Hikaru Kume

Case Report. A case of chromoblastomycosis effectively treated with terbinafine. Characteristics of chromoblastomycosis in the Kitasato region, Japan

A 38‐year‐old male with history of trauma in the left gluteal region 20 years ago presented with a dark red skin eruption at the traumatized area. It gradually grew to form an erythematous plaque with a well‐defined border. Clinical findings and mycological cultures resulted in the diagnosis of chromoblastomycosis due to Fonsecaea pedrosoi. After initial administration of 5‐fluorocytosine and local heat an almost complete cure was achieved with terbinafine combined with local heat therapy. A review is given on the chromoblastomycosis cases observed in the Kitasato region in Japan.

Increase in aspergillosis and severe mycotic infection in patients with leukemia and MDS : Comparison of the data from the Annual of the Pathological Autopsy Cases in Japan in 1989, 1993 and 1997

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.

Epidemiology of visceral mycoses in autopsy cases in Japan: the data from 1989 to 2009 in the Annual of Pathological Autopsy Cases in Japan

To identify recent trends in the frequency of mycoses in autopsy cases, we analyzed, on a four-year basis, the 1989-2009 data in the Annual of Pathological Autopsy Cases in Japan. Of the 13,787 (9235 males) autopsies conducted in 2009, 4.5% (633/13,787) involved fungal infections and of the latter, 60.3% (368/633) were found to have severe clinical manifestations. Among the 610 (96.4%) cases involving a single etiologic angent, the predominant pathogens were Aspergillus (299 cases; 49%) and Candida (184 cases; 30.2%). However, it should be noted that the prevalence of severe aspergillosis and candidiasis has been decreasing. Although the frequency of cases involving zygomycetes seemed to be generally remaining stable from 1989-2009, we noted for the first time a peak in 2009 in such infections in patients less than one year old. Finally, deep-seated infections caused by unidentified fungi would appear to be decreasing over the time of the survey. Our finding, it is hoped, will encourage physicians to actively pursue viscerial fungal infections.

Butenafine hydrochloride (Mentax®) cream for the treatment of hyperkeratotic type tinea pedis and its transfer into the horny layer, with or without concomitant application of 20% urea ointment (Keratinamin®)

Summary. Forty‐five patients were divided into two groups: group I, 23 patients, treated with butenafine hydrochloride (Mentax®) cream alone, and group II, 22 patients, treated with butenafine hydrochloride and 20% urea ointment (Keratinamin®) to evaluate the usefulness of the treatments. We also measured the transfer of these drugs to the horny layer in some patients. The clinical improvement rate of dermatological symptoms (marked improvement+ improvement) was 91.3% in group I, 100% in group II, with therapeutic effects evident earlier in group II than in group I. The mycological eradication rate was found to be 47.4% in group I, 50.0% in group II after 4 weeks of treatment, and 81.8 and 87.5% at 12 weeks thereafter, respectively, with no adverse reactions found. The clinical utility rate (markedly useful+useful) was 91.3% in group I and 86.4% in group II. These results demonstrate that application of butenafine hydrochloride alone was extremely effective for the treatment of hyperkeratotic‐type tinea pedis and that combination application with urea ointment resulted in an earlier improvement of dermatological symptoms. The concentration of butenafine in the horny layer from healthy volunteers reached a steady state in both groups I and II at 2 weeks after the application, with a lower concentration found in group II (about 70 ng mg−1) than in group I (about 100 ng mg−1). Although some variations in concentration were found in case by case, patients in whom the treatment was determined to be ‘markedly effective and effective’ showed the increase in concentration of the drug in the lesional horny layer to be directly proportional to the number of days of treatment, with a lower concentration found in group II than in group I. This trend was also seen in healthy volunteers.

Usefulness of Lanoconazole (Astat®) cream in the treatment of hyperkeratotic type tinea pedis. Comparative study of monotherapy and combination therapy with 10% Urea Ointment (Pastaron®)

Summary  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.

Recent statistical survey of visceral aspergillosis in Japan, and experimental studies on the pathogenicity of aspergillus fumigatus in rabbits*

A statistical survey of visceral aspergillosis in Japanese pathological autopsies (1972-1981) was carried out. It was found that the infection has increased remarkably in recent years, and the results obtained were briefly described. Pathogenicity of several strains of Aspergillus fumigatus in rabbits was studied on three occasions in the past 31 years. The pathogenicity appeared to be unchanged even after long subcultures for 13 years, while lowered pathogenicity was noted with long-term subcultures over 30 years. However, the lowered pathogenicity of the fungus seemed to be recovered by animal passage.

