Skin Mycobiome of Psoriasis Patients is Retained during Treatment with TNF and IL-17 Inhibitors.

BACKGROUND: Biological treatment relieves refractory skin lesions in patients with psoriasis; however, changes in the fungal microbiome (the mycobiome) on the skin are unclear. METHODS: The skin mycobiome of psoriasis patients treated with TNF inhibitors (TNFi, n = 5) and IL-17 inhibitors (IL-17i, n = 7) was compared with that of patients not receiving systemic therapy (n = 7). Skin swab samples were collected from non-lesional post-auricular areas. Fungal DNA was sequenced by ITS1 metagenomic analysis and taxonomic classification was performed. RESULTS: An average of 37543 reads/sample were analyzed and fungi belonging to 31 genera were detected. The genus Malassezia accounted for >90% of reads in 7/7 samples from the no-therapy group, 4/5 from the TNFi group, and 5/7 from the IL-17i group. Biodiversity was low in those three groups. Few members of the genus trichophyton were detected; the genus Candida was not detected at all. Among the Malassezia species, M. restricta was the major species in 6/7 samples from the no-therapy group, 4/5 from the TNFi group, and 5/7 from the IL-17i group whose the other largest species revealed M. globosa. CONCLUSIONS: The mycobiome is retained on post-auricular skin during systemic treatment with TNF and IL-17 inhibitors.

The MAT1-1:MAT1-2 ratio of Sporothrix globosa isolates in Japan.

In order to understand the reproductive biology of pathogenic species in the Sporothrix schenckii complex, we characterized the partial mating type (MAT1-1) loci of Sporothrix schenckii, as well as the S. globosa MAT1-1-1 gene, which encoded 262 amino acid sequences. The data confirmed that the MAT1-1 locus of S. globosa was divergent from the MAT1-2 locus of the opposite mating type, suggesting that the fungus is heterothallic. To determine the mating type ratio of 20 isolates from Japanese patients, we analyzed the MAT loci by specific PCR amplification of MAT1-1-1 and MAT1-2-1 genes. The MAT1-1-1 was detected in 5 isolates but not in the other 15 isolates with the presence of MAT1-2-1. The MAT1-1:1-2 ratio of S. globosa isolates in Japan was estimated to be 1:3. Phylogenetic analysis indicated that the sequences of the MAT1-1-1 were identical among S. globosa isolates but different from S. schenckii and Ophiostoma montium.

A survey of 165 sporotrichosis cases examined in Nagasaki prefecture from 1951 to 2012.

A total of 165 sporotrichosis cases occurring in Nagasaki prefecture, and examined at Nagasaki University Hospital, were evaluated. Both males and females were equally affected, with no significant differences in the affected body regions. Lesions were frequently seen on the face (49 cases, 29.5%) and upper limbs (101 cases, 60.9%). The localised cutaneous type of sporotrichosis (105 cases, 62.9%) was much more frequent than the lymphocutaneous type (62 cases, 37.1%). The infection rate in patients over 50 years of age was 73.1%. The most frequent occupation among the patients was farming (52 cases, 37.4%), and 34 patients had a history of injury. Regarding the geographical distribution of sporotrichosis, 48 cases occurred in the Shimabara peninsula (31.2%) and this is much higher than expected for the population size. Before 1994, almost all sporotrichosis cases (112 cases, 96.5%) were treated with potassium iodide (KI). After 1995, the number of patients treated with KI decreased (nine cases, 23.1%), and itraconazole (ITZ) was used in 21 cases (59.0%) and terbinafine in six cases (15.3%). The time between ITZ and KI treatment and cure was 13.8 weeks and 12.5 weeks, respectively. All 116 cases, for which the outcome was known, were cured or improved.

Cutaneous hyalohyphomycosis by Scedosporium apiospermum in an immunocompromised patient.

Scedosporium apiospermum is a ubiquitous filamentous fungus that may infect immunocompetent patients after trauma and may cause severe and often fatal infections in immunocompromised hosts. Here, we present the case of a 28-year-old female with S. apiospermum infection on the left forearm that had developed while she was on long-term immunosuppressant therapy. Analysis of a skin biopsy specimen showed a mixed cell granuloma with hyaline septate hyphae. Culture of the abscess revealed S. apiospermum which was identified as S. apiospermum sensu stricto by sequencing of the internal transcribed spacer-1 region of ribosomal DNA genes. Resection of the eruption and oral itraconazole (100 mg day(-1)) therapy for 4 months was effective in curing the infection.

