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This study examined whether children’s social behavior mediated the associations between specific dimensions of temperament and peer acceptance, and whether these associations were moderated by gender. We also explored the role of child’s age on the associations between temperament and social functioning. Primary caregiver reports of temperament and peer reports of social behavior and peer acceptance were obtained for 140 boys and 135 girls (8–16 years, M = 11.9) from 275 different classrooms. Dimensions of temperament reflecting general activity, flexibility-rigidity, and attentional focus were found to be particularly important to children’s social functioning at school, and their associations with peer acceptance were found to be significantly mediated by social behaviors. Additionally, we found that while linkages between dimensions of temperament and social acceptance were present for boys and girls, the pathways (mediators) were often different. Our exploratory analyses suggested that linkages between temperament and social functioning are strong for younger children, but less so for older youth. Findings are discussed in the context of their implications for theory and clinical applications, emphasizing the importance of considering gender differences in the contributions of temperament to social functioning.

Acute, zigzag-shaped livid skin markings developed on both thighs of a 55-year-old woman who had been on dialysis for 6 years. Within 7 days these areas increased in size to about 10 cm in diameter and contained central dry and painful necroses. On legs, lower arms and hands hard subcutaneous nodules were palpable with a diameter up to 3 mm. For many years the phosphate and parathormone levels, as well as alkaline phosphatase activity had been raised. The patient had often failed to follow treatment recommendations.There were increased serum concentrations of calcium (2.8 mmol/l) and phosphate (1.78 mmol/l). The calcium phosphate ion product was 4.98 (mmol/l)2. Furthermore, there were raised levels of alkaline phosphatase (315 U/l) and parathormone (1076 ng/l, normal: 10-65). X-ray film of the hands showed soft tissue and arterial calcifications, while histological examination of a deep skin biopsy revealed calcium phosphate emboli of the main vessels.Excision of the cutaneous necroses was followed by parathyroidectomy at which only three parathyroid glands were identified and removed. The parathormone level fell postoperatively, but rose again after 4 weeks. The fourth parathyroid gland was then found and removed, after which the parathormone level fell below measurable levels. The skin ulcers healed completely 4 weeks after the second operation.

The Torre-Muir syndrome belongs to a group of hereditory cancers and expresses itself in the occurrence of cutaneous gland tumors and (often multiple) carcinoma of the colon. The syndrome is probably a phenotypical manifestation of the "cancer family" syndrome, in which familial carcinoma of the colon also occurs. A case of Torre-Muir syndrome in a 43-year-old man is described. Because of the dermatological features, the colon carcinoma was diagnosed in time. Family investigations revealed another case of complete Torre-Muir syndrome, as well as a remarkable frequency of colon carcinoma in one family branch. Inheritance is autosomal dominant. The characteristic morphological features of the sebaceous gland neoplasias makes an early, often life-saving, diagnosis possible.

Kutane Lymphome sind extranodale Non-Hodgkin-Lymphome reifer T-oder B-Lymphozyten, welche die Haut als Zielorgan haben und dort persistieren. Sie zeigen eine grose Bandbreite klinischer und histologischer Erscheinungsformen. Aktuelle Daten aus der Grundlagenforschung zur Tumorbiologie von Malignomen ermoglichten die Entwicklung neuer Ansatze fur eine zielgerichtete Therapie. Zahlreiche Studienergebnisse zeigen vielversprechende Daten. Diese Arbeit gibt einen Uberblick uber den aktuellen Stand zielgerichteter Therapien bei Patienten mit kutanen T- und B-Zell-Lymphomen – auf der Basis von Fusionsproteinen, monoklonalen Antikorpern sowie der neuen Gruppe der Histon-Deacetylase-Inhibitoren.

