... What Happens in the Operating Room? Skin Problem: Psoriasis KidsHealth > For Kids > Skin Problem: Psoriasis A A ... Do? en español Problemas en la piel: psoriasis Psoriasis = Red, Flaky Skin If you have psoriasis, you ...
... time before returning to another type of treatment.Sunlight also can help psoriasis, but be careful not ... to your doctor about how to safely try sunlight exposure as a psoriasis treatment. Light therapy may ...
... As the skin cells die, they form silvery scales that eventually flake off. Psoriasis is passed down ... symptoms: raised red areas of skin with silvery scales dry, cracked skin that may bleed at times ...
Di Meglio, Paola; Villanova, Federica; Nestle, Frank O.
Psoriasis is a common chronic inflammatory skin disease with a spectrum of clinical phenotypes and results from the interplay of genetic, environmental, and immunological factors. Four decades of clinical and basic research on psoriasis have elucidated many of the pathogenic mechanisms underlying disease and paved the way to effective targeted therapies. Here, we review this progress and identify future directions of study that are supported by a more integrative research approach and aim at further improving the patients' life. PMID:25085957
Navarini, Alexander A; Trüeb, Ralph M
Psoriasis is a skin disease typically presenting with sharply demarcated, inflammatory, erythematous plaques with characteristic silver-white scaling due to epidermal hyperproliferation and parakeratosis secondary to the inflammation. The name derives from pisigmaomicronrhoalpha (mange or scabies), and in ancient times the disease was confused with leprosy resulting in expulsion from society. Hence, both itching and social stigmatization are major problems affecting patients with psoriasis. Today, psoriasis is recognized as a genetically determined, autoimmune, T cell mediated systemic disease manifesting on the skin, nails and joints and associated with a number of co-morbidities. Accordingly, therapeutic strategies are antiinflammatory, antiproliferative and keratolytic. The extent and severity of disease (PASI), impairment of life quality (DLQI), and affected anatomic regions (inverse, palmoplantar, nails) as well as co-morbidities (arthritis, metabolic syndrome, cardiovascular disease, depression) determine the therapy. In 80 % of cases psoriasis is mild or moderate and sufficiently treated with topical corticosteroids, vitamin D-analogues, and phototherapy. 20 % of patients suffer from severe psoriasis, necessitating systemic drugs such as acitretin, methotrexate, ciclosporin A or the newer biologic agents. Especially in severe psoriasis, psychological strain, co-morbidities, and medico-economic aspects must be taken into account.
... of people who get psoriasis develop guttate psoriasis. Inverse Inverse psoriasis shows up as very red lesions in ... type of psoriasis in the genital region is inverse psoriasis, but other forms of psoriasis can appear ...
Resources - psoriasis ... The following organizations are good resources for information about psoriasis : American Academy of Dermatology -- www.aad.org/skin-conditions/dermatology-a-to-z/psoriasis National Institute of ...
Engin, Burhan; Aşkın, Özge; Tüzün, Yalçın
Palmoplantar psoriasis refers to a localized psoriasis variant. The disease can be associated with many clinical forms, including predominantly pustular lesions to thick scaly, hyperkeratotic plaques, or an overlapping of both of them. Palmoplantar psoriasis accounts for 3-4% of all psoriasis cases in most studies. Although it is localized only on the palms and the soles, the fissures, the hardening of the tissue, and hyperkeratosis affect daily routine activities. Taking the body surface area as a measure of severity can sometimes be misleading. In clinical practice, the level of functional impairment should be taken into account rather than relying on traditional instruments to evaluate the severity. Palmoplantar psoriasis is usually managed with topical therapy as a first step. Systemic therapy is needed when the topicals fail or when the disease becomes more severe. Sometimes, biologic agents are required for adequate maintenance of clinical response.
Mizutani, Hitoshi; Yamanaka, Keiichi; Konishi, Hiroshi; Murakami, Takaaki
Investigation of psoriasis and pustular psoriasis is presently hampered by the lack of appropriate animal models. So far, more than ten models have been developed in mice by spontaneous gene mutations and by gene manipulation. However, none of them has satisfactorily reproduced the clinicopathological and immunopathological phenotypes of these diseases. Xenotransplantation techniques have been used for designing models of psoriasis vulgaris, in which CD4(+) T cells have been shown to play an important role. An ideal model for pustular psoriasis should have an immunological background and fulfill the diagnostic criteria of psoriasis.
... accompanied by fever, chills, severe itching, and fatigue. Inverse psoriasis. This causes smooth, raw-looking patches of ... a healthy weight. This decreases the risk of inverse psoriasis. Remind your child to keep skin clean ...
... get less sun. A moderate amount of direct sunlight can help to improve psoriasis. continue Symptoms People ... daily exposure to the sun, but too much sunlight can make psoriasis worse. More aggressive forms of ...
Mahajan, Rahul; Handa, Sanjeev
Psoriasis is a chronic inflammatory papulosquamous disease characterized by multiple remissions and relapses. For long, it was believed to be primarily a disorder of keratinization. However, the successful use of traditional immunosupressants and newer immunomodulatory agents in the treatment of psoriasis led to the belief that psoriasis is primarily a disease of Th1 cell immune dysregulation. Recent developments have brought up several new findings such as the role of Th17 cells and evidence of skin barrier dysfunction in psoriasis, akin to atopic dermatitis. The present review aims to focus on these new developments and explain the pathogenesis of psoriasis on the basis of currently available information.
Dawn, Aerlyn; Yosipovitch, Gil
Itch is an important, but underestimated symptom in psoriasis. Many therapies are available for pruritus; however, few are effective for psoriatic itch. Antipruritic therapies that are potentially effective in psoriasis include coal tar products, topical corticosteroids, topical salicylates, menthol and pramoxine, capsaicin, phototherapy, vitamin D analogs, topical immunomodulators, methotrexate, oral mirtazapine, and biologics. Using these therapies can benefit psoriasis patients in the outpatient clinical setting.
Furue, Masutaka; Kadono, Takafumi
Psoriasis is a chronic inflammatory skin disease characterized by a significant deterioration in the quality of life of affected individuals. Notably, psoriasis is significantly associated with cardiovascular and metabolic syndrome and other autoimmune disorders. Recent progress in biologic therapies has revealed the fundamental role of tumor necrosis factor-α, interleukin (IL)-23 and the IL-17A axis together with aberrant overproduction of epidermal IL-36γ in the pathogenesis of psoriasis. This review provides an update on the clinical, pathological and therapeutic advancements involving psoriasis.
Baliwag, Jaymie; Barnes, Drew H; Johnston, Andrew
Psoriasis is a common inflammatory skin disease with an incompletely understood etiology. The disease is characterized by red, scaly and well-demarcated skin lesions formed by the hyperproliferation of epidermal keratinocytes. This hyperproliferation is driven by cytokines secreted by activated resident immune cells, an infiltrate of T cells, dendritic cells and cells of the innate immune system, as well as the keratinocytes themselves. Psoriasis has a strong hereditary character and has a complex genetic background. Genome-wide association studies have identified polymorphisms within or near a number of genes encoding cytokines, cytokine receptors or elements of their signal transduction pathways, further implicating these cytokines in the psoriasis pathomechanism. A considerable number of inflammatory cytokines have been shown to be elevated in lesional psoriasis skin, and the serum concentrations of a subset of these also correlate with psoriasis disease severity. The combined effects of the cytokines found in psoriasis lesions likely explain most of the clinical features of psoriasis, such as the hyperproliferation of keratinocytes, increased neovascularization and skin inflammation. Thus, understanding which cytokines play a pivotal role in the disease process can suggest potential therapeutic targets. A number of cytokines have been therapeutically targeted with success, revolutionizing treatment of this disease. Here we review a number of key cytokines implicated in the pathogenesis of psoriasis.
Rosenberg, E. W.; Noah, P. W.; Skinner, R. B.
It has been suggested previously that psoriasis is best explained as a distinctive inflammatory response to a variety of microbial stimuli, all acting primarily through activation of the alternative complement pathway. For the past several years we have conducted a "Problem Psoriasis Clinic" based on that premise. Patients are questioned, examined, and subjected to microbiologic laboratory investigations in an attempt to identify possibly relevant microorganisms, and then are treated with antibiotics. This article lists the most commonly found microorganisms in psoriasis patients and describes the usual treatment for each. Results obtained with this approach compare favorably with those achieved with more usual anti-psoriasis treatments. We recommend that a microbiologic investigation and a trial of antimicrobial treatment should precede any plan to treat psoriasis patients with anything more than the simplest topical agents. PMID:8040907
Bonifati, C; Berardesca, E
Several tools have been introduced in clinical trials to quantify the severity and the response to a given therapeutic regimen of both psoriasis and psoriatic arthritis. Each method present specific advantages and limitations. Here we will discuss some of the most popular clinical outcome measures of both psoriasis (Psoriasis Severity Index, Physician Global Assessment, National Psoriasis Fundation-Psoriasis Score, Dermatology Life Quality Index) and psoriatic arthritis (American College Rheumatology response criteria, Psoriatic Arthritis Response Criteria).
Gerdes, S; Mrowietz, U; Boehncke, W-H
Psoriasis is a systemic chronic inflammatory disease associated with comorbidity. Many epidemiological studies have shown that psoriasis is associated with psoriatic arthritis as well as cardiovascular and metabolic diseases. Furthermore, obesity and psychological diseases such as depression and anxiety disorders are linked with psoriasis and play a central role in its management. The association of psoriasis and its comorbidity can be partly explained by genetic and pathophysiological mechanisms. Approximately 40 psoriasis susceptibility loci have been described with the majority linked to the innate and adaptive immune system. In some associated diseases, such as psoriatic arthritis, an overlap of their genetic susceptibility exists. Pathophysiologically the "psoriatic march" is a model that describes the development of metabolic and cardiovascular diseases due to the presence of underlying systemic inflammation. Dermatologists are the gatekeepers to treatment for patients with psoriasis. The early detection and the management of comorbidity is part of their responsibility. Concepts for the management of psoriasis and tools to screen for psoriatic comorbidity have been developed in order to support dermatologists in daily practice.
Machado-Pinto, Jackson; Diniz, Michelle dos Santos; Bavoso, Nádia Couto
Psoriasis is a chronic inflammatory disease associated with several comorbidities. A few decades ago, it was considered an exclusive skin disease but today it is considered a multisystem disease. It is believed that 73% of psoriasis patients have at least one comorbidity. Studies have demonstrated the association of psoriasis with inflammatory bowel disease, uveitis, psychiatric disorders, metabolic syndrome and its components and cardiovascular diseases. The systemic inflammatory state seems to be the common denominator for all these comorbidities. This work aims at presenting a review of the current literature on some new comorbidities that are associated with psoriasis as osteoporosis, obstructive sleep apnea and chronic obstructive pulmonary disease. While there is still controversy, many studies already point to a possible bone involvement in patients with psoriasis, especially in the male group, generally less affected by osteoporosis. Psoriasis and chronic obstructive pulmonary disease present some risk factors in common as obesity, smoking and physical inactivity. Besides, both diseases are associated with the metabolic syndrome. These factors could be potential confounders in the association of the two diseases. Further prospective studies with control of those potential confounders should be developed in an attempt to establish causality. Existing data in the literature suggest that there is an association between obstructive sleep apnea and psoriasis, but studies performed until now have involved few patients and had a short follow-up period. It is, therefore, premature to assert that there is indeed a correlation between these two diseases. PMID:26982772
Torres, Tiago; Sales, Rita; Vasconcelos, Carlos; Selores, Manuela
Psoriasis is a common, chronic and systemic inflammatory disease associated with several comorbidities, such as obesity, hypertension, diabetes, dyslipidaemia and metabolic syndrome, but also with an increased risk of cardiovascular disease, like myocardial infarction or stroke. The chronic inflammatory nature of psoriasis has been suggested to be a contributing and potentially independent risk factor for the development of cardiovascular comorbidities and precocious atherosclerosis. Aiming at alerting clinicians to the need of screening and monitoring cardiovascular diseases and its risk factors in psoriatic patients, this review will focus on the range of cardiometabolic comorbidities and increased risk of cardiovascular disease associated with psoriasis.
