**3. Fungal infection in animals with AD**

Fungal infection in animals with AD has been reported mainly in canines and felines. For instance, Morris et al. (2002) reported that cell-mediated and humoral reactivities to *M. pachydermatis* contribute to the pathogenesis of AD in dogs but are not directly correlated. They investigated whether the potential cell-mediated immune response of atopic dogs to the yeast *M. pachydermatis* is correlated with the type-1 hypersensitivity (humoral) response of the same population of dogs. Atopic dogs with cytologic evidence of *Malassezia* dermatitis had an increased lymphocyte blastogenic response to crude *M. pachydermatis* extract, compared with clinically normal dogs and dogs with *Malassezia* otitis. The blastogenic responses in atopic

Fungus as an Exacerbating Factor

of Atopic Dermatitis, and Control of Fungi for the Remission of the Disease 145

higher levels of total serum IgE including anti-*C. albicans* IgE antibody. In other words, the delayed-type hypersensitivity to *C. albicans* antigen, which is highly prevalent in atopics

without dermatitis as well as non-atopics, was reduced in most of the AD patients.

Fig. 1. Shift of Th1-type immunity to Th2-type immunity in allergic diseases including atopic dermatitis (AD). In healthy individuals, dendritic cells present fungal antigen to naive T cells which in turn differentiate to Th1 type cells, resulting in the cellular immune response. In AD patients, Th1-type immunity shifts to Th2-type immunity in which Th2

The lipophilic fungus *M. furfur* indigenously inhabits the seborrheic region of the body, such as head, neck and upper part of the back. It was also reported that the fungus may be implicated in rosacea-like dermatitis and edematous erythema, which are chromic and intractable symptoms characteristic to the face with adult-type AD (Mukai et al., 1997), and that *Malassezia*-specific IgE level is high in the head and neck of AD patients (Bayrou et al., 2005; Darabi et al., 2009). Regarding the 11 currently recognized *Malassezia* species as an exacerbating factor in AD, *M. globosa* and *M. restricta* are found to frequently colonize the skin of AD patients. For instance, specific IgE antibodies against eight *Malassezia* species (*M. dermatitis*, *M. furfur*, *M. globosa*, *M. obtusa*, *M. pachydermatis*, *M. slooffiae*, *M. sympodialis*, and *M. restricta*) in sera from AD patients were examined using an enzyme-linked immunosorbent assay, and it was found that the specific IgE value against *M. restricta* was

It has been hypothesized that excessive colonization by *C. albicans* in the gastrointestinal tract may constitute an aggravating factor in AD, but this remains controversial (Faergemann et al., 2002; Lacour et al., 2002; Nikkels & Pierard, 2003). To date, laboratory and clinical investigations have demonstrated that IgE mediated food allergy plays a pathogenic role in a subset of AD patients (Eigenmann et al., 1998; Lever et al., 1998; van Reijsen et al., 1998). Some reports have shown increased gastrointestinal permeability in

clones produce IL-4, IL-5 and IL-10 and induce IgE production.

greater than those against the other *Malassezia* species (Kato et al., 2006).

**4.2** *Candida albicans* **gut colonization** 

control dogs (without *Malassezia* dermatitis or otitis) did not differ significantly from those in atopic dogs with *Malassezia* dermatitis. No significant correlation was found between the lymphocyte blastogenic response and the type-1 hypersensitivity response to *M. pachydermatis* within any of the groups, suggesting that modification of the dysregulated immune response toward *M. pachydermatis* may assist in the reduction of pathologic changes associated with an AD phenotype in dogs. In another study, Chen et al. (2002) compared IgE responses to separated proteins of *M. pachydermatis* in atopic dogs with *Malassezia* dermatitis and clinically normal dogs. The results of their study showed that the majority of atopic dogs with *Malassezia* dermatitis have a greater IgE response than normal dogs, suggesting an IgE-mediated immune response may be clinically important in the pathogenesis of the disease. In felines, *Malassezia* spp. have been more frequently isolated from healthy ear canals and skin in feline leukaemia (FeLV)- or feline immunodeficiency virus (FIV)-infected cats than in those noninfected (Sierra et al., 2000). In addition, *Malassezia* spp. overgrowth has been described in feline localized benign exfoliative skin diseases, such as chin acne and the idiopathic facial dermatitis of Persian cats (Jazic et al., 2006; Bond et al*.*, 2000). Based on these findings, Ordeix et al. (2007) conducted a multicentre, retrospective and descriptive study to document *Malassezia* spp. overgrowth in allergic cats. Their results suggested that *Malassezia* spp. overgrowth may represent a secondary cutaneous problem in allergic cats particularly in those with greasy adherent brownish scales on their skin. The favorable response to treatment with antifungal agent alone suggests that, as in dogs, *Malassezia* spp. may be partly responsible for both pruritus and cutaneous lesions in allergic cats.
