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PDF file - 54K, Primers and probes used for Quantitative RT-PCR assay.

PDF file - 53K, Selected upregulated canonical Pathways in IL-32 treated MyLa cells.

PDF file - 316K, Selected upregulated and down regulated genes of IL-32 treated MyLa and HH cells.

The key role of RUNX3 in physiological T-cell differentiation has been extensively documented. However, information on its relevance for the development of human T-cell lymphomas or leukemias is scarce. Here, we show that alterations of RUNX3 by either heterozygous deletion or methylation of its distal promoter can be observed in the tumor cells of 15 of 21 (71%) patients suffering from Sezary syndrome, an aggressive variant of cutaneous T-cell lymphoma. As a consequence, mRNA levels of RUNX3/p46, the isoform controlled by the distal promoter, are significantly lower in Sezary syndrome tumor cells. Re-expression of RUNX3/p46 reduces cell viability and promotes apoptosis in a RUNX3/p46low cell line of cutaneous T-cell lymphoma. Based on this, we present evidence that RUNX3 can act as a tumor suppressor in a human T-cell malignancy and suggest that this effect is predominantly mediated through transcripts from its distal promoter, in particular RUNX3/p46.

This chapter focuses on the immunophenotypical analysis of the sub-populations. It highlights the impact of this approach for routine dermatopathology as well as for the general understanding of the pathogenesis of certain dermatoses. The chapter utilizes the characteristics of this cell type as “coordinates” to define the members of the dermal monocyte/macrophage system. It provides evidence that the cells of the monocyte/macrophage system located within the human dermis reveal an unexpected heterogeneity. The initial point of view of macrophages being little more than “big eaters” has long been replaced by a more differentiated concept. Identification of monocytes or macrophages is possible by enzyme cytochemical methods as well as immunohistochemical procedures using antibodies. Analysis of cells belonging to the monocyte/macrophage lineage is complicated by the finding that these cells also express markers previously regarded as T cell specific. Inflammatory dermatoses revealed a modest increast in the number of FXIIIa + cells in and around areas showing a dermal inflammatory infiltrate.

Acne inversa (AI; also designated as hidradenitis suppurativa) is a chronic inflammatory disease with still unknown pathogenesis that affects the intertriginous skin of perianal, inguinal, and axillary sites. It leads to painful nodules, abscesses, and fistulas with malodorous secretion and is frequently associated with metabolic alterations. Here, we demonstrate that one of the most highly upregulated molecules in AI lesions is matrix metalloproteinase 8 (MMP8), an enzyme specialized in the degradation of extracellular matrix components and the HDL component apolipoprotein A-I. Granulocytes, which were present in AI lesions, secreted high amounts of MMP8 especially after TNF-αstimulation. Furthermore, activated fibroblasts but not keratinocytes were found to express MMP8. The high lesional MMP8 levels were accompanied by elevated blood levels that positively correlated with TNF-αblood levels and disease severity assessed by Sartorius score, especially with the number of regions with inflammatory nodules/abscesses and fistulas. Additionally, we found a negative correlation between blood MMP8 and HDL-cholesterol levels, suggesting a contributory role of MMP8 in metabolic alterations in AI. In summary, we demonstrate elevated MMP8 levels in AI lesions, suggest their role in skin destruction and metabolic alterations, and recommend the use of MMP8 as blood biomarker for AI disease activity assessment.

Objective Comparison of fluorescence optical imaging (FOI) with grayscale (GS) and power Doppler ultrasound (PDUS) to detect joint inflammation in patients with confirmed or suspected psoriatic arthritis (PsA). Methods Patients (n = 60) with psoriasis and tenderness and/or swelling of joints were separated into two groups: diagnosis confirmed by the treating dermatologist before the start of the study (n = 26), and suspected PsA (n = 34). GS/PDUS of the hand most clinically affected was performed with a dorsal/palmar view (wrist, MCP, PIP, DIP2-5). FOI examination was carried out in a standardized manner by analyzing the predefined Phases 1-3. Results FOI was found to be more sensitive than ultrasound (US) for detection of inflammation in PIP/DIP joints (p = 0.035). Confirmed PsA patients showed more findings in FOI P2 and P3, while suspected PsA patients showed more findings in P1. In the confirmed PsA group, most involved joints were MCP joints, while in the suspected PsA group, more involved wrist joints and DIP joints (p = 0.006) were detected with FOI. Conclusions The differences between the confirmed and suspected groups indicate that FOI is helpful in the detection of early PsA since P1 may correspond to acute inflammation, whereas P2 and P3 enhancement reflect chronic inflammation. Fluorescence optical imaging might therefore be a novel diagnostic tool for early PsA diagnosis.