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Young, Melodie; Bergman, Martin Jan
Psoriasis is a dynamic systemic disease that can have a profound affect on a patient’s self-esteem. Fortunately, numerous therapeutic advances have been made over the last 10 years. In order to help patients manage their disease, healthcare providers should be aware of the modifiable risk factors that may exacerbate psoriasis. Additionally, exploring the impact the disease has on a patient and how it may change over their lifespan will help ensure appropriate therapies are used. Patients are unique so one medication will not fit all of our patients’ needs. In this paper, the authors look at available treatment options for psoriasis and psoriatic arthritis. Educating psoriasis patients, in addition to collaborating with patients and other healthcare providers, may help initiate therapies that will result in patients living their lives to the fullest. PMID:28360971
Mahil, Satveer K; Capon, Francesca; Barker, Jonathan N
Psoriasis is a common and debilitating immune-mediated skin disease with a complex genetic basis. Genetic studies have provided critical insights into the pathogenesis of disease. This article focuses on the results of genetic association studies, which provide evidence that psoriasis susceptibility genes are involved in innate and adaptive immunity and skin barrier functions. The potential for disease stratification and the development of more effective treatments with fewer side effects using genetic data are highlighted.
de Oliveira, Maria de Fátima Santos Paim; Rocha, Bruno de Oliveira; Duarte, Gleison Vieira
Psoriasis is a chronic inflammatory systemic disease. Evidence shows an association of psoriasis with arthritis, depression, inflammatory bowel disease and cardiovascular diseases. Recently, several other comorbid conditions have been proposed as related to the chronic inflammatory status of psoriasis. The understanding of these conditions and their treatments will certainly lead to better management of the disease. The present article aims to synthesize the knowledge in the literature about the classical and emerging comorbidities related to psoriasis. PMID:25672294
Islam, M T; Paul, H K; Zakaria, S M; Islam, M M; Shafiquzzaman, M
A cross-sectional study was conducted on 102 cases having clinical manifestation of psoriasis with a view to evaluate the epidemiological determinants of psoriasis. Psoriasis constituted 1.49% of the total dermatological disorder. Seventy patients (68.6%) were males and thirty two (31.4%) were females with a male to female ratio of 2.18:1. The mean age was 30.76±13.17 years in male and 26.94±14.94 years in female. Sixteen (15.7%) patients had one or more family member having psoriasis with male and female in equal frequency. Regarding precipitating factors, psoriasis was developed after trauma in 4.9%, infection 3.9%, stressful life events 6.9% and drugs 2.9%; and was exacerbated after trauma in 5.9%, infection 5.9%, stressful life events 35.3% and drugs 12.7%. The disease showed improvement in summer (27.5%) and found deteriorated in winter (47.1%). Sunlight had beneficial effect in 33.3% of cases. During pregnancy improvement was observed in 50% but flare up in 22.2% of cases. Fifty percent of patients were smokers, 41.2% were non-smokers and 13.7% were ex-smokers. Forty percent had Body Mass Index (BMI) between 22 to 26 Kg/m², 40.2% had less than 22 Kg/m² and 15.7% had above 26 Kg/m². It was concluded that the prevalence of psoriasis among dermatological patients was similar to results reported in Turkey and in Northern India. The precipitating factors, such as smoking, stressful life events, infection, trauma, sunlight, pregnancy, drugs, and seasonal variations could influence the development of psoriasis and affect its clinical expression.
Di Domizio, Jeremy; Conrad, Curdin; Gilliet, Michel
Psoriasis is a chronic autoimmune skin disease affecting approximately 2 % of the population with a major psychosocial and socioeconomic impact. A causal therapy leading to permanent cure is not available, and current treatments only lead to limited amelioration, and therefore new therapeutic targets need to be identified. Recent works demonstrated a predominant role of TH17 cells in the pathogenesis of psoriasis; yet the underlying molecular mechanisms driving the development of the disease are still largely elusive. Several mouse models of psoriasis including drug-induced models (topical application of imiquimod to the skin) and genetically engineered mice (constitutive activation of epidermal STAT3, epidermal deletion of JunB/c-Jun, and epidermal overexpression of Tie2) have been used to study the pathophysiology of the disease; however such models cannot fully recapitulate all molecular and cellular pathways occurring in human psoriasis. Xenotransplantation of human pre-psoriatic skin onto immunodeficient mice and triggering its conversion into a psoriatic plaque is the best model to dissect the mechanisms occurring during the development of human psoriasis. One model is based on the transplantation of human pre-psoriatic skin onto SCID mice followed by the transfer of activated autologous T cells. The ex vivo activation of T cells required to induce the psoriatic conversion of the graft limits the study of early events in the pathogenesis of psoriasis. Another model is based on transplantation of human pre-psoriatic skin onto AGR129 mice. In this model, the skin grafting is sufficient to activate human cells contained in the graft and trigger the conversion of the graft into a psoriatic skin, without the need of transferring activated T cells. Here we review the methodological aspects of this model and illustrate how this model can be used to dissect early events of psoriasis pathogenesis.
Psoriasis is one of the most common chronic inflammatory human skin diseases. Though clinically well characterized, the exact etiological and pathogenic mechanisms are still not known in detail. Current knowledge indicates distinct overlap to other inflammatory as well as autoimmune disorders. However, the one or more relevant autoantigens could not be characterized so-far. On the other side, several autoimmune diseases were shown to be associated with psoriasis. In addition, serological autoimmune phenomena, namely diverse circulating specific autoantibodies could be demonstrated in the past. A matter of current debate is if psoriasis is a primary autoimmune disease or secondarily evolving into autoimmunity as seen in other chronic inflammatory diseases. Related to this aspect is the concept of autoinflammation versus autoimmunity where psoriasis shares mechanisms of both entities. Though T-cells remain among the most important cellular players in the pathogenesis of psoriasis and current therapeutic strategies successfully target these cells or their products irrespective of these concepts, autoimmunity if relevant will add to the treatment armamentarium by using protective and prophylactic antigen-specific modalities.
Grozdev, Ivan; Korman, Neil; Tsankov, Nikolai
Psoriasis is an inflammatory immune-mediated disease that affects the skin and has pathogenic effects with systemic impact. The relationship between psoriasis and comorbidities remains controversial. The hypothesis of a causative role of psoriasis in its cardiovascular and metabolic comorbidities is based on pathophysiologic concepts establishing a link between chronic inflammation in psoriasis, endothelial dysfunction, formation of atherosclerotic plaques, and the different compounds of metabolic syndrome. Psoriasis management has to be multidisciplinary. It implicates identification and treatment of psychological disorders, addictions, and associated cardiovascular and metabolic diseases, together with improvement of quality of life of patients.
Lowe, N J; Lazarus, V; Matt, L
Retinoids are potent therapuetic agents that have been found to be effective in a variety of skin diseases. They are of benefit in various forms of severe psoriasis. With severe plaque psoriasis, they are used most effectively in combination with other forms of therapy, such as phototherapy. With generalized pustular psoriasis, they are effective monotherapy and are frequently helpful for the control of exfoliative psoriasis. A variety of new retinoid analogs have been studied in clinical investigations. This article discusses important aspects of the use of etretinate, isotretinoin, acitretin, and arotinoid ethyl ester in the treatment of severe forms of psoriasis.
Romaní de Gabriel, J
Darwinian medicine, or evolutionary medicine, regards some pathological conditions as attempts by the organism to solve a problem or develop defense mechanisms. At certain stages of human evolution, some diseases may have conferred a selective advantage. Psoriasis is a high-penetrance multigenic disorder with prevalence among whites of up to 3%. Psoriatic lesions have been linked with enhanced wound-healing qualities and greater capacity to fight infection. Leprosy, tuberculosis, and infections caused by viruses similar to human immunodeficiency virus have been postulated as environmental stressors that may have selected for psoriasis-promoting genes in some human populations. The tendency of patients with severe psoriasis to develop metabolic syndrome may reflect the body's attempt to react to environmental stresses and warning signs by triggering insulin resistance and fat storage.
The exact association between psoriasis and arthritis remains an enigma. Some investigators consider that the two disorders constitute a disease entity, psoriatic arthritis, while others support the thesis that psoriasis and arthritis are common diseases and occur simultaneously by chance. The author upholds the latter view as viable. To underscore his viewpoint he presents a comprehensive overview of the controversial opinions through an historical perspective as well as reporting on his epidemiologic and clinical findings from large population studies in the Netherlands. Therapeutic regimens for the management of both skin and joint problems are presented.
The development of targeted biologic agents has revolutionized the treatment of psoriasis. In this review, the authors focus on the published long-term (≥ one year) safety data for the use of tumor necrosis factor-α antagonists etanercept, infliximab, and adalimumab, as well as the IL-12/IL-23 antagonist ustekinumab, in adult patients with moderate-to-severe psoriasis. The efficacy of these currently available biologic therapies has been demonstrated in several studies, and their safety profiles are also reassuring. PMID:25741401
Lowes, Michelle A.; Suárez-Fariñas, Mayte; Krueger, James G.
The skin is the front line of defense against insult and injury and contains many epidermal and immune elements that comprise the skin-associated lymphoid tissue (SALT). The reaction of these components to injury allows an effective cutaneous response to restore homeostasis. Psoriasis vulgaris is the best-understood and most accessible human disease that is mediated by T cells and dendritic cells. Inflammatory myeloid dendritic cells release IL-23 and IL-12 to activate IL-17-producing T cells, Th1 cells, and Th22 cells to produce abundant psoriatic cytokines IL-17, IFN-γ, TNF, and IL-22. These cytokines mediate effects on keratinocytes to amplify psoriatic inflammation. Therapeutic studies with anticytokine antibodies have shown the importance of the key cytokines IL-23, TNF, and IL-17 in this process. We discuss the genetic background of psoriasis and its relationship to immune function, specifically genetic mutations, key PSORS loci, single nucleotide polymorphisms, and the skin transcriptome. The association between comorbidities and psoriasis is reviewed by correlating the skin transcriptome and serum proteins. Psoriasis-related cytokine-response pathways are considered in the context of the transcriptome of different mouse models. This approach offers a model for other inflammatory skin and autoimmune diseases. PMID:24655295
Farber, E.M.; Nall, L. )
Prevention and detection screening programs as a public health service in curtailing the ever-increasing incidence of all forms of skin cancer are reviewed. The effect of solar and artificial ultraviolet radiation on the general population and persons with psoriasis is examined. 54 refs.
Dantow, James E.
Psoriasis is a common skin disease with a variety of clinical presentations. Fortunately, many treatment options are available to the patient and to the physician. Topical, systemic, and physical therapies can be tailored to the patient's needs. Patient compliance and a knowledgeable, caring physician are vital to successful control of the disease. Continuing research offers hope for the chronically disabled. PMID:21221381
Interleukin-22 (IL-22) is an IL-10 family cytokine that was recently discovered to be released by T helper 17 (Th17) cells, Th22 cells, etc. Recently, there is emerging evidence that IL-22 is involved in the development and pathogenesis of psoriasis. For instance, IL-22 can inhibit keratinocyte terminal differentiation and can induce psoriasis-like epidermis alterations; serum IL-22 levels were correlated with the disease severity of psoriasis patients, and IL-22 mRNA was positively expressed in the psoriatic skin lesions, but negatively expressed in the normal controls. All these findings suggest that IL-22 may be implicated in psoriasis; therapeutics targeting IL-22 may have promise as a potential therapeutic target for treating psoriasis. In the present review, we summarize recent advances on the role of IL-22 in the pathogenesis and treatment of psoriasis.
Boehncke, W H
Co-existing inflammation and epidermal hyperproliferation characteristic for psoriasis have been shown to be reproducible in several animal models utilizing a variety of different strategies. These models highlight some points of the multicausal pathogenesis of psoriasis. Based on observations made in the animal models, a hypothesis is proposed for the pathogenesis of psoriasis, the elements of which can be tested in a recently established xenogeneic transplantation model.
Abreu, José Luís Pio Da Costa; Reis, José Pedro Gaspar Dos; Figueiredo, Américo Manuel Da Costa
Introduction and objective: Psoriasis is a chronic skin disease with a high impact on self-esteem and patients’ health-related quality of life. In the last decades some studies have pointed out mental disorders associated with psoriasis and the etiopathogenic mechanisms behind that co-existence. This work compiles psychopathology associated with psoriasis and further analyzes the etiopathogenesis of psoriasis and mental disorders. Methods: A systematic review of the literature was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and using the “5S” levels of organization of evidence from healthcare research, as previously described. Results: Psoriasis is linked with many mental disorders, both in the psychotic and neurotic sprectrum. Chronic stress diminishes hypothalamic-pituitary-adrenal axis and upregulates sympathetic-adrenal-medullary responses, stimulating pro-inflammatory cytokines. Then, it maintains and exacerbates psoriasis and some of its mental disorders. High levels of pro-inflammatory cytokines connect psoriasis, psychiatric conditions, and other comorbidities of psoriasis (such as atherosclerosis) within a vicious cycle. Furthermore, the etiopathogenesis of the link between each psychiatric comorbidity and psoriasis has its own subtleties, including the cooccurrence of other comorbidities, the parts of the body affected by psoriasis, treatments, and biological and psychosocial factors. Conclusion: The study of psychopathology can amplify our understanding about the etiopathogenesis of psoriasis and associated mental disorders. Patients would benefit from a psychodermatologic approach. The adequate treatment should take into account the mental disorders associated with psoriasis as well as the circumstances under which they occur. PMID:27386050
Pfeffer, J; Kaufmann, R; Boehncke, W-H
Psoriasis is characterized by a complex phenotype and pathogenesis along with polygenic determination. Several psoriasis animal models have only been able to incompletely reproduce the disease. A xenogeneic transplantation approach, grafting skin from psoriatic patients onto mice with a severe combined immunodeficiency (SCID), was the first to meet the criteria for a psoriasis model. During the last 10 years, this psoriasis SCID-mouse model not only allowed telling experiments focusing on pathogenetic aspects, but also proved being a powerful tool for drug discovery with a good predictive value.
