**4. References**

164 Atopic Dermatitis – Disease Etiology and Clinical Management

lead the authors to conclude that, as no gold standard for aeroallergen provocation in AEDS exists, the relevance of aeroallergens for AEDS may be evaluated by APT in addition to SPT and sIgE. Moreover, in children with respiratory symptoms an exclusive positivity to APT with dust mites was observed (43). On the other hand, it was reported that in 63 children with mite-induced asthma and rhinitis, all with positive SPT and sIgE in serum, 16 (25%) were positive to mite APT too, indicating that delayed hypersensitivity

These observations lead us to investigate the possible factors underlying the positive result of APT in subjects with respiratory symptoms. In our first study, conducted on 297 children (45), we could demonstrate that in patients with asthma or rhinitis a positive APT to dust mite was strongly associated with the presence of current or past AEDS. Instead, most subjects with respiratory disease but a negative history for AEDS had a positive SPT. Multivariate analysis showed that there was a high probability of a positive APT result in patients with AEDS (odds ratio 17.4), in patients with AEDS and respiratory disease (odds ratio 21.9), and in patients with past AEDS and respiratory disease (odds ratio 22.8). These observations were confirmed in a study on a large population of 465 children aged 0.4 to 17.6 years. They were divided into four groups: group A, current AEDS (40 patients); group B, current AEDS with respiratory symptoms (156 patients); group C, past AEDS with respiratory symptoms (203 patients); and the control group, respiratory symptoms with no history of AEDS (66 patients). The APT was significantly more frequently positive in groups with current AEDS (groups A and B) or past AEDS (group C) than in the control group, while SPT and RAST were significantly more frequently positive in the control group (46). Such significant differences in response to APT in patients with diverse clinical expressions suggest that distinctive immunologic mechanisms lie beneath the different manifestations of hypersensitivity to dust mites. It seems conceivable that in subjects with a negative history for AEDS sensitization occurs by respiratory route and leads to the development of a Th2 pattern of response with ongoing production of specific IgE and consequent positive SPT and in vitro IgE tests. By contrast, in the case mite allergens enter through the skin, as it occurs in exposure to common indoor concentrations of the major allergen Der p 1 (47), such entering being facilitated by its proteolytic activity and in the presence of a filaggrin-dependent skin barrier dysfunction, a different chain of events is likely to take place. This is ultimately

revealed by positive APT and negative SPT and *in vitro* IgE tests.

The recent observations on the diagnostic significance of APT in patients with different clinical expressions of the disease highlighted the importance of delayed hypersensitivity in AEDS. This brings into question the role of simple IgE sensitization in AEDS and also the appropriateness of the term atopic when applied to AEDS. In fact, current evidence shows that up to two thirds of patients with AEDS are not atopic, therefore even to continue using the term atopic dermatitis is to be considered problematic (48, 49). In fact, the definition of atopy as "a personal or familial tendency to produce IgE antibodies in response to low doses of allergens" (50) seems not to be appropriate for AEDS, as many patients show a positive result to APT but not to IgE tests. At the same time, the definition atopy patch test seems unfounded, because the test does not reveal atopy, i.e. a type I hypersensitivity, but a type IV hypersensitivity according to Gell and Coombs classification (51). A unifying solution should be the use, in both cases, of the term allergy, which is defined as "a hypersensitivity

reactions were involved (44).


Atopic Dermatitis: From Pathophysiology to Diagnostic Approach 167

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**11** 

*China* 

**Advances in Assessing the** 

Zheng-Hong Di, Li Zhang, Ya-Ni Lv,

**Severity of Atopic Dermatitis** 

Li-Ping Zhao, Hong-Duo Chen and Xing-Hua Gao

*Department of Dermatology, No.1 hospital of China Medical University* 

Atopic dermatitis (AD) is a chronic, relapsing and pruritic inflammatory skin disorder. The prevalence of AD has been increasing significantly in recent decades, especially in developed nations. The pathogenesis of AD is still not completely understood. AD may be the results of interactions of abnormalities of immune system, genetics, environment and epidermal barrier defects. There is a wide spectrum of clinical manifestations in AD. Accordingly, there have been a number of methods and laboratory markers to assess the severity of AD. In spite of the facts that various severity assessing criteria and laboratory markers were reported or, more or less, applied, owing to the complexity of disease, race differences and environmental uncertainties, there is disagreement about the definitions and clinical application of these criteria or markers. Nevertheless, easy and quick assessing severity methods for AD are required to guide both the daily clinical and research studies.

Here, we describe some recent advances in the assessment of the severity of AD.

AD is a chronic, inflammatory, itchy condition that usually begins in infancy but may continue into adult life; the disease is genetically predisposed, and its expression is modified by environmental factors. The prevalence of AD is unevenly distributed worldwide, varying between 0.73-23% (Levy et al., 2003).There is a tendency of increased prevalence of AD in recent years, especially in developed industrial nations. For example, the prevalence of AD at the ages of 12-15 almost doubled in the last 20 years of 20th century in Japanese, suggesting the strong impact of environmental factors in AD development(Sugiura et al., 1998).The incidence of an infant to develop AD is 25% in three months after birth, or 50% in two years after birth, given that the mother is an AD sufferer; The incidence of AD in the offspring reaches as high as 79%, if both the parents are atopic patients, suggesting the key role of genetic predisposition in the pathogenesis of AD(Bradley er al., 2000).Key clinical manifestations of AD include itchy, dry skin, inflammatory rashes and other atopic conditions. Though not fully clarified, the clinical phenotype characterizing AD is the product of interactions between susceptibility genes, the environment, defective skin barrier function, and immunologic responses. These complex interactions would induce biological and immunological responses at cellular or molecular levels, involving the skin, immune

**1.1 Overview of the epidemiology of AD** 

system or even the integument as a whole.

**1. Introduction** 