Hidradenitis suppurativa (HS) (also designated acne inversa) is a chronic inflammatory disease characterized by painful purulent skin lesions and progressive destruction of skin architecture. Despite the high burden for the patients, pathogenetic pathways underlying HS alterations remain obscure. When we examined the HS cytokine pattern, IL-1β turned out to be a highly prominent cytokine, overexpressed even compared with psoriatic lesions. Analyses of IL-1β–induced transcriptome in various cell types showed overlapping profiles, with upregulations of molecules causing immune cell infiltration and extracellular matrix degradation, and of specific cytokines including IL-6, IL-32, and IL-36. Matching cellular IL-1 receptor levels, dermal fibroblasts showed both the strongest and broadest IL-1β response, which was not clearly shared or strengthened by other cytokines. The IL-1β signature was specifically present in HS lesions and could be reversed by application of IL-1 receptor antagonist. Search for blood parameters associated with IL-1β pathway activity in HS identified serum amyloid A, which was synergistically induced by IL-1β and IL-6 in hepatocytes. Consequently, strongly elevated blood serum amyloid A levels in HS correlated positively with the extent of inflammatory skin alterations. In summary, the IL-1β pathway represents a pathogenetic cascade, whose activity may be therapeutically targeted and monitored by blood SAA levels.

IMPORTANCE: Hidradenitis suppurativa (HS) leads to disfigurement and painful eruptions in terminal hair follicles of the intertriginous skin, mainly of axillary, genitofemoral, and perianal sites. It is associated with an excessive impairment of quality of life, psychiatric disorders, and sexual distress. Body image impairment has been linked to depression and anxiety and has been described for some dermatologic disorders but has not yet been investigated in patients with HS. OBJECTIVES: To investigate whether body image is diminished in patients with HS and whether disease severity, age at onset, disease duration, obesity, depression, and anxiety are linked to body image impairment. DESIGN, SETTING, AND PARTICIPANTS: This 12-month (August 1, 2009, to August 31, 2010) case-control study with a prospective, observational, cross-sectional design recruited 47 consecutive patients with HS entering a tertiary care center and 45 healthy control individuals matched for age, sex, and body mass index (BMI). One patient and 4 controls failed to complete the questionnaire and were excluded from the evaluation. Data analysis was performed from December 1, 2013, to February 15, 2014. MAIN OUTCOMES AND MEASURES: The Frankfurt Body Concept Scale (FKKS) and the Hospital Anxiety and Depression Scale (HADS) were given to patients and controls. Correlations among FKKS, HADS, and disease features were calculated. RESULTS: Of the 46 patients and 41 controls included in the evaluation (mean [SD] age, 35.6 [1.6] years; 40 [46%] male and 47 [54%] female), HS significantly reduced body image (mean FKKS score, 234.2 [5.4] in patients and 276.9 [5.7] in controls; P

Maligne Tumoren der Haut sind die haufigste Krebsart des Menschen. Basalzellkarzinome werden in einem anderen Kapitel abgehandelt (Kap. „Basalzellkarzinom“), wahrend die weiteren epithelialen malignen Tumoren hier betrachtet werden. Die Ursachen von Hautkrebs sind vielfaltig und umfassen genetische Faktoren, wie beispielsweise eine herabgesetzte DNA-Reparaturkapazitat, exogene kanzerogene Faktoren (uberwiegend UV-Bestrahlung), aber auch verschiedene humane Papillomviren (HPV), chemische Karzinogene, ionisierende Strahlen und Immunsuppression. Individuelle Faktoren, wie etwa Hautfarbe, Dicke des Stratum corneum, Immunstatus oder chronisch entzundliche Erkrankungen der Haut, konnen weitere Risikofaktoren sein.