Aspergillus Vegetative Endocarditis Complicated with Schizocytic Hemolytic Anemia in a Patient with Acute Lymphocytic Leukemia

Aspergillus vegetative endocarditis developing in a patient with acute lymphocytic leukemia during the phase of hematological remission has led to a fatal outcome, complicated with severe hemolytic anemia with red cell fragmentation. Systemic aspergillosis may involve heart valves with underlying disorders, but seldom affects intact valves even in severely compromised hosts. Among such rare cases so far reported, only 2 cases have been documented in acute leukemia, despite a huge prevalence of pulmonary and systemic aspergillosis in hematological malignancies. Our present case is essentially the same as in the preceding two cases in that endocarditis occurred during the hematological remission. These clinical, observations may suggest that every leukemic patient suffering from aspergillosis is susceptible to the valvular complication after, rather than during, the period of severe myelosuppression, because platelets play an important role in the formation of thrombotic lesions.

Bifonazole (Mycospor® cream) in the treatment of moccasin‐type tinea pedis. Comparison between combination therapy of bifonazole cream +10% urea ointment (Urepearl®) and occlusive dressing therapy with the same agents

Moccasin‐type tinea pedis(MTTP) is a hardly curable superficial dermatomycosis primarily characterized by hyperkeratosis of the sole. In this study, we compared the usefulness of combination therapy of bifonazole (Mycospor® cream)+10% urea ointment (Urepearl®) (overlapping application group=group I) with occlusive dressing therapy with the same agents (group II) in the treatment of MTTP, and obtained the following results.

Multicenter Evaluation of Commercial Frozen Plates for Microdilution Broth Antifungal Susceptibility Testing of Yeasts and Comparison of MIC Limits Recommended in NCCLS M27–A2

A commercial kit, Frozen Plate for Antifungal Susceptibility Testing of Yeasts, Eiken (Eiken Chemical Co., Ltd., Tokyo), was tested in a multi‐institute study to evaluate the agreement between inter‐institute MICs and National Committee for Clinical Laboratory Standards (NCCLS) M27–A2 recommendation limits of MIC value. The kit was reported as a method equivalent to the standardized guidelines for antifungal susceptibility testing by the Committee for Clinical Laboratory Standards—1994, the Japanese Society for Medical Mycology, and which is widely used in Japan for amphotericin B, flucytosine, fluconazole, miconazole, and itraconazole. The degrees of inter‐institute and NCCLS agreements were good to excellent especially with 48‐hr incubation for all antifungal agents. However, the percent agreements to NCCLS recommendations against itraconazole were poor. Overall, MIC values obtained using the frozen plate antifungal susceptibility testing kit, with 48‐hr incubation, were thought to be reliable and convenient alternatives to the data obtained by the NCCLS M27–A2 reference macrodilution and microdilution method. This kit will allow matching of results between international laboratories. However, the MIC value for itraconazole requires careful interpretation.

Case Report. Kerion Celsi effectively treated with terbinafine. Characteristics of kerion Celsi in the elderly in Japan

A 75‐year‐old non‐working male living in Sagamihara, Kanagawa Prefecture, had erythematous plaques with scales associated with follicular pustules in the head area extending from the occipital to right temporal regions about 1 month prior to his initial visit, when hair loss increased. The diagnosis was kerion Celsi. Trichophyton rubrum was isolated from scales and tissues taken from lesions in the head. Histopathological examinations showed irregular epidermal thickening with dense cell infiltration from the dermis to subcutaneous adipose tissues. Granulomatous reactions involving neutrophils, histiocytes and giant cells were seen mainly in the hair follicles. Periodic acid‐Schiff (PAS) and Grocott‐positive microbial elements were detected in the horny layer, and inside and outside the hair follicles. Pustules disappeared 1 week after starting the oral treatment with terbinafine (125 mg day−1). A cure was achieved 2 weeks after starting the treatment, with only slight scales remaining. No recurrence has been observed to date. Terbinafine was thought to be very effective and safe for kerion Celsi. We reviewed 27 cases of kerion Celsi reported in patients, aged at least 70 years, in Japan and found that the major characteristics of this disease in Japan include the following: (1) female cases outnumber male cases; (2) the causative organism was T. rubrum in 14 of 27 patients (51.9%); and (3) topical application of steroids often induces this disease in patients with superficial tinea capitis.