Epstein, J. David
Psoriasis is a relatively common chronic dermatosis that is genetically determined and environmentally influenced. Because it is ideopathic, therapy is presently supportive, directed at optimal control, patient understanding, and prevention of recurrence. Because this multifactorial condition may involve skin and nails, musculoskeletal system, and psyche in various combinations and degrees, an organized co-operative team approach involving the patient, the family, and appropriately experienced health-care providers is most beneficial. Many topical and systemic medications, as well as physical therapeutic modalities, both established and innovative, are available for use sequentially or in various combinations to suite the individual and his/her particular psoriasis. This brief review will outline the better established dermatologic therapeutic principles and options currently available for this patient group. PMID:21263959
Lebwohl, M; Ting, P; Koo, J
Even before the recent development of biological agents, a long list of effective treatments has been available for patients with psoriasis. Topical therapies such as corticosteroids, vitamin D analogues, and retinoids are used for localised disease. Phototherapy including broadband ultraviolet B (UVB), narrowband UVB, PUVA, and climatotherapy are effective for more extensive disease. Systemic therapies such as methotrexate, retinoids, and ciclosporin are effective for patients with refractory or extensive cutaneous disease. PMID:15708945
Costa, Juliana Bastos; de Sousa, Virna Lygia Lobo Rocha; da Trindade Neto, Pedro Bezerra; Paulo Filho, Thomás de Aquino; Cabral, Virgínia Célia Dias Florêncio; Pinheiro, Patrícia Moura Rossiter
Norwegian scabies is a highly contagious skin infestation caused by an ectoparasite, Scarcoptes scabiei var. Hominis, which mainly affects immunosuppressed individuals. Clinically, it may simulate various dermatoses such as psoriasis, Darier's disease, seborrheic dermatitis, among others. This is a case report of a 33-year-old woman, immunocompetent, diagnosed with generalized anxiety disorder (cancer phobia), who had erythematous, well-defined plaques, covered with rupioid crusts, on her neck, axillary folds, breast, periumbilical region, groin area, besides upper back and elbows, mimicking an extremely rare variant of psoriasis, denominated rupioid psoriasis. PMID:23197214
... the left. It can cause a silvery-white scale and temporary hair loss as shown on the ... and inflamed. Dandruff-like flaking and silvery-white scale . Scalp psoriasis can look a lot like dandruff. ...
The scalp is involved in up to 80% of individuals with psoriasis. Eighty percent of those with scalp psoriasis experience a negative impact on quality of life. Topical treatment with corticosteroids with or without vitamin D3 analogues is the mainstay of treatment. Topical therapy most suitable for the scalp is formulated as a solution, lotion, gel, foam, spray, oil, or shampoo. Twice weekly maintenance in frequent relapsers may decrease the time to first relapse. Intralesional steroids, phototherapy and the excimer laser are occasionally used for resistant cases. In patients with moderate-to-severe psoriasis, apremilast, adalimumab and etanercept have been shown to significantly improve scalp psoriasis. They should be considered in patients who have failed topical therapy.
Zhu, J F; Kaminski, M J; Pulitzer, D R; Hu, J; Thomas, H F
Psoriasis is a chronic, remitting and relapsing inflammatory skin disorder with a strong genetic predisposition. Psoriasis affects 1-3% of the world's population in their early lives representing a disabling condition with significant social and economic impact. Despite a great deal of research on the etiology and tissue destruction mechanisms, the disease is not well understood. The purpose of this paper is to provide current information from the literature with a special focus on oral manifestations. The major signs and symptoms presented in the oral environment of a psoriasis patient may include geographic tongue, fissure tongue, gingival and/or mucosal lesions. Inflammatory temporomandibular joint lesions have been reported in less than 5% of psoriasis patients. Multiple treatment strategies, be they topical or systemic, have been applied to these patients for symptom relief but not for cure.
Balato, Anna; Scalvenzi, Massimiliano; Cirillo, Teresa; Gallo, Lucia; Ayala, Fabio; Balato, Nicola
Psoriasis is a chronic, immune-mediated, inflammatory systemic disease which targets primarily the skin. It presents a genetic basis, affecting 1 to 3% of the white population. Nevertheless, the existence of two psoriasis incidence peaks has been suggested (one in adolescence before 20 years of age and another in adulthood) onset may occur at any age, including childhood and adolescence, in which its prevalence ranges between 0.7% and 1.2%. As for adult psoriasis, pediatric psoriasis has recently been associated with obesity, metabolic syndrome, increased waist circumference percentiles, and metabolic laboratory abnormalities, warranting early monitoring and lifestyle modifications. In addition, due to psoriasis chronic nature and frequently occurring relapses, psoriatic patients tend to have an impaired quality of life, often requiring long-term treatment. Therefore, education of both pediatric patients and their parents is essential to successful and safe disease management. However, systemic treatment of children is challenging as the absence of standardized guidelines and the fact that evidence-based data form randomized controlled trials are very limited. This review shows an overview of the current understanding of the pathogenesis, comorbidities, differential diagnosis, treatment and prevention of pediatric psoriasis, also presenting with an emphasis on the necessity of an integrated treatment approach involving different specialists such as dermatologist, pediatricians, rheumatologists, etc.
Kaçar, Cahit; Sezer, Ilhan; Kocabaş, Hilal; Cay, Hasan Fatih; Cevikol, Can; Alpsoy, Erkan; Melikoğlu, Meltem Alkan; Akman, Ayşe
Psoriasis is a skin disorder that is associated with arthritis. Sacroiliac joint involvement is considered to be less frequent than the other types of psoriatic arthritis. Additionally, the psoriatic sacroiliitis is considered to be asymmetric in general. We aimed to define the frequency and type of sacroiliac involvement in patients with psoriasis. Patients with psoriasis were included the study. Characteristics of skin, nail and articular involvement were noted. Psoriasis area and severity index was calculated. Antero-posterior pelvic X-rays were obtained and graded by two rheumatologists and a radiologist independently. One hundred and thirty-three patients were included. Thirty-seven of patients (27%) have articular involvement symptomatically. The sacroiliac joint involvement was observed in 34 (26%) of patients. More than one-half of sacroiliac involvement was bilateral while less than one-half was in symptomatic patients regarding sacroiliitis. Fifty-seven percentages of all patients have psoriatic nail involvement. Sacroiliac joint involvement did not show any significant association with psoriatic nail involvement or the severity of skin disease. We found higher frequency of sacroiliac joint involvement and bilateral sacroiliitis in patients with psoriasis. This is in contrast to present information about the association of psoriasis and sacroiliitis. These findings need confirmation by further studies and with more sophisticated techniques such as magnetic resonance imaging.
Lehman, Julia S; Rahil, Anudeep K
While childhood psoriasis is fairly common, congenital psoriasis appears to be rare and has not been well characterized. We present a patient with histologically confirmed congenital psoriasis. By reviewing the literature, we aim to both define this disease and compare it to infantile and childhood psoriasis. Electronic searches found articles reporting patients with biopsy-proven congenital psoriasis. We recorded clinical features, such as family history, anatomic involvement, and disease severity. We compared these data with previous descriptions of infantile and childhood psoriasis. We included nine patients with congenital psoriasis in our analysis. No patient had a first-degree family history of psoriasis. While the face, scalp, chest, and trunk were frequently involved, the buttocks generally were spared. Several patients had persistent disease despite therapy. In this series, congenital psoriasis differed from infantile and childhood psoriasis in several respects. Specifically, congenital psoriasis was associated with a lower prevalence of relevant family history, which could increase over time, and a different pattern of anatomic involvement, which may reflect exposure to age-associated environmental factors. Although several patients with congenital psoriasis had severe disease, this likely represents publication bias. Additional reports of congenital psoriasis with extended follow-up are needed to better characterize this condition.
Goyal, N N; Wong, G A
We describe a case of a 67-year-old woman with a 1-year history of nail thickening and a non-itchy erythematous scaly eruption on the fingertips. She was diagnosed with psoriasis and started on methotrexate after having had no response to topical calcipotriol. The diagnosis was reviewed after it was revealed by another consultant that the patient's husband had been attending dermatology clinics for several years with chronic pruritus, which had been repeatedly thought to be due to scabies. Our patient was found to have crusted scabies after a positive skin scraping showed numerous mites. She was treated with topical permethrin, keratolytics and oral ivermectin. We also review the literature on crusted scabies and its management, with recommendations.
... fullstory_164498.html Men More Prone to Severe Psoriasis: Study Researchers say this may explain why more ... 2017 THURSDAY, April 6, 2017 (HealthDay News) -- Severe psoriasis is much more common in men than women, ...
Prakash, Anupam; Deepshikha
A 25-year-old male symptomatic of heart disease for four months presented with biventricular failure. Echocardiography revealed dilated cardiomyopathy. He had skin lesions for 10 years which were clinically and histopathologically identified as psoriasis. Association of cardiomyopathy with psoriasis is uncommon and intriguing. The link between dilated cardiomyopathy and psoriasis on a common inflammatory background is discussed. PMID:21063523
Creţu, Anca; Crihan, Elena; Oanţă, A; Sălăvăstru, Carmen; Brănişteanu, D; Brănişteanu, Daciana Elena
Psoriasis is a chronic inflammatory disease that can affect up to 1% of children. Genetic (family history of psoriasis) and environmental factors (bacterial or viral infections, stress, and trauma) are frequently involved in its occurrence. Napkin psoriasis is a particular form of psoriasis affecting mainly children younger than 2 years of age and can be classified together with other diseases under diaper rash. We present the case of a 4-month-old infant, born at term, naturally, weight and height within the normal range, who was brought to the Dermatology Clinic for the occurrence of erythematosquamous lesions in the anogenital area, buttocks and upper third of the thighs, with subsequent dissemination of lesions. The onset of symptoms began a few days after a respiratory tract infection. Initially he received treatment with systemic antibiotic and topical corticosteroid and antibiotic with unfavorable outcome. Laboratory tests revealed iron-deficiency anemia, leukocytosis, thrombocytosis, accelerated ESR, marked hepatic cytolysis, hyperphosphatemia and nasal carriage of Staphylococcus aureus. A systemic antihistamine and nonspecific desensitization treatment was administered. Topical treatment consisted in the removal of predisposing factors and irritants (diaper, urine) by rigorous hygiene, application of topical non-fluorinated cortico-steroid and use of emollients, with favorable course of the lesions. The peculiarity of the case is that the diagnosis of psoriasis was based on history, physical examination and laboratory tests, in the absence of a pathology examination to confirm the diagnosis. Pathology examination could not be performed due to patient's age as biopsy required general anesthesia.
Napolitano, Maddalena; Caso, Francesco; Scarpa, Raffaele; Megna, Matteo; Patrì, Angela; Balato, Nicola; Costa, Luisa
Psoriasis frequency ranges from 1 to 3 % in white population, and arthritis occurs in 10-40 % of psoriasis patients, representing a relevant health issue. Psoriatic arthritis (PsA) is an inflammatory arthropathy, associated with psoriasis, in which ocular-, intestinal-, metabolic-, and cardiovascular-related manifestations can variably coexist. In order to favor early PsA and psoriasis diagnosis, it is crucial to rule out other conditions that can resemble the disease and delay appropriate therapeutic approach. Therefore, the aim of this review is to focus on PsA and psoriasis differential diagnosis.
Dyring-Andersen, Beatrice; Skov, Lone; Zachariae, Claus
Psoriasis is a prevalent chronic inflammatory skin disease of unknown etiology. Recent advances in understanding the pathogenesis of psoriasis suggest that IL-17 is a key proinflammatory mediator present in the skin. Several agents targeting IL-17 or its receptor are in clinical trials for the treatment of psoriasis. This review focuses on the biological rationale and the results of clinical trials with ixekizumab, a humanized IgG4 monoclonal antibody. Ixekizumab binds the IL-17A homodimer, thereby blocking the binding of IL-17A to the IL-17 receptor. The currently available Phase I-III data indicate that ixekizumab is a promising drug, although long-term data of efficacy and safety are needed before ixekizumab and other IL-17 targeting therapeutics can find their place in clinical practice.
Kawamura, Ai; Ochiai, Toyoko
Pustular eruptions caused by anti-hypertension drugs are relatively rare. They have been reported with beta-adrenergic blocking agents, calcium channel blocker and angiotensin converting enzyme (ACE) inhibitors. Angiotensin II type 1 (AT 1) receptor antagonists, as a new class of drug for hypertension, has become an established and popular treatment. We describe a patient with generalized pustular psoriasis induced by candesartan cilexetil (AT1 receptor antagonist), who was previously diagnosed as flexural psoriasis. It is known that AT1 receptor antagonists do not increase the bradykinin level, inhibiting the renin-angiotensin system more potently than ACE inhibitor. But our results suggest that AT 1 receptor antagonists could have some ACE inhibitor potency as an up-regulator for bradykinin in our patient, with pustular eruptions developing on the psoriatic background. To the best of our knowledge, there have been no reported cases of pustular psoriasis associated with AT1 receptor antagonists.
Roberson, Elisha D.O.; Bowcock, Anne M.