Interleukin (IL)-10, initially described as cytokine synthesis inhibitory factor, is a pleotropic cytokine produced by many cell populations. Its main biological functions appear to be quite diverse: on the one hand it is involved in the limitation and termination of inflammatory responses and the regulation of differentiation and proliferation of several immune cells, and on the other hand it mediates immunostimulatory properties that support the elimination of infectious and non-infectious particles with limited inflammation. Numerous investigations, including expression analyses in patients, and both in vitro and in vivo studies suggest a major physiological and pathophysiological impact of IL-10. Activation of the neuro-endocrine axis following acute stress reactions leads to systemic IL-10 release, preventing hyperinflammatory reactions. IL-10 is overexpressed in many solid tumors and lymphomas and considered to promote further tumor development. In contrast, a relative IL-10 deficiency has been observed and is regarded to be of pathophysiological relevance in certain inflammatory disorders characterized by a type 1 cytokine pattern such as psoriasis. Recombinant human IL-10 has been tested in several clinical trials including rheumatoid arthritis, inflammatory bowel disease, psoriasis, organ transplantation, and hepatitis C. The results are heterogeneous and give new insight into the immunobiology of IL-10. However, further investigations would be desirable to better determine the effect/side effect profile as well as the best first line target indication and optimal therapeutic regimen.

Summary Background Efalizumab (anti-CD11a), a humanized monoclonal antibody, blocks multiple T-cell-dependent functions implicated in the pathogenesis of psoriasis, including T-cell activation, migration to the skin, reactivation in psoriatic skin and interactions with keratinocytes. Objectives This multinational, randomized, double-blind, placebo-controlled, parallel-group trial was designed to evaluate the safety and efficacy of subcutaneous efalizumab 1·0 mg kg−1 once weekly for 12 weeks compared with placebo in a population that included high-need patients, defined as those for whom at least two systemic therapies were unsuitable because of lack of efficacy, intolerance or contraindication. Patients/methods Patients with moderate-to-severe plaque psoriasis [involvement of ≥ 10% of total body surface area and Psoriasis Area and Severity Index (PASI) ≥ 12·0 at screening] were randomized in a 2 : 1 ratio to receive efalizumab or placebo. The primary efficacy endpoint was the proportion of patients achieving ≥ 75% PASI improvement (PASI-75 response) at week 12 in the intention-to-treat population; secondary endpoints included changes in PASI, static Physician's Global Assessment, Physician's Global Assessment of change from baseline and percentage of body surface area affected. Results We enrolled 793 patients (529 received efalizumab and 264 placebo), including 526 high-need patients (342 received efalizumab and 184 placebo). Week 12 PASI-75 rates were 29·5% for efalizumab compared with 2·7% for placebo among high-need patients (P

Aim Fine needle aspiration cytology (FNAC) is widely used in oncology to obtain the diagnosis of unclear tumours in cancer patients. However, because the method is established only in few melanoma centers, we performed this study to evaluate ultrasound guided FNAC in routine follow-up of melanoma patients. Method Unclear tumours recognised during routine follow-up of melanoma patients underwent ultrasound guided fine needle aspiration with cytological examination. The results were then compared to subsequent histopathology or future clinical outcome. Results 275 unclear tumours received ultrasound guided fine needle aspiration with cytological examination. Sensitivity showed to be 95.6% [95% CI: 91.5-98.1], specificity was 100% [95% CI: 96.2-100.0]. The positive predictive value was 100.0% [95% CI: 97.9-100.0], the negative predictive value 92.2% [95% CI: 85.1%-96.9%]. In 89 cases lesions turned out to be cytologically benign thus diagnosis avoiding surgery. In lesions with diameters up to 10 mm sensitivity and specificity were 91.4% and 100.0%, respectively. Conclusion Ultrasound guided FNAC proved to be a minimal invasive procedure in the diagnosis of unclear tumours in the follow-up of melanoma patients. It allows definite diagnosis and avoids unnecessary diagnostic surgery.

Primary cutaneous T-cell lymphomas (CTCL) are defined as clonal proliferation of skin-infiltrating T lymphocytes. Despite their heterogeneity, CTCL are generally incurable, which has led to the development of various treatment strategies including vaccination. Here, the attempts to vaccinate against lymphoma will be reviewed with special emphasis on CTCL. Because an universal tumour antigen is not available so far, different targets - including whole tumour cells, idiotypes, cancer/testis antigens, proteins derived from tumour-associated mutations, and mimotopes - have been investigated for their applicability in CTCL vaccination. The antigenic information can be delivered in different ways. So far, tumour cells fused to dendritic cells, idiotypic proteins/peptides and DNA/RNA preparations have been applied in lymphoma. As most targets are weak immunogens, adjuvants and other helpers - including dendritic cells, immunogenic peptides and oligonucleotides, cytokines, and viral vectors - are required to enable proper presentation of the antigens and sufficient activation of the immune system. Although first data from CTCL patients prove the suitability of vaccination in CTCL therapy, the number of available antigens, carriers, adjuvants and application schemes creates a multitude of vaccine formulations; identification of the best-suited approach remains nearly impossible. Furthermore, the relationship between lymphoma and the host immune system is complex and incompletely understood. As a result, CTCL vaccination still requires a lot of research.

