Yeast

A yeast, which may result in allergy symptoms in sensitised individuals.

Unexpected exposure

As the allergic potential of the Trichosporon genus and all its individual members has not been evaluated, it may be important to consider the genus as a whole.

A number of reports demonstrates the presence of Trichosporon in settings that may expose individuals to this genus. For example, T. asahii may be found in Cocoa beans during heap and tray fermentation (8).

Massive air contamination caused by T. asahii was reported in a haematology ward, both in the room where neutropenic patients were staying and the corridor immediately outside the room. The contamination was caused by T. asahii released by the removal of the urinary catheter from a patient who presented with an asymptomatic infection caused by this microorganism (9).

Manteca, a traditional milk product of southern Italy, produced from whey derived from caciocavallo podolico cheese-making, was shown to have high numbers of yeasts after 7 days of ripening. A total of 179 isolates were identified, of which T. asahii was one of the most prevalent. Biogenic amines were formed by proteolytic strains, T. asahii being one; prominent among the amines were phenylethylamine, putrescine and spermidine. Spermidine was produced by all the yeasts tested in this research, but only Trichosporon produced a great quantity of this compound. Histamine was not detectable (10).

Contamination has been reported of the curd during cheddar and gouda cheese making by yeast. Contaminants included T. asahii (11).

Trichosporon has been found in Parrot droppings (12).

Allergen Exposure

Geographical distribution

Potentially allergenic molds form a broadly distributed group of organisms. They exist almost worldwide, and are found in a great variety of environments, since they are adapted, and continue to adapt, to make use of a wide spectrum of food sources, which as microorganisms with airborne spores they can infiltrate easily and unobtrusively. Of greatest concern for possible allergic sensitisation is the prominence of these molds in domestic and work environments and in infections of humans. In this latter capacity we can characterise potentially allergenic molds most distinctly, as they have been fairly extensively studied as infectious agents, but hardly at all as allergens.

The genus Trichosporon consists of non- or weakly fermentative fungi. There is no sexual reproduction phase. Their primary mode of reproduction is the formation of arthrospores and blastospores. Trichosporon colonies are yeast-like, rapidly growing, wrinkled, raised, folded, glabrous to velvety, and white to yellowish-white. The wrinkles become more prominent in time. Heaping at the centre of the colony is typical. Urease enzyme production is a significant feature of this genus (1).

A rearrangement of the genus has been proposed as a result of the use of modern molecular biology study (2-3). The newly proposed nomenclature holds that there are 17 species, of which 6 are associated with infections in humans (2). This nomenclature has not yet been fully accepted.

The species causing human diseases are said to be the following:

• T. cutaneum syn. T. beigelii
• T. asteroids
• T. ovoides
• T. inkin
• T. asahii
• T. mucoides

Other species of Trichosporon are T. brassicae, T. coremiformis, T. dulcitum, T. faecalis, T. gracile, T. jirovecii, T. lowideri, T. montevidense, T. muwides, T. paehachi, T. pullulans, and T. sporotrichoides.

Trichosporon spp. are the causative agents of white piedra (superficial infections of hair shafts), onychomycosis (infections of the nails), other superficial infections, and invasive trichosporonosis. In recent years, this fungus has emerged as an opportunistic fungal pathogen. Immunocompromised hosts are particularly at risk of developing invasive infections (4). Cutaneous lesions as a manifestation of disseminated infection are also likely in these patients. Trichosporon is one of the fungi isolated from patients with fungemia. Trichosporon frequently induces summer-type hypersensitivity pneumonitis, which is the most prevalent type of hypersensitivity pneumonitis in Japan (5).

Trichosporon beigelii is a minor component of normal skin flora, and is widely distributed in nature, but nevertheless is the most significant pathogen in the genus Trichosporon. (The name Trichosporon cutaneum is often used synonymously with Trichosporon beigelii.) T. beigelii causes white piedra, onychomycosis, otomycosis, and superficial skin infections. This organism is also associated with the summer-type hypersensitivity pneumonitis commonly found in Japan (6).

T. inkin and T. ovoides are associated with white piedra (T. ovoides with cranial white piedra and T. inkin with pubic white piedra). T. asteroides and T. cutaneum are associated with superficial skin lesions. T. asahii and T. mucoides are associated with systemic infection and disseminated trichosporonosis (7)

Environment

Trichosporon is a cosmopolitan yeast, common in soil, fresh and sea water, vegetables, mammals and birds. It has also been isolated from garden compost, sewage sludge, inter-tidal sand, and mud. It is a common coloniser of human skin and GI tracts. As well as being a member of the normal flora of mouth, skin and nails, it is the causative agent of superficial and deep infections in humans. (See above under Geographical distribution.)

No allergens have yet been characterised.

The allergenic potential of this species or other species in the genus has not been well studied. Because the types of non-allergic clinical symptoms caused by the various species differ considerably, a common allergen, although possible, should not be assumed, and therefore neither should cross-reactivity among species. Intraspecies diversity has been demonstrated (13).