Psoriasis is a common incurable inflammatory skin disease affecting 2–3% of the European population. Psoriatic skin contains large numbers of immune cells which produce many cytokines, chemokines and inflammatory molecules. The epidermis divides much faster than normal and has a defective outer layer or barrier which under normal circumstances protects from infection and dehydration. Psoriatic skin is characterized by a distinct set of inflammation and epidermal proliferation and differentiation markers, and it has not been clear if the genetic basis of psoriasis is due to defects of the immune system or the skin. One genetic determinant lies within the major histocompatibility complex class 1 region. Genome-wide association studies have revealed genetic susceptibility factors that play a role in the formation of immune cells found in psoriasis lesions. Others affect epidermal proliferation and the formation of the skin’s barrier. Hence, genetic components of both the immune system and the epidermis predispose to disease. PMID:20692714
de la Brassinne, M; Failla, V; Nikkels, Af
Psoriasis affects about 2 to 3% of the caucasian population. It is a chronic inflammatory disease affecting predominantly the skin with the involvement of autoimmune mediated mechanisms. Typical pathogenic features include an increased renewal of epidermal keratinocytes, the enlargement of the germinating compartment, papillomatosis, altered epidermal differentiation, angiogenesis, lymphangiogenesis and inflammatory infiltration. Several types of psoriasis are distinguished and may be present simultaneously in some patients. Up to 20 candidate genes have been evidenced in psoriasis. Genetic variability explains different types of the disease and influences response to therapeutics. Furthermore, psoriasis is triggered or aggravated by infections, traumatisms, medications, stress, tobacco, alcohol and endocrine factors. Severe psoriasis is frequently associated with co-morbidities as obesity, diabetes, metabolic syndrome and cardiovascular diseases. For this reason, the similar pathogenic mechanisms of psoriasis and other IMID's (Immune Mediated Inflammatory Diseases) and the use of systemic treatments shared with other specialties, an updated vision of psoriasis for the internist is mandatory.
Danilenko, D M
Psoriasis is the most common autoimmune disease in man and is characterized by focal to coalescing raised cutaneous plaques with consistent scaling and variable erythema. The specific pathogenesis of psoriasis is not completely understood, but the underlying mechanisms involve a complex interplay between epidermal keratinocytes, T lymphocytes as well as other leukocytes (including dendritic cells and other antigen presenting cells [APCs]), and vascular endothelium. Mirroring the complexity of mechanisms that underlie psoriasis, there are a relatively large number of models of psoriasis. Each model is based on a slightly different pathogenic mechanism, and each has its similarities to psoriasis as well as its limitations. In general, psoriasis models can be very broadly divided on the basis of the pathogenic mechanisms that interplay to cause psoriasis, with the addition of several relatively poorly defined spontaneous murine mutant models. Other than the spontaneous mutant models, murine models of psoriasis can be divided into those that are genetically engineered (transgenic and knockout-with manipulation of either the epidermis, leukocytes, or the endothelium), and those that are induced (either by immune transfer or by xenotransplantation of skin from psoriatic patients). In addition to the murine models, in vitro human epidermal models have recently become more widely utilized. While no one single model of psoriasis is ideal, many have proven to be extremely valuable in investigating and better understanding the molecular mechanisms that underlie the complex interplay between epidermal keratinocytes, the innate and adaptive immune system, and the vascular endothelium in psoriasis.
Dogra, Alka; Arora, Amanjot Kaur
Nail involvement is an extremely common feature of psoriasis and affects approximately 10-78% of psoriasis patients with 5-10% of patients having isolated nail psoriasis. However, it is often an overlooked feature in the management of nail psoriasis, despite the significant burden it places on the patients as a result of functional impairment of manual dexterity, pain, and psychological stress. Affected nail plates often thicken and crumble, and because they are very visible, patients tend to avoid normal day-to-day activities and social interactions. Importantly, 70-80% of patients with psoriatic arthritis have nail psoriasis. In this overview, we review the clinical manifestations of psoriasis affecting the nails, the common differential diagnosis of nail psoriasis, Nail Psoriasis Severity Index and the various diagnostic aids for diagnosing nail psoriasis especially, the cases with isolated nail involvement. We have also discussed the available treatment options, including the topical, physical, systemic, and biological modalities, in great detail in order to equip the present day dermatologist in dealing with a big clinical challenge, that is, management of nail psoriasis. PMID:25071247
Wilson, P B; Bohjanen, K A; Ingraham, S J; Leon, A S
Psoriasis is a common, chronic inflammatory skin disease that can cause significant discomfort and impairment to quality of life. Recent research indicates that individuals with moderate-to-severe psoriasis are likely at greater risk for chronic cardiometabolic co-morbidities such as cardiovascular disease, type 2 diabetes, obesity and metabolic syndrome. Physical activity can be an effective primary and adjunctive treatment for these maladies in other populations. Unfortunately, only a limited number of studies have examined physical activity in psoriasis, which are limited by poor design and lack of validated physical activity assessment methodologies. A variety of data suggest shared physiologic pathways between physical activity, psoriasis, and psoriasis cardiometabolic co-morbidities. Increased adiposity, inflammation, oxidative stress, adhesion molecules and lipids are physiologically linked to psoriasis, the risk of psoriasis cardiometabolic co-morbidities, and low levels of physical activity. In addition, epigenetic pathways are involved in psoriasis and could be influenced by physical activity. The physical and psychosocial impairments common in psoriasis may make it difficult to participate in regular physical activity, and future studies should aim to determine if physical activity interventions improve functioning and reduce co-morbidities in psoriasis.
Gordon, Kenneth B
Knowledge about the pathophysiology of psoriasis has evolved substantially in recent years, since the identification of the T helper 17 (Th17) cells. Cytokines produced by these cells appear to play major roles in psoriatic inflammation. The cytokine interleukin (IL)-23 appears to promote regulatory T cells to differentiate into Th17 cells. Available and investigational therapies act on targets within these pathways.
Gligora, M; Arzensek, J; Rems, D; Troskot, N; Banjanin, M
This study was performed during a 10-year period at several hospitalization centres from various districts in Slovenia and Croatia. The number of elderly patients, above 65 years, compared with the total number of inpatients in the aforementioned departments and clinics in the course of 10 years ranged from 12% to 25%. The percentage of psoriatics, according to the total number of elderly in-patients was 1.8% in Rijeka, 2.3% in Maribor, 4% in Celje and up to 6.1% in Zagreb. On the whole, 241 psoriatics (165 males and 76 females) were treated in the above centres during a 10-year period. The number of patients with psoriasis vulgaris was 214 on the whole; among them 13 presented with psoriasis arthropatica, 6 with pustular psoriasis (one with the palmo-plantar variety) and 8 with erythrodermic psoriasis. Retinoids (etretinate) increase serum lipids and decrease HDL cholesterol in the long-term treatment, thus increasing the already existing risk of atherosclerosis and of coronary heart diseases in older life age. Serum lipids, HDL and LDL cholesterol and A and B apolipoprotein are therefore monitorized each week when etretinate has been given.
Schons, Karen Regina Rosso; Knob, Cristiane Faccin; Murussi, Nádia; Beber, André Avelino Costa; Neumaier, Walter; Monticielo, Odirlei André
Nails are considered epidermal appendages, and as such, are commonly affected in patients with psoriasis, 80% of whom are likely to develop nail psoriasis as a result of their condition. Two patterns of nail disorders have been shown to be caused by psoriasis. Nail matrix involvement can result in features such as leukonychia, pitting (punctures or cupuliform depressions), red spots in the lunula and crumbling. Nail bed involvement, on the other hand, can cause onycholysis, salmon or oil-drop patches, subungual hyperkeratosis and splinter hemorrhages. Nail disease causes aesthetic and functional impairment, and is indicative of more severe forms of psoriasis as well as of joint involvement. The treatment for nail psoriasis involves behavioral interventions, topical medications, or systemic therapy in case of extensive skin or joint involvement. This article presents a review of the main features of nail psoriasis, its clinical presentation, diagnostic and assessment methods, clinical repercussions, and of its available treatment options. PMID:24770509
Schons, Karen Regina Rosso; Knob, Cristiane Faccin; Murussi, Nádia; Beber, André Avelino Costa; Neumaier, Walter; Monticielo, Odirlei André
Nails are considered epidermal appendages, and as such, are commonly affected in patients with psoriasis, 80% of whom are likely to develop nail psoriasis as a result of their condition. Two patterns of nail disorders have been shown to be caused by psoriasis. Nail matrix involvement can result in features such as leukonychia, pitting (punctures or cupuliform depressions), red spots in the lunula and crumbling. Nail bed involvement, on the other hand, can cause onycholysis, salmon or oil-drop patches, subungual hyperkeratosis and splinter hemorrhages. Nail disease causes aesthetic and functional impairment, and is indicative of more severe forms of psoriasis as well as of joint involvement. The treatment for nail psoriasis involves behavioral interventions, topical medications, or systemic therapy in case of extensive skin or joint involvement. This article presents a review of the main features of nail psoriasis, its clinical presentation, diagnostic and assessment methods, clinical repercussions, and of its available treatment options.
Vasku, Vladimir; Bienertova Vasku, Julie; Slonková, Veronika; Kanková, Katerina; Vasku, Anna
The expression of matrix metalloproteinase-2 was observed to be significantly upregulated in psoriasis. The aim of this study was to associate the DNA polymorphic variants in MMP-2 promoter gene with psoriasis and/or with psoriasis phenotypes related to psoriasis and comorbid heredity. In the total of 582 Czech Caucasian individuals (386 patients with psoriasis and 196 controls of similar age and sex distribution without personal or family history of chronic disease of the skin), four MMP-2 promoter polymorphisms (-1575G/A, -1306C/T, -790T/G and -735C/T) were detected by PCR methods. A significant association of GG genotype of -790 MMP-2 polymorphism with psoriasis was observed (Pcorr = 0.04). Although no significant case-control differences in frequency of associated GG(-1575)CC(-1306)TT(-790) MMP-2 promoter genotype were observed, the genotype was found to be significantly less frequent in patients with family history of psoriasis (close as well as distant), family history of diabetes and personal history of allergy (2/11 vs. 55/32, odds ratio (OR) for GGCCTT 0.11, 95% confidential interval 0.02-0.50, Pcorr = 0.01). The significant difference between psoriatic patients with positive anamnestic data on diabetes, psoriasis and allergy compared with psoriatic patients that have only positive family history of diabetes was also observed (2/11 vs. 38/31, P = 0.009, Pcorr = 0.04; OR 0.15, 95% CI = 0.03-0.72 for psoriatic patients with GGCCTT genotype and family history of psoriasis, diabetes and personal history of allergy). To conclude, the associated GGCCTT genotype in the promoter of MMP-2 gene was less frequent in patients with positive family history of psoriasis, diabetes and personal history of allergy compared with psoriatic patients without them (2/11 vs. 68/57, P = 0.007, Pcorr = 0.04; OR = 0.15, 95% CI = 0.03-0.72 for psoriatic patients with family history of psoriasis and diabetes and with allergy). Based on our results, we suggest that the MMP-2 located in
Lobato, Laís Cruz; Coutinho, Jéssica Castiel; Frota, Maria Zeli Moreira; Schettini, Antonio Pedro Mendes; Santos, Mônica
Psoriasis is a chronic inflammatory disease of multifactorial etiology influenced by genetic, immunological, and environmental factors. We report the case of a patient with psoriasis for more than 25 years who developed hyperuricemia and chronic tophaceous gout with unusual appearance. In psoriasis, hyperuricemia may occur by increased epidermal cell turnover, which accelerates purine metabolism and has uric acid as the product of its catabolism. The association of psoriasis with hyperuricemia can trigger the onset of gouty arthritis, and pose a greater risk of developing other inflammatory comorbidities. Therefore, it is important to periodically investigate uric acid levels in order to treat changes triggered by hyperuricemia. PMID:28225966
Napolitano, Maddalena; Megna, Matteo; Balato, Anna; Ayala, Fabio; Lembo, Serena; Villani, Alessia; Balato, Nicola
Psoriasis is a chronic, immune-mediated, inflammatory skin disease, affecting 1-3% of the white population. Although the existence of two psoriasis incidence peaks has been suggested (one in adolescence before 20 years of age and another in adulthood), its onset may occur at any age, including childhood and adolescence, in which the incidence is now estimated at 40.8 per 100,000. As for adult psoriasis, pediatric psoriasis has recently been associated with obesity, metabolic syndrome, increased waist circumference percentiles and metabolic laboratory abnormalities, warranting early monitoring and lifestyle modifications. In addition, due to psoriasis' chronic nature and frequently occurring relapses, psoriatic patients tend to have an impaired quality of life, often requiring long-term treatment. Therefore, education of both pediatric patients and their parents is essential to successful and safe disease management. Given the lack of officially approved therapies, the very limited evidence-based data from randomized controlled trials, and the absence of standardized guidelines, to date, pediatric psoriasis treatment is primarily based on published case reports, case series, guidelines for adult psoriasis, expert opinions and experience with these drugs in other pediatric disorders coming from the disciplines of rheumatology, gastroenterology and oncology. This review focuses on the use of systemic treatments in pediatric psoriasis and their specific features, analyzing the few literature evidences available, expanding the treatment repertoire and guiding dermatologists in better managing of recalcitrant pediatric psoriasis.
