Although onychomycoses are caused by dermatophytes, yeasts or non-dermatophyte molds, tinea unguium describes chronic fungal infections by dermatophytes only. Tinea unguium is a common fungal infection of the nail plate or nail bed with increasing prevalence worldwide. It is not self-limited and shows a higher frequency among the elderly population. In Japan, approximately 10% of the entire population is estimated to have tinea unguium. During the period when only griseofulvin was available for treatment, it was a very difficult disease to treat. Since in the 1990's, however, the introduction of new oral antifungals, itraconazole and terbinafine, initiated a new era in the treatment of tinea unguium. Many excellent textbooks, review articles, and original articles have already been published. This paper considers the circumstances in Japan, epidemiology, causative agents including non-dermatophyte molds, differential diagnosis, diagnostic techniques, the quality of life of the patients with tinea unguium, and then the treatment options are reviewed again.

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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.

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This study aimed to examine the genotype distribution of Candida albicans and the major genotypes involved in superficial candidiasis. The genotypes of C. albicans isolated from the infection sites of patients with superficial candidiasis (referred to as infection isolates) were analyzed by fragment analysis using 4 microsatellite markers (HIS3, CDC3, CAI and CAIII). Genotypes of the infection isolates were compared with those of C. albicans isolated from oral mucosa of non-candidiasis patients (referred to as oral isolates). Isolates of C. albicans showed 4 major genotypes for HIS3/CAI (“ a ” for 148 : 148 / 23 : 23,“ b ” for 148 : 160 / 33 : 41,“ c ” for 148 : 164 / 32 : 41 and “ d ” for 152 : 152 / 18 : 27). The genotypes “ a ”,“ b ” and “ d ” were commonly found in oral (4.7, 8.8 and 7.6%, respectively) and infection (6.6, 9.2 and 15.4%, respectively) isolates. No isolates of genotype “ c ” were isolated from infection sites. The genotype “ a ” was found in the isolates from patients with genitalia candidiasis. Genotyping of multiple isolates from an individual patient showed that C. albicans from infection sites was genetically homogenous as compared with that of oral isolates, even in the same patient with candidiasis.

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Twenty-five cases of dermatophytoses caused by Microsporum canis were encountered during a 3-year period (January 2008-December 2010). Their diagnosis was based on detection of fungal elements by direct microscopy and identification of M. canis by fungal culture. There were 17 women and 8 men ; they ranged in age from 4 to 85 years (mean, 34.6). The affected site was the head (n=5), face (n=8), neck (n=5), arm (n=8), leg (n=5), and trunk (n=5) ; exposed sites were those most often affected. A lone eruption was seen in 13 and multiple eruptions in 12 patients. The disease type was tinea corporis in 21 patients, tinea capitis in 5, and a combination of tinea corporis and tinea capitis in one. The disease showed familial onset in 10 patients (5 pairs), including 2 sibling pairs, 2 mother-child pairs, and 1 grandmother-granddaughter pair. Twenty-four patients had a history of contact with animals, and animals kept at home may have served as the infection source (cats in 23 patients and a dog in one). Hairbrush culture of the pets was positive in 9 patients. The patients with a lone eruption were treated with topical antifungal agents, while those with multiple eruptions of tinea capitis and tinea corporis were treated with oral itraconazole or terbinafine hydrochloride for 2-14 weeks, combined with topical antifungal therapy. Although reports of dermatophytoses caused by M. canis have been decreasing, our experience indicates the necessity of considering possible transmission of this disease from pets such as cats.

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We examined the therapeutic effects of cinnamaldehyde and the potentiation of those effects with cassia and cinnamaldehyde when combined with the food additive methylcellulose against murine oral candidiasis. When 19.5mg/ml of cinnamaldehyde was administered in the oral cavity of Candida infected mice, the oral symptoms were improved. Furthermore, when either a cassia or a cinnamaldehyde preparation in combination with methylcellulose was administered to oral candidiasis-inflicted mice, the therapeutic effects of cassia or cinnamaldehyde potentiated. Methylcellulose itself did not affect the oral symptoms or the viable number of C. albicans cells. GC/MS analysis showed that the dose of cinnamaldehyde remaining in the tongue tissue of mice treated with the cinnamaldehyde-methylcellulose mixture was higher than that in mice administered cinnamaldehyde alone, and also showed that cinnamaldehyde was not detected in the blood of any of the tested mice. These findings suggested that the combination of cassia or cinnamaldehyde and methylcellulose may be a useful prophylactic or therapeutic tool against oral candidiasis.

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Antithrombotic activity of a protease purified from a medicinal mushroom, Ganoderma lucidum, has been evaluated platelet aggregation in vitro and pulmonary thrombosis in vivo. The purified protease exhibited concentration dependent inhibitory effects on platelet aggregation induced by ADP (adenosine diphosphate), with an IC₅₀ value of 2.4 mg/mL. The purified protease protected mice against thrombotic death or paralysis induced by collagen and epinephrine in a dose dependent manner when administered orally. It produced a significant inhibition of thrombotic death or paralysis at 60μg/kg body weight, while aspirin produced a significant inhibition of thrombosis at 10-20 mg/kg body weight. The purified protease also has showed fibrinolytic activity and alters coagulation parameters such as activated partial thromboplastin time (APTT), and thrombin time (TT) in rat platelet. These results suggested that the antithrombotic activity of Ganoderma lucidum protease might be due to antiplatelet activity rather than anticoagulation activity.

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