. Here, we report what may be the first case of onychomycosis caused by Fusarium lactis. We analyzed the mycology and characterized previously reported cases of onychomycosis caused by Fusarium spp. A 73-year-old otherwise healthy woman presented with discoloration and thickening of her right thumbnail with paronychia. Direct microscopy revealed unevenly swollen hyphae, and a Grocott-stained nail specimen showed septate hyphae. Based on the morphological features and gene analysis of fungus isolated from the nail, we diagnosed onychomycosis caused by F. lactis belonging to Fusarium fujikuroi species complex. Partial nail removal and topical application of 1% luliconazole solution resolved the condition in 6 months. Minimum inhibitory concentrations for isolated F. lactis showed high sensitivity to luliconazole but not itraconazole or terbinafine. The isolated F. lactis was temperature-sensitive. A search of the literature revealed 57 cases of onychomycosis caused by Fusarium spp. with delineated clinical characteristics. Since those cases were investigated using morphological and/or molecular methods, we analyzed them by species complex as well as species. Onychomycosis caused by Fusarium spp. is predominantly found on the big toe, with Fusarium solani species complex and Fusarium oxysporum species complex accounting for over 70% of cases. Infection of only one digit with paronychia is a characteristic clinical manifestation of onychomycosis caused by Fusarium spp. Since there has been an increase in instances of molecular determination of Fusarium spp., it is deemed necessary to clarify its clinical and fungal nature. Due to its characteristic drug sensitivity and temperature-sensitive nature, new treatments are expected to be developed.

Multilocus Microsatellite Analysis of the Molecular Epidemiology of Microsporum canis Isolated in Japan.

Microsporum canis, a major causative agent of zoonotic dermatophytosis, has become prevalent in Japan. Molecular epidemiological surveys using multilocus microsatellite typing (MLMT), a sensitive genotyping tool for fungi, have been conducted to reveal intraspecies polymorphisms of M. canis.The present study utilized MLMT optimized for Japanese strains of M. canis to analyze epidemic trends of fungal infection. Six individual loci were targeted; namely, MS1, 2, 4, 5, 6, and 7. Analysis of data from 1974 through 2022 identified 416 strains, which were sorted into 60 genotypes by MLMT.The major genotypes showed changes in dominance during this period-changes that may reflect historical increases and decreases in the numbers of patients infected with M. canis patients. The main origins of infection included animal breeders and pet stores, as well as stray cat communities. Forty-nine episodes of familial outbreaks and cohabitant animal infections were recorded, and genotypes responsible for each episode were determined. MLMT analysis is not only a robust tool to understand population structures, but likely the most suitable method for tracking M. canis infections.

A Case of Oral Candidiasis Caused by Candida dubliniensis During Treatment of Humanized Monoclonal Antibody to Interleukin-17A.

We report the case of a 77-year-old woman who had been diagnosed with psoriasis vulgaris at another hospital at age 33 and treated with various therapies since then. At 61 years old, she was diagnosed with psoriatic arthritis with phalangitis, swelling of both hands, and sacroiliac arthritis, and was treated with oral immunotherapy. At age 76, treatment with a humanized monoclonal antibody to interleukin-17A (ixekizumab) was started due to increased pain associated with her hand inflammation. After ten months of this treatment, she visited our hospital with the complaint of tongue pain and white fungi on the tongue surface. Direct KOH examination of the fungi showed pseudomycelia and spores, and fungal culture (CHROMagar®Candida) showed green and dark green wet colonies. Sequencing of the D1D2 region of ribosomal RNA gene of the nuclear DNA of fungi from the colony identified Candida dubliniensis. She was treated with amphotericin B gargle (Fungizone®syrup) for two weeks, and the lesion improved. Since then, the patient has been treated with ixekizumab with no recurrence of oral candidiasis.

Genotyping of Trichophyton tonsurans strains isolated between 2016 and 2020, and terbinafine susceptibility of the species in Japan.

Trichophyton tonsurans is the most prevalent fungus which causes dermatophytosis among contact sports players in Japan. We previously surveyed the epidemic of T. tonsurans in Japan from early 2000, and determined the genotypes of isolates by analysis of restriction enzyme fragment length polymorphisms in the non-transcription spacer (NTS) region of ribosomal RNA gene, which enabled discrimination of eight genotypes, namely NTS I to NTS VIII. In the present study, we performed genotyping of T. tonsurans isolated between 2016 and 2020, and investigated the trend of the epidemic and resistance of the pathogen to antibiotic terbinafine (TBF). Regardless of which contact sport they played, the genotype of all 123 strains of T. tonsurans isolated from athletes was NTS I. Genotypes NTS II and III, which were isolated in considerable numbers mainly from wrestlers between 2000 and 2015, were conspicuously absent. TBF susceptibility was screened in 237 T. tonsurans strains isolated between 2000 and 2020 with 28 of these further assessed for minimum inhibitory concentration of TBF and squalene epoxidase gene sequences. None of the strains showed TBF resistance. TBF may still be effective to control the epidemic of T. tonsurans.