BACKGROUND: This open-label, multicenter, dose-escalation study evaluated the safety, tolerability, and efficacy of subcutaneous pegylated (40 kD) interferon α-2a (PEG-IFN α-2a) in patients with cutaneous T-cell lymphoma (CTCL). PATIENTS AND METHODS: PEG-IFN α-2a was administered subcutaneously at 180 (n = 4), 270 (n = 6), or 360 μg (n = 3) once weekly for 12 weeks. Efficacy was assessed by the proportion of patients with complete response (CR) or partial response (PR). RESULTS: PEG-IFN α-2a was generally well tolerated, with a moderate number of reductions or withholding of doses because of adverse events (AEs) (25% (n = 1), 66% (n = 4), and 0% (n = 0) in the 180-, 270-, and 360-μg/week groups, respectively). The only dose-limiting toxicity was a grade 3 elevation of liver enzymes in the 270-μg dose group. The most common AEs were fatigue, acute flu-like symptoms, and hepatic toxicity. The major response rate (CR or PR) was 50% in the 180-μg group (CR, 50%; PR, 0%), 83% in the 270-μg group (CR, 67%; PR, 17%), and 66% in the 360-μg group (CR, 33%; PR, 33%). CONCLUSION: PEG-IFN α-2a at doses up to 360 μg once weekly was well tolerated in patients with CTCL up to the highest dose group and showed good response rates. Due to their good tolerance even in high doses, they might be an option for patients not tolerating standard IFN-α preparations. However, for this purpose and to evaluate comparability between standard and PEG-IFN larger clinical trials are needed, alone and in combination with oral photochemotherapy (PUVA).

SummaryBackground Acne inversa (AI)/hidradenitis suppurativa is a chronic inflammatory disease characterized by painful axillary, inguinal and perianal skin lesions with deep-seated nodules, abscesses and fistulae. Objectives This study aimed to identify and characterize the key players in AI pathogenesis. Methods Epidemiological and anamnestic data for patients with AI were collected, and blood and skin samples were also taken. Healthy participants and patients with psoriasis served as controls. Assessment of samples and cultures of primary cells was performed by enzyme-linked immunosorbent assay, quantitative polymerase chain reaction on reverse transcribed mRNA, and immunohistochemistry. Results Of 35 mediators quantified in the blood of patients with AI, lipocalin-2 (LCN2) appeared as one of the most significantly upregulated parameters compared with healthy participants [85·8 ± 12·2 (n = 18) vs. 41·8 ± 4·2 (n = 15); P < 0·001]. Strongly elevated LCN2 expression was present in AI lesions, with granulocytes and keratinocytes being sources of this expression. In vitro, these cells upregulated LCN2 production in response to tumour necrosis factor (TNF)-α, and a positive relationship between systemic TNF-α and LCN2 levels (rs = 0·55, P = 0·011; n = 20) was evident for AI. LCN2 blood levels correlated with AI disease severity (rs = 0·65, P < 0·001; n = 29), but not with disease duration, age, sex, body mass index or smoking habit. Detailed analyses revealed a link with the number of skin regions containing nodules and fistulae, but not scars. Conclusions LCN2 might serve as a blood biomarker for the objective assessment of inflammatory activity in AI. We suggest a self-amplification loop comprising TNF-α, neutrophilic granulocytes and LCN2, which contributes to the recurrent skin neutrophil infiltration in AI, clinically evident as pus.

Purpose: Primary cutaneous T-cell lymphomas (CTCL) are neoplastic disorders of skin-homing T cells. Affected skin areas show morphologic similarities with alterations in other T-cell–mediated dermatoses. Furthermore, as in atopic dermatitis but in contrast with psoriasis, patients with CTCL are frequently afflicted by cutaneous bacterial infections that support the survival of lymphoma cells. Our aim was to investigate the mechanisms of elevated susceptibility to cutaneous infections in patients with CTCL. Experimental Design: Skin samples from CTCL, psoriasis, and atopic dermatitis patients were used to illuminate the antibacterial competence status and the presence of its modulating cytokines. For substantiation of findings, 3-dimensional epidermis models, isolated and in vitro generated Th-subpopulations, were applied. Parameters were analyzed via qPCR and IHC. Results: CTCL lesions compared with psoriatic lesions presented an impaired upregulation of antibacterial proteins (ABPs), with levels even below those in atopic dermatitis. This was associated with a relative deficiency of the ABP-inducing cytokine IL-17 and a strong presence of the ABP-downregulating cytokine IL-13. The simultaneous presence of the Th17-cell cytokine IL-26 indicated that IL-17 deficiency in CTCL lesions results from functional deviation of Th17 cells. Accordingly, IL-17 but not IL-26 production by Th17 cells in vitro was inhibited by IL-4Rα ligand. Levels of other ABP inducers were comparable between CTCL and psoriasis lesions. The same was true about IL-22/TNF-α targets, including the keratinocyte hyper-regeneration marker K16 and the matrix-degrading enzyme MMP1. Conclusion: Our results suggest that the cutaneous bacterial infections in CTCL are caused by impaired ABP induction as consequence of Th2-mediated biased Th17-cell function. Clin Cancer Res; 20(21); 5507–16. ©2014 AACR.

