SynopsisAs the proportion of the ageing population in industrialized countries continues to increase, the dermatological concerns of the aged grow in medical importance. Intrinsic structural changes occur as a natural consequence of ageing and are genetically determined. The rate of ageing is significantly different among different populations, as well as among different anatomical sites even within a single individual. The intrinsic rate of skin ageing in any individual can also be dramatically influenced by personal and environmental factors, particularly the amount of exposure to ultraviolet light. Photodamage, which considerably accelerates the visible ageing of skin, also greatly increases the risk of cutaneous neoplasms. As the population ages, dermatological focus must shift from ameliorating the cosmetic consequences of skin ageing to decreasing the genuine morbidity associated with problems of the ageing skin. A better understanding of both the intrinsic and extrinsic influences on the ageing of the skin, as well as distinguishing the retractable aspects of cutaneous ageing (primarily hormonal and lifestyle influences) from the irretractable (primarily intrinsic ageing), is crucial to this endeavour. Ré suméComme le pourcentage de la population vieillissante dans les pays industrialisés s'accroît, les préoccupations dermatologiques des personnes âgées augmentent en importance sur le plan médical. Les modifications structurelles intrinsè-ques sont une conséquence naturelle du vieillissement et sont génétiquement déterminées. La vitesse de vieillissement diffère significativement selon les différentes populations et selon les différ-ents sites anatomiques, même pour un seul individu. La vitesse intrinsèque du vieillissement de la peau pour un individu peut être aussi très influencée par les facteurs personnels et environnementaux, en particulier le taux d'exposition à la lumière ultra-violette. La photodégradation qui accélère considérablement le vieillissement visible de la peau augmente également beaucoup le risque de formation de néoplasme cutané. Au fur et à mesure que la population vieillit, il faut davantage se préoccuper de diminuer la morbidité réelle associée au vieillissement de la peau, plutôt que de palier à ses conséquences cosméti-ques. Il est donc crucial de s'efforcer à mieux comprendre les facteurs intrinsèques et extrinsè-ques qui agissent sur le vieillissement de la peau et aussi de faire la distinction entre les aspects réversibles du vieillissement cutané (facteurs essentiellement hormonaux et mode de vie) et les aspects irréversibles (principalement le vieillissement intrinsèque). The demographics of the U.S.A. are changing rapidly with respect to its elderly population; by 2030, one of every five Americans is expected to be over 65 [3]. It is predicted that life expectancy in the U.S.A. and other industrialized countries will continue to increase, hitting 100 years by about 2025 [4]. Women, with longer average life expectancies than men, can expect to spend more than one-third of th...

Alitretinoin given at well-tolerated doses induced clearing of CHE in a substantial proportion of patients with severe disease refractory to standard therapy.

Melanoma and nonmelanoma skin cancers are among the most prevalent cancers in the human population. Solar ultraviolet radiation is considered a major etiological factor but the relationship between dose, timing, and nature of exposure to tumor development is still unclear. Free radicals are generated by normal physiologic processes, including aerobic metabolism and inflammatory response, but may inflict cellular damage when generation is increased and antioxidant defense mechanisms are overwhelmed. Important findings supporting the free radical hypothesis in skin carcinogenesis are: (1) Reactive oxygen species (ROS) are generated in UVA- and UVB-irradiated skin in excessive doses, (2) the natural cutaneous antioxidant defense is impaired upon UV-exposure, (3) free radicals are involved in all steps of carcinogenesis, (4) supplementation with antioxidants can inhibit skin carcinogenesis, and (5) conditions that increase ROS generation enhance photocarcinogenesis. These findings provide a promising rationale for the development of powerful new antioxidant strategies in the prevention and therapy of skin cancer.

There is increasing evidence for the generation of reactive oxygen species in skin upon ultraviolet exposure, but little is known about their pathophysiologic relevance in human skin in vivo. We hypothesized that chronic and acute photodamage is mediated by depleted antioxidant enzyme expression and increased oxidative protein modifications. Biopsies from patients with histologically confirmed solar elastosis, from non-ultraviolet-exposed sites of age-matched controls, and from young subjects were analyzed. To evaluate the influence of acute ultraviolet exposures, buttock skin of 12 healthy subjects was irradiated repetitively on 10 d with a solar simulator and compared intraindividually to non-ultraviolet-treated contralateral sites. The antioxidant enzymes catalase, copper-zinc superoxide dismutase, and manganese superoxide dismutase were investigated by immunohistochemistry. Protein carbonyls were analyzed by immunohistochemical and immunoblotting techniques in human skin and in cell models. Whereas overall expression of antioxidant enzymes was very high in the epidermis, low baseline levels were found in the dermis. In photoaged skin, a significant depletion of antioxidant enzyme expression was observed within the stratum corneum and in the epidermis. Importantly, an accumulation of oxidatively modified proteins was found specifically within the upper dermis of photoaged skin. Upon acute ultraviolet exposure of healthy subjects, depleted catalase expression and increased protein oxidation were detected. Exposures of keratinocytes and fibroblasts to ultraviolet B, ultraviolet A, and H2O2 led to dose-dependent protein oxidation and thus confirmed in vivo results. In conclusion, the correlation between photodamage and protein oxidation was demonstrated for the first time, which hence may be a relevant pathophysiologic factor in photoaging.