Lobato, Laís Cruz; Coutinho, Jéssica Castiel; Frota, Maria Zeli Moreira; Schettini, Antonio Pedro Mendes; Santos, Mônica
Psoriasis is a chronic inflammatory disease of multifactorial etiology influenced by genetic, immunological, and environmental factors. We report the case of a patient with psoriasis for more than 25 years who developed hyperuricemia and chronic tophaceous gout with unusual appearance. In psoriasis, hyperuricemia may occur by increased epidermal cell turnover, which accelerates purine metabolism and has uric acid as the product of its catabolism. The association of psoriasis with hyperuricemia can trigger the onset of gouty arthritis, and pose a greater risk of developing other inflammatory comorbidities. Therefore, it is important to periodically investigate uric acid levels in order to treat changes triggered by hyperuricemia.
Klemp, P.; Staberg, B.
The disappearance rate of /sup 133/Xe was studied in 20 patients with psoriasis vulgaris, using an epicutaneous labeling technique in involved skin lesions or normal-appearing skin of the proximal extensor site of the forearm. Control experiments were performed in 10 normal subjects. Calculations of the cutaneous blood flow (CBF) in psoriatic skin lesions were performed using a tissue-to-blood partition coefficient for /sup 133/Xe, lambda c,pso, of 1.2 ml/100 g/min. lambda c,pso was estimated after the relative content of water, lipids, and proteins had been analyzed in psoriatic skin biopsies of 6 patients with untreated psoriasis. The mean relative content of water was markedly reduced to 23.5 +/- 1.5% (SEM), and lipids and proteins were markedly increased to 2.5 +/- 0.7% and 74.0 +/- 2.2, respectively, compared to previously published data for normal skin (water 72.5%, lipids 1%, proteins 26.5%). Mean CBF in untreated psoriatic skin was 63.5 +/- 9.0 ml/100 g/min. This was significantly higher than the mean CBF in 10 normal subjects, 6.3 +/- 0.5 ml/100 g/min (p much less than 0.0001). Mean CBF in normal-appearing skin in patients with psoriasis was 11.0 +/- 1.3 ml/100 g/min. This was significantly higher than CBF in normal subjects (p less than 0.0002).
Marcinkiewicz, Kamil; Bergler-Czop, Beata; Brzezińska-Wcisło, Ligia
Introduction Psoriasis is associated with a major additional psychological burden. Aim To investigate whether the extent of skin involvement, stigmatization, and perceived social support are related to depressive symptoms in psoriasis patients. Material and methods One hundred and forty-eight psoriasis patients completed in the BSA, the Beck Depression Inventory, Stigmatization Scale, and Multidimensional Scale of Perceived Social Support. Results Almost 13% of participants obtained a BDI total score indicating moderate depressive symptoms. The results of regression analysis revealed that greater depression severity in psoriasis patients is associated with higher levels of psoriasis-related stigma, lower perceived social support, female gender and a shorter duration of the disease, explaining 43% of the variance of depression. The stigmatization was the most powerful predictor of depressive symptoms for psoriasis patients and accounted for 33% of the variance. Conclusions The extent of psoriasis does not directly lead to mood disturbance in these patients. Rather, social stigma accounted for this relationship. Strategies for reducing the stigma attached to patients with psoriasis are required. PMID:28261029
Garg, Tarun; Rath, Goutam; Goyal, Amit K
Psoriasis is a chronic disorder with erythematous scaly patches, which typically affects the exposed surfaces of the body and scalp. Various factors such as bacterial infection, genetic and environmental factors, and immune disorders play an important role in causing psoriasis. Different types of psoriasis can be observed, such as guttate psoriasis, inverse psoriasis, pustular psoriasis, and psoriatic arthritis. Various ancient, topical, and systemic approaches have been used to control the disease, but have failed to achieve a complete reduction of the disease, besides causing toxic effects. Therefore, our main aim in this review article is to introduce the different advanced nanotechnological approaches for effective treatment of psoriasis.
Kavli, G; Førde, O H; Arnesen, E; Stenvold, S E
In a survey for coronary risk factors 14 667 adult men and women answered a questionnaire on lifestyle, diet, and health, including whether they had psoriasis. The overall prevalence of psoriasis was 4.79% in men and 4.85% in women. The data showed an increasing incidence of psoriasis. The association with family history, lifestyle, diet, and health was explored by multiple regression analysis. The occurrence of psoriasis in first degree relatives contributed to more than 90% of the explained variance for both sexes. Of the other variables, only the positive association with rheumatoid arthritis was significant in both sexes. It is concluded that the examined environmental factors have only minor effects on the prevalence of psoriasis.
Nakamura, Mio; Farahnik, Benjamin; Bhutani, Tina
Phototherapy involves repeated exposure of the skin to ultraviolet light to treat various inflammatory skin conditions such as psoriasis. Recent studies have identified specific immunologic effects of phototherapy that may underlie phototherapy efficacy. Furthermore, recent advancements have been made in developing safe and effective targeted phototherapy modalities for difficult-to-treat areas such as scalp psoriasis. Targeted phototherapy in the form of the excimer laser holds potential for more aggressive, effective treatment and long-lasting remission of psoriasis. Phototherapy is now also used successfully with biologic agents as combination therapy to treat recalcitrant psoriasis. Therefore, though one of the oldest therapeutic modalities for psoriasis, phototherapy remains a mainstay treatment with promise for further advancement. PMID:27499849
Shelling, Michael L; Federman, Daniel G; Prodanovich, Srdjan; Kirsner, Robert S
Psoriasis is an immune disease most commonly recognized for its skin and joint manifestations. These produce significant physical, social, and psychological distress in affected patients and resultant reductions in their quality of life. As expected, these concerns are vital in providing symptomatic improvement and in selecting an individualized therapy. Yet, the approach in management of these patients is likely to change given the growing body of evidence linking psoriasis and vascular disease. Stemming from an anecdotally described relationship, the association between psoriasis and vascular disease has become a focus of current research to further elucidate the pathophysiology underlying and connecting these two diseases. This article includes a review of the classical cardiovascular risk factors, the atherothrombotic markers, and the environmental stressors associated with psoriasis, as well as a critical review of the observed vascular diseases, the proposed mechanism of atherosclerosis, and the benefits of treatment of psoriasis.
Broshtilova, Valentina; Lozanov, Valentina; Miteva, Ljubka
Introduction: Polyamines – putrescine, spermidine and spermine are polycationic compounds ubiquitous for all living organisms. They are essential for the cell growth and differentiation, the control of cell cycle progress, apoptosis, and cancerogenesis. Accumulated scientific evidence suggests the central role of polyamines in the process of keratinocytic proliferation, differentiation, and regulation. Objective: To elucidate the polyamine metabolic changes that occur in benign keratinocytic proliferation. Fifty eight patients were enrolled in the study, 31 with plaque-form of psoriasis vulgaris, which had been referred to as a model of benign keratinocytic proliferation, and 27-healthy controls. Materials and Methods: An original, innovative chromatographic method was used to detect the levels of putrescine, spermidine, and spermine in all skin samples. Results: Were significantly proven (P < 0.05). No difference was found between the polyamines levels of non-lesional psoriatic skin and healthy controls. Psoriatic lesions showed a two-time higher concentration of all polyamines in lesional, compared to non-lesional skin. Spermine had the highest concentration and highest proliferation trend, which demonstrated the importance of propylamine synthesis in the pathogenesis of psoriasis. Spermine highest concentrations suggested the leading role of adenosine methionine decarboxylase (AMDC) in the pathogenesis of benign keratinocytic proliferations. Conclusions: Non-lesional skin in psoriatic patients did not show latent changes in polyamine metabolism. Psoriatic lesions demontrated two-time higher levels of the most essential biogenic polyamines compared to healthy controls. The highest level of spermine proved the crucial role of AMDC in the polyamine metabolism changes in psoriasis. Future therapeutic approaches should be focused on reduction of exogenic spermine intake, utilizing new spermine blockers, and synthesis of AMDC inhibitors. PMID:23919004
Arcilla, John; Joe, Daniel; Kim, Johnathan; Kim, Yohanan; Truong, VuAnh N.; Jaipaul, Navin
Erythroderma is a rare potentially deadly exfoliative dermatitis characterized by diffuse cutaneous erythema which may be associated with multi-organ dysfunction. Therefore, it is imperative to recognize and treat it promptly. Erythrodermic psoriasis is the most common form of erythroderma. Management of this condition is largely based on aggressive supportive care and the use of anti-inflammatory immunosuppressive and biologic agents. We describe a case of psoriatic erythroderma which was triggered by withdrawal from systemic steroids and successfully treated with apremilast and cyclosporine. Apremilast induced atrial fibrillation limited its continued use after the initial response period. PMID:27942369
Dogra, Sunil; Mahajan, Rahul
On the basis of current evidence derived from hospital-based studies, mostly from North India, the prevalence of psoriasis in adults varies from 0.44 to 2.8%, with a much lower prevalence in children. The peak age at onset in adults is in the third and fourth decade of life, with a slight male preponderance. It is recommended that population-based large epidemiologic studies should be undertaken in different parts of the country for estimating the correct prevalence of psoriasis in general population. Chronic plaque-type psoriasis is the most common morphologic presentation of psoriasis, accounting for more than 90% of all cases. Other morphologic variants that deserve special mention include palmoplantar psoriasis, pustular psoriasis, and recalcitrant psoriasis. For epidemiologic purposes, psoriasis can be classified into early and late onset psoriasis. Psoriasis can be classified on the basis of morphology and extent of involvement into localized and widespread disease. For the purpose of clinical trials, psoriasis may be classified as mild psoriasis, moderate psoriasis, and severe psoriasis. The literature shows that there is a significant risk of psoriatic arthritis (7–48%) in patients with plaque-type psoriasis. Hence, it is recommended to evaluate for its presence by detailed history taking and clinical examination, and if necessary, by appropriate radiological investigations. Evidence on the association between plaque-type psoriasis and cardiovascular disease risk factors and ischemic heart disease isinconsistent. On the basis ofavailable evidence, it is prudent to proactively look for metabolic syndrome, dyslipidemia, and obesity, especially in patientswith severe psoriasis (Level 1+ evidence based on systematic reviews and meta-analysis). Based on the current evidence, the psoriasis area severity index appears to be the most valid and reproducible clinical severity score in the management of adult patients with plaque-type psoriasis. PMID:27990381
Burness, Celeste B; McKeage, Kate
Adalimumab (Humira(®)) is a fully human monoclonal antibody against tumour necrosis factor (TNF), formulated for subcutaneous administration. It is well established in the treatment of adults with moderate-to-severe chronic plaque psoriasis and has recently received approval in the EU for the treatment of severe chronic plaque psoriasis in children and adolescents from 4 years of age. In a phase III trial in paediatric patients, a significantly greater proportion of patients receiving adalimumab 0.8 mg/kg (to a maximum of 40 mg) every other week (eow) achieved a ≥75 % improvement from baseline in Psoriasis Area and Severity Index than those receiving methotrexate after 16 weeks of treatment. In adults, well-designed randomized clinical trials demonstrated that adalimumab 40 mg eow effectively reduced the signs and symptoms of psoriasis and improved dermatology-specific and general measures of health-related quality of life, with these benefits sustained during long-term treatment. Adalimumab was generally well tolerated, compared with placebo or methotrexate, during clinical trials in paediatric and adult patients with chronic plaque psoriasis. Thus, adalimumab remains an important treatment strategy in adults with moderate-to-severe chronic plaque psoriasis and provides a promising new systemic treatment option for children and adolescents from 4 years of age with severe psoriasis.
Jain, Sonia P.; Gulhane, Sachin; Pandey, Neha; Bisne, Esha
Psoriasis is an autoimmune chronic inflammatory skin disease known to be triggered by streptococcal and HIV infections. However, human papilloma virus infection (HPV) as a triggering factor for the development of psoriasis has not been reported yet. We, hereby report a case of plaque type with inverse psoriasis which probably could have been triggered by genital warts (HPV infection) and discuss the possible pathomechanisms for their coexistence and its management. PMID:26692619
Raposo, Inês; Torres, Tiago
For many years psoriasis was considered an inflammatory condition restricted to the skin. However, nowadays it is considered an immune-mediated, systemic inflammatory condition associated with numerous medical comorbidities, particularly cardiometabolic diseases, and overall cardiovascular mortality. Several studies have suggested that psoriasis may be an independent risk factor for atherosclerosis, indicating that psoriasis itself poses an intrinsic risk for cardiovascular disease, probably due to the disease's inflammatory burden. However, other causes beyond systemic inflammation and traditional cardiovascular risk factors may be implicated in cardiovascular disease in psoriasis. Recently, epicardial adipose tissue, an emerging cardiovascular risk factor, has been shown to be increased in psoriasis patients and to be associated with subclinical atherosclerosis, providing another possible link between psoriasis and atherosclerosis. The reason for the increase in epicardial adipose tissue in patients with psoriasis is unknown, but it is probably multifactorial, with genetic, immune-mediated and behavioral factors having a role. Thus, along with the increased prevalence of cardiometabolic risk factors and systemic inflammation in psoriasis, epicardial adipose tissue is probably another important contributor to the higher cardiovascular risk observed in psoriasis.