The effect of tissue-tolerable plasma (TTP) on inflammatory diseases such as psoriasis was investigated. Three plaques of six psoriatic patients were subjected to different treatments (A: TTP, brine baths (BB)+5% salicylic acid ointment (SAO); B: BB+SAO; C: BB, UV irradiation, SAO+dithranol). While redness and infiltration was reduced in groups A and C, scaling was reduced in group C. TTP temporarily reduced the bacterial colonization on the skin lesions. In summary, the treatment of psoriatic plaques with TTP showed no significant advantage over conventional therapies.

Background: The antioxidant status of the human skin provides protection against the destructive action of free radicals. Most antioxidants cannot be synthesized by the human organism itself, but have to be ingested with a healthy nutrition rich in fruit and vegetables. The Korean cuisine is known to be one of the healthiest worldwide. This binational study investigated the cutaneous carotenoid concentrations in German subjects, South Korean subjects and immigrant Korean subjects resident in Germany and examined whether dietary- and lifestyle-related differences are reflected in the cutaneous carotenoid concentrations. Methods: Measurements of the carotenoid concentrations of 714 healthy volunteers were performed using a non-invasive spectroscopic measurement system based on reflectance spectroscopy. Results: In the present study South Korean residents showed a significantly higher antioxidant status than both native German residents and Korean immigrants living in Germany (p < 0.001). The first generation of Korean immigrants to Germany over the age of 50 mostly preserved Korean dietary habits, showing significantly higher concentrations (p < 0.001) than the German-born second and third Korean generations under the age of 50. Conclusion: The results of the study indicate that a healthy nutrition alone does not provide a high antioxidant status unless the stress exposure can be reduced simultaneously.

The 6q23-27 region, recurrently deleted in Sézary syndrome (SS), was characterized at the molecular level in 13 SS patients and SS cell line SeAx. Using fine-tiling comparative genomic hybridization, deletions within the 6q23-27 region were detected in half of the samples (six patients and SeAx). All samples with deletions were further analyzed by ligation-mediated PCR. In addition, in one patient sample and in SeAx, paired-end next-generation sequencing was performed on the HiSeq2000 Illumina platform. Using those techniques, 23 rearrangements associated with the deletions were identified. The majority of rearrangements showed enormous complexity and diversity, including eight inversions, three transpositions, and four translocations (with chromosomes 3, 17, 10, and 12). Fifteen genes were disrupted by those rearrangements, the MYB proto-oncogene three times and the interleukin-22 receptor subunit alpha-2 gene (IL22RA2) twice. All three patients with MYB alterations showed low MYB expression, whereas seven of the remaining patients showed overexpression. Most patients overexpressing MYB also presented increased expression of MYC, HSPA8, and BCL2. Five gene fusions were identified, of which two, CCDC28A-IL22RA2 and AIG1-GOSR1, both in SeAx, were in the same orientation and were expressed at the messenger RNA level.

Summary Background The monoclonal antibody rituximab directed against the B-cell antigen CD20 was approved for the treatment of B-cell lymphomas and maintenance therapy in follicular lymphomas more than a decade ago. However, median follow-up in case series of intravenous rituximab therapy in primary cutaneous B-cell lymphomas (CBCL) lasts only up to 3 years. We retrospectively analysed a cohort of CBCL patients treated with rituximab to gain more long term information. Patients and methods Eighteen patients, treated intravenously with rituximab for a primary cutaneous B-cell lymphoma [follicle centre lymphoma (PCFCL), n = 11; diffuse large B-cell lymphoma, leg type (PCLBCL, leg type), n = 5; marginal zone B-cell lymphoma (PCMZL), n = 2] were included. The response rate (RR), time to relapse (TTR), and course of the disease after treatment were analysed. Results The overall RR was 89% (16 of 18 patients). Within the median follow-up time of 52 months, 81% (13 of 16) of patients experienced a relapse; the median TTR was 25 months. The duration of remission was significantly shorter in patients presenting with generalized skin lesions at start of therapy. Both nonresponding patients suffered from PCLBCL, leg type, with extracutaneous manifestations. In responders severe adverse events, the occurrence of extracutaneous dissemination or nodal lymphomas were not observed during follow-up. Conclusions Therapy with rituximab is effective and safe for the treatment of PCFCL, but relapses, in particular in patients with generalized skin involvement, are commonly observed. However, all patients with relapses responded well to treatment and therefore maintenance therapy does not seem to be indicated. Patients with PCLBCL, leg type, should receive chemotherapy in addition to rituximab.