Interleukin (IL)-10 is an important immunoregulatory cytokine that mediates its effects via a transmembrane receptor complex consisting of two different chains, IL-10R1 and IL-10R2. While IL-10R2 is ubiquitously expressed and does not bind IL-10 primarily, the expression of IL-10R1 determines cellular responsiveness. However, the current knowledge about the expression and regulation of IL-10R1 is still limited. Here we analyzed the expression of IL-10R1 on monocytic cells and demonstrated that human blood monocytes carried about 720 IL-10-binding sites on their surface. Compared with lymphocytes and various tissue cells and tissues, blood monocytes expressed the highest IL-10R1 levels. The in vitro differentiation of these cells into macrophages provoked a further increase of IL-10R1 surface expression. In contrast, their differentiation into myeloid dendritic cells (mDCs) resulted in reduced surface IL-10R1 levels. The different IL-10R1 levels expressed by monocyte-derived antigen-presenting cell populations were reflected in their different responsiveness toward IL-10. Importantly, also in vivo developed immature macrophages and mDCs showed different IL-10 sensitivity. These data suggest that, compared with monocytes and macrophages, mDCs partially escape from IL-10's inhibitory mechanisms by downregulating IL-10R1.

Systemic hypocomplementaemic urticarial vasculitis unresponsive to several immunosuppressive and immunomodulatory drugs was seen in two women aged 43 and 45 years. Cyclophosphamide-dexamethasone pulse therapy was started in both patients and resulted in significant clinical improvement. The pulse treatment was well tolerated in both patients and no major adverse effects occurred. These cases indicate that cyclophosphamide-dexamethasone pulse therapy is efficient in the treatment of hypocomplementaemic urticarial vasculitis.

The argon laser treatment of port-wine stains and other benign lesions rich in small blood vessels is an old but well-established procedure. The formation of small superficial atrophic scars is a common unwanted side-effect and this is due to accompanying thermal effects arising from the treatment. This paper describes a new method of chilling the skin which the authors have called ‘Translucent Argon Laser Treatment’. This is based on the transmission of the argon laser light through specially produced bubble-free ice cubes which couple the light to the skin surface. In this way, the skin can be chilled in a safe and efficient manner before, during and after the application of the laser beam. When compared with the standard procedure without skin chilling, the number of scars formed in 62 patients treated was reduced from 32 to 1. Lesion lightening was not affected by chilling. Treatment is less painful using ice as a coupling medium and was therefore more acceptable to the patients.

Previous studies have shown that barrier requirements regulate epidermal liquid and DNA synthesis. In the present study, we examined the possibility that the integrity of the permeability barrier influences epidermal Langerhans cells involved with the immune response. Barrier disruption was achieved by treatment of human skin with acetone, sodium dodecylsulphate (SDS), or tape stripping, until a 10-20-fold increase in transepidermal water loss was achieved. Serial biopsies were performed 6-168 h after treatment, and Langerhans cells were complexed with anti-CD1a (Leu6) or S-100 antibodies, and visualized with an immunoperoxidase technique. Acetone treatment resulted in an increase in epidermal Langerhans cell density, reaching a maximum of 94% over control (P < 0.01) by 24 and 48 h post-treatment. Following SDS treatment or tape stripping, epidermal Langerhans cell density was increased by 100 and 175% (P < 0.01), respectively. There was a linear correlation between the degree of barrier disruption and the increase in epidermal Langerhans cell density. Studies with the Ki-S3 proliferation-associated nuclear antigen revealed a two- to threefold increase in epidermal proliferation after barrier disruption. The time curves of the increase in Langerhans cell density and the increase in epidermal proliferation were similar, suggesting that there was a coordinate regulation. In contrast with our previous studies employing patch test reactions to allergens or irritants, disruption of barrier function neither resulted in an increased dermal Langerhans cell density, nor influenced T lymphocytes (CD3+, Leu4+), macrophages (KiM8+), ICAM-1 or ELAM-1 expression in the skin. In addition, barrier disruption did not result in either dermal inflammation or epidermal spongiosis. In summary, these findings support our hypothesis that the permeability barrier influences epidermal Langerhans cell density, which is involved in maintaining an immunological barrier.