Psoriasis is a chronic recurrent inflammatory skin disease with prevalence of 1-3%. Nail psoriasis affects 10-90% of patients with plaque psoriasis. The aim of the article is to review the literature for the correlation between nail psoriasis and psoriatic arthritis (PsA) to provide rheumatologists a short review on features of nail psoriasis, methods of their assessment and possible clinical repercussions. The PubMed database was searched using the key words 'nail psoriasis' and 'psoriatic arthritis'. Psoriasis involving the nail matrix shows up as changes such as pitting, Beau lines, leukonychia, red spots in the lunula, or nail plate crumbling. Nail bed psoriasis manifests as onycholysis, oil drops (or salmon patches), dyschromia, splinter hemorrhages, or subungual hyperkeratosis. Nail psoriasis and psoriatic lesions in the gluteal cleft and on the scalp usually accompany PsA, especially in adult men.
Molina-Leyva, Alejandro; Leyva-Garcia, Ana; Ruiz-Carrascosa, Jose Carlos; Naranjo-Sintes, Ramon; Jiménez-Moleon, Jose Juan
Psoriasis is a disease that affects many facets of life. Psoriasis patients have needs that cannot be addressed within the traditional consultation structure. Although the Internet provides a number of health resources, the quality of the information is variable, and many sites are not editorially independent. After reviewing the contents available on the Internet related to psoriasis, the staff of the psoriasis unit at San Cecilio University Hospital (Granada, Spain) developed a Web site to meet the needs of psoriasis patients. A group of 241 patients who attended a follow-up visit to our psoriasis unit evaluated the Web site and provided feedback through an online survey. The result of the Web development process was the creation of "Psoriasis365" (https://sites.google.com/site/psoriasis365/). Overall, the Web site achieved high scores, the most popular section being "research." These results suggest that the Web site can complement the healthcare of psoriasis patients and is potentially useful for research purposes.
Nascimento, Bianca Angelina Macêdo do; Carvalho, Alessandra Haber; Dias, Carolina Moraes; Lage, Thaiane Lima; Carneiro, Clívia Maria Oliveira; Bittencourt, Maraya de Jesus Semblano
Lithium has been implicated in the exacerbation of pre-existing psoriasis, in the induction of psoriasis on previously uninvolved skin of psoriasis patients, and in the triggering of psoriasis for the first time in patients without a personal or family history. Lithium-induced psoriasis (and its resistance to treatment) is one of the major reasons for noncompliance in patients treated with lithium. We describe a male patient who developed generalized ostraceous psoriasis whose clinical appearance mimicked dermatitis neglecta, 10 months after starting therapy with lithium.
do Nascimento, Bianca Angelina Macêdo; Carvalho, Alessandra Haber; Dias, Carolina Moraes; Lage, Thaiane Lima; Carneiro, Clívia Maria Oliveira; Bittencourt, Maraya de Jesus Semblano
Lithium has been implicated in the exacerbation of pre-existing psoriasis, in the induction of psoriasis on previously uninvolved skin of psoriasis patients, and in the triggering of psoriasis for the first time in patients without a personal or family history. Lithium-induced psoriasis (and its resistance to treatment) is one of the major reasons for noncompliance in patients treated with lithium. We describe a male patient who developed generalized ostraceous psoriasis whose clinical appearance mimicked dermatitis neglecta, 10 months after starting therapy with lithium. PMID:26312715
Psoriasis is a partly inflammatory hyperproliferative skin disease. Its origin has not been clarified yet, but numerous immunologic, bioregulatory, and biochemical changes accompanying this disease are known. Many cell types and a number of immunity system factors forming a perfectly interlinked network are involved in the immunity processes in the psoriasis-affected skin. This network is a common place where antipsoriatics operate. There is no therapeutic means known which guarantees permanent elimination of psoriasis symptoms. External as well as internal therapeutic methods having effect on the pathogenetic processes at various levels are combined. UV radiation treatment (SUP), sometimes combined with psoralens (PUVA), tar, and dithranol are some of the classical methods of psoriasis treatment. Topical medicamentous treatment with corticoids, vitamin D derivatives, salicylic acid, urea, and tar plays an important part here.
González-Parra, E; Daudén, E; Carrascosa, J M; Olveira, A; Botella, R; Bonanad, C; Rivera, R
Psoriasis is a chronic inflammatory disease that has been associated with cardiovascular and metabolic comorbidities, particularly in young patients and patients with more severe forms of the disease. Recent studies have also linked psoriasis to kidney disease, and this would seem only logical, as the kidney is both a target of classic cardiovascular risk factors and susceptible to the toxic effects of some of the traditional drugs used to control psoriasis. In this article, we would like to draw readers' attention to this recently described comorbidity and stress the importance of early detection, as once chronic kidney disease develops, it cannot be reversed. When evaluating patients with psoriasis, particularly when they are candidates for systemic therapy, we believe it is important to order laboratory tests including glomerular filtration rate and a simple urine test to screen for albuminuria (albumin/creatinine ratio).
Akbulut, Sabiye; Gür, Günes; Topal, Firdevs; Topal, Fatih Esad; Alli, Nuran; Saritas, Ülkü
Background The possible relationship between psoriasis and coeliac disease (CD) has been attributed to the common pathogenic mechanisms of the two diseases and the presence of antigliadin antibodies in patients has been reported to increase the incidence of CD. Objective The aim of this report was to study CD-associated antibodies serum antigliadin antibody immunoglobulin (Ig)A, IgG, anti-endomysial antibody IgA and anti-transglutaminase antibody IgA and to demonstrate whether there is an increase in the frequency of those markers of CD in patients with psoriasis. Methods Serum antigliadin antibody IgG and IgA, antiendomysial antibody IgA and anti-transglutaminase antibody IgA were studied in 37 (19 males) patients with psoriasis and 50 (23 males) healthy controls. Upper gastrointestinal endoscopy and duodenal biopsies were performed in patients with at least one positive marker. Results Antigliadin IgA was statistically higher in the psoriasis group than in the controls (p<0.05). Serological markers were found positive in 6 patients with psoriasis and 1 person from the control group. Upper gastrointestinal endoscopy was performed in all these persons, with biopsies collected from the duodenum. The diagnosis of CD was reported in only one patient with psoriasis following the pathological examination of the biopsies. Whereas one person of the control group was found to be positive for antigliadin antibody IgA, pathological examination of the duodenal biopsies obtain from this patient were found to be normal. Conclusion Antigliadin IgA prominently increases in patients diagnosed with psoriasis. Patients with psoriasis should be investigated for latent CD and should be followed up. PMID:24003271
Leonardi, Craig L; Gordon, Kenneth B
This article discusses the scientific rationale for the use of cytokine inhibitors, including ustekinumab, an inhibitor of the interleukin (IL)-12 and IL-23 pathways in psoriasis. Also addressed are the efficacy and safety data for this agent, as well as for several emerging therapies that target other cytokine pathways in psoriasis: the IL-17 inhibitors secukinumab, ixekizumab, and brodalumab, the IL-23 blocker tildrakizumab, and the small-molecule kinase inhibitors apremilast (a phosphodiesterase-4 blocker) and tofacitinib (a Janus kinase inhibitor).
▼ Apremilast (Otezla - Celgene Europe Ltd.) is a novel orally administered immunomodulatory medicine licensed for the treatment of plaque psoriasis and psoriatic arthritis. The company suggests that it has demonstrated proven and durable efficacy in both conditions and has a favourable safety profile with no requirement for drug-specific pre-screening or ongoing laboratory monitoring. Here we review the evidence on the safety and efficacy of apremilast in the management of psoriasis and psoriatic arthritis.
Campanati, Anna; Ganzetti, Giulia; Giuliodori, K; Molinelli, Elisa; Offidani, A
This review focuses on the emerging concepts concerning the efficacy profile of biological drugs in psoriasis ranging from moderate to severe, and attempts to provide the most recent individual positioning of biologics in treating psoriasis. Biologic agents targeting towards specific immune mediators have emerged as treatment options for patients with moderate to-severe plaque psoriasis unresponsive or intolerant to traditional systemic agents. Data on the safety of biologics are available for up to 5 years in psoriasis and are on the whole reassuring. National registries are still evolving and will provide data on safety, to help the long-term monitoring of patients with psoriasis ongoing biological treatment. Although several biologics have demonstrated good efficacy and tolerability in short-term trials, treatment guidelines recommend them as third line therapies due to relative lack of long-term safety data, especially for those who have been commercialized recently. Here, we have reviewed the long-term safety data obtained from National Registries, randomized controlled trials, open-label extension studies and meta-analyses on etanercept, infliximab, adalimumab, and ustekinumab in the treatment of adults with moderate to severe plaque psoriasis.
Gisondi, Paolo; Di Mercurio, Marco; Idolazzi, Luca; Girolomoni, Giampiero
Psoriasis is a lifelong chronic inflammatory disease affecting 2-3% of the worldwide population. Current understanding of the pathogenesis of psoriasis assigns central importance to an interaction between acquired and innate immunity. The disease is characterized by a series of linked cellular changes in the skin, including hyperplasia of epidermal keratinocytes, angiogenesis, and infiltration of T lymphocytes, neutrophils, and other types of leukocytes in the affected skin. Plaque psoriasis is the most common clinical form and is characterized by red and scaly plaques generally localized at extensor sites such as elbows and knees. Major determinants of psoriasis severity include the extent of skin involvement; localization in highly affected areas such as scalp, palms, and soles; pruritus; presence of comorbidities including psoriatic arthritis; and impairment on quality of life. About one-third of patients have moderate to severe psoriasis defined as PASI (Psoriasis Area and Severity Index) and/or Dermatology Life Quality Index>10, and/or affected body surface area>10%. The optimal treatment goal is to safely achieve complete or almost complete skin clearance. Treatments available are various and they are chosen according to disease features, comorbidities, and patient characteristics and priorities. Topical treatments including corticosteroids and Vitamin D analogs are reserved for mild disease. Phototherapy, cyclosporine, methotrexate, acitretin, or biologics such as tumor necrosis factor-α antagonists and ustekinumab are reserved for the moderate to severe forms.
Piruzian, A.; Korsunskaya, I.; Goldenkova, I.; Hertsen, A.; Sarkisova, M.; Egorenkova, L.
Psoriasis is a chronic, genetically-determined disease, characterized by an immuno-mediated pathogenesis. Treatment of psoriasis is often complicated and remains a challenge. Along with the many new immunomodulatory approaches, various laser systems have been employed for chronic plaque psoriasis treatment. Recently, it has been demonstrated that the light produced by xenon-chloride excimers (generated by sophisticated devices with peak emission of 308 nm) is effective in the treatment of several psoriasis forms. We treated patients, ranging in age from 35 to 55 years, affected by plaque-type psoriasis vulgaris with monochromatic excimer light (MEL). We used MEL in a complex with basic treatment. Therapy was administered three times a week. At the end of the 3th week of treatment all patients showed an improvement, as evidenced by flattening of plaques, decreased scaling and erythema, and decreased vesicle and pustule formation. Unwanted side effects such as pain, blistering was not observed. Minimal erythema and a hyperpigmentation were noted in some patients. It was concluded that the MEL therapy may be a valuable option for treatment of plaque-type psoriasis vulgaris in shorter time compare with traditional NB UVB, with exposure to lower cumulative doses
Aksoy, Nurten; Ozgöztas, Orhan; Sezen, Hatice; Yesilova, Yavuz; Turan, Enver
Introduction Psoriasis is a chronic, inflammatory, T-cell-mediated and hyperproliferative skin disease characterized by erythematous, squamous, sharply circumscribed and infiltrated plaques. The metabolisms of the collagen proteins undergo considerable changes due to the acceleration of their turnovers as a result of increased prolidase activity in psoriasis patients. Aim To determine the level of prolidase activity in psoriasis patients and evaluate its relationship with the oxidative system. Material and methods The serum prolidase enzyme activity, total antioxidant levels and total oxidant levels of 40 psoriasis patients and a control group including 47 healthy individuals were analyzed by using their serum samples, and their oxidative stress indices were calculated. Results The prolidase levels (p < 0.01), total oxidant levels (p < 0.01) and oxidative stress index levels (p < 0.001) of the patient group were higher than the corresponding parameters in the control group. The total antioxidant level was low (p < 0.01). Although a positive correlation was found between the prolidase and total antioxidant levels and the total oxidant level, no correlation was found between prolidase and the oxidative stress index. Conclusions It has been determined that the activity of the prolidase enzyme increases due to the increased collage turnover in psoriasis patients. Increased serum oxidant levels and oxidative stress indices values may play a role in the pathogenesis of psoriasis. PMID:26015776
Kempter, W; Stein, A; Bauer, A; Wozel, G
A 61-year-old patient had a 25-year history of erythematous scaling lesions, diagnosed and treated as psoriasis vulgaris. He presented with a growing nodule within the erythematous plaque. Biopsy shows epithelioid cell granulomas with prominent Langhans giant cells. There was no sign of a squamous cell carcinoma. The tuberculin test was strongly positive and M. tuberculosis complex was detected in the biopsy material by PCR. He was diagnosed with lupus vulgaris, the most frequent form of cutaneous tuberculosis. Other types include tuberculosis verrucosa cutis, tuberculosis cutis orificialis and disseminated military tuberculosis. The patient was treated with rifampicin, isoniazid, pyrazinamide and ethambutol for two months, following a four month treatment with rifampicin and isoniazid. The skin lesions rapidly resolved under antituberculotic treatment.
