The pathogenesis of inflammatory dermatoses, especially psoriasis

The skin contains a variety of cell types and mediators, which together constitute the skin's immune system and play a key role in protecting the human body against dangers from outside. Dysregulation of the skin's immune system, however, frequently occurs and can result in undesirable inflammatory processes in the skin. A typical example of an undesirable inflammation in the skin is the chronic inflammatory skin disease psoriasis. In the pathogenesis of psoriasis, both genetic and environmental factors play a key role. In psoriasis, the complex interactions between T-lymphocytes, antigen-presenting cells, keratinocytes and pro-inflammatory cytokines and chemokines are disturbed. The two most widely accepted hypotheses are: (a) psoriasis is a T-cell mediated autoimmune disease, and (b) psoriasis is the result of a too finely adjusted system for regulating inflammation in the skin. The result of both mechanisms is a chronic inflammatory reaction fuelled by pro-inflammatory type-I cytokines that lead to the psoriasis-skin phenotype. With the development ofbiologicals, it has become feasible to target specific molecules in the immune process, for example type-I cytokines and the molecules present on pathogenic T-cells. This approach has already proved successful in the treatment of rheumatoid arthritis and Crohn's disease, creating novel therapeutic options for psoriasis and other inflammatory dermatoses.     

Gut Microbiota in Psoriasis

Psoriasis is a chronic inflammatory skin disease with autoimmune pathogenic characteristics and is caused by chronic inflammation, which results in uncontrolled keratinocyte growth and defective differentiation. The link between the gut microbiota and immune system regulation opened a novel angle to understand the pathogenesis of many chronic multifactorial diseases, including psoriasis. Current evidence suggests that modulation of the gut microbiota, both through dietary approaches and through supplementation with probiotics and prebiotics, could represent a novel therapeutic approach. The present work aims to highlight the latest scientific evidence regarding the microbiome alterations of psoriatic patients, as well as state of the art insights in terms of microbiome-targeted therapies as promising preventive and therapeutic tools for psoriasis.     

维生素D及衍生物治疗银屑病的研究现状

银屑病是一种常见的慢性复发性炎症性皮肤病,全球大约2.5％的人群罹患此病.紫外线光疗是治疗方法之一,可促使表皮产生1,25(OH)2D.维生素D活性代谢产物1,25(OH)2D及其衍生物通过其细胞核受体即维生素D受体发挥重要的生理作用,除了经典的调节钙、磷代谢外,1,25(OH)2D及其衍生物抗增殖及促分化的免疫调节作用正在被逐渐认识.它可能通过调节皮肤局部的免疫反应、抑制角质细胞的增殖并诱导分化从而有效地治疗银屑病.因此,进一步了解维生素D及衍生物在银屑病中的作用机制,对于更有效地治疗银屑病具有重要的意义.     

Immunogenetics of psoriasis: Update

Bachground: Psoriasis is a chronic inflammatory skin disease often benign, affecting 2-3% of the total world population. Psoriasis is a multifactorial disease. Aim: To present recent advances in the immunologic mechanisms and susceptibility genes involved in the pathogenesis of psoriasis. Methods: We presented a literature review of recent genetic and immunological basis of psoriasis to better understand the pathomecanisms of this disease and discuss the contribution of the Tunisian work in this area. Results: Recent works focalized mainly in immunology and genetics. Current progresses in molecular biology have allowed to better characterize the immunogenetic abnormalities in psoriasis. Conclusion: Psoriasis is a multifactorial disease model in which environmental factors (psychological, climate, traumatic, infectious, and viral) seem to be triggering factors when associated with a particular immunogenetics predisposition.     

Pustular psoriasis in childhood in 15 cases

Psoriasis is a common, chronic and recurrent, inflammatory disease of the skin. Children were affected in 30% of cases. Severe form can be observed: pustular psoriasis (PP), psoriatic arthropathy and erythrodermic psoriasis. There were 15 children with PP, with an age range of 1-15.5 years, (mean age 7.56 years). Psoriasis constituted 5% of the total dermatological disorders in children. The severe forms of psoriasis were rare in children Annular PP was the most common form of PP in children. Juvenile PP had generally better prognostic than in adults, but the evolution is characterized by recurrences.     

