The characteristic pathological feature of dermatomycosis is numerous neutrophilic infiltrates within the epidermis. However, the precise mechanism of this infiltration remains unknown. In this study, interleukins 1β, 6, and 8, monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor (TNF)-α levels in the medium where keratinocytes were co-cultured with Candida albicans, Malassezia and Trichophyton mentagrophytes, were determined by enzyme-linked immunosorbent assays (ELISAs) in order to estimate the effect of these fungi on the cytokine production from human keratinocytes.
The IL-8 level in the supernatants increased with 1 to 14 hours of co-culture in response to live C. albicans, but the other cytokines were undetectable. Furthermore, the mRNA of IL-8 in keratinocytes was also confirmed to increased. This data suggested that C. albicans directly induce interleukin 8 production from human keratinocytes without activated macrophages.
The IL-6, IL-8, and TNF-α levels in the culture supernatants increased with 1 to 24 hours of co-culture with keratinocytes and Malassezia species but the MCP-1 level was undetectable.
The IL-8 and TNF-α levels in the culture supernatants increased with 1 to 24 hours of co-culture with keratinocytes and Trichophyton mentagrophytes but the other cytokine levels were undetectable.
The ELISA analysis of cytokine production by human keratinocytes will provide useful information in understanding the pathogenesis of dermatomycosis.

View full abstract

It is reported that antimycotic agents are effective for the treatment of patients with atopic dermatitis (AD). We studied in vitro effects of antimycotics on T helper-1 and T helper-2 cytokine production in anti-CD3 plus anti-CD28-stimulated T cells from AD patients and normal donors. The amounts of interleukin-4 (IL-4) and IL-5 secreted by anti-CD3/CD28-stimulated T cells were higher in AD patients than in normal donors. Azole derivatives, ketoconazole, itraconazole, miconazole and non-azole terbinafine hydrochloride and tolnaftate reduced IL-4 and IL-5 secretion without altering that of IFN-γ and IL-2 in anti-CD3/CD28-stimulated T cells from both AD patients and normal donors. The azole derivatives were more inhibitory than non-azole antimycotics. These antimycotics reduced the anti-CD3/CD28-induced mRNA expression and promoter activities for IL-4 and IL-5. The cAMP analogue dibutyryl cAMP reversed the inhibitory effects of the antimycotics on IL-4 and IL-5 secretion, mRNA expression, and promoter activities. Anti-CD3/CD28 transiently (≤5min) increased intracellular cAMP in T cells, and the increase was greater in AD patients than in normal donors. The increase of cAMP by anti-CD3/CD28 correlated with IL-4 and IL-5 secretion by anti-CD3/CD28. The transient cAMP increase was suppressed by antimycotics, and azole derivatives were more suppressive than non-azoles. Azole derivatives inhibited the activity of cAMP-synthesizing adenylate cyclase while terbinafine hydrochloride and tolnaftate enhanced the activity of cAMP-hydrolyzing cyclic nucleotide phosphodiesterase in AD and normal T cells. These results suggest that the antimycotics may suppress IL-4 and IL-5 production by reducing cAMP signal, and strengthen the concept of their potential use for the suppression of T helper-2-mediated allergic reactions.

View full abstract

Objective: To compare the international standard regimen of itraconazole pulse therapy with low dailydose pulse therapies, which are widely conducted in Japan.
Design: Randomized, double-blind, parallel-group comparative study.
Patients: 186 patients with a big toenail showing onychomycosis symptoms such as opacity.
Intervention: Patients were assigned to Group I (200mg/d, 3 cycles), Group II (200mg/d, 6 cycles) or Group III (400mg/d, 3 cycles). All received itraconazole orally.
Main Outcome Measure: Cure or complete response-assessment based on improvement in the opacity ratio and microscopic examination.
Results: The clinical response rates (cure plus complete response) at week 24 were Group I: 14.9%;Group II: 25.5%; Group III: 32.7%. At week 48, 17 patients were cured in Group III-up from 3 at week 24. At week 48 the area under the nail plate concentration-time curves (AUC) was: Group I: 6084±3696ng·h/g; Group II: 10448±6980ng·h/g; Group III: 24189±15157ng·h/g. There was no difference among the three groups in the incidence of adverse drug reactions.
Conclusions: The clinical response rates demonstrated that the pulse therapy of 400mg/d itraconazole for 3 cycles was most effective. The significantly higher Group III AUC (week 48) (p<0.01) suggests that, when the same total amount of itraconazole is administered, this drug remains in nail plates longer following pulse therapy with a higher daily dose. It was also suggested that clinical efficacy correlated with the duration of the presence of itraconazole.

