In this paper, we describe the major characteristics of hyperkeratotic tinea pedis and review therapeutic results obtained in the Department of Dermatology of Kitasato University Hospital and those reported in the literature in Japan and abroad.
To study the relationship between the changes in visceral mycoses rates and recently advanced medical care in hematological settings, data on visceral mycosis cases with leukemia and myelodysplastic syndrome (MDS) that had been reported in the Annual of the Pathological Autopsy Cases in Japan in 1989, 1993 and 1997 were analyzed. The frequency rate of visceral mycoses with leukemia and MDS was 27.9% (435/1557) in 1989, 23.0% (319/1388) in 1993 and 22.3% (246/1105) in 1997. In comparing the rate of mycoses in recipients of organ or bone marrow transplantation with that of non-recipients, that of recipients was approximately 10% higher. The predominant causative agents were Candida and Aspergillus, at approximately the same rate as in 1989. The rate of candidosis decreased to one-half that of aspergillosis by 1993. Furthermore, severe mycotic infections clearly increased from 58.9% in 1989 to 75.6% in 1997. Among a total of 1000 cases with mycotic infection in those 3 years, acute lymphatic leukemia and acute myeloid leukemia were the major diseases (40.6% and 34.8%, respectively), followed by MDS (26.1%). The reasons for increased rates of aspergillosis and of severe mycotic infection can be surmised to be: (i) candidosis had become controllable by prophylaxis and by empiric therapy for mycoses with effective antifungal drugs; (ii) the marketed antifungal drugs were not sufficiently effective against severe infections or Aspergillus infections; and (iii) the number of patients surviving in an immunocompromised state had increased due to developments in chemotherapy and progress in medical care.
The data on visceral mycoses reported in the " Annual of Pathological Autopsy Cases in Japan " were analyzed epidemiologically every four years from 1989 to 2005, and in 2007. The frequency rates of visceral mycoses dropped sharply between 1989 (4.5%) and 1994 (3.2%), but by 2001 had risen again and have remained (4.4-4.6%) generally stable since then. The predominant causative agents were Candida and Aspergillus. Although the rate of candidosis showed a gradual decrease, the rate of aspergillosis showed an increase by degrees. Furthermore, the rate of aspergillosis exceeded that of candidosis in 1994, and the difference in the rates between the two conditions apparently further increased until 2001. After 2005, however no changes in this difference were observed. For complicated infections, the incidence of coinfection with Aspergillus and Candida showed a decreasing, and that with Aspergillus and Zygomycetes showed an increasing tendency. Severe infections with Zygomycetes showed a clear increase from 57.4% in 1989 to 88.9% in 2007. Comparing underlying diseases with mycoses in 1989 and 2007, leukemia (including myelodysplastic syndrome) decreased from 26.1% to 18.8% and bacterial infections (including interstitial pneumonia) increased from 11.1% to 22.1%. By age, the highest frequency rate of mycoses was observed in the range of 60-79 years, and the frequency rate of exogenous fungal infections such as aspergillosis, cryptococcosis, zygomycosis and trichosporonosis showed an increasing trend in the less than one-year old group.
In this study, in addition to studying the efficacy and safety of the once-daily administration of 100-mg capsules of fluconazole over an 8-week administration period with six patients with hyperkeratotic-type tinea pedis, we also measured the serum and horny layer concentrations of fluconazole to study the mobility into the horny layer in diseased areas of the sole skin. The final overall efficacy and overall safety were both 100% (six out of six), and no side-effects, including abnormal laboratory changes, were observed in any of the patients. The drug mobility study revealed that in the horny layer of the skin a steady state was reached after 4 weeks of administration, with the mean concentration being 12.8 micrograms g-1. This concentration was a high concentration that was no less than 13 times the geometric mean MIC (0.972 microgram ml-1) for fresh clinical isolates of Trichophyton rubrum. Based on the above results, fluconazole is considered to be highly useful for treating various kinds of dermatomycosis, including hyperkeratotic-type tinea pedis.
Hyperkeratotic type tinea pedis is a refractory type of superficial dermatomycosis. Treatment for hyperkeratotic type tinea pedis is mainly with oral antimycotics, such as griseofulvin, and healing is generally considered to be difficult with only topical antimycotics. In this randomized comparative study, the usefulness of a topical application of 1% lanoconazole cream (Astat) monotherapy (group I) was compared with that of combination therapy with 1% lanoconazole cream and 10% urea ointment (Pastaron) (group II) in a series of patients with hyperkeratotic type tinea pedis. The clinical improvement rates (percentage of 'marked improvement' plus 'moderate improvement') was 70.0% in group I and 95.7% in group II. The fungal eradication rate was 5.0% in group I and 43.5% in group II after 4 weeks of treatment, and was 70.0% and 95.7% after 12 weeks of treatment, respectively. The usefulness rate (percentage of 'very useful' plus 'useful') was 70% in group I and 95.7% in group II. Both lanoconazole monotherapy and the combination therapy with 10% urea ointment were highly effective and safe. Both treatments should be recommended for patients with hyperkeratotic type tinea pedis for whom an oral treatment is not appropriate or for whom a sufficient improvement with oral medications cannot be expected.
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