... news/fullstory_162876.html Weight Loss May Ease Psoriasis Symptoms, Study Finds Quality-of-life boost seen ... 4, 2017 (HealthDay News) -- Could weight loss combat psoriasis? Danish researchers are reporting that obese people with ...
Psoriasis is a chronic recurrent inflammatory skin disease with prevalence of 1–3%. Nail psoriasis affects 10–90% of patients with plaque psoriasis. The aim of the article is to review the literature for the correlation between nail psoriasis and psoriatic arthritis (PsA) to provide rheumatologists a short review on features of nail psoriasis, methods of their assessment and possible clinical repercussions. The PubMed database was searched using the key words ‘nail psoriasis’ and ‘psoriatic arthritis’. Psoriasis involving the nail matrix shows up as changes such as pitting, Beau lines, leukonychia, red spots in the lunula, or nail plate crumbling. Nail bed psoriasis manifests as onycholysis, oil drops (or salmon patches), dyschromia, splinter hemorrhages, or subungual hyperkeratosis. Nail psoriasis and psoriatic lesions in the gluteal cleft and on the scalp usually accompany PsA, especially in adult men. PMID:28386142
... does a doctor tell the difference between scalp psoriasis and seborrheic dermatitis of the scalp? Answers from ... such as pitting. Compare signs and symptoms Scalp psoriasis Red skin covered with flakes and silvery scales ...
Andressen, C; Henseler, T
Detailed pedigrees were established in 2,035 families with psoriasis, including 30 twin pairs, and evaluated by means of computer analysis. The following results on the devolution of psoriasis were drawn: the hypotheses of the irregular dominant and the bifactorial recessive inheritance appear to be inacceptable. The findings suggest a multifactorial etiology of psoriasis with a polygenic mode of inheritance. The risk for relatives to be affected by psoriasis is calculated.
Dreyer, Lois N; Brown, Gwen Cohen
Psoriasis is a chronic immune-mediated disease of unknown etiology that affects the skin and mucous membranes. According to the National Institutes of Health (NIH), approximately five million Americans, 3% of the population, have been diagnosed with psoriasis. Oral manifestations of psoriasis are less well recognized than skin lesions, and treatment for oral lesions is not standardized. This article will review the clinical presentation of skin and mucous membrane psoriasis, along with the therapeutic modalities available to oral health-care providers.
De Biase, A; Guerra, F; Polimeni, A; Ottolenghi, L; Pezza, M; Richetta, A G
Psoriasis is primarily an inherited inflammatory skin disease, it is characterized by erythemato-squamous lesions that usually involve elbows, knees and the scalp. Oral manifestations are rare in psoriasis, infact, oral psoriasis involves 2% of psoriatic patients and usually it is observed with the onset of cutaneous lesions and progresses with them. Differential diagnosis should be done for Reiter's syndrome, leukoplakia and geographic tongue. The authors describe a case of tongue psoriasis without cutaneous lesions.
Caruso, Roberta; Botti, Elisabetta; Sarra, Massimiliano; Esposito, Maria; Stolfi, Carmine; Diluvio, Laura; Giustizieri, Maria Laura; Pacciani, Valentina; Mazzotta, Annamaria; Campione, Elena; Macdonald, Thomas T; Chimenti, Sergio; Pallone, Francesco; Costanzo, Antonio; Monteleone, Giovanni
T cells are crucial mediators of the skin damage in psoriasis. We here show that interleukin-21 (IL-21), a T cell-derived cytokine, is highly expressed in the skin of individuals with psoriasis, stimulates human keratinocytes to proliferate and causes epidermal hyperplasia when injected intradermally into mice. In the human psoriasis xenograft mouse model, blockade of IL-21 activity resolves inflammation and reduces keratinocyte proliferation. Blocking IL-21 may represent a new therapeutic strategy in psoriasis.
... form seems to be linked to strep infections. Inverse. Skin redness and irritation occur in the armpits, ... The goal of treatment is to control your symptoms and prevent infection. ... and shampoos. These are called topical treatments. Pills ...
... raised edges that are red with silvery-white scales (called plaques) Rashes on genitals, scalp, or in ... most common form with plaques covered in silvery scales. The plaques can occur anywhere on the body, ...
... 2017 American Academy of Dermatology. All rights reserved. Reproduction or republication strictly prohibited without prior written permission. ... 2017 American Academy of Dermatology. All rights reserved. Reproduction or republication strictly prohibited without prior written permission.
Tsianakas, A; Mrowietz, U
Psoriasis is a common chronic inflammatory disease with an incidence of about 0.5-3 %. Previously psoriasis was not primarily regarded to be associated with pruritus; however, this perception has changed in recent years. Meanwhile data conclusively show that between 64 and 97 % of patients report about pruritus that can be severe in a number of cases. Apart from suffering from psoriasis, the presence of pruritus causes additional stress and leads to a significant impairment of health-related quality of life. Neurogenic inflammation at least in part contributes to the development of pruritus in psoriasis skin lesions. A number of neuropeptides including substance P and calcitonin gene related peptide can act as pro-inflammatory mediators. There is evidence for a dysbalance between κ‑ and µ‑opioid receptors in lesional skin favoring inflammation and pruritus. After clearing of psoriasis lesions, pruritus is relieved as well. Therefore, specific treatment of pruritus is not necessary in general. In cases where severe pruritus is a prominent symptom, targeted therapy with mirtazapin or doxepin or neuroleptic compounds such as pregabalin or gabapentin or drugs affecting the κ‑ und µ‑opioid receptor balance can be administered. Today the importance of pruritus as a prominent symptom of psoriasis lesions has been widely accepted. In recent and running clinical trials with new drugs, pruritus at baseline and the effect of these drugs on pruritus is always assessed. This awareness also fuels basic research about pruritus in psoriasis.
Koley, Sankha; Mandal, Rajesh Kumar; Chatterjee, Kingshuk; Hassan, Sk Masud; Pathak, Swapan
Psoriasis is a disease of considerable clinical and histopathological diversity. We report a rare case of elephantine psoriasis responding very well to methotrexate. Histopathology revealed abnormal papillomatosis with finger-like projections in addition to alternating orthokeratosis with overlying hypergranulosis and parakeratosis with overlying hypogranulosis. We believe that this finding may represent an odd histopathologic type in elephantine psoriasis. PMID:26120152
Albert, A; Hein, R; Ring, J; Jakob, T
Erythema annulare centrifugum-type psoriasis with pustules represents a subtype of psoriasis pustulosa generalisata von Zumbusch. It presents with a typical morphology characterized by a lack of classical erythematosquamous skin lesions during its acute eruption phase. Diagnosis is usually established on the basis of clinical presentation and dermatopathology, which often shows a substrate typical for psoriasis, sometimes with spongiform pustules.
Sarac, Gulbahar; Koca, Tuba Tulay; Baglan, Tolga
Psoriasis is a chronic inflammatory dermatosis that is thought to onset as a result of T lymphocyte-mediated immunological response. Disease may manifest itself in different modalities with regard to clinical features and severity. Clinical type of psoriasis is an important element in determining the therapy regimen. This article reviews clinical types of psoriasis. PMID:28058392
de la Brassinne, M; Nikkels, Af
The treatment of psoriasis is mainly based on anti-inflammatory and/or anti-hyperproliferative agents. The topical steroids appeared in the fifties and were the first therapeutic breakthrough for psoriasis, followed by methotrexate and phototherapy in the sixties, photochemotherapy (PUVA) in the seventies and acitretin and cyclosporine in the eighties. The targeted biologic therapies represent a whole new era of therapeutic possibilities with a highly beneficial safety record. The choice of treatment depends on a large series of factors, including the type and extend of the psoriasis, the patient's preferences, co-medications, comorbidities and drug tolerance. This overview presents the currently available topical and systemic agents for treating psoriasis, including topical corticosteroids, vitamin D derivatives, UV-light based therapies, methotrexate, cyclosporine, acitretin, and the biologic agents such as the TNF antagonists etanercept, adalimumab and infliximab, as well as the anti-p40 IL12/23 agent ustekinumab. Newer, very promising, agents aiming the Th17 pathway are under development for psoriasis.
Daneshpazhooh, Maryam; Moslehi, Homayoon; Akhyani, Maryam; Etesami, Marjan
Background Our objective was to study tongue lesions and their significance in psoriatic patients. Methods The oral mucosa was examined in 200 psoriatic patients presenting to Razi Hospital in Tehran, Iran, and 200 matched controls. Results Fissured tongue (FT) and benign migratory glossitis (BMG) were the two most frequent findings. FT was seen more frequently in psoriatic patients (n = 66, 33%) than the control group (n = 19, 9.5%) [odds ratio (OR): 4.69; 95% confidence interval (CI): 2.61–8.52] (p-value < 0.0001). BMG, too, was significantly more frequent in psoriatic patients (28 cases, 14%) than the control group (12 cases, 6%) (OR: 2.55; 95% CI: 1.20–5.50) (p-value < 0.012). In 11 patients (5.5%), FT and BMG coexisted. FT was more frequent in pustular psoriasis (7 cases, 53.8%) than erythemato-squamous types (56 cases, 30.4%). On the other hand, the frequency of BMG increased with the severity of psoriasis in plaque-type psoriasis assessed by psoriasis area and severity index (PASI) score. Conclusions Nonspecific tongue lesions are frequently observed in psoriasis. Further studies are recommended to substantiate the clinical significance of these seemingly nonspecific findings in suspected psoriatic cases. PMID:15527508
Carrascosa, J M; Bonanad, C; Dauden, E; Botella, R; Olveira-Martín, A
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver condition in the West. The prevalence and severity of NAFLD is higher and the prognosis worse in patients with psoriasis. The pathogenic link between psoriasis and NAFLD is chronic inflammation and peripheral insulin resistance, a common finding in diseases associated with psoriasis. NAFLD should therefore be ruled out during the initial evaluation of patients with psoriasis, in particular if they show signs of metabolic syndrome and require systemic treatment. Concomitant psoriasis and NAFLD and the likelihood of synergy between them place limitations on general recommendations and treatment for these patients given the potential for liver toxicity. As hepatotoxic risk is associated with some of the conventional drugs used in this setting (e.g., acitretin, methotrexate, and ciclosporin), patients prescribed these treatments should be monitored as appropriate. Anti-tumor necrosis factor agents hold the promise of potential benefits based on their effects on the inflammatory process and improving peripheral insulin resistance. However, cases of liver toxicity have also been reported in relation to these biologics. No evidence has emerged to suggest that anti-p40 or anti-interleukin 17 agents provide benefits or have adverse effects.
The simultaneously recorded disappearance rates of /sup 133/xe from subcutaneous adipose tissue in the crus were studied in 10 patients with psoriasis vulgaris using atraumatic labeling of the tissue in lesional skin (LS) areas and symmetrical, nonlesional skin (NLS) areas. Control experiments were performed bilaterally in 10 younger, healthy subjects. The subcutaneous washout rate constant was significantly higher in LS, 0.79 +/- 0.05 min-1 x 10(2) compared to the washout rate constant of NLS, 0.56 +/- 0.07 min-1. 10(2), or the washout rate constant in the normal subjects, 0.46 +/- 0.17 min-1 x 10(2). The mean washout rate constant in NLS was 25% higher than the mean washout rate constant in the normal subjects. The difference was, however, not statistically significant. Differences in the washout rate constants might be due to abnormal subcutaneous tissue-to-blood partition (lambda) in the LS--and therefore not reflecting the real differences in the subcutaneous blood flow (SBF). The lambda for /sup 133/Xe was therefore measured--using a double isotope washout method (/sup 133/Xe and (/sup 131/I)antipyrine)--in symmetrical sites of the lateral crus in LS and NLS of 10 patients with psoriasis vulgaris and in 10 legs of normal subjects. In LS the lambda was 4.52 +/- 1.67 ml/g, which was not statistically different from that of NLS, 5.25 +/- 2.19 ml/g, nor from that of normal subcutaneous tissue, 4.98 +/- 1.04 ml/g. Calculations of the SBF using the obtained lambda values gave a significantly higher SBF in LS, 3.57 +/- 0.23 ml/100 g/min, compared to SBF in the NLS, 2.94 +/- 0.37 ml/100 g/min. There was no statistically significant difference between SBF in NLS and SBF in the normal subjects. The increased SBF in LS of psoriatics might be a secondary phenomenon to an increased heat loss in the lesional skin.
Foulkes, Amy C; Warren, Richard B
Psoriasis is a model disease for the development of pharmacogenomic markers of treatment response, with ready access to diseased tissue and objective validated outcome measures. With the application of state-of-the-art technologies and investment in careful experimental design, the goal of stratified medicine in psoriasis may be possible. Current pharmacogenomic studies in psoriasis show excellence in many areas, including the investigation of a broad range of psoriasis therapies. To facilitate the advent of stratified medicine in psoriasis, uniformity of study design is required, with high quality, consistent phenotyping strategies for participants; definitions of outcome; and the publication of reproducible methodologies.