Psoriasis is a chronic, genetically predisposed skin disorder, characterised by thickened scaly plaques. Although no therapy is recognised as curative, therapies aimed at symptom control include biologic agents that are generally designed to block molecular activation of cellular pathways of a pathogenic immune response. Although biologics are often described as a class, they can be further sub-classified according to properties including structure and molecular target. For example, the two main groups of biologics for the treatment of psoriasis are those targeting cytokines and those targeting T-cells or antigen-presenting cells. Agents that inhibit cytokines can be broadly split into anti-p40 agents, which target the p40 subunit of IL-12 and IL-23 (such as ustekinumab), and anti-TNF agents. Anti-TNF agents may then be further divided into soluble receptors (etanercept) and monoclonal antibodies (adalimumab and infliximab). Even within the same subclass, agents may display variations in structure, function, route of administration and pharmacokinetics, which are reflected in their clinical profiles. For example, of the TNF antagonists, infliximab, provides a rapid onset of response, high efficacy, high peak serum concentrations, anti-granulomatous activity, potential for tuberculosis reactivation and frequent antibody formation; adalimumab provides a fast response, high efficacy, potential for tuberculosis reactivation and the possibility of antibody formation; and etanercept provides a slower response, good efficacy, rare antibody formation and is rarely linked to tuberculosis cases. This suggests that biologic agents exhibit unique properties, which appear to be more relevant than a 'class effect' in assessing risk-benefit profiles for this diverse group of drugs. With a range of agents available, studying the immunogenesis of psoriasis is likely to be useful in profiling individuals best suited to the characteristics of particular drugs. It should also be noted that because differences between agents may affect safety profiles, long-term patient registries are an important tool to assess tolerability and develop guidelines for the most effective use of these drugs.

Cutaneous T-cell lymphomas represent extranodal non-Hodgkin lymphomas of mature T-cells, which accumulate in the skin. They have been recognized as a heterogeneous group with distinct variability in clinical presentation and histopathology, with divergent biological behaviour and prognosis. Therefore the exact diagnosis is an important prerequisite for an adequate and stage-adapted treatment.

Primary cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group with Sézary syndrome (SS) as one of the most aggressive variants. Recently, we identified a loss of E2A as a recurrent event in SS, which enhanced proliferation via upregulation of the proto-oncogene MYC. MYC-induced transformation usually requires deleterious alterations of key apoptotic genes including p53; however, p53 functionality and mutation status in SS are unclear.We investigated functionality of p53 signalling by pharmacological treatment with the MDM2 antagonist nutlin-3, which might result in p53 activation. Furthermore, we analysed the TP53 mutation status in CTCL cell lines and highly purified tumour cells from patients with SS by mRNA and DNA sequencing.We analysed the apoptosis induction due to nutlin-3 treatment in various SS cell lines and primary patient samples by annexin V/propidium iodide staining. Induction of p53 target genes was analysed by immunoblotting, and TP53 was sequenced at the mRNA and DNA level.We identified various TP53 mutations and an impaired p53 signalling in the vast majority of the investigated cell lines and primary SS cells.In accordance with the importance of MYC deregulation in SS, p53 signalling is frequently nonfunctional in SS. However, although most likely ineffective as exclusive treatment in SS, it remains possible that pharmacological p53 activation could be beneficial in combination with other approaches including classical chemotherapeutics.

Primary cutaneous lymphomas (CLs) are a heterogeneous group of diseases arising from B or T lymphocytes. CLs are grouped according to their clinical behaviour into indolent, intermediate and aggressive types. Indolent CLs respond well to therapy but frequently relapse, resulting in prolonged periods of follow-up.To evaluate the outcome of follow-up examinations in indolent CL.We retrospectively analysed a cohort from a CL outpatient clinic at a tertiary referral centre. Seventy-five patients with indolent cutaneous T-cell lymphomas (CTCLs) and 34 patients with indolent cutaneous B-cell lymphomas (CBCLs) were included. The value of clinical examination, blood tests and imaging procedures for detection of recurrence or progression was assessed.In patients with CTCL all but one disease recurrences were detected by clinical examination. Lymph node or organ involvement was detected by imaging procedures in seven patients, of whom all but one had recurrent or persistent CL lesions. In CBCL all recurrences were detected by clinical examination.Patients with indolent CL confined to the skin should be followed primarily by clinical examination. However, in patients who are refractory to treatment regular screening of lymph nodes by ultrasound may enable earlier detection of disease recurrence or progression.