Nutritional Therapy in Persons Suffering from Psoriasis

Psoriasis is a chronic inflammatory skin disease. Immunological, genetic, and environmental factors, including diet, play a part in the pathogenesis of psoriasis. Metabolic syndrome or its components are frequent co-morbidities in persons with psoriasis. A change of eating habits can improve the quality of life of patients by relieving skin lesions and by reducing the risk of other diseases. A low-energy diet is recommended for patients with excess body weight. Persons suffering from psoriasis should limit the intake of saturated fatty acids and replace them with polyunsaturated fatty acids from the omega-3 family, which have an anti-inflammatory effect. In diet therapy for persons with psoriasis, the introduction of antioxidants such as vitamin A, vitamin C, vitamin E, carotenoids, flavonoids, and selenium is extremely important. Vitamin D supplementation is also recommended. Some authors suggest that alternative diets have a positive effect on the course of psoriasis. These diets include: a gluten-free diet, a vegetarian diet, and a Mediterranean diet. Diet therapy for patients with psoriasis should also be tailored to pharmacological treatment. For instance, folic acid supplementation is introduced in persons taking methotrexate. The purpose of this paper is to discuss in detail the nutritional recommendations for persons with psoriasis.     

The bodily suffering of living with severe psoriasis: in-depth interviews with 22 hospitalized patients with psoriasis

Psoriasis is one of the most common chronic skin diseases. The author presented results from a qualitative study focusing on patients with severe psoriasis in an acute phase and their experience of living with the disease. Twenty-two hospitalized patients with psoriasis were interviewed in depth. The interviews were consecutively analyzed according to grounded theory methodology. Bodily suffering emerged as a core variable in the data. Bodily suffering includes the following categories: the visible body, staying on an even keel, coping with an all-consuming disease, and social vulnerability. The results of this study indicate that the criterion for the management of soriasis should be the patients' own perception of the consequences of the disease.     

The immune system of the skin and stereotyped reaction patterns in inflammatory skin diseases

The clinical and histological presentation of inflammatory disease in the skin is exceedingly heterogeneous. Nonetheless, most inflammatory dermatoses can be classified according to five stereotypical tissue-reaction patterns: the spongiotic, the lichenoid, the psoriasiform, the vesiculo-bullous and the vasculopathic. By means of potent antigen-presenting cells, cytokine and chemokine cascades and a skin-specific cutaneous lymphocyte antigen (CLA)-positive lymphocyte population, the skin is able to respond very efficiently to pathogens that threaten the individual. Inflammatory skin diseases follow the rules and routes of the physiological reaction to inflammation but however for various reasons the immune response may be inadequate, enhanced or chronic. In allergic contact dermatitis, which is a prototype of the spongiotic reaction pattern, the inflammation is directed against an otherwise harmless antigen, for which the body is sensibilized. Lichenoid dermatitis (like erythema multiforme, graft versus host disease or lupus erythematodes) is based on a primary cytotoxic reaction against the basal epithelial cell, due to alterations in its antigenic make-up or due to an altered immune response. In psoriasis, an example of psoriasiform dermatitis, the interaction between inflammatory cells, antigen presenting cells and epithelial cells is disturbed.     

Effects of Dietary Protein Intake on Cutaneous and Systemic Inflammation in Mice with Acute Experimental Psoriasis

Background: Psoriasis is a systemic inflammatory disorder, primarily characterized by skin plaques. It is linked to co-morbidities including cardiovascular disease and metabolic syndrome. Several studies demonstrate that dietary habits can influence psoriasis development and severity. However, the effect of different dietary protein levels on psoriasis development and severity is poorly understood. In this study, we examine the influence of dietary protein on psoriasis-like skin disease in mice. Methods: We fed male C57BL/6J mice with regular, low protein and high protein chow for 4 weeks. Afterwards, we induced psoriasis-like skin disease by topical imiquimod (IMQ)-treatment on ear and back skin. The local cutaneous and systemic inflammatory response was investigated using flow cytometry analysis, histology and quantitative rt-PCR. Results: After 5 days of IMQ-treatment, both diets reduced bodyweight in mice, whereas only the high protein diet slightly aggravated IMQ-induced skin inflammation. IMQ-treatment induced infiltration of myeloid cells, neutrophils, and monocytes/macrophages into skin and spleen independently of diet. After IMQ-treatment, circulating neutrophils and reactive oxygen species were increased in mice on low and high protein diets. Conclusion: Different dietary protein levels had no striking effect on IMQ-induced psoriasis but aggravated the systemic pro-inflammatory phenotype.     