View full abstract

A statistical study on dermatomycoses for the 30 years from 1968 to 1997 in the dermatologic section of Sendai National Hospital was carried out with the following results. The total number of dermatomycosis patients was 14, 259 and accounted for 9.59% of all new outpatients during this period. These cases of dermatomycoses were composed of the following: dermatophytoses 10, 656, candidiasis 3, 287, malassezia infection 566, sporothrichosis 20, aspergillosis 7, and chromomycosis 1. Annual changes in number of dermatophytoses varied in each clinical type: tinea corporis and tinea cruris had increased by the end of the 1970s, and there after decreased gradually until recent years. Tinea pedis and tinea unguium, on the contrary, increased after the 1980s. Age distribution of all clinical forms of dermatophytoses changed gradually, and its peak of the distribution curve shifted to an older site each year, while the number of younger generation patients decreased. Mycologically Trichophyton (T.) rubrum was mainly isolated from all types of dermatophytoses, and T. mentagrophytes followed. The ratio of these two species (R/M) in tinea pedis was 1.25, and the ratio of T. mentagrophytes was relatively high. Epidermophyton floccosum was continuously isolated, but its frequency in recent years has decreased. Microsporum canis infection increased from the middle period of this research, but after 1990 decreased gradually. The other dermatophytes were found sporadically. In recent years the species isolated have become more simplified. Among candidiasis, infantile candidiasis increased dramatically in the 1970s but soon decreased. Intertrigo type also increased in the same period and then decreased to an intermediate level. Paronychia, onychia and erosio interdigitale were constantly found in small numbers, while malassezia infection remained at a constant level and was found more in male patients.

View full abstract

Restriction fragment length polymorphism (RFLP) analysis was performed on the internal transcribed spacer regions of 204 Sporothrix schenckii isolates and on one strain each of the related fungi, S. schenckii var. luriei, S. curviconia, S. inflata and Ceratocystis stenoceras. S. schenckii isolates, which have been collected from around the world, have already been typed according to their mitochondrial DNA (mtDNA), and are kept in the Department of Dermatology, Kanazawa Medical University, Japan.
Approximately 600bp of the internal transcribed spacer region 1 (ITS1) of their nuclear ribosomal RNA gene (rDNA), 5.8S rDNA and ITS2 was amplified by PCR. From ITS-RFLP analysis of the PCR products, S. schenckii isolates comprised 4 types, rDNA types I-IV. The rDNA type I-III strains corresponded to the Group A strains (mtDNA types 1-3, 11, 14-19, 22 and 23), while the rDNA type IV strains corresponded to the Group B strains (mtDNA types 4-10, 12, 13, 20 and 21), as previously categorized according to their mtDNA-RFLP. The ITS-RFLP patterns of the above 4 related fungi all differed from those of the 4 rDNA types of S. schenckii.
Furthermore, only 22 (3.5%) out of a sequence of about 620 bases of the ITS regions of the rDNA differed among representatives of the mtDNA types 1-5, 7, 11, 14-19, 22 and 23. This difference in the ITS region is smaller than the 10% difference among isolates when estimated by mtDNA-RFLP. From the phylogenetic tree based on the base sequences, rDNA type I-III strains belong to Group I, while rDNA type IV strains belong to Group II which correspond with Groups A and B based on their mtDNA. The Group I strains are predominant in South America and Africa, while Group II are predominant in Australia and Asia.
ITS-RFLP analysis is better than mtDNA-RFLP in allowing faster discrimination and identification, and for its ability to divide the 4 types into groups, which is useful in clinical diagnosis and epidemiological investigations of S. schenckii.

View full abstract

We herein report a case of tinea capitis initially showing a couple of nodular lesions. The patient was a 66-year-old woman who had seen a nearby dermatologist for itching on her head and had been treated with a topical steroid followed by tacrolimus application for one month. Because pseudolymphoma-like erythematous nodules developed at two sites, she visited us.
Two weeks after stopping all medication, some slight scaling was found around these nodules. On KOH direct microscopic examination, many filamentous elements around hair shafts were observed. Biopsy of the nodules confirmed the destruction of hair follicles surrounded by granulomatous inflammation histologically. Grocott staining of the same specimen revealed a few short fungal hyphae as well as spores. She was also diagnosed as tinea pedis by direct microscopic examination of her feet. Trichophyton rubrum was isolated from scales of both her head and feet on Sabouraud's dextrose agar at 25°C.
Kerion celsi (KC) is usually clinically preceded by a gray patch or black dots. Such a typical course of KC, however, was not observed in our patient. Tacrolimus was thought to have possibly played an important role in modifying tinea capitis.

View full abstract