ROMAN, IULIA IOANA; CONSTANTIN, ANNE-MARIE; MARINA, MIHAELA ELENA; ORASAN, REMUS IOAN
Psoriasis vulgaris is a chronic, common skin disease, which affects the patient’s quality of life to the highest degree. Several exogenous factors and endogenous hormonal changes may act as triggers for psoriasis. The skin possesses a true endocrine system, which is very important in multiple systemic diseases. A number of conditions are associated with psoriasis, and its severity can also be influenced by hormones. Even though the sex hormones and prolactin have a major role in psoriasis pathogenicity, there are a lot of other hormones which can influence the psoriasis clinical manifestations: glucocorticoids, epinephrine, thyroid hormones, and insulin. PMID:27004020
Kim, Dae Hun; Jeong, Nam Ji; Im, Myung; Lee, Young; Seo, Young Joon; Lee, Jeung Hoon
Trastuzumab (Herceptin), a humanized monoclonal antibody, is a cancer drug developed to target the human epidermal receptor (HER) 2, which is overexpressed in some cancer cells. Cutaneous side effects, such as folliculitis, xerosis, and alopecia have not been reported with therapies targeting HER2, in spite of the frequent observances of such with the therapies targeting the epidermal growth factor receptor. We experienced a patient in whom psoriasis was triggered by the trastuzumab treatment for breast cancer. She was a 57-year-old woman with erythematous and scaly plaques occurring a few months after starting trastuzumab, with repeated aggravation after the re-administration of trastuzumab for the breast cancer. Histologic examination showed the typical features of psoriasis with parakeratosis, epidermal hyperplasia, elongation of the rete ridges, and a lymphocytic and polymorphonuclear cell infiltrate in the dermis. To the best of our knowledge, this is the first report of psoriasis triggered by trastuzumab treatment for breast cancer.
Chandra, Aditi; Ray, Aditi; Senapati, Swapan; Chatterjee, Raghunath
Psoriasis is a chronic inflammatory skin disease whose prevalence varies among different populations worldwide. It is a complex multi-factorial disease and the exact etiology is largely unknown. Family based studies have indicated a genetic predisposition; however they cannot fully explain the disease pathogenesis. In addition to genetic susceptibility, environmental as well as gender and age related factors were also been found to be associated. Recently, imbalances in epigenetic networks are indicated to be causative elements in psoriasis. The present knowledge of epigenetic involvement, mainly the DNA methylation, chromatin modifications and miRNA deregulation is surveyed here. An integrated approach considering genetic and epigenetic anomalies in the light of immunological network may explore the pathogenesis of psoriasis.
Caca Biljanovska, N; V'lckova Laskoska, M
Psoriasis is a chronic, systemic T-cell mediated autoimmune skin disease, potentially associated with arthritis. The new understanding of immunopathogenesis and inflammatory cytokine pathways was actually the rationale for developing and introducing biological drugs in the treatment of moderate to severe psoriasis and psoriatic arthritis. Different from the traditional systemic drugs that impact the entire immune system, bio-logics target only specific points of the immune system. This review focuses on five biologics which target either T-cells (alefacept) or TNF-alpha (etanercept, adalimumab and infliximab) or interleukin IL-12/IL-23 (ustekinumab)--their efficacy, safety, patient monitoring and recommended dosage. The purpose of the treatment guidelines presented here is to provide a high standard of continuing care of psoriasis and psoriatic arthritis patients.
Kofoed, Kristian; Skov, Lone; Zachariae, Claus
In recent years, the increased understanding of the pathophysiology of psoriasis has resulted in several new treatments. The success of ustekinumab proved the importance of the IL-23/T helper cell 17 axis in psoriatic diseases. Several new biologics targeting this axis will reach the clinic in the next years. Biologics are costly, require injections, and some patients experience tacaphylaxis, thus, the development of orally available, small-molecule inhibitors is desirable. Among small-molecules under investigation are A3 adenosine receptor agonists, Janus kinase inhibitors, and phosphodiesterase inhibitors. We review published clinical trials, and conference abstracts presented during the last years, concerned with new drugs under development for the treatment of psoriasis. In conclusion, our psoriasis armamentarium will be filled with several new effective therapeutic options the coming years. We need to be aware of the limitations of drug safety data when selecting new novel treatments. Monitoring and clinical registries are still important tools.
Ruiz, V; Manubens, E; Puig, L
Scarce scientific evidence is available to define the precise effects that certain drugs might have on embryonic and fetal development if taken by pregnant women with psoriasis, given the ethical concerns that preclude enrolling such women in clinical trials. The little information on the use of biologics during gestation that has been published is based on retrospective and observational studies, and experience with these drugs in this context in psoriasis is still very limited. The literature seems to suggest that biologic therapy is safe during pregnancy, but there is no certainty. This detailed review of accumulated experience with biologic therapy during pregnancy relies mainly on descriptions of the management of other types of rheumatic disease, although the use of these agents in psoriasis is growing steadily.
Mehta, Nehal N.; Yu, YiDing; Pinnelas, Rebecca; Krishnamoorthy, Parasuram; Shin, Daniel B.; Troxel, Andrea B.; Gelfand, Joel M.
Background Recent studies suggest that psoriasis, particularly if severe, may be a risk factor for major adverse cardiac events such as myocardial infarction, stroke, and mortality from cardiovascular disease. We compared the risk of major adverse cardiac events between patients with psoriasis and the general population and estimated the attributable risk of severe psoriasis. Methods We performed a cohort study in the General Practice Research Database. Severe psoriasis was defined as receiving a psoriasis diagnosis and systemic therapy (N=3,603). Up to 4 patients without psoriasis were selected from the same practices and start dates for each patient with psoriasis (N=14,330). Results Severe psoriasis was a risk factor for major adverse cardiac events (hazard ratio 1.53; 95% confidence interval 1.26, 1.85) after adjusting for age, gender, diabetes, hypertension, tobacco use and hyperlipidemia. After fully adjusted analysis, severe psoriasis conferred an additional 6.2% absolute risk of 10-year major adverse cardiac events. Conclusions Severe psoriasis confers an additional 6.2% absolute risk of 10-year rate of major adverse cardiac events compared to the general population. This potentially has important therapeutic implications for cardiovascular risk stratification and prevention in patients with severe psoriasis. Future prospective studies are needed to validate these findings. PMID:21787906
Bangsgaard, Nannie; Rørbye, Christina; Skov, Lone
Psoriasis is a chronic inflammatory disease with a well-documented negative effect on the quality of life of affected patients. Psoriasis often occurs in the reproductive years, during which the issue of pregnancy needs to be addressed. The course of psoriasis during pregnancy is unpredictable, and many patients face the challenge of needing treatment during pregnancy. In this review we provide an overview of the key considerations for managing psoriasis in pregnant women, covering the potential effects of active psoriasis and co-morbid conditions on the health of the mother and fetus, as well as the effects of psoriasis treatment options on the developing fetus. Although there are no robust data on the safety of systemic treatment of pregnant women, increasing evidence regarding the safety of cyclosporine (ciclosporin) treatment as well as anti-tumor necrosis factor-α is available and should be considered in pregnant women with moderate to severe psoriasis unresponsive to local corticosteroids and UVB light treatment.
Srinivasan, T.N.; Suresh, T.R.; Devar, J.V.; Jayaram, Vasantha
SUMMARY Studies on association of psychiatric diseases and immunopathology has been an area of recent research activities. Alcohol has been implicated in some immune mediated disorders. Observation of occurrence of psoriasis, an immune mediated skin disorder in alcoholic patients has not been reported anywhere in literature. We report here 4 cases of alcoholism related psoriasis and discuss the possible immunological relationship between these two disorders. The need for study of effect of alcoholism on cell-medicated immunity associated conditions like auto-immune disorders and malignancy is presented. PMID:21897472
Antúnez-Lay, Andrea; Cabrolier, Jorge; Andino-Navarrete, Romina
Apart from involving skin, psoriasis can compromise the nails and adjacent structures. Even though there are multiple therapeutic alternatives, there is great interest in biological therapy, but no consensus on its role exists. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified two systematic reviews including three randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded it is not clear whether biological therapy is superior to placebo in the treatment of nail psoriasis because the certainty of the evidence is very low.
Deiana, L; Pes, G M; Carru, C; Tidore, M; Cherchi, G M
Psoriasis is a common relapsing dermatosis characterized by an increased epidermal cell proliferation. In this work we studied the lipid and lipoprotein pattern in 17 patients affected by long-standing psoriasis and in 20 normal controls. Total cholesterol, triglyceride, HDL-cholesterol and Apolipoprotein AI and B levels were measured; VLDL, LDL and HDL chemical composition was assessed by preparative ultracentrifugation. Plasma lipid and lipoprotein levels were significantly lower in the patient group; chemical analysis of the main lipoprotein classes showed compositional abnormalities consistent with an accelerated turnover of these particles. We believe that epidermal cell proliferation can play a role in determining these changes.
Carrascosa, J M; Rocamora, V; Fernandez-Torres, R M; Jimenez-Puya, R; Moreno, J C; Coll-Puigserver, N; Fonseca, E
Obesity, particularly abdominal obesity, is currently considered a chronic low-grade inflammatory condition that plays an active role in the development of the pathophysiologic phenomena responsible for metabolic syndrome and cardiovascular disease through the secretion of proinflammatory adipokines and cytokines. In recent years clear genetic, pathogenic, and epidemiologic links have been established between psoriasis and obesity, with important implications for health. The relationship between the 2 conditions is probably bidirectional, with obesity predisposing to psoriasis and psoriasis favoring obesity. Obesity also has important implications in the treatment of psoriasis, such as a greater risk of adverse effects with conventional systemic drugs and reduced efficacy and/or increased cost with biologic agents, for which dosage should be adjusted to the patient's weight.
van de Kerkhof, P C M; Vissers, W H P M
According to the patients, improvement of efficacy, long-term safety and improvement of compliance are needed. The topical treatment has been innovated during the last decade. Most important are the introduction of two new classes of treatments: topical vitamin D(3) analogues and the retinoid tazarotene. To what extent, however, have we achieved developments which are in line with the needs as expressed by the patients? Improved efficacy has been realized by successful combinations of topical treatments. In particular, the combinations of dithranol, vitamin D(3) and tazarotene with a topical corticosteroid proved to be very effective with a reduced profile of side-effects. The efficacy of vitamin D(3) analogues and tazarotene is such that the efficacy of a potent corticosteroid (betamethasone-17-valerate) is approached; calcipotriol even showed an efficacy which is at least as good as this corticosteroid. The long-term safety of new compounds has been evaluated for at least 12 months in large studies. Remarkably for corticosteroids such information is available for only 12 weeks. However, intermittent applications of a topical corticosteroid in combination with another topical treatment provide an effective and safe long-term control of psoriasis. Compliance is a conditio sine qua non for an effective topical treatment. Important progress has been made to increase compliance. Short-contact dithranol has been popularized as an ambulatory treatment which is a highly effective approach as a care instruction programme. Formulations which are better from a cosmetical point of view have been developed for various topical treatments. Reduction of the frequency of applications proved to be possible for most treatments. Once daily applications for corticosteroids, vitamin D(3) analogues and retinoids have been developed, and intermittent applications, a few times per week, are possible for corticosteroids, which proved to be very effective with a reduced profile of side
Zhang, Hong; Hou, Wenhong; Henrot, Laurence; Schnebert, Sylvianne; Dumas, Marc; Heusèle, Catherine; Yang, Jin
We present a computational model to study the spatio-temporal dynamics of epidermis homoeostasis under normal and pathological conditions. The model consists of a population kinetics model of the central transition pathway of keratinocyte proliferation, differentiation and loss and an agent-based model that propagates cell movements and generates the stratified epidermis. The model recapitulates observed homoeostatic cell density distribution, the epidermal turnover time and the multilayered tissue structure. We extend the model to study the onset, recurrence and phototherapy-induced remission of psoriasis. The model considers psoriasis as a parallel homoeostasis of normal and psoriatic keratinocytes originated from a shared stem cell (SC) niche environment and predicts two homoeostatic modes of psoriasis: a disease mode and a quiescent mode. Interconversion between the two modes can be controlled by interactions between psoriatic SCs and the immune system and by normal and psoriatic SCs competing for growth niches. The prediction of a quiescent state potentially explains the efficacy of multi-episode UVB irradiation therapy and recurrence of psoriasis plaques, which can further guide designs of therapeutics that specifically target the immune system and/or the keratinocytes.
Genetic epidemiological studies have demonstrated a significant genetic basis to both psoriasis and psoriatic arthritis (PsA). Although candidate gene association studies had identified genes for disease susceptibility, recent genome-wide association studies have demonstrated robust associations both within and outside the major histocompatibility region on chromosome 6p. The susceptibility genes identified include HLA-C, IL13, IL4, TNFAIP3, IL23A, IL23R, IL28RA, REL, IFIH1, ERAP, TRAF3IP2, NFKBIA, TYK2, ZNF313, NOS2