Identification of Langerhans cells in dermatology

This paper describes our own findings on the role of Langerhans' cells in dermatology and discusses literature data on their detection in seven different dermatoses. The skin is an integral part of immune system. During the past 30 years, increasing evidence has been accumulated that the skin contains cellular elements which are needed for the initiation and expression of immune response. Langerhans' cells (LCs) are dendritic cells originating in the bone marrow. They reside mainly within stratified squamous epithelia and constitute approximately 2-4% of epithelial cells. LCs are epidermal antigen presenting cells which play a crucial role in allergic contact hypersensitivity, viral diseases, graft versus host disease and elimination of neo-plastic cell clones. They express antigens conjugated with major histocompatibility complex (MHC) class II positive molecules on their surfaces for presentation to T-helper lymphocytes. LCs cannot be identified in routinely prepared histologic testing but can be visualised at the light microscope level by histochemical and immunologic techniques. Appropriate methods for the detection of Langerhans' cells in dermatology (also shown by our own experience) are histoenzymatic methods of adenosintriphosphatase (ATP-ase), acid phosphatase (AP), alpha-naphthylacetatesterase (ANAE and peroxidase-antiperoxidase immunohistochemistry method with polyclonal S-100 protein antibody (PAP). LCs are the only cells in normal skin with ATP-ase activity. Histoenzymatic methods used in patients with atopic dermatitis, vitiligo, mycosis fungoides, Behcet's disease, lichen ruber planus, psoriasis vulgaris, irritant dermatitis and allergic contact dermatitis demonstrated LSs in epidermis and dermis. ANAE and AP showed concordance and were suitable histochemical markers for LC distribution and macrophages in the dermis in mycosis fungoides, atopic dermatitis, psoriasis vulgaris, irritant chronic dermatitis and Bechet's disease. Our experience of the human skin showed a strong activity of calcium-activated adenosine triphosphatase in LCs. LCs in the guinea pig skin can be demonstrated by Mg++ and Ca++ activated adenosine triphosphatase, but a stronger activity of Ca++ activated adenosine triphosphatase in LCs after irritation. Ca++ ATP-ase as an indicator of energy-dependent pump is the reflection of intracellular calcium level, which is a significant factor for regulating the growth and metabolism of the cells. LCs are found as target cells during the efferent phase of contact allergic reaction. Immunohistochemical methods, define the role of LCs in dermatology more precisely and allow complete immunologic recognition within the epidermis.     

New systemic treatments for psoriasis: etanercept, infliximab, adalimumab, efalizumab and alefacept

The chronic skin disease psoriasis frequently requires long-term systemic treatment with agents that suppresses the immune system with little specificity, which can lead to systemic side effects. Today, using recombinant techniques, it is possible to produce modified proteins, the so-called biologicals, that target specific molecules in the inflammatory process. For the biologicals etanercept, infliximab, adalimumab, efalizumab and alefacept, the clinical efficacy expressed in the rates of partial remission (75% reduction in skin lesions) in patients with plaque psoriasis range from 12 to 88%, compared with 22 to 87% for existing systemic therapies for psoriasis. The side effects of biologicals are usually mild to moderate, but can sometimes be severe. The biologicals should be prescribed with caution, given that they have been on the market for a relatively short period, and because all forms of immune suppression carry an increased risk of oncologic degeneration. The guideline of the Dutch Society of Dermatology and Venereology states that the use of a biological may be considered when a patient cannot tolerate or is unresponsive to conventional systemic therapy, or has an increased risk of adverse events. Biologicals increase the number of options for treatment-resistant plaque psoriasis, which allows therapy to be tailored to the individual patient.     