Sunscreens are a key pillar of the multimodal protection strategy against short- and long-term impacts of intermittent and continuous UV exposure. Hitherto, an unanswered part of current scientific discourse is the question whether a cosmetic pretreatment has an impact on distribution and adhesiveness of sunscreens on the skin and therefore affects UV protection. In order to evaluate the homogeneity of sunscreen filter distribution, water resistance as a parameter of adhesiveness and effective UV protection of sunscreens after a pretreatment with cream or lotion was investigated in 18 volunteers who were examined before and after swimming, using the established combination of the tape stripping procedure and UV/VIS spectroscopy. It was shown that a cosmetic skin pretreatment affects neither filter homogeneity nor effective UV protection prior to water contact. However, compared to nonpretreated skin, a considerable loss of water resistance is caused. Therefore, using a cream or lotion before application of sunscreens is not to be recommended.

Background The objective of the present study was the investigation of hair follicle morphology in eight mammalian species in order to evaluate the species-specific contribution of hair follicles to skin penetration particularly with regard to the utilization of the different animal species as skin models for human skin. Methods Cyanoacrylate skin surface biopsy method (CSSB), light microscopy and also digital photography were used for the measurements of hair follicle morphology. Results The results revealed species-specific differences regarding the pattern of hair follicle distribution and also differences with regard to hair follicle parameters and characteristics. The results also showed that hair follicles generally possess enormous reservoir capacities, regarding the follicular volume. In all examined species, hair follicles reached at least one-fifth of stratum corneum storage capacity. The results were compared with human data obtained in a previous study. Conclusion With regard to hair follicle morphology and skin structure, the porcine skin seems to be the most appropriate skin model for human skin analog to previous investigations, whereas the skin of dog, cat, and rabbit showed the most significant differences.

Background The monitoring of wound-healing processes is indispensable for the therapeutic effectiveness and improved care of chronic wounds. Histological sections provide the best morphological assessment of wound recovery, but cause further tissue destruction and increase the risk of infection. Therefore, it is reasonable to apply a diagnostic tool that allows a non-invasive and reliable observation of morphological changes in wound healing. Methods Optical coherence tomography (OCT) is an imaging technique for in vivo evaluation of skin diseases with a resolution close to histopathology. The aim of this study was to investigate whether OCT is suited to display the phases of wound healing. For this purpose, six patients with chronic wounds were objectively characterized by OCT during a period of 2 weeks. Results Comparable results between histological findings and OCT were achieved. OCT allowed the detection of partial loss of the epidermis, vasoconstriction, vasodilatation and epithelialization. Conclusion Consequently, OCT could be a potential non-invasive diagnostic tool for the characterization and monitoring of cutaneous wound-healing processes over time.

Rudolf Stadler, Chalid Assaf, Claus-Detlev Klemke, Dorothee Nashan, Michael Weichenthal, Reinhard Dummer, Wolfram Sterry (1) Department of Dermatology, Johannes Wesling Klinikum, Minden, Germany (2) Department of Dermatology, HELIOS Klinikum, Krefeld, Germany (3) Department of Dermatology, Venereology, and Allergology, Mannheim University Hospital, Germany (4) Department of Dermatology, Dortmund Hospital, Germany (5) Department of Dermatology, Venereology, and Allergology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Germany (6) Department of Dermatology, Zurich University Hospital, Switzerland (7) Department of Dermatology, Venereology, and Allergology, Charite – Universitatsmedizin Berlin, Germany

Summary Background Acne inversa (AI) is a common chronic inflammatory disease that has a profound impact on the patientsi quality of life. We hypothesized a higher level of depression in AI patients compared to controls. Objectives We studied depression in patients with AI and control subjects. Additionally, we evaluated whether the severity of the disease, anxiety, sexual distress and acute inflammation may have an influence on depression. Patients and Methods The Hospital Anxiety and Depression Scale (HADS) was given to 90 voluntary study participants to assess depression in AI patients and in age-, gender-, and BMI-matched controls. Moreover, the correlation between depression and conjectural influencing factors was evaluated. Results This study demonstrated that AI patients have a higher depression score than matched controls. Importantly, 38.6% of AI patients are affected by depression compared to 2.4% of the control subjects. In contrast to the duration of the disease and the AI patientsi age, anxiety and sexual distress showed a strong correlation with the degree of depression. Conclusions Patients with AI have a higher risk of developing depression. Physicians should be alert to the possible development of depression when treating patients with this disorder.