Tinea Capitis Caused by Microsporum audouninii: A Report of Two Cases from Côte D'Ivoire, West Africa.

We report here two cases of tinea capitis caused by Microsporum (M.) audouinii in Côte d'Ivoire, West Africa. The patients were a three-year-old boy and a six-year-old girl who presented with scaly patches on the scalp. The causative fungus was isolated using an adhesive tape-sampling method and cultured on Sabouraud dextrose agar plates. It was identified as M. audouinii both by its macroscopic and microscopic features, confirmed by DNA sequencing. These are the first documented cases of M. audouinii infections confirmed with DNA sequencing to be reported from Côte d'Ivoire. The practicality of the tape-sampling method makes it possible to carry out epidemiological surveys evaluating the distribution of these dermatophytic infections in remote, resource-limited settings.

Epidemiological survey of 42 403 dermatophytosis cases examined at Nagasaki University Hospital from 1966 to 2015.

The causative species of a total of 42 403 dermatophytosis cases that occurred during 1966-2015 were surveyed. The most prevalent clinical type was tinea pedis, followed by tinea unguium, corporis, cruris, manus, faciei and capitis. The prevalence of tinea faciei and capitis has increased since the late 1990s and the late 2000s, respectively. The most prevalent dermatophyte species was Trichophyton rubrum, followed by Trichophyton mentagrophytes (the majority of the isolates were Trichophyton interdigitale in the latest nomenclature). These dermatophytes were detected in over 80% of the isolates identified in tinea pedis, unguium, cruris and manus cases. Recently, Microsporum canis and Trichophyton tonsurans have been increasingly identified. The frequency of M. canis isolated from tinea corporis, faciei and capitis cases started to rise in the early 1990s. T. tonsurans was first identified in Nagasaki in 2003. T. rubrum was the most commonly isolated pathogen in tinea faciei and corporis cases. However, the proportion of cases attributed to it has decreased since the early 1990s, whereas M. canis and T. tonsurans are being increasingly isolated since the early 2000s. In tinea capitis cases, the proportion of each pathogen isolated has changed dramatically. M. canis was first identified in the late 1970s, with an increasing prevalence up to the early 1990s. In contrast, the prevalence of T. tonsurans has increased since the early 2000s. In the 2010s, the most common fungus causing tinea capitis was T. tonsurans, followed by M. canis and T. rubrum.

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.

Primary Oral Mucormycosis Due to Rhizopus microsporus after Allogeneic Stem Cell Transplantation.

We herein report a rare case of oral mucormycosis following allogeneic hematopoietic stem cell transplantation. Oral mucormycosis due to Rhizopus microsporus manifested as localized left buccal mucositis with a 1-cm black focus before neutrophil recovery. Combination therapy with liposomal amphotericin B was initiated and surgical debridement was performed; however, the patient died due to progressive generalized mucormycosis. Considerable attention needs to be paid to the diagnosis and management of oral mucormycosis in post-transplant patients, thereby suggesting the importance of fully understanding the risk factors.

[Clinical study of 57 cases of infection with Trichophyton tonsurans examined at a dermatology clinic in Saga Prefecture, Japan].

This paper is a clinical study of 57 cases of infection with Trichophyton tonsurans (T. tonsurans) examined in our clinic between January 2004 and July 2006. The patients were 31 high school students, 19 junior high school students, 2 primary school students, 1 kindergartener, and 4 sports instructors. The male:female ratio was 51:6. Most patients were male Judo practitioners. Patients were clinically categorized as follows: 13 cases of tinea capitis {10 containing black dot ringworms (BDR), 2 scaled, and 1 with inflammation}, 41 cases of tinea corporis, 1 case of tinea manum, and 7 carriers. Five patients displayed both tinea capitis and tinea corporis. Among tinea corporis patients, 21 displayed annular erythemas, whereas 19 displayed small circular eythemas characterized by a lightly inflamed non-typical rush. In 3 tinea corporis cases, we sampled T. tonsurans from hair grown inside the skin rash. Eleven of the tinea corporis patients displayed multiple lesions. Compared to patients with singular lesions, these 11 cases had a larger degree of comorbidity with BDR or HB positivity. A 6-8 week treatment with griseofulvin was efficient in 90% of the tinea capitis cases. Tinea corporis patients were healed following a 4-9 week treatment with topical antifungals and griseofulvin. When examining T. tonsurans infections, patients with BDR or lightly inflamed tinea corporis as well as asymptomatic carriers can be easily overlooked or misdiagnosed. Therefore, we suggest that mycological examination, including careful observation of the rash and KOH mount, is essential in these cases.

