Under the motto “Skin is Vital” the 21. Congress of the EADV convened in Prague. The EADV meetings are developing more and more into international meetings with a growing number of participants not only from all over Europe, but also from all parts of the world. At the EADV press conference, several topics that are not in the main focus of dermatologists, were discussed.

Prof. Dr. med. Johannes Ring (Director of the Department of Dermatology and Allergology, Technical University Munich) lectured on the somewhat neglected field of food allergies. Untoward reactions to food represent an increasing problem in clinical medicine, including not only toxic reactions or infectious diseases with gastrointestinal problems, but more and more often, hypersensitivity reactions to food or food ingredients.

The diagnosis of adverse food reactions is complex. When it is IgE-mediated, skin prick tests and in-vitro IgE-diagnostics are helpful. Often – and in pseudo-allergic reactions always – only oral provocation tests (OPT) are able to bring diagnostic clarity. By the increase of allergic respiratory diseases like hay-fever and asthma and atopic eczema, also pollen-associated food allergies have increased tremendously during the last decades. Outbreaks of food allergy in senior citizen homes have been described, when individuals had been treated with high doses of proton pump inhibitors (BPI).

Dermatologists should be aware of these interactions between nutrition, skin and allergy in order to give the right therapeutic recommendations. Allergy diets only make sense when they are truly indicated and individually specific which requires often a controlled OPT.

CHEK2 gene and the risk of malignant melanoma

Why do we develop so few cancers? This question was posed by Prof. Dr. Martin Röcken (Dept. of Dermatology, Eberhard Karls University, Tübingen, Germany). It may seem provocative, since cancer is one of the major killers in Europe and the industrialized world. Yet it becomes relevant, if we imagine the huge number of genetic errors that each dividing cell has to correct on a daily base. Three additional cancer-driving forces increase this workl

oad: a.) the DNA damaging effects from the environment (UV irradiation etc.) b.) Intracellular metabolic or signalling events that affect the velocity of cell divisions and also affect the accuracy of the “DNA repair mechanism” and the sensitivity to DNA damaging stress factors. c.) The environment. There is an increasing number of data demonstrating that the “local micro-environment” determines whether one given cell with a given “genotype” behaves either as a benign or as a malignant cell.

M. Weischer and  B. Nordestgaard had previously shown that certain CHEK2 gene variants predispose women for the development of breast cancer. The CHEK2 protein is an important cell cycle regulator. It is involved in the recognition and repair of DNA double strand breaks (a major cause  of cancer). Similarly important is the CHEK2-mediated regulation of p53, as p53 is the most important gate keeper of appropriate DNA repair. p53 determines the time a cell has to repair DNA damage and, in addition, p53 determines the precision of the DNA repair process. Based on these deep insights they collaborated with one of the major melanoma centres in Europe to ask whether  the germeline variant CHEK2 1100delC also predisposes their carriers for the development of melanomas. Indeed they found that individuals with the CHEK2 1100delC variant have a roughly two-fold increased risk of developing any type of melanoma.

Most importantly, recent large scale cancer genomics show that errors in cell cycle control genes are among the most frequent cancer driver mutations: in view of these findings, the paper by Weischer et al. raises the key question whether minute errors at various sites of the  cell cycle control, either caused by germeline mutations, as here, or caused by the micro-environment are the key drivers of cancers of general, and melanomas in specific. This question is hot in view of the striking effect low dose aspirin has in preventing cancers, including melanomas.

Dermatoporosis, the functional face of skin ageing

Prof. Jean-Hilaire Saura (Chairman University Dept. of Dermatology Geneva, Switzerland)  presented a new emerging syndrome that is considered to be the functional face of skin aging. With an increasing number of elderly population, health care professionals should be aware of the potential epidemics of dermatoporosis. Chronic systemic or topical steroid therapy and chronic exposure to ultraviolet irradiation appear to be the major causes of dermatoporosis. CD44-hyaluronate molecular pathways play an important role in the pathogenesis. Further research and clinical trials are needed to find preventive or therapeutic solutions for dermatoporosis.

With increasing life span, we experience a functional dimension of skin aging which extends beyond cosmetics and appearance. This dimension is related to the agingassociated gradual loss of hyalu-ronate (HA) which is a major component of the extracellular matrix of the skin functioning normally as a viscoelastic buffering system between epidermal and dermal structures.

 Clinical features of dermatoporosis

First clinical manifestations of dermatoporosis start at around 40-60 years with wrinkles and appearance changes but fully-developed disease is seen between 70 and 90 years. Two types of clinical features can be identified: a.) morphological markers such as skin atrophy, senile purpura and pseudoscars, and b.) functional aspects such as skin laceration, delayed wound healing and deep dissecting hematoma.

Treatment and prevention

Based on the observations indicating the potential role of a CD44 platform deficiency in dermatoporosis, the possibility of activating the CD44 platform to reverse skin atrophy was explored. “For this purpose we developed hyaluronate fragments (HAF) of defined size and used them as CD44 ligands to activate the CD44-mediated molecular pathways leading to skin hyperplasia”. Topical application of HAF of defined size twice a day for 1 month caused a significant reversal of skin atrophy in dermatoporosis patients. A Combination of a topical retinoid, retinaldehyde, which upregulates the CD44 and hyaluronate synthases increased the levels of CD44 and HA in the skin of dermatoporosis patients and corrected the skin atrophy by showing a synergistic effect at both molecular and clinical levels. But Large scale and well-designed randomized clinical trials will be necessary to test the efficacy of such novel candidates for prevention or therapy of this new emerging syndrome.

Source:

Press Conference EADV Congress 2012 in Prague, Friday, 28 September 2012