Dose-finding comparative study of 2 weeks of luliconazole cream treatment for tinea pedis--comparison between three groups (1%, 0.5%, 0.1%) by a multi-center randomised double-blind study.

Luliconazole is a newly developed imidazolyl antifungal agent. A randomised double-blind comparative study was designed to assess the efficacy and safety of 1% luliconazole cream (group A), 0.5% cream (group B) and 0.1% cream (group C), in tinea pedis (interdigital type and plantar type), when used once daily for 2 weeks. Follow-ups were performed at 4 weeks after the end of topical treatment. A total of 241 patients were enrolled and 213 patients were evaluated for efficacy. Rates of improvement of skin lesions in the A, B and C groups assessed at week 4 were 90.5%, 91.0% and 95.8%, respectively. Rates of mycological cure (negative result of microscopy) in the A, B and C groups assessed at week 4 were 79.7%, 76.1%, 72.2% and at week 6 (at 4 weeks after the end of topical treatment) were 87.7%, 94%, 88.9%, respectively. For the mycological effect on tinea pedis of the interdigital type at 2 weeks, the negative conversion of fungi showed a concentration-dependent relationship and indicated a difference in tendency statistically 81.1% (1%- treatment), 62.9% (0.5%- treatment), 58.3% (0.1%- treatment) (Fisher's exact test, P = 0.079) and there was a trend between three groups by Cochran-Mantel-Haenszel method (P = 0.038). The incidence of adverse events in which a causal relationship to this drug could not be ruled out was low (2.6%). All of the adverse events were mild in severity and insignificant clinically.

A comparative clinical study between 2 weeks of luliconazole 1% cream treatment and 4 weeks of bifonazole 1% cream treatment for tinea pedis.

The aim of the study was to compare the efficacy and safety of luliconazole 1% cream and bifonazole 1% cream as applied in the treatment of tinea pedis (interdigital-type and plantar-type). A multi-clinic, randomised single-blind, parallel group study with 34 hospitals and 11 clinics formed the study design. Five hundred and eleven patients with mycologically confirmed tinea pedis were included. Of the 489 evaluable patients, 247 were randomised to luliconazole, and 242 to bifonazole. Luliconazole 1% cream applied once a day for 2 weeks, followed by a placebo cream for 2 weeks, thereafter. Bifonazole 1% cream applied once a day for 4 weeks. Mycological effect (negative result on microscopy) and improvement of skin lesions were measured at weeks 1, 2, 3 and 4. Safety frequency and severity of adverse reactions were also measured. The improvement of skin lesions after 4 weeks was comparably good with rates of 91.5% vs. 91.7% (luliconazole vs. bifonazole). The mycological effect was characterised by high negative rates of 76.1% vs. 75.9% (luliconazole vs. bifonazole). The progression of tinea-related signs and symptom scores differed insignificantly between evaluated luliconazole and bifonazole treatment groups comprising a total of 500 patients. Both substances appeared to be comparably safe and well-tolerated.

[A case of onychomycosis induced by Scopulariopsis brevicaulis].

The patient was a 57-year-old woman who initially consulted our department on May 31, 2002 with a chief complaint of other dermatoses. The initial examination demonstrated deformation of approximately 1/3 of the inner part of the nail plate in the right hallux, in addition to brown discoloration and keratin hypertrophy under the deformed nail plate. KOH-prepared direct microscopy revealed the presence of large round spores and hyphae. Since colonies similar to those of Trichophyton rubrum were obtained by culture, daily administration of terbinafine (125 mg/day) was initiated from June 17, 2002 based on a suspicion of tinea unguium induced by T. rubrum. However, the morphology of the colonies began to change toward a brown powder-like configuration after 2-3 weeks of culture, and band forms were also detected by slide culture, resulting in the diagnosis of onychomycosis induced by Scopulariopsis brevicaulis. From August 6, 2002, the dose of terbinafine was increased to 250 mg/day, which was maintained until November 22, 2002. When the patient visited our department approximately 2 months later, KOH-prepared direct microscopy revealed that she was still positive for S. brevicaulis. Therefore, terbinafine (250 mg/day) was administered again for 1 month from April 25, 2003, followed by a judgment of complete healing on July 4, 2003. Thereafter, there was no recurrence of onychomycosis up until January 29, 2005.

[Comparative study between culture and PCR-RFLP analysis on identification of the causative agent of Tinea Unguium].

BACKGROUND: To identify the pathogenic fungi of dermatophytosis, restriction fragment length polymorphism (RFLP) analysis of PCR amplified ribosomal DNA including internal transcribed spacers (ITS) has been established in Japan. Our purpose was to evaluate the usability of PCR-RFLP analysis to identify the causative agent of tinea unguium directly from a nail sample. METHOD: Samples of tinea unguium from 100 nails were collected and cultured on Sabouraud's glucose agar and observed for 2 months. DNA was extracted from these samples, and the PCR product was digested with restriction enzymes Mva I and Hinf I. Weight of the samples was determined. RESULT: Sensitivity of PCR-RFLP analysis (73%) was higher than that of culture (20%) showing that PCR is more advantageous for identification of the causative agent of tinea unguium. Sensitivity of PCR-RFLP did not depend on weight of the nail sample.

