**2.2.5 Possible interactions between a human host and microorganisms**

Interactions of humans and members of the microbiota or among the members themselves (Fig. 2) are difficult to investigate because the phenomenon is often quite complex. Research is under way despite such difficulties.

Fig. 2. Scheme of interactions between a human host and microorganisms. SC, stratum corneum; E, viable part of epidermis; AP, antimicrobial peptide; FFA, free fatty acid. The text encased in red rectangles indicates adverse effects towards microorganisms, and the text encased in yellow rectangles implies beneficial effects for them.

#### **2.3 Characteristics of the microbiota in the skin of atopic dermatitis patients and its implications**

Unlike the skin of healthy humans, the skin of AD patients is a 'rough ground' with less natural immunity. In a typical population of AD patients, the mutation in filaggrin gene (Palmer et al., 2006; Sasaki et al., 2008) results in impairment of the barrier function, and it allows the water content to evaporate. In addition, the sweat production is decreased because of the atrophy of the sweat glands. The resulting dry and rough surface allows easy colonisation of environmental bacteria. Moreover, a decrease in the amount of antimicrobial peptides in the sweat exaggerates the lack of immune function.

#### **2.3.1 Bacteria in AD**

The major outcome of AD is the presence of *Staphylococcus* species in very high numbers. The staphylococcal population in AD patients is about 10-100 times larger than that of normal individuals (Gloor et al., 1982). The *Staphylococcus* species here includes both

Microorganisms and Atopic Dermatitis 113

Colonisation is a condition wherein parasitic organisms become attached to the skin and multiply without an apparent reaction of the host. Colonization is clinically invisible but may be detected in a culture test. When a microorganism colonises a host, there is a possibility that the microorganism will only harm the host incrementally. It may therefore

On the other hand, infection accompanies apparent host reaction in addition to colonisation. A host reaction is a kind of defence mechanism, and at the skin it is expressed as inflammation or oozing. Inflammation is a cytokine-mediated complex mechanism. Oozing is also a defensive reaction, because serum prevents microorganisms from multiplying. Therefore, when human skin is infected, a mixed reaction of inflammation and oozing occur.

The colonisation may change to infection. This is due to a shift of the host defence mechanism (Table 2) and when it occurs, hidden pathogens increase in number and become infectious to do apparent harm; *Streptococcus* species is such an example in AD to develop impetigo. Therefore, doctors should be aware of this phenomenon and instruct patients to

**Possible triggers converting colonisation to infection** 


Table 2. Triggers to potentially causing a decline in the host defence mechanisms in the skin

Impetigo is a bacterial infection caused by *S. aureus* or *Streptococcus* species. The former causes bullous impetigo and the latter causes non-bullous (or crusted) impetigo. This condition is typically seen in children but adult patients with AD are also affected and sometimes pre-sepsis occurs with high fever. In children without AD, the pathogen is considered to originate from the environment, but in patients with AD, it may also originate

As these pathogens often reside on the skin of AD patients as members of the microbiota, they may not originate directly come from the outer environment, as they do for impetigo patients without AD. It is impossible to assess whether the pathogen originates from a patient's own microbiota or the environment, but it is meaningful to evaluate the patient's

The clinical appearance of impetigo in AD patients includes sudden oozing, crust, and itching (Fig. 3). Culture tests using a scrubbed swab usually show the presence of pathogenic Gram-positive cocci. However, culture results require 2-3 days, so treatment should be administered before identification of the pathogen. Therefore, diagnosis by professional observation is needed. Otherwise, Gram stain may be used to visualise the pathogen at the point of consultation. Treatment should include a combination of oral and topical antibiotics. Usually treatment fails when only topical antibiotics are prescribed.


The clinical expression of this is redness, oozing, itching, and pain.


microbiota by using culture analysis after a successful treatment.

Washing helps improvement of the healing process.

avoid activities that may cause such infections.

**3.1 Colonisation and infection** 

become a hidden pathogen.


of AD patients

**3.2 Impetigo** 


from their own colonising microbiota.

coagulase-negative *Staphylococcus*, a major member of normal microbiota, and *S. aureus*, a harmful enemy from the environment that irritates the skin. In the skin of AD patients, the former is higher than usual while the latter also increases.

Coagulase-negative *Staphylococcus* provides a protective function to the skin by producing antimicrobial peptides against *S. aureus* (Cogen et al., 2010). Therefore, the growth of *S. aureus* leads to their production of exotoxins which exaggerate AD while the coagulasenegative *Staphylococcus* tries to eliminate them by they produce. The skin of AD patients is a battlefield of outnumbered 'the good' and growing 'the evil'.

Furthermore, *Stenotrophomonas maltophilia*, a previously unidentified bacterium on the skin and occasionally causes opportunistic sepsis in immunodeficient patients, was detected on the skin of patients with AD at a high frequency (Dekio et al., 2007). This species is closely related to *Pseudomonas* species and is considered to have high pathogenicity. This bacterial species may thus plays a specific role in development of AD.

#### **2.3.2 Fungus in AD**

In addition to bacteria, fungal species also contribute to the pathogenesis of AD. Although there is no convincing report that the *Malassezia* species in patients with AD differs from the *Malassezia* species of healthy humans, Sugita et al. (2004) reported that the genome sequence of the intergenic spacer (IGS) of *M. restricta*, one of the major members of the microbiota, differs between AD patients and healthy humans. Possessing a certain group of strains of *M. restricta* may be a worsening factor of AD.

Moreover, 10-20% of patients with AD have specific IgE against *Malassezia* species in the serum and show a positive result to the prick test of the fungus. Such AD patients tend to present a diffuse erythema on the face and neck (Darabi et al., 2008). This condition is often observed in adult humans and is improved by frequent washing, unlike most symptoms of AD.

#### **2.3.3 Conclusion**

A complete picture of the skin microbiota has not yet been attained. Therefore, its distinction in AD patients is also underinvestigated. However, biochemical and genomic techniques focused on specific molecules should lead to a total understanding in the near future.

#### **3. Infections in atopic dermatitis**

The skin of patients with AD often causes a variety of secondary infections. This may be due to dryness, impairment of natural immunity, scratching behaviour, and application of topical drugs. The dryness attracts pathogens because the rough surface yields a high point of scaling that easily captures environmental pathogens and deep crevices that make the pathogens accessible to deeper tissues. The presence of *S. aureus* in high numbers irritates the skin and results in aggravation of dryness. The decrease of antimicrobial peptides in the sweat exaggerates the possibility of the pathogen growing at the site. Extensive scratching by the patient enlarges the area of infection and also helps the pathogen to degrade the skin and invade it further. Topical drugs commonly used for treatment of AD, such as steroids and pimecrolimus/tacrolimus, suppress the immune function of the host and allows infectious microorganisms to grow at the site. In such cases, the diagnosis becomes difficult because it is not easy to ascertain that the lesion is caused by a secondary infection or by AD itself.
