**2.2 Control of fungi in AD patients**

142 Atopic Dermatitis – Disease Etiology and Clinical Management

are used in AD patients with signs of a fungal infection (Sugita et al., 2005; Bäck et al., 1995). Antifungal therapy may remit the severity of AD by controlling these *Malassezia* yeasts.

The yeasts of the genus *Malassezia* are members of the normal cutaneous flora. However, *Malassezia* colonization on the skin of AD patients shows a different pattern from that on healthy skin (Faergemann, 2002; Gupta et al., 2001; Nakabayashi et al., 2000; Sandström et al., 2005; Sugita et al., 2004, 2006) and may aggravate AD due to an allergic reaction, especially on the head and neck area in adults (Brehler & Luger, 2001; Broberg et al., 1992; Faergemann, 1999; Huang et al., 1995; Jensen-Jarolim et al., 1992; Lintu et al., 1997; Rokugo et al., 1990; Schmidt et al., 1997; Nakabayashi et al., 2000; Savolainen et al., 2001; Scalabrin et al., 1999). Scalabrin et al. (1999) measured total IgE and specific IgE to *Malassezia furfur* in 73 AD patients. In the AD patients, specific IgE to *M. furfur* was observed more frequently in adults than children. The reaction of specific IgE to *M. furfur* was 132 times higher than that in healthy subjects. This result suggests that *Malassezia* yeast is associated with IgE-mediated

Culture-dependent methods have been used for the detection of *Malassezia* species from AD patients (Nakabayashi et al., 2000; Sandström et al., 2005). However, in recent years, many researchers have attempted the detection of *Malassezia* species from AD patients by means of a molecular-based culture-independent method that is not affected by the isolation medium, sampling method, or incubation period. Table 1 summarizes the three major studies applying molecular based PCR assay to detect *Malassezia* species from AD patients and healthy subjects, indicating that the number of detected *Malassetia* species was similar to AD patients and healthy subjects (Sugita et al., 2001; Tajima et al., 2008; Kaga et al., 2009).

Species Sugita et al. Tajima et al. Kaga et al.

*M. globosa* 93.8\*\* 44.4 100 86.7 100 100 *M. restricta* 87.5 61.1 97.2 83.3 100 100 *M. furfur* 40.6 11.1 33.3 26.7 16.1 12.5 *M. sympodialis* 40.6 50.0 58.3 36.7 65.2 62.5 *M. slooffiae* 6.3 0 30.6 16.7 17.9 6.3 *M. obtuse* 0 0 27.8 10 14.3 12.5 *M. pachydermatis* 0 0 - - - - *M. yamatoensis* - - 13.9 6.7 21.4 15.6 *M. japonicum* - - 33.3 10 10.7 12.5 *M. dermatis* - - 30.6 30 37.5 34.4 \* Number of cases. \*\* Percentage of the number of patients. AD, atopic detmatitis; HS, healthy

Table 1. Comparison of published research on *Malassezia* colonization in AD patients and

In both AD patients and healthy subjects, the predominant species were *M. globosa* and *M. restricta*. However, the study by Kaga et al. (2009), who applied real-time PCR to determine the number of rDNA copies of *M. globosa* and *M. restricta*, revealed that *Malassezia* colonization in severe AD patients was approximately two to five times higher than that in

AD (32)\* HS (18) AD (36) HS (30) AD (56) HS(32)

**2.1 Related pathogenic fungi** 

skin inflammation in AD.

subjects. -, not detected.

healthy subjects.

Ketoconazole and itraconazole, azole antimycotics, have been the most frequently studied therapeutic agents for AD. The antimycotics showed strong antifungal activities against *Malassezia* species isolated from AD patients *in vitro* (Sugita et al. 2005). In clinical studies, ketoconazole and itraconazole have shown a significant therapeutic effect on AD patients. Bäck et al. (1995) assessed the efficacy of oral ketoconazole treatment on 20 AD patients using a positive radioallergosorbent test. The AD patients were treated with ketoconazole 200 mg daily for 2 months and 200 mg twice a week for another 3 months. Of the 20 patients, 18 completed the ketoconazole treatment regimen for 5 months and most patients showed a good to moderate response for ketoconazole 200 mg daily during the 2 months but no further improvement after the administration of ketoconazole 200 mg twice a week for another 3 months. Svejgaard et al. (2004) evaluated the efficacy of oral itraconazole in the treatment of AD patients with head and neck dermatitis in a randomized, double-blind, placebo-controlled study. The AD patients were treated daily with itraconazole 200 mg, 400 mg or placebo for 7 days. The treatment with 200 mg and 400 mg of itraconazole exerted a remarkable therapeutic effect on AD patients. Therefore, the systemic antimycotic administration is expected to be highly effective in treating AD patients.

Meanwhile, the application of topical antimycotics could decrease *Malassezia* colonization and the severity of eczematous lesions in AD patients. For instance, as reported by Broberg et al. (1995), the treatment of AD patients who had head and neck dermatitis with twicedaily miconazole-hydrocortisone cream and twice weekly ketoconazole shampoo for 4 weeks resulted in decreased *Malassezia* colonization although clinical scores were not greatly improved. In addition, they confirmed the effect of ciclopiroxolamine on AD patients with moderate to severe head and neck dermatitis, which is often difficult to be treated, in a double-blind, placebo-controlled study.