Hybrid cell vaccination is a novel approach for immunotherapy of cancers by inducing specific antitumor immunity (1 ,2). The hybrid cells are generated by electrofusing autologous tumor cells with allogeneic MHC class II expressing cells such as B lymphocytes. The fused cells are irradiated and injected subcutaneously as a vaccine. This immune therapeutical approach aims at recruitment of T-cell help for the induction of tumor-specific cytolytic immunity. It is based on the observation that epitope linkage is a prerequisite for productive T-T cell collaboration, i.e., cytolytic precursor and helper T cells have to be activated by the same antigen presenting cell that displays epitopes for both T-cell types on the corresponding MHC class I and class II molecules (3 ,4). Neither of the two epitopes nor the corresponding T cells need to be related. The implications of this concept are, first, only MHC class I and II expressing cells can induce cytolytic T-cell responses (5 -7), second, cognate antigens must be presented for both T-cell and MHC types (4 ,8) and, third, there must be T cells with the corresponding specificities in the T-cell receptor repertoire of the response-competent individual.

Actinic cheilitis (AC) represents the equivalent of actinic keratosis on the lip. Various treatment modalities are available and the efficacy of diclofenac in hyaluronic acid has recently been described. Reflectance confocal microscopy (RCM) is a non-invasive imaging technique which has recently been applied for the diagnosis of actinic keratoses. Herein, we describe the applicability of RCM for the diagnosis of AC and for monitoring of treatment response of AC to diclofenac in hyaluronic acid.Ten Caucasian patients with clinical suspicion for AC were included in this study. To obtain a non-invasive diagnosis, RCM was performed at baseline, followed by biopsy and respective confocal-histopathological correlation. Six patients with a histological diagnosis of AC were treated with diclofenac in hyaluronic acid, whereby monitoring was performed by RCM.Reflectance confocal microscopy was able to correctly identify 6/7 cases of AC and 3/3 cases of benign lesions. The most important RCM criteria for diagnosis of AC were cellular atypia at the stratum spinosum and granulosum with atypical honeycomb pattern. One patient with AC was misclassified as inflammatory cheilitis by RCM as it showed marked inflammatory response and lacked clear signs of cellular atypia on RCM imaging. Following topical treatment with diclofenac gel, 5/6 patients (83%) showed a good treatment response with regression of dysplasia on consecutive RCM examination.Reflectance confocal microscopy is a promising tool for the non-invasive diagnosis and monitoring of actinic cheilitis. However, marked inflammation represents a potential diagnostic pitfall. In this regard, biopsy should be performed in doubtful cases.

Cutaneous T-cell lymphomas (CTCL) represent clonal proliferations of neoplastic skin homing T-cells. Within the group of primary CTCL, mycosis fungoides (MF) is the most common entity, affecting the skin as a primary site. MF initially presents in the skin with a slow indolent course of a characteristic stepwise progression from patches to plaques and tumors accompanied by distinctive histological changes. Routine diagnosis is based on these clinical and histological features. However, due to similarities with benign lymphoproliferative or reactive skin diseases, especially at the initial presentation of the disease, diagnosis can be difficult. Although the etiology of mycosis fungoides is still unknown, important insights have been gained in the immunological and genetic perturbations, which are associated with the disease. In the last years the emergence of molecular genetic techniques allowing to analyze the clonality status in lymphocytic infiltrates, has provided new tools with the potential to increase the accuracy of diagnosis, staging and therefore stage-adapted treatment. Nevertheless, it is important to notice that some limitations restrict the predictive value of the results obtained by these analyses. Diagnostic tool of MF, including clinical, histo- and immunohistological findings as well as molecular genetic analysis will be covered in this review.