Treatment outcome and relapse with short-term oral terbinafine (250 mg/day) in tinea pedis.

A total of 168 patients with tinea pedis, but without onychomycosis, were treated with 1 cycle of terbinafine (TBF) (1 cycle: defined as 250 mg/day for 1 week). KOH preparation for direct microscopy was performed 4, 8 and 12 weeks after starting therapy to determine if testing was positive for tinea. Patients with no negative results on KOH examination or no evidence of obvious clinical improvement at 8 weeks, another cycle of the therapy was prescribed. The "cure", "no cure", "dropout", and "discontinuation/unevaluable" rates were 89.3%, 4.8%, 4.8% and 1.2%, respectively. The number of cycles required for cure in the plantar type was 1 cycle in 65.9% and 2 cycles in 54.5% of cases; in the interdigital type, 1 cycle in 79.1% and 2 cycles in 20.9% of cases; and mixed type, 1 cycle in 29.1% and 2 cycles in 60.9% cases. Among patients who were followed for at least 3 years after cure, the relapse rates were about 10% each year: 1 year, 11.3%; 2 years, 8.9%; and 3 years, 11.2%. The relapse rate of about 10% each year over a 3-year period suggests that reinfection may be likely.

[Examination of the causative agent of pityriasis versicolor].

Pityriasis versicolor (PV) is a superficial infection of the stratum corneum caused by Malassezia. Eleven species have been recognized within this genus, namely M. globosa, M. restricta, M. sympodiasis, M. furfur, M. obtusa, M. slooffiae, M. pachydermatis, M. dermatis, M. japonica, M. yamatoensis, M. nana. To examine the distribution of the microorganism in the skin of patients with PV, we detected Malassezia species without M. pachydermatis and M. nana using a non-culture-based method that consisted of nested PCR with specific primers. The most frequently isolated species were M. globosa and M. restricta (both 93.9%). M. globosa was detected in scales in which only the mycelial form (yeast cells, < 10/sample) were observed microscopically; M. restricta was not found. We suggest that M. globosa is the causative agent of PV.

[Evaluation of the efficacy of miconazole nitrate shampoo for prevention against T. tonsurans infection].

UNLABELLED: We report the efficacy of miconazole nitrate shampoo (Furfur Shampoo) to prevent T. tonsurans infection. METHOD: Experimental models were made from stratum corneum of healthy human heel or guinea pig skin. Before and/or after T. tonsurans was applied, samples were washed with miconazole nitrate shampoo, then inoculated on a Sabouraud culture plate. RESULT: Though miconazole nitrate shampoo did not eliminate T. tonsurans on the sample completely, the time required to develop the colony (9.9 days) was obviously extended (7.7 days by control). DISCUSSION: We concluded that miconazole nitrate shampoo is a useful method of preventing T. tonsurans infection, and should be used every day (before/after the chance to infect).

[Experimental studies on the penetration of dermatophytes into the human stratum corneum and the effects of washing].

After several types of dermatophytes were applied to the stratum corneum obtained from a healthy human heel, we evaluated the penetration speed of fungal elements into the stratum corneum and the effect of washing its surface. We designed the following two environments, assuming tinea pedis after applying fungal elements to the surface of the stratum corneum. The samples were incubated under conditions simulating the daily life of those who wear socks in a house: (1) 90% humidity for 8 hours, and 100% humidity for 16 hours, and those who have bare feet in a house: (2) 80% humidity for 8 hours and 100% humidity for 16 hours. We took the samples out every 24 hours and made observations by PAS stain and scanning electron microscope before and after washing them. Although fungal elements were not removable in (1), even if washed one day later, they could be removable one and two days later in (2). We suggest that fungal elements were easily removable even if dermatophytes had begun to penetrate the surface of the stratum corneum, because the soles retained a low humidity when the shoes were removed, and the soles and interdigital regions were washed every day. Moreover, in an experiment assuming tinea corporis, fungal elements were applied to the cutting side of the stratum corneum, incubated at 80% humidity, and observed after PAS stain. The penetration of Trichophyton tonsurans to the cutting side of the stratum corneum began in 0.5 days, which was sooner than other dermatophytes. We believe this is one factor of the latest expansion of T. tonsurans infection in Japan.

[Trichophyton violaceum infection in three black brothers].

