Fungus is known to be one of the important causative allergens of allergic diseases such as bronchial asthma, allergic rhinitis and atopic dermatitis. Not only outdoor airborne fungi but also indoor fungi such as Aspergillus restrictus and Eurotium have recently received attention as causative fungal allergens of allergic diseases. In addition to careful history taking, in vivo testing methods such as skin test and conjunctival or bronchial provocation tests are sometimes necessary to diagnose the causative allergen. Problems requiring resolution are: 1. fungal allergens composed of multiple allergenic components, 2. difficulty of environmental monitoring of fungal allergens, 3. special characteristics as microorganisms, and 4. characteristics of normal flora allergy, etc.

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Fungi related to allergies are commonly found in dwelling environments. The predominant fungi Cladosporium, Penicillium, Aspergillus, Alternaria, Wallemia and Rhodotorula live mainly in indoor air, house dust(HD), futons, clothes and contaminated building materials. Fungi in HD are especially important allergens. The fungal CFU and predominant fungi in HD are 10⁴-10⁶·g^-1 and are composed of xerophilic or osmophilic species Aspergillus restrictus, Wallemia and Eurotium but not many yeasts and actinomycetes. Fungal contamination of materials is a serious human health problem because the fungal cells scatter from the materials in the air or HD.
The biological activities by fungi also have health implications from the viewpoint of fungal allergens. In this paper, fungal germination, enzyme activities, contaminating cell form and viable or nonviable cells are also discussed.

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A 41-year-old Japanese-Brazilian man, living in Japan since 1991, visited our hospital in August 1998 complaining of a scaly annular erythema which had been present on his right forearm since 1996. Granulomatous inflammation was revealed in the dermis upon skin biopsy. Sclerotic cells were present within the granulomatous lesions. Fonsecaea pedrosoi was isolated from tissue cultures. The restriction fragment length polymorphism pattern of mitochondrial DNA of the causative fungus was compatible with F. pedrosoi type 1, the commonest type in Japan. Since type 4 is usually found in South America, the patient was assumed to have become infected in Japan. An oral dose of terbinafine at 125mg/day was ineffective. 125mg/day single dose of terbinafine reaches an average plasma concentration of only 0.69μg/ml, where as 250mg/day reaches 0.96μg/ml. Because the minimum inhibitory concentration (MIC) of terbinafine against the isolated fungus was found to be 0.76μg/ml, the terbinafine dose was increased from 125mg/day to 250mg/day, which slowly led to remission.
Chromomycosis is caused by several species of dematiaceous fungi, and terbinafine efficacy may vary depending on the causative fungus. MIC values may differ even within the same species. It is important to isolate the pathogenic fungus in each case and measure the MIC value to determine the optimal dose of terbinafine.

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The lipophilic yeasts Malassezia species are the causative agents of tinea versicolor and known also to be a member of normal skin flora. They are commonly isolated from the skin of humans and animals, but not from the environment. This is the first report of the isolation of Malassezia sp. from the environment (a hospital floor). The results of assimilation tests of lipids and karyotyping showed that these isolates were M. furfur. They assimilated not only lipids including floor wax and car wax but also some ointments (except antifungal agents) used clinically. The results suggest that we need to take care when using such ointments to treat skin diseases.

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Cryptococcus neoformans is an important fungal pathogen in immunocompromised hosts. Capsulation, urease and melanin synthesis activity of the fungus are well known virulence factors. Although artificial melanin-deficient mutants of Cr. neoformans have been investigated, the clinical mutant is rare. We found a Cr. neoformans isolate in the cerebrospinal fluid of an AIDS patient which produced a light tan colony on a caffeic acid cornmeal agar (CACA) plate. The mycological feature of the isolate was as follows; normal capsulation, defective inositol assimilation ability, serotype A; ureasepositive; mating type α; haploid; extremely slow growth in RPMI 1640 medium, Sabouraud dextrose broth, brain heart infusion broth and yeast nitrogen base; lower production of melanin with L-DOPA substrate; and low virulence to ddY mice. We also investigated the partial DNA sequence of CNLAC1 gene between the 3085th to 3623rd base. There were many substitutions, 3 insertions and 3 deletions in the isolate compared with GenBank accession number L22866. The result indicated some functional disorder in the gene. Although the CACA plate is an excellent selective medium for Cr. neoformans, other identification methods should also be used.