Remarkable Works and Cases in the History of Medical Mycology in Japan.

Several pathogenic fungi and cases related to Japanese medical mycologists were reviewed. Trichosporon inkin (as Sarcinomyces inkin) was reported as a pathogen of scrotal lesion by Oho in 1921, and Trichosporon asahii was isolated from generalized keratotic lesions in 1922 by Akagi in Japan. They were once included in Trichophyton beigelii, but then based on revision using DNA molecular technology, were returned to their original names.Microsporum ferrugineum was reported by Ota as a causative dermatophyte of tinea capitis in Japan and surrounding areas. It was once classified under the genus Trichophyton, but after the discovery of characteristic rough-walled macroconidia belonging to genus Microsporum, the fungus was again assigned to the original name.

[An epidemiological survey of dermatomycoses in Japan, 2002].

An epidemiological survey of dermatomycoses and the causative fungus flora of dermatophytoses in Japan for 2002 was made on a total number of 72,660 outpatients who visited 14 dermatological clinics throughout Japan. The results were as follows: 1) Dermatophytosis was the most prevalent cutaneous fungal infection (7,994 cases) seen in these clinics, followed by candidiasis (755 cases) and then Malassezia infections (220 cases). 2) Among dermatophytoses, tinea pedis was the most frequent (4,813 cases: male 2,439, female 2,374), then in decreasing order, tinea unguium (2,123 cases: male 1,093, female 1,030), tinea corporis (497 cases: male 281, female 216), tinea cruris (299 cases: male 249, female 50), tinea manuum (248 cases: male 144, female 104) and tinea capitis including kerion (14 cases, male 6, female 8). 3) Tinea pedis and tinea unguium are seen to increase in summer season, among the aged population and among males in each clinic. When compared to the previous surveys (1992 and 1997) by clinical form, t. unguium patients increased from 1.9% of total outpatients in 1992, to 2.0% in 1997, then to 2.9% in 2002. 4) As the causative dermatophyte species, Trichophyton rubrum was the most frequently isolated among all dermatophyte infections except tinea capitis. 5) T. rubrum was isolated from 63.3%(1,431/2,262) of tinea pedis lesions, followed by Trichophyton mentagrophytes (36.6%, 829/2,262), and also 88.8% (325/366) of t. corporis, 95.4% (185/194) of t. cruris and 85.6% (462/540) of t. unguium. 6) Cutaneous candidiasis was seen in 755 cases (1.0%) of 72,660 outpatients. Intertrigo (347 cases) was the most frequent clinical form, followed by erosio interdigitalis (103 cases) and diaper candidiasis (102 cases). It has a tendency to affect the aged being complicated with topical predisposing factors. 7) Cutaneous Malassezia infections and other superficial fungal infections are seen in 220 cases, without any characteristic features by gender or clinical form.

Mycological Education for Dermatologists.

Mycotic infections remain important in dermatological clinics. Therefore the mycological training curriculum needs to be reorganized starting from the beginning of dermatological education, including routine examination procedures, such as potassium hydroxide examination, culture of pathogenic fungi, histopathology, treatment guidelines, and the recent advances in medical mycology.Several mycological institutes will be selected and announced in the journal to provide support for mycological examinations and to publish important cases treated in clinics. The roles of the Japanese Society for Medical Mycology in these activities are discussed.

Disseminated Ochroconis gallopavum infection in a chronic lymphocytic leukemia: a case report and review of the literature on hematological malignancies.

Disseminated fungal infection is an important cause of morbidity and mortality among patients with hematological malignancies. Ochroconis gallopavum is a dematiaceous and thermotolerant fungus that causes opportunistic infections in immunocompromised hosts. About only 30 cases of this organism infection have been reported worldwide. We report a disseminated Ochroconis gallopavum infection in a B-cell chronic lymphocytic leukemia patient. In spite of intensive anti-fungal treatment, no improvement in the clinical condition was observed and the patient died 4 months after diagnosis of the infection. Ochroconis gallopavum infection is a potentially fatal disease in hematological malignancies.