Multiple sclerosis and the role of immune cells

Multiple sclerosis (MS) is a complex disease with many different immune cells involved in its pathogenesis, and in particular T cells as the most recognized cell type. Recently, the innate immune system has also been researched for its effect on the disease. Hence, cells of the immune system play vital roles in either ameliorating or exacerbating the disease. The genetic and environmental factors, as well as the etiology and pathogenesis are of utmost importance for the development of MS. An insight into the roles play by T cells, B cells, natural killer cells, and dendritic cells in MS and the animal model experimental autoimmune encephalomyelitis, will be presented. Understanding the mechanisms of action for current therapeutic modalities should help developing new therapeutic tools to treat this disease and other autoimmune diseases.     

The relationship between demographic and clinical variables,and quality of life aspects in patients with psoriasis

There is a strong need for health care programmes to promote functioning and quality of life in patients suffering from psoriasis. The aim of the present study is to highlight the relationships between demographic and clinical variables and disease-specific disability, health status, the perception of living with a chronic disease and the overall quality of life in patients suffering from psoriasis. A further aim is to examine the extent to which the effects of demographic and clinical variables on mental health and the overall quality of life are mediated by disability, physical health and the perception of living with psoriasis. The sample examined in this study comprised 334 patients (20% in-patients and 80% out-patients) who were treated consecutively at three dermatology departments in eastern Norway. A total of 282 patients completed the testing procedures, yielding a response rate of 85%. The following questionnaires were used: The Psoriasis Disability Index, the Sf-36 and the Quality of Life Scale. Correlation and multiple linear regression analyses were performed to address the core issue. Results show that demographic and clinical variables combine to explain variance in health status, the perception of living with psoriasis and overall quality of life. While most of the variance is explained by the clinical variables, the disease-specific disability variable seems to be an important mediating factor.     

Item-Level Psychometric Properties for a New Patient-Reported Psoriasis Symptom Diary

ObjectivesThis research evaluated the psychometric properties of a new Psoriasis Symptom Diary, identified diary responder definitions for use in determining whether a patient has experienced clinically meaningful change, and refined diary item content for use in future clinical trials.MethodsThe Psoriasis Symptom Diary was administered in a phase 2 clinical trial of AIN457 to US adult outpatients (N = 172) with physician-diagnosed moderate to severe chronic plaque-type psoriasis. Participant compliance with daily diary administration and item score variability, reliability, construct and discriminant validity, sensitivity to change, and interpretation were all evaluated.ResultsParticipants completed 94% of scheduled diary assessments across 12 study weeks. Diary items were generally normally distributed, and no floor or ceiling effects were observed. Item reliability (reproducibility) was acceptable (intraclass correlation coefficients > 0.80), with an exception for one item (skin color). At week 12, items significantly related to criterion measures as predicted (Psoriasis Area and Severity Index r = 0.27–0.57; Investigator’s Global Assessment r = 0.25–0.59), with the exception of items that measured skin color and difficulty using hands. Most items generated change scores that were synchronous to changes as measured by the Psoriasis Area and Severity Index, Investigator’s Global Assessment, Dermatology Life Quality Index (r > 0.37), as well as the Patient Global Impression of Change. Responders experienced a 2- to 3-point and 3- to 5-point change in item scores for minimal and large improvements, respectively. Four items that did not perform well were dropped from the diary.ConclusionsThe 16-item Psoriasis Symptom Diary demonstrated favorable psychometric properties and is a brief, useful tool for measuring patient-based symptoms and the impact of chronic plaque psoriasis.     

Photo dermatology

Photodermatology has become an important part of the dermatologist's area of focus. This subspeciality is not only involved with studying basic biological processes such as the effects of ultraviolet (UV) irradiation on the skin's immune system (photo-immunology), melanocytes or DNA (carcinogenesis), but also with clinical issues such as photoprotection, photosensitive skin diseases (photodermatoses) and phototherapy. Increasing knowledge about the effects of UV irradiation on the skin, with or without photosensitising agents, has led to the development of new forms of photo(chemo)therapy. These allow good therapeutic results to be achieved in the treatment of not only psoriasis, but also other chronic inflammatory skin diseases, with minimal side effects. DNA can absorb UV irradiation. This can lead to irreversible DNA damage and mutations in genes responsible for cell cycle control. These events can lead to skin cancer. The presence of pheomelanin, which is an inferior type of UV light-absorbing melanin, can add to this process of DNA damage. The three most important types of skin cancer are basal cell carcinoma (more than 30,000 new patients per year in the Netherlands), squamous cell carcinoma and melanoma.     

