Allergies and the skin, an interdisciplinary approach in GA<sup>2</sup>LEN and EAACI activities
Authors: T. Zuberbier, M. Worm
Journal: Allergy (2006)

The skin, as the largest organ of the human being, is frequently involved or at least partly involved in the majority of allergic reactions. This is not only evident in the easily visible signs like a macular papular exanthema in drug allergy, eczema in contact hypersensitivity, atopic eczema or wheals and angioedema. Also the more subtle, probably genetically determined changes associated with atopy in allergic rhinitis and allergic asthma such as Dennie Morgan fold, the Hertoghé sign or the increased dryness and sensitivity of the skin, are important to note. It is well known that in Europe the field of allergy in practice and in science is very diverse because of the heterogeneity of the medical systems. Whereas in many southern European countries, allergology is a specialty of its own, in many, especially of the northern European countries, this is not the case. In the German-speaking and Scandinavian countries, allergology is frequently closely linked to dermatology with a broad spectrum of topics. This is also reflected in this issue of Allergy where a variety of subjects is covered starting from experimental research in eosinophils as well as clinical research, epidemiological research and the active participation in the development of position papers. While the diversity in the clinical and scientific world of allergy in Europe can be regarded as a problem, it also offers a very high chance of tackling the problem by bringing together this broad range of expertise. Both the European Academy of Allergy and Clinical Immunology (EAACI) and the Global Allergy and Asthma European Network (GA2LEN), are on the road to successfully meeting this challenge (1). EAACI, organized in the different sections, clearly encourages the collaboration and exchange between these sections and the position paper written by Kristiina Turjanmaa on atopy patch testing (2) in this issue is a good example of collaboration between the section of dermatology and paediatrics, which has also been earlier demonstrated in joint allergy schools (http://www.ga2len.net; accessed 19 October 2006). In GA2LEN it is one of the central aims to support intense collaboration of the various participating partners and collaborating centres not only in research but also in harmonizing the clinical routine (3). Jointly, GA2LEN and EAACI have decided to work in the field of position papers to increase the impact, and the paper on atopy patch test is already the third in a short time (4, 5). Manns et al. (6) have identified a possible new tool in inactivating chemokine receptors in human eosinophils. A close look at the molecular mechanisms in allergy will surely bring new possibilities in research and later therapeutics in the future and may lead into the field of biologics. A window which has until now only been opened for IgE-mediated respiratory allergy with anti-IgE (7–10), but as IgE also represents an important mechanism in atopic dermatitis (11) and other dermatological diseases, more can be expected to come. Looking at the levels of eosinophilia in the skin, which is a common feature in many allergic reactions, Igawa and colleagues have looked at a possible involvement of galectin-9 in dermal eosinophilia of Th1-polarized skin inflammation (12). The paper interestingly highlights the cross-talk between resident cells of the skin (fibroblasts and keratinocytes) with inflammatory blood-derived cells. This is in line with previous findings (13, 14). In addition, Jockers and Novak (15) have looked at possible alterations in monocytes of patients with atopic eczema. These studies once more underline that complex, partly genetic alterations affecting different cell types in atopic eczema in the skin are important (16–18). However, alterations are not only limited to the skin itself, also a constant activation of inflammatory skin homing blood-derived cells and of the immune system in general is present, as observed earlier for T-cells (10) and B-cells (19). Atopic dermatitis is also a disease where hypersensitivity of the skin is experienced by many patients. Recent data showing a defect of filaggrin expression in AD patients underline the importance of an impaired barrier function of the skin in this disease (20). Augmented activation of cutaneous nerves has been described in the literature (21, 22). Raap et al. (23) add further insight into these processed describing the increase of NGF and BDNF in both extrinsic and intrinsic type of atopic dermatitis, which is further underlining the possibility of an immunological network in atopic dermatitis. This is also clearly observed in parallel findings in allergic asthma (24, 25). While in atopic eczema everyone realizes that changes in the dermal blood flow resulting either in erythema or pallor are a core feature of the disease. However, also in atopic individuals without current visible cutaneous signs of atopic dermatitis, minimal involvement of the skin appears to be frequent. This is further emphasized by the work of Schuster et al. (26) looking at the changes of the vascular pattern of the palms in patients with atopy compared with non-atopic individuals. Another interesting research topic is the involvement of climatic conditions on the status of the skin. Especially in patients with atopic eczema who have a higher sensitivity of the skin and a frequently disrupted skin barrier function, this may be an important aggravating factor. In the work of Byremo et al. (27) an interesting experiment is described with a comparison of children sent from an arctic climate to a subtropical climate for 4 weeks. This work shows that the improvement in the quality of life and in the SCORAD (28) of these children remains for even 3 months after the return and is in line with three older studies investigating the effect of a climate (29–31). The atopy patch test is of interest for the diagnosis of some patients who have a true IgE-mediated sensitization without positive skin prick tests (32–34). In the case of inhalant allergy, these tests may be sufficient but allergen avoidance may not be very effective (35). On the other hand, for foods, these tests should be usually confirmed by oral challenges (36). The results may help for the dietary treatment of atopic dermatitis (37) which is still a matter of discussion (38). In particular, the role of probiotics needs more data to be fully understood (39). Last but not least, the current issue also includes an interesting original article about diagnostics in type 4-allergy. The report of Brasch and colleagues (40) is remarkable in two aspects. First, it clearly shows that the only available method of investigating allergic contact hypersensitivity reactions, the patch test, is remarkably robust. Already in previous studies, it has been shown that negative patch test reactions do not influence adjacent positive test reactions (41). However, the so-called ‘angry back’ (42, 43) is a phenomenon well-known to any dermatologist, which clearly limits the use of the patch test. Some authors have then speculated that it might be of advantage to locally separate the places used for testing with related allergens as far as possible. However, in this report Brasch and colleagues now show that the local distribution of the patches on the back is not critical but false-positive results might more easily occur with the increasing number of other unrelated positive allergic reactions. The practical consequence of this paper is, in patients where we expect a high number of contact hypersensitivity reactions due to the history, it might be of advantage to limit the number of tests performed on one occasion and rather perform additional patch tests a few weeks later. Especially in the setting of occupational dermatology, this is of high relevance in order not to produce falsely positive results. However, the second reason why this paper is remarkable is the fact that it could only be generated by a well-functioning network. The Information Network of Departments of Dermatology is formed by a group of mostly university departments of dermatology and allergy in Germany, Austria and Switzerland. The current study has evaluated a subset of the data, in total nearly 50 000 patients, retrospectively in a time frame between 1992 and 2004. Already in the past, the IVDK has repeatedly reported results (44–46) that helped allergology to the early recognition of epidemiological trends and this has also led to consequences for instance in the manufacturing of cosmetics, changing fragrances or preservatives. For type 1-allergic reactions, such a network is currently not existent, especially not on a European scale. For this reason, the GA2LEN initiative has started to standardize the skin prick test for inhalant allergens in the group of - by now - more than 60 partners and collaborating centres (47, http://www.ga2len.net; accessed 19 October 2006). 25 of these partners have also agreed to collect the epidemiological data and this means, it can be hoped that we will get more information about sensitizations of our patients throughout the many very different regions in Europe in the near future.