[Survey of Trichophyton tonsurans Infection in the Kyushu, Chugoku and Shikoku areas of Japan].

A survey on the infestation of dermatophytosis caused by T. tonsurans was made by inquiry to dermatologists. Patients strongly suggestive of having skin lesions due to T. tonsurans were seen in all areas examined, and were mainly schoolboys, including those practicing judo, of high schools and junior high schools. In Nagasaki, a mycological examination was done on 21 judo students and their teacher in a high school in which a patient with T. tonsurans infection was mycologically confirmed and treated by antimycotics. Mycological examinations failed to isolate T. tonsurans, but even after the examination sporadic cases were reported among the group members. In Saga prefecture, Kyushu, a mycological screening for T. tonsurans infection among judoists and wrestlers in 13 high-schools and 7 junior high schools was done using the blush sampling method. Fifty-six strains of T. tonsurans were isolated from 248 students. The problems concerning the control of this infection were discussed.

Cutaneous nocardiosis developing around gravel inserted during a traffic injury.

A 65-year-old Japanese woman with nocardial mycetoma which developed five years after a compound bone fracture of the left foot due to a traffic accident was reported. During this accident, two small pieces of gravel had entered her foot. Nocardia asteroides, which had been attached to the gravel, was probably inserted 5 years previously during the trauma. The lesion did not respond to oral minocycline and trimethoprim-sulfamethoxazole and was finally removed surgically; she has been free from recurrences for one year, of follow-up.

[Cutaneous manifestations of systemic mycoses].

The systemic mycoses are increasing in importance as opportunistic infections. Cutaneous lesions resulting from systemic mycoses may first alert clinicians to the presence of a life-threatening disorder, or even the presence of an unsuspected immunodeficiency state. Skin involvement is generally uncommon in disseminated aspergillosis, zygomycosis but is more common in systemic candidiasis (candidemia) and cryptococcosis. The blanket terms, hyalohyphomycosis and phaeohyphomycosis, cover the infections caused by diverse fungal opportunists. A variety of manifestations of skin lesions of the systemic mycoses are reviewed. These specific and/or non-specific lesions require early recognition, diagnosis, and aggressive antifungal treatment.

Case of Fusarium paronychia successfully treated with occlusive dressing of antifungal cream.

We report a case of refractory Fusarium paronychia in a 42-year-old man with Behçet's disease receiving oral cyclosporin and corticosteroid. Symptoms resembling candidal paronychia of his little finger could not be cured by topical ketoconazole and oral terbinafine. The pathogen was identified as Fusarium solani species complex by gene analysis, and was multiple drug resistant. The case eventually resolved by occlusive dressing therapy with 0.5% amorolfine cream for 3 months.

Sporothrix schenckii (sensu strict S. globosa) mating type 1-2 (MAT1-2) gene.

Sporotix schenckii is a pathogenic fungus that causes human and animal sporotrichosis, and based on morphology of the sessile conidia and molecular analysis, it was recently recognized as a species complex comprising at least the following six sibling species: S. albicans, S. brasiliensis, S. globosa, S. luriei, S. mexicana and S. schenckii. However, apart from S. schenckii sensu strict, only S. brasiliensis, S. globosa and S. luriei are associated with human and animal infection. S. globosa has been most commonly isolated in Asia, Europe and the USA; therefore, molecular epidemiological study for S. globosa is important in relation to human sporotrichosis in Japan. To the best of our knowledge, this is the first study to determine the mating type 1-2 (MAT1-2) gene of Sporothrix schenckii with the aim of understanding the taxonomy of the genus Sporothrix. The MAT1-2 gene (1618 bp) encodes a protein sequence of 198 amino acids. Reverse transcription polymerase chain reaction analysis also detected MAT1-2 gene mRNA expression in all of the S. schenckii strains examined, indicating that this gene is expressed in S. schenckii cells. Phylogenetic analysis of the MAT1-2 gene fragments of Ophiostoma himal-ulmi, O. novo-ulmi, O. ulmi and S. schenckii indicated that these isolates could be classified into four clusters. MAT1-1 gene-specific polymerase chain reaction was positive in 15 isolates, but negative in four human isolates and one feline isolate.