Ultraviolet A-I phototherapy for skin diseases]

Favourable effects of sunlight on various skin diseases include inhibition of rapid proliferation of cells (psoriasis), modulation of cells in an inflammatory infiltrate (atopic eczema) and stimulation of proteolytic enzymes (scleroderma). The ultraviolet (UV) fraction of the solar spectrum is the most biologically active because it is almost completely absorbed by the skin. UVB and the combination of psoralens with UVA (PUVA) have become important therapeutic modalities, especially for psoriasis and eczema. Lamps producing long wave UV radiation are available: UVA-I light. Owing to its longer wavelength it penetrates more deeply into the skin and gives less risk of development of skin cancer than other forms of UV radiation. Good results are reported of application of UVA-I in patients suffering from atopic dermatitis, scleroderma, urticaria pigmentosa, and systemic lupus erythematosus.     

趋化因子CCL27在寻常型银屑病患者血清的表达以及与PASI的相关性

目的观察寻常型银屑病患者血清CCL27表达水平与PASI的相关性。方法采用ELISA方法，比较试验组（寻常型银屑病患者）与对照组（健康人）血清中CCL27表达水平；并比较试验组血清CCL27水平与PASI评分的相关性。结果寻常型银屑病组血清CCL27表达水平明显高于健康组，P〈0．01，CCL27在寻常型银屑病组血清的表达水平与PASI呈明显正相关（r=1000，P〈001）。结论患者血清CCL27水平与寻常型银悄病病情发生发展密切相关。     

Quality of life improvement in treatment of psoriasis with intermittent short course cyclosporin (Neoral®)

Due to concern over long term safety of continuous treatment with cyclosporin, the aim of this 1-year study was to assess the effect of intermittent therapy with cyclosporin (Neoral) on the quality of life of patients suffering from chronic plaque psoriasis. A total of 41 patients with chronic plaque psoriasis (26 male, mean age: 36 years, range: 18-61; duration of psoriasis 17 years, range: 2-31) entered a 9-centre open study in which cyclosporin was taken as an initial dose of 5 mg/kg/daily for a maximum of 12 weeks for up to three cycles. Each patient completed a psoriasis specific QOL measure (Psoriasis Disability Index, PDI) at the beginning and end of each treatment cycle and at the end of study. Clinical parameters including Psoriasis Area and Severity Index (PASI) were measured. The PDI scores showed a significant improvement (p < 0.01) between the beginning and end of all three treatment cycles. The various clinical assessments for each treatment period also showed significant improvement (p < 0.001) for all three cycles. When comparing the last follow-up value to baseline there was a clear indication of relapse, but these scores were still significantly better than at baseline (p < 0.01). Notably, the mean PASI score improved by more than 50% (p < 0.001) between first baseline and end of the study. These findings indicate that a short course of intermittent therapy with cyclosporin in microemulsion formulation, used at starting doses of 5 mg/kg/day, improves QOL of patients with chronic plaque psoriasis. Once again, the applicability and validity of the PDI as a useful QOL tool has been demonstrated.     

The Role of Nutrition in Immune-Mediated,Inflammatory Skin Disease: A Narrative Review

Immune-mediated inflammatory skin diseases are characterized by a complex multifactorial etiology, in which genetic and environmental factors interact both in genesis and development of the disease. Nutrition is a complex and fascinating scenario, whose pivotal role in induction, exacerbation, or amelioration of several human diseases has already been well documented. However, owing to the complexity of immune-mediated skin disease clinical course and breadth and variability of human nutrition, their correlation still remains an open debate in literature. It is therefore important for dermatologists to be aware about the scientific basis linking nutrition to inflammatory skin diseases such as psoriasis, atopic dermatitis, hidradenitis suppurativa, bullous diseases, vitiligo, and alopecia areata, and whether changes in diet can influence the clinical course of these diseases. The purpose of this narrative review is to address the role of nutrition in immune-mediated inflammatory skin diseases, in light of the most recent and validate knowledge on this topic. Moreover, whether specific dietary modifications could provide meaningful implementation in planning a therapeutic strategy for patients is evaluated, in accordance with regenerative medicine precepts, a healing-oriented medicine that considers the whole person, including all aspects of the lifestyle.