Case 1 was a 3-year-old with tinea capitis, while Case 2 was a 5-year-old with kerion celsi. These conditions developed between December 1997 and January 1998 when the patients were living in Canada. Case 3 was a 7-year-old who developed kerion celsi in March 1998 in Japan. For Cases 1 and 2, the referring doctor had detected a fungal infection a few weeks previously, and griseofulvin was administered orally to Case 1 for three weeks and Case 2 for one week prior to consultation at our department. Both Cases 1 and 2 visited our department initially on May 7, 1998 with the causative agent separated from their lesions by the referring doctor respectively. The causative agent was identified as Trycophyton violaceum by our department. KOH-prepared direct microscopy and culture were positive for Case 1, but negative for Case 2. Infected hairs of Case 1 showed a chain of large arthrospores arranged in parallel rows inside the hair. Case 3 visited our department initially on May 21, and T. violaceum was also isolated from this patient's lesion. A reddish purple isolate that was stored for five months after isolation and culture was subcultured using a Sabouraud agar containing thiamin. After two months, brown colonies without red pigment were seen in the reddish purple colonies. Slide culture performed for both colonies showed intercalary and terminal chlamydospores, thus confirming that they were the same fungus. These findings appear to represent the conversion of T. violaceum into T. glabrum.

[Effects of temperature, humidity, minor injury and washing on penetration of dermatophytes into human stratum corneum].

We evaluated the minimum time for penetration of Trichophyton mentagrophytes into human stratum corneum using an experimental model of tinea pedis. After fungal elements were applied on the surface of stratum corneum obtained from a healthy human heel, samples were incubated under designated conditions of temperature and humidity. The penetration of fungal elements was much faster at 35 degrees C than 27 degrees C despite the fact that the latter is an optimal temperature for fungal growth. At 35 degrees C and 100% humidity the minimum time required for penetration was one day. When we applied fungal elements on an abraded surface of stratum corneum, fungi penetrated within a half day under the same conditions. This suggests that minor injury of stratum corneum is a significant factor for infection. The development of tinea pedis does not occur frequently in daily life. We examined the effect of washing the surface of stratum corneum to which T. mentagrophytes had been applied. The samples were incubated under conditions simulating daily life: i.e. with 80% humidity for 8 hours, and 100% humidity for 16 hours. After washing, nearly all the fungal elements had been removed from the surface of stratum corneum within one day. The data suggests that to prevent tinea pedis, daily washing of soles and interdigital regions is effective.

A case of seborrheic blepharitis; treatment with itraconazole.

We report a case of seborrheic blepharitis treated with oral itraconazole during a short period. Direct examination using Parker KOH revealed numerous hyphae and spores of Malassezia in the scale. Low-dose itraconazole pulse therapy (200 mg daily, 7 days a month) was quite effective. This is the second case in which we also observed a unique fungal conformation which looked like tinea versicolor. The evidence strongly suggests that Malassezia is one of the major causative agents of seborrheic blepharitis.

[Seven days of intermittent terbinafine 250 mg treatment in Tinea pedis].

Tinea pedis responds well to topical antifungal therapy, however, relapse of the disease is not uncommon. Long-term application of antifungals is usually necessary to control relapse. We conducted an open trial of a 7 day intermittent course of oral terbinafine treatment at 250 mg/day for plantar type and interdigital type of tinea pedis. Seventy-five patients of plantar type and 49 patients of interdigital tinea pedis were treated with a 7 day course of terbinafine 250 mg/day. Clinical assessments were made at baseline and every 4 weeks. Another 7 day course of the same amount of terbinafine were given depending on the clinical and the mycological response. Of the 75 plantar type tinea pedis with 8 patients excluded, 66 of the remaining 67 (98.5%) were evaluated as cured. Of the 49 interdigital tinea pedis (3 excluded), 43 of 46 patients (93.5%) cured. Relapse of the disease was observed in 4 of 51 patients at 1 year after treatment, 4 of 25 at 2 years, and 2 of 9 at 3 years in the plantar type, and in 4 of 30 at 1 year, 0 of 14 at 2 years, and 0 of 6 at 3 years in the interdigital tinea pedis group. Intermittent terbinafine therapy is thus effective in the treatment of tinea pedis.

A case of confluent and reticulated papillomatosis responsive to ketoconazole cream.

We described here a case of a 43-year-old male who developed confluent and reticulated papillomatosis (CRP). The patient was found to be slightly obese and had no family history of such eruption. Numerous small red-brown erythemas were scattered over a wide area of the back and, in many areas, the erythemas coalesced and formed a reticular pattern. The eruptions appeared 10 days prior to the initial visit to our outpatient clinic. The Parker-KOH preparation of scraped scales revealed numerous round and budding non-clustering cells and no mycelial elements. Histological examination showed subtle papillomatosis and sparse perivascular lymphohistiocytic infiltrations. Periodic acid schiff stain showed a few spores in the stratum corneum. Topical application of 2% ketoconazole cream produced complete resolution of the eruption in 7 days. The course and histological findings of our patient suggest the eruptions were developing CRP lesions. Application of topical antifungal agents appears to be a beneficial initial treatment for early CRP lesions.