There is abundant and accumulating evidence on the classification of psoriasis as a systemic disease that exhibits a host of co-morbidities. As a consequence, the second Interdisciplinary Conference on Co-morbidities and Lifestyle Modification, convened by the International Psoriasis Council, has concluded that specialist physicians, primary care physicians and dermatologists are faced with an opportunity to impact, not just psoriasis disease understanding and management, but overall patient well-being. The conference panel was represented by the disciplines of dermatology, cardiology, rheumatology, epidemiology, endocrinology, hepatology and gastroenterology, and medical specialists with particular expertise in obesity, diabetes mellitus, inflammation and genetics. The multiple co-morbidities associated with psoriasis were reviewed with a view to identify possible mechanisms linking psoriatic disease with obesity, metabolic syndrome, diabetes, cardiovascular disease and non-alcoholic fatty liver disease. Consensus was established on the association of psoriasis with other co-morbidities and disease states. Consequently, there is a significant opportunity for specialist and primary care physicians to collaborate with dermatologists in the management of the overall health of psoriasis patients. First, there is an important need for physicians to routinely screen psoriasis patients for the multiple susceptibility risk factors and co-morbidities associated with psoriasis. Second, the design and implementation of lifestyle modification plans including exercise, diet and the limitation of alcohol and tobacco intake, will not only benefit their general medical health but also their psoriasis.

Human papillomaviruses infect the squamous epithelia of the skin and cause warts, and are occasionally found in squamous cell carcinomas. Since cell-mediated immunity plays a crucial role in the control of HPV-infections, organ transplant recipients, unable to mount an adequate T-helper 1 cell-mediated immune surveillance, frequently develop widespread and resistant induced warts. Skin tumors, especially squamous cell carcinomas, are the most common post-transplantation neoplasm. Warts, actinic keratoses and invasive squamous cell carcinomas are known to develop at the same time in the areas. The role of HPV in the development of invasive squamous cell carcinoma under immunosuppression, remains to be elucidated in respect to common risk factors and increased numbers of warts potentially identifying patients at increased risk for carcinoma. We prospectively studied 1690 organ transplant recipients in the dermatology clinic at the Charité University Hospital in Berlin, to evaluate risk factors being involved in the development of HPV-induced warts and to assess a potential association of with the development of non-melanoma skin cancers in this population. The cumulative incidence of warts steadily increased throughout the post-transplant years. The presence of more than 10 verrucae was associated with the development of actinic keratoses, invasive squamous cell carcinoma and basal cell carcinoma. This study shows clear evidence that certain risk factors of skin carcinogenesis in organ transplant recipient such as increased age at transplantation, a high dose of immunosuppression related to a specific type of graft and use of azathioprine or cyclosporine are strongly associated with an increased incidence of warts. Furthermore, HPV-induced verrucae vulgares could be used as a potential predictor for the development of coincidental non melanoma skin cancer in organ transplant recipients and therefore could serve as an early identification marker of skin cancer high-risk patients. The challenging management of warts in organ transplantation patients is reviewed.

In order to study the relevance of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and endothelial leukocyte adhesion molecule 1 (ELAM-1) for lymphocyte extravasation in the early phase of allergic contact dermatitis, the time courses of lymphocyte infiltration and adhesion molecule expression during initiation of this disorder were determined. Sequential biopsies of positive allergic patch test reactions were obtained 4, 8, 16 and 24 h after antigen application, cryostat sectioned and stained with monoclonal antibodies for ICAM-1, VCAM-1, ELAM-1 and lymphocytes by use of an immunoperoxidase technique. The slides were evaluated semiquantitatively according to appropriate gradation scales that had been defined separately for the staining with each antibody. Our results show that there is a significant upregulation of VCAM-1 and ELAM-1 expression within the first 8 h after antigen application, when lymphocyte extravasation is just beginning. In contrast, ICAM-1 is already expressed in higher levels in normal skin and is hardly enhanced during the first 8 h of patch test reactions. The main influx of lymphocytes occurs 16-24 h after antigen application and is accompanied by a further increase in all three adhesion molecules. We conclude that VCAM-1 and ELAM-1 rather than ICAM-1 may be of particular importance for the start phase of allergic contact dermatitis and that all three of them contribute to an amplification of this inflammation.