The development of malignancies during therapy with biologics has been discussed controversially. A patient with extensive pityriasis rubra pilaris failed to respond to standard therapeutic approaches. While receiving immunomodulatory therapy, lastly with ustekinumab, the patient developed a CD30(+) anaplastic large cell lymphoma.

Background Spontaneous remission is recognized in mycosis fungoides (MF) and Sezary syndrome (SS). Objective We analyzed the outcome of 44 patients with previously treated CD25-positive (CD25+), recurrent/persistent MF/SS randomly assigned to receive placebo as part of a phase III trial. Methods This trial investigated the efficacy and safety of two doses of denileukin diftitox in patients with MF/SS who had received up to 3 prior therapies. The primary end point was overall response rate. Multivariate regression analyses were used to assess the relationship between baseline covariates and clinical outcomes. Results The overall response rate was 15.9% for placebo recipients (complete response: 2.3%; partial response: 13.6%), reflecting the baseline rate of disease remission that can be expected in a clinical trial. The median progression-free survival (PFS) in the placebo arm was moderately short at 4.4 months compared with the active-agent arm but important to consider in the context of recent single-arm phase II studies of other therapies for MF/SS that report PFS of approximately 6 months. Multivariate analyses identified no significant effects of any baseline factors on either overall response rate or PFS, although there was a trend toward poorer PFS with advanced age. Because sepsis occurred significantly more often in the placebo arm versus the active-treatment arm, the role of antibiotics in causing remission cannot be discounted (6.8% vs 0%; P Limitations This study had a relatively small sample size, yielding a wide 95% confidence interval. Conclusion The results may serve as a useful comparator for other active-treatment studies of MF/SS that lack a placebo-control arm.

Mycosis fungoides (MF) progresses from patch to tumor stage by expansion of malignant T-cells that fail to be controlled by protective immune mechanisms. In this study, we focused on IL-32, a cytokine, highly expressed in MF lesions. Depending on the other cytokines (IL-4, GM-CSF) present during in vitro culture of healthy volunteers' monocytes, IL-32 increased the maturation of CD11c+ myeloid dendritic cells (mDC) and/or CD163+ macrophages, but IL-32 alone showed a clear ability to promote dendritic cell (DC) differentiation from monocytes. DCs matured by IL-32 had the phenotype of skin-resident DCs (CD1c+), but more importantly, also had high expression of indoleamine 2,3-dioxygenase. The presence of DCs with these markers was demonstrated in MF skin lesions. At a molecular level, indoleamine 2,3-dioxygenase messenger RNA (mRNA) levels in MF lesions were higher than those in healthy volunteers, and there was a high correlation between indoleamine 2,3-dioxygenase and IL-32 expression. In contrast, Foxp3 mRNA levels decreased from patch to tumor stage. Increasing expression of IL-10 across MF lesions was highly correlated with IL-32 and indoleamine 2,3-dioxygenase, but not with Foxp3 expression. Thus, IL-32 could contribute to progressive immune dysregulation in MF by directly fostering development of immunosuppressive mDC or macrophages, possibly in association with IL-10.

The International League of Dermatological Societies (ILDS), a global, not-for-profit organization representing 157 dermatological societies worldwide, has identified the consequences of skin aging as one of the most important grand challenges in global skin health. Reduced functional capacity and increased susceptibility of the skin with development of dermatoses such as dry skin, itching, ulcers, dyspigmentation, wrinkles, fungal infections, as well as benign and malignant tumors are the most common skin conditions in aged populations worldwide. Environmental (e.g., pollution) and lifestyle factors (e.g., smoking, sunbed use) negatively affect skin health. In turn altered appearance, dry skin, chronic wounds, and other conditions decrease general health and reduce the likelihood for healthy and active aging. Preventive skin care includes primary, secondary, and tertiary interventions. Continuous sun protection from early childhood onward is most important, to avoid extrinsic skin damage and skin cancer. Exposure to irritants, allergens, or other molecules damaging the skin must be avoided or reduced to a minimum. Public health approaches are needed to implement preventive and basic skin care worldwide to reach high numbers of dermatological patients and care receivers. Education of primary caregivers and implementation of community dermatology are successful strategies in resource-poor countries. Besides specialist physicians, nurses and other health care professionals play important roles in preventing and managing age-related skin conditions in developing as well as in developed countries. Healthy skin across the life course leads to better mental and emotional health, positive impact on social engagement, and healthier, more active, and productive lives.