In a study of a number of yeasts (Candida albicans, C. pseudotropicalis, C. krusei, C. parapsilosis, C. tropicalis, C. guilliermondi, C. humicola, C. norwegica, C. utilis, Cryptococcus albidus, Geotrichum candidum, Pityrosporon pachydermatis, P. ovale, Rhodotorula minuta, R. rubra, Saccharomyces cerevisiae, Torulopsis glabrata, and Trichosporon cutaneum) for common allergenic properties, enzyme immunoassay studies showed remarkable immunological cross-reactivity only between the Candida species. However, there was significant multiple sensitivity to the extracts of C. albicans, C. utilis, Cr. albidus, R. rubra, and S. cerevisiae in skin prick testing in atopic patients, suggesting the possible presence of 1 or more common skin-reactive allergens (14).

IgE-mediated reactions

Hypersensitivity reactions to the Trichosporon genus, in particular IgE-mediated reactions, have not been well studied. It appears that organisms in the genus rarely induce IgE-mediated reactions in sensitised individuals, but whether this impression is a result of limited research or the actual low allergenic potential of the fungi is not clear. Whether few or many or all members of the genus can result in allergic reactions cannot be deduced; a conservative view is probably reasonable, as the types of non-IgE clinical reactions vary considerably among the various species. Moreover, only T. mucoides (19) and T. asahii have been associated with IgE-mediated responses, and these responses appear to be uncommon (15). This is in spite of Trichosporon species producing airborne spores that are often found in spore counts.

A 46-year-old Japanese man was reported who developed asthma induced by T. asahii, following symptoms of hypersensitivity pneumonitis attributable to the same pathogen. Similarly to other patients with summer hypersensitivity pneumonitis, his serum was also positive for anti-T asahii antibody. Nevertheless, provocation tests, including returning home and inhalations of T. asahii antigen, reproduced airway hyperresponsiveness and reversible bronchoconstriction, which are asthma-like symptoms but not features of hypersensitivity pneumonitis. Skin-specific IgE tests using the same antigen evoked an immediate allergic reaction. However, serum-specific IgE to this pathogen was not detected. Nonetheless, the authors concluded that this was a case of extrinsic asthma with coexistent asthma and hypersensitivity pneumonitis induced by T. asahii (15).

A 46-year-old man was reported with a chronic cough with sputum eosinophilia caused by T. asahii. The diagnosis was made after an inhalation challenge test with T. asahii antigen. However, he did not have bronchial hyperresponsiveness to methacholine, and bronchodilator therapy was ineffective for his cough. His symptoms worsened on returning home, suggesting the existence of some aetiologic agent in his house. A high titer of serum anti-Trichosporon antibody was detected, and an antigen provocation test with the Trichosporon extract was positive, the results consisting of the development of a cough 6 hours later and a decrease in the cough threshold to inhaled capsaicin 48 hours later (16).

However, hypersensitivity pneumonitis induced by 2 members of the Trichosporon species, T. asahii and T. mucoides, is a common disease in certain parts of the world, in particular as a summer-type hypersensitivity pneumonitis which is the most common form of hypersensitivity pneumonitis in Japan (13, 17).

Hypersensitivity pneumonitis is a granulomatous interstitial lung disease resulting from an immunologic reaction to the repeated inhalation of organic dusts and active chemicals. There are 50 or more groups of hypersensitivity pneumonitis, depending on a variety of occupational or environmental inhalants; these syndromes include Farmer's Lung, Bird Fancier's Disease, Humidifier Lung, and Air-Conditioner Disease. Although summer-type hypersensitivity pneumonitis is an especially common illness in Japan, it may also be found in other countries, including many Western countries, because T. asahii and T. mucoides are widely distributed in temperate and subtropical areas of the world. The fungus grows in warm, moldy, decaying organic matter, and scatters into the air (18).

The serum IgE level is usually not high in hypersensitivity pneumonitis because this is a Type III or Type IV Gell-Coombs-type reaction. However, infiltration of lymphocytes and mast cells in patients with summer-type hypersensitivity pneumonitis and a high serum IgE level has been reported (19). One group of researchers encountered a 56-year-old woman with summer-type HP who had a high serum IgE level and a positive skin reaction to the causative antigen. She was admitted to a hospital because of coughing, fever, and dyspnoea. On admission, a chest X-ray film and a chest CT scan disclosed ground-glass opacity and diffuse small nodular shadows. Her FEV1 was normal. Summer-type HP was diagnosed because of a positive test for serum antibody to Trichosporonmucoides and a positive result on an antigen challenge test, and because pathological examination of specimens obtained by transbronchial lung biopsy showed severe infiltration of lymphocytes. A skin test for the causative antigen was done to study the early immunological reaction, and a positive result (22 mm x 24 mm) was obtained for T. mucoides in only 15 minutes. Doctors could not elicit any history of atopy that may have been associated with the high serum IgE level and the positive skin test. Therefore, it was suspected that this patient had had an early immunologic reaction (Type I allergy) to T. mucoides, and that Type I allergy was involved in the development of HP (19).

Other reactions

Opportunistic fungal infections are becoming more frequent complications during cancer therapy, after organ transplantation and in AIDS infections, especially after better control of bacterial infections in immunocompromised patients. Unusual species such as Fusarium, Trichosporon, and non-albicans Candida species are becoming more frequent, and are often resistant to conventional therapy (20).

Trichosporon pneumonia is very rare. A 78-year-old man with leukemia complicated with pulmonary infections due to T. pullulans was reported (21).