Anthracyclines, such as pegylated liposomal doxorubicin (PLD) and epirubicin (EP), are effective for the treatment of malignant tumors. Unfortunately, their implementation in therapy is limited due to severe side-effects such as palmar-plantar erythrodysesthesia (PPE).As the exact pathogenesis of PPE still remains unclear, laser scanning microscopy was utilized to detect PLD, EP and their metabolites in and on the skin surface of patients.It was shown that PLD was significantly more frequently detectable on the skin than was EP (p0.05), whereas both substances were most frequently seen in the palms and soles. Additionally, it has been visualized that the substances reach the skin surface via sweat, where they distribute and then penetrate back into the skin.It was concluded that a high density of sweat glands and a thick stratum corneum might represent important predestined factors for the development of PPE. These findings will help to develop efficient prevention and therapy strategies for PPE.

Nanoparticles are experiencing an increasing application in dermatology and cosmetics. In both application areas, the requirements of nanoparticles are in most cases widely different. As a component of sunscreens, the nanoparticles are supposed to remain on the skin surface or in the upper most layers of the stratum corneum to protect the skin against UV-radiation of the sun. Whereas, on the other hand, when particulate substances are used as carrier systems for drugs, they have to cross the skin barrier to reach the target sites within the living tissue. We discuss the perspectives and risks of the topical application of nanoparticles.

Primary cutaneous T-cell lymphomas (PCLs) mycosis fungoides (MF) and Sézary syndrome (Ss) belong to the group of non-Hodgkin lymphomas (NHL), which are characterized by clonally proliferating CD4+ cells localized in the skin. Although there already exist many conventional skin-directed and systemic cytotoxic treatment options, in long-term only a transient remission without curative results will be reached in most cases. The aim of this article was to present actual assumed treatment modalities, as well as new therapeutic strategies which passed already through clinical trials showing promising results in the treatment of PCLs.

Atopic dermatitis (AD) is a severe and chronic eczematous skin disease, to which increased IgE levels and imbalances of CD4+ T cells are related. CD4+ T cells, however, are heterogeneous and include at least two subpopulations being designated as CD4+ naive and memory T cells. They represent sequential maturational stages (naive into memory) in CD4+ T cell development differing in function and phenotype. Of these two subpopulations the CD4+ memory T cell compartment is a potent producer of γ-interferon which suppresses IgE synthesis in B cells. Therefore we speculated whether an inborn maturation defect of CD4+ memory T cells causes the increased IgE production in AD. In patients with AD and age- and sex-matched controls (both n = 10) we analyzed the distribution of both subpopulations in peripheral blood by two-color flow cytometry using monoclonal antibodies against the CD4, CD45RA and CD29 antigen. We provide evidence that the numerical values of CD4 + memory T cells and CD4 + naive T cells are equivalent in both groups. This supports the view that functional disturbances of lymphocytes or lymphocyte subsets are responsible for IgE excess and the pathogenesis of AD.

In the past, it was assumed that the intercellular route was the only relevant penetration pathway for topically applied substances. Recent results on follicular penetration obtained at the Center for Experimental and Applied Cutaneous Physiology, Charité - Universitätsmedizin Berlin, Germany, emphasize that the hair follicles represent a highly relevant and efficient penetration pathway and reservoir for topically applied substances.

A neutrophil-activating peptide (NAP)/IL-8 produced by LPS-stimulated human peripheral blood monocytes was biochemically purified and functionally characterized by different investigators. Work conducted in our laboratory showed that NAP/IL-8 as well as variants of this peptide are produced by a variety of cells (e.g., monocytes, T lymphocytes, endothelial cells) and that lesional psoriatic scales contain large amounts of biologically active NAP/IL-8. We now investigated human dermal fibroblasts for production of NAP/IL-8. The peptide was detected by immunocytochemistry by using the mAb 46E5. NAP/IL-8 mRNA was visualized by high resolutive fluorescent in situ hybridization with biotinylated antisense/sense RNA probes. Among the various stimuli used [human (h)rIL-1 alpha, hrTNF-alpha, hrIL-3, hr-granulocyte-macrophage-CSF, LPS, FMLP, and platelet-activating factor (PAF)] only hrIL-1 alpha (100 U/ml) and hrTNF-alpha (100 ng/ml) induced the transcription and translation of NAP/IL-8. In contrast to monocytes, LPS was without effect in cultured human dermal fibroblasts. Both NAP/IL-8 and NAP/IL-8 mRNA were found in the cytoplasm adjacent to the nucleus, but interestingly NAP/IL-8 mRNA was not restricted to the cytoplasm. In positive cells only two small bright spots were randomly distributed in the nucleus. Most likely these spots represent transcription sites where NAP/IL-8 mRNA is accumulated during gene expression. Our observations show that stimulation of dermal fibroblasts with the cytokines hrIL-1 alpha and hrTNF-alpha results in expression of IL-8.