Contact allergy to at least one allergen of the European baseline series was diagnosed in more than one-quarter of the general European population. Therefore measures to improve the primary prevention of contact allergy have to be enforced.

Hand eczema (HE) is one of the most frequent skin diseases and has often a chronically relapsing course with a poor prognosis resulting in a high social and economic impact for the individual and the society. In this article, we highlight the results of an expert workshop on the 'management of severe chronic hand eczema' with the focus on the epidemiology, the burden of severe HE, its classification and diagnostic procedures, and the current status of treatment options according to an evidencebased approach (randomized controlled clinical trials, RCTs). We conclude that despite the abundance of topical and systemic treatment options, disease management in patients with severe chronic HE is frequently inadequate. There is a strong need for RCTs of existing and new treatment options based on clearly diagnosed subtypes of HE and its severity. Without doubt, hand eczema (HE) is a very common dermatological condition that often has a high impact on the affected individual and the society. HE is not a uniform disease and varies because of aetiology, severity, and morphology. Although different treatment options exist, the management of patients with chronic HE is often unsatisfactory. In this article, we briefly review the epidemiology, the burden of chronic HE, its classification and diagnostic procedures, and the current status of treatment options. Epidemiology of HEEczema is the most frequent dermatosis affecting the hands. Clinically, HE is characterized by signs of erythema, vesicles, papules, scaling, fissures, hyperkeratosis, and symptoms of itch and pain. If also mild cases are included, the 1-year prevalence of HE is estimated to be up to 10% in the general population (1, 2). About 50% of all patients with hand dermatitis seek dermatological treatment, and about 5% of those are on sick leave from work (3). The proportion of chronic severe HE is estimated to be 5-7% in all patients with HE and those who are refractory to topical treatment are estimated to represent 2-4%. If inability to work is taken as a parameter of severity, 15% of HE cases result in an exclusion from the labour market (4). In most studies, the prevalence among women is higher than among men. Recent results indicate that the high frequency of HE in women in comparison with men is caused by environmental and not genetic factors (5). The increased risk for women to develop HE seems to be present in the age group 20-29 years only, while no increased risk for women is present beyond the age of 30 years (6). Based on a retrospective questionnaire study, the annual incidence of HE is estimated at 5 per 1000 (6). The incidence of notified (i.e. usually more severe) occupation-related cases is estimated to be above 0.7 people per 1000 per year (7). However, the prevalence of work-related HE is underreported and might be 30-50 times higher (8). Among certain occupational groups engaged in wet work or exposed to irritant and/or allergic substances such as hairdressers, cooks, health care workers, metal industry workers, cleaners etc., the 1-year pre...

The guidelines aim to provide advice on the management of hand eczema (HE), using an evidence- and consensus-based approach. The guidelines consider a systematic Cochrane review on interventions for HE, which is based on a systematic search of the published literature (including hand-searching). In addition to the evidence- and consensus-based recommendation on the treatment of HE, the guidelines cover mainly consensus-based diagnostic aspects and preventive measures (primary and secondary prevention). Treatment recommendations include non-pharmacological interventions, topical, physical and systemic treatments. Topical corticosteroids are recommended as first line treatment in the management of HE, however continuous long-term treatment beyond six weeks only when necessary and under careful me-dical supervision. Alitretinoin is recommended as a second line treatment (relative to topical corticosteroids) for patients with severe chronic HE. Randomized control trials (RCT) are missing for other used systemic treatments and comparison of systemic drugs in “head-to-head” RCTs are needed.The guidelines development group is a working group of the European Society of Contact Dermatitis (ESCD) and has carefully tried to reconcile opposite views, define current optimal practice and provide specific recommendations, and meetings have been chaired by a professional moderator of the AWMF (Arbeitsgemeinschaft der Wis-senschaftlichen Medizinischen Fachgesellschaften; Association of the Scientific Medi-cal Societies in Germany).No financial support was given by any medical company. The guidelines are expected to be valid until December 2017 at the latest.

Changes of dermal collagen and elastin content are characteristic for skin aging as well as for pathological skin conditions. To evaluate these changes, we used in vivo multiphoton laser tomography to measure two-photon excited autofluorescence (AF) and second harmonic generation (SHG). We tested 18 patients of all ages and calculated the SHG-to-AF aging index of dermis (SAAID). We observed a negative relationship between the SAAID and age, which was accelerated for the female (n=7) subgroup. The current findings are the first in vivo demonstration of this relationship, and they show that specific characteristics of aged skin such as the ratio of extracellular matrix components collagen and elastin can be evaluated by in vivo AF and SHG measurements using near-IR femtosecond laser pulses.