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To evaluate the viability of dermatophytes in tinea unguium, we applied neutral red staining (NRS) for nail powder obtained from direct microscopic examination (DME) of positive tinea unguium patients.
The nail powder from tinea unguium patients by grinder was applied following three sets of examinations, NRS, DME, and culture on Mycosel medium. The positive rates of nail powder obtained from 50 tinea unguium patients were 35 (70%), 37 (74%) and 2 (4%), respectively. Correlation of three sets of examinations were as follows: twenty-five patients were NRS positive, DME positive and culture negative, 10 patients were NRS negative, DME positive and culture negative, and 8 patients were NRS positive, DME negative and culture negative.
These findings suggest that application of NRS for nail powder from tinea unguium patients is a practical method for evaluation of the viability of fungal elements.

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For the past 4 years a 23 y-old female has noticed erythema on the dorsum of the right foot, where skin was grafted due to a traffic accident 20 years ago. She visited the Department of Dermatology of Gifu Prefectural Hospital on Oct. 19, 1998; her general health was good. Physical examination disclosed a swelling with erythema, papules and pustules on the dorsum of the right foot. The results of routine laboratory investigations were within normal limits except for the white blood cell count (11, 300/mm³), blood sediment rate (25mm/hrs), C reactive protein (1.21) and rheumatoid factor (×16.6). Several yellowish and verrucous or wrinkled colonies were grown on Sabouraud's agar culture from the biopsied specimen of the foot.
Histopathological features showed epidermal hyperplasia with elongation of rete ridges and granulomatous changes in the dermis; many mononuclear and giant cells were present, and several positive fine filamentous and irregularly branching structures with PAS and Grocott stains were seen in the granulomatous nests. Both clinical and histopathological features led to speculation of Nocardia infection, and Nocardia brasiliensis was determined. The patient was treated by surgical total resection including the grafted skin. Although a soybean-sized nodule was seen on the border of the skin-graft of the foot three months later, there was no recurrence after the local resection.

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Cutaneous protothecosis developed in a 63-year-old Japanese female. The patient had a long history of steroid use for bronchial asthma. A tender, swollen, erythematous plaque with white papules covered the dorsal aspect of the patient's right hand. Histopathological examination showed typical protothecosis with numerous “mulberry-like” sporangia positive for periodic acid-Schiff stain. The pathogen was identified as Prototheca wickerhamii. After a 6-week course of 150-200mg/day itraconazole (ITCZ) therapy, the patient's culture was negative for P. wickerhamii. No recurrence was seen after 12 weeks of ITCZ therapy. This case of protothecosis and those of 16 patients are summarized. All the patients had lived in mid- to southern Japan.
Only 12 cases of protothecosis treated with ITCZ have been reported in the literature; 8 of these cases were cured with ITCZ therapy alone. In cases treated with ITCZ at no more than 100mg/day, medication was typically needed for 2 months; most of the cases treated with ITCZ at 200mg/day were successfully cured within 2 months. A 2-month course of ITCZ at 200mg/day appears to be adequate treatment for human protothecosis.

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We report a case of lymphocutaneous sporotrichosis in a 69-year old man who had nodular-ulcerated lesions on the right hand and forearm. Small nodules remained on the right hand after 8 weeks of 0.5g daily treatment with potassium iodide. Alternatively, terbinafine therapy (125mg/day) resulted in healing with atrophic scars after 9 weeks without side effects.
We reviewed 67 patients of cutaneous sporotrichosis in Japan from 1993 to 1999. Those cure rates (and mean durations of treatments in parentheses) are 90.9% (8.1 weeks) with potassium iodide, 86.6% (12.6 weeks) with itraconazole (100mg/day) and 71.4% (12.8 weeks) with terbinafine (125mg/day) treatments, respectively. These results lead us to consider a daily dose of 250mg as more appropriate for terbinafine.

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