Actinic keratoses (AK) frequently occur on sun-exposed skin and are considered as in situ squamous cell carcinoma. To date, no treatment algorithm exists for first or second line therapies due to the lack of comparative studies.This study compared the initial and 12-month clinical clearance, histological clearance, and cosmetic outcomes of topically applied 5% imiquimod (IMIQ) cream, 5% 5-fluorouracil (5-FU) ointment and cryosurgery for the treatment of AK.Patients were randomised to one of the following three treatment groups: one or two courses of cryosurgery (20-40 s per lesion), topical 5-FU (twice daily for 4 weeks), or one or two courses of topical imquimod (three times per week for 4 weeks each).Sixty-eight per cent (17/25) of patients treated with cryosurgery, 96% (23/24) of patients treated with 5-FU, and 85% (22/26) of patients treated with IMIQ achieved initial clinical clearance, p = 0.03. The histological clearance rate for cryosurgery was 32% (8/25), 67% (16/24) for 5-FU, and 73% (19/26) in the IMIQ group, p = 0.03. The 12-month follow-up showed a high rate of recurrent and new lesions in the 5-FU and cryosurgery arms. The sustained clearance rate of initially cleared individual lesions was 28% (7/25) for cryosurgery, 54% (13/24) for 5-FU and 73% (19/26) for IMIQ (p0.01). Sustained clearance of the total treatment field was 4% (1/25), 33% (8/24), and 73% (19/26) of patients after cryosurgery, 5-FU, and IMIQ, respectively (p0.01). The patients in the IMIQ group were judged to have the best cosmetic outcomes (p = 0.0001).Imiquimod treatment of AK resulted in superior sustained clearance and cosmetic outcomes compared with cryosurgery and 5-FU. It should be considered as a first line therapy for sustained treatment of AK.

In the USA, Imiquimod 5% cream is approved for use 2-3 times per week over 16 weeks for the treatment of actinic keratoses (AKs). This study evaluated the efficacy of imiquimod in another treatment schedule, for AKs on the head.Open-label, phase IIIb.180 dermatology clinics and practices in Germany.Patients were eligible if they had clinically typical, visible AK lesions located anywhere on the head, excluding the upper and lower eyelids, nostrils, lip vermilion, and inside the ears.Patients applied study cream to the treatment area once daily 3x/week for 4 weeks (course 1) followed by a 4-week post-treatment period. Patients with AK lesions remaining in the treatment area underwent a second 4-week treatment course.Primary variable was the complete clearance rate, defined as the proportion of patients with no clinically visible AK lesions in the treatment area at the course 1 or course 2 post-treatment visit.829 patients entered the study. Overall, the complete clearance rate was 68.9% (571/829) and the partial clearance rate (percentage of patients with/= 75% reduction in the number of baseline AK lesions) was 80.2%. Local skin reactions (LSRs) and application site reactions (ASRs) were the most commonly reported adverse events. Four patients discontinued from the study due to LSRs or ASRs.Shorter treatment regimen of imiquimod 5% cream can produce complete clearance rates similar to those seen with 16 weeks of treatment and has the advantage of lower drug exposure, resulting in a better benefit-risk profile for the patient.

Experts on psoriasis convened with authorities from other medical specialties to discuss the recently described association between psoriasis, obesity and subsequent cardiovascular comorbidity. Similar to other diseases of increased systemic inflammation, psoriasis has been linked to a heightened risk of myocardial infarction, especially in the more severely affected, younger patients. However, unlike in other inflammatory diseases - such as rheumatoid arthritis - more severely affected patients with psoriasis are much more likely to be obese. Importantly, the pathophysiology of both psoriasis and obesity shows many shared cytokines that are known to contribute to features of the metabolic syndrome, such as hypertension, dyslipidaemia and insulin resistance. The strong association between psoriasis and obesity potentially makes psoriasis an important healthcare issue that requires an update in its standard of care. This meeting reviewed the evidence-based literature and addressed how, moving forward, dermatologists and other specialists may redefine the magnitude of health risk associated with more severe psoriasis and its comorbidities, while clarifying both the epidemiology and pathophysiology of the association with obesity.