Cladophialophora bantiana infection mimicking neuromyelitis optica.

Cladophialophora bantiana (C. bantiana) is a life-threatening melanized mycelial fungus causing brain abscess. C. bantiana is usually observed in tropical countries, including India. We report a Japanese case of C. bantiana presenting with myelitis mimicking neuromyelitis optica (NMO) and brain abscess. A 73-year-old man was administered prednisolone (30 mg/day) for antineutrophil cytoplasmic antibody (ANCA)-related vasculitis 100 days before admission. He had right side-dominant paraplegia and sensory loss in the right leg. T2-weighted spinal cord MRI revealed longitudinal high-intensity signals at the T7 to T12 levels. A ring-enhancing lesion at the T10 level was detected on gadolinium (Gd)-enhanced MRI. He was tentatively diagnosed with NMO, and steroid pulse therapy was performed. One month later, an abscess at the right cerebropontine angle was noted on Gd-enhanced brain MRI. Two months later, several subcutaneous intramuscular tumors were detected. Based on the morphological study of the cultured organelle obtained by tumor enucleation and the internal transcribed spacer sequence of ribosomal RNA, the pathogen was identified as C. bantiana. Although he received liposomal amphotericin B treatment, the patient died of respiratory insufficiency. C. bantiana infection should be considered in patients with myelitis presenting with longitudinal lesions and CNS abscess in an immunocompromised state.

A Case of Cutaneous Mycosis Caused by Scedosporium dehoogii on an Immunocompromised Patient.

This report describes a 77-year-old man with cutaneous mycosis caused by Scedosporium dehoogii while taking oral betamethasone and tacrolimus for the treatment of rheumatoid arthritis. At examination in our clinic, the patient had multiple cystic lesions and nodules with slight tenderness, varying in size up to 4 cm, on his left knee and shin. He had not noticed any traumatic injury at the site of the lesions. Fungal cultures of samples taken from the abscesses, scales, and crusts of the lesions yielded white, later grayish brown, fluffy surfaced colonies. Partial sequencing of the ß-tubulin gene confirmed the species of the isolate. The patient was initially treated with oral voriconazole and local hyperthermia, but experienced hepatic injury 2 weeks later. His treatment was changed to itraconazole (ITC) and local hyperthermia, followed by a combination of ITC and terbinafine. The patient recovered completely during the 12-month course of treatment.

Molecular Markers Useful for Intraspecies Subtyping and Strain Differentiation of Dermatophytes.

Dermatophytosis is a very common skin disorder and the most frequent infection encountered by practicing dermatologists. The identification, pathogenicity, biology, and epidemiology of dermatophytes, the causative agents of dermatophytosis, are of interest for both dermatologists and medical mycologists. Recent advances in molecular methods have provided new techniques for identifying dermatophytes, including intraspecies variations. Intraspecies subtyping and strain differentiation have made possible the tracking of infections, the identification of common sources of infections, recurrence or reinfection after treatment, and analysis of strain virulence and drug resistance. This review describes molecular methods of intraspecies subtyping and strain differentiation, including analyses of mitochondrial DNA and non-transcribed spacer regions of ribosomal RNA genes, random amplification of polymorphic DNA, and microsatellite markers, along with their advantages and limitations.

Polyclonality of Trichophyton rubrum Isolates in aDermatophytosis Patient with Multiple Lesions.

We cultured 15 isolates of Trichophyton rubrum and one isolate of Trichophyton mentagrophytes from an 82-year-old male tinea patient with multiple lesions. To determine whether feet lesions were the source of dermatophytes of other tinea lesions, we extracted total cellular DNA from the T. rubrum isolates（13 from feet, two from right waist and buttock）. PCR targeting the non-transcribed spacer（NTS）region of ribosomal RNA gene was performed. Molecular polymorphisms were detected by length variation of amplicons.Four molecular types were found among the 15 isolates. The predominant type, which we previously named Type III, comprised seven isolates cultured from both feet and from left waist and buttock. This was followed by Type VI, five isolates; Type V, two isolates; and Type IV, one isolate. Apart from type III, which was cultured from both feet, isolates were cultured from one foot only. The patient was successfully treated for all types with a six-month course of oral terbinafine and topical luliconazole. The molecular typing supported the notion that tinea pedis was the source of tinea corporis in the patient.

Molecular markers useful for epidemiology of dermatophytoses.

Dermatophytosis is a very common skin disorder and the most prevalent infectious disease treated by dermatologists. Recent developments in molecular techniques have markedly changed methods of identifying dermatophytes, with these methods showing intraspecies polymorphisms in some molecular markers. Intraspecies subtyping and strain differentiation have made possible the tracking of infections, the identification of common sources of infections and recurrence or reinfection after treatment. This review describes methods of intraspecies differentiation using mitochondrial DNA, random amplification of polymorphic DNA, non-transcribed spacer regions of ribosomal RNA genes and microsatellite markers, as well as their usefulness and limitations.

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.

Molecular epidemiology of a major subgroup of Arthroderma benhamiae isolated in Japan by restriction fragment length polymorphism analysis of the non-transcribed spacer region of ribosomal RNA gene.

Arthroderma benhamiae vectored by small animals, such as household pets, causes tinea lesions on human skin. The number of tinea cases caused by this species is increasing in Japan. We attempted to develop a simple molecular method for strain discrimination, which is expected to be useful in molecular epidemiology. Out of the 61 strains of A. benhamiae registered at our institute, 46 A. benhamiae strains showed very high degrees of sequence similarity on cluster analysis of the internal transcribed spacer regions of ribosomal RNA (rRNA) genes. These 46 strains, including 22 strains isolated from Japan, were further used for strain typing by analyzing the non-transcribed spacer (NTS) region of the rRNA gene. Polymerase chain reaction was performed using a primer pair designed for amplification of a part of the NTS region, and the amplicons were successfully discriminated by restriction fragment length polymorphism (RFLP) analysis performed using MvaI. RFLP analysis showed 11 NTS types (NTS1-NTS11) among the 46 strains. Out of the 22 Japanese strains, 10 were of the NTS8 type; 6, of the NTS1 type; 3, of the NTS2 type; and 3, of the NTS5 type. Molecular typing showed consistency of NTS types among the strains isolated from different lesions on the same patient, among the strains derived from the same family, and among the strains from pets and their owners. We observed that 3 out of the 4 NTS types among the Japanese strains were detected outside Japan as well.

Matings among three teleomorphs of Trichophyton mentagrophytes.

Three genetically hybrid F1 progenies produced between a clinical isolate of Arthroderma simii (KMU4810) and a tester strain of A. vanbreuseghemii (RV27961) were crossed with two tester strains of A. vanbreuseghemii (RV27961 and RV27960) and a tester strain of A. benhamiae (RV30001), respectively. Three crossings yielded hybrid second progenies. Another interspecies crossing between A. simii (KMU4810) and a tester strain of A. benhamiae (RV26680) yielded one hybrid F1 progeny (Asb57). The second crossings of F1 progeny (Asb57) with A. vanbreuseghemii (RV27961) and A. benhamiae (RV30001) yielded many hybrid second progenies. Some hybrid second progenies produced between F1 progeny and A. vanbreuseghemii were confirmed to have genes from three species. The gene exchangeability among three Arthroderma species was shown and the meaning of these events discussed.

Case of remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome) showing dermatomyositis-like eruption.

A 73-year-old woman developed linear erythema at the sites of scratching-induced scars on the bilateral thighs 2 weeks before the initial consultation. Subsequently, edematous erythema developed in the upper eyelids, dorsum of the nose and the face, and pitting edema in the dorsum of the bilateral hands and feet. The C-reactive protein (CRP) level was 8.2 mg/dL and erythrocyte sedimentation rate (ESR) 121 mm/h. The antinuclear antibody titer was 1:160, and rheumatoid factor (RF) and anti-Jo-1 antibody were negative. X-ray examination of the bilateral hands showed neither narrowing of the joint spaces nor bone erosion. Ga scintigraphy showed synovitis of the bilateral wrists. A diagnosis of remitting seronegative symmetrical synovitis with pitting edema syndrome (RS3PE) was made. The erythema disappeared after diclofenac sodium administration. However, because the joint swelling and pitting edema did not improve, p.o. administration of prednisolone (20 mg/day) was initiated. The CRP and ESR levels normalized 2 months after the initiation of administration, and pitting edema disappeared after 3 months. We report this case because linear erythema like that observed in dermatomyositis has not been described as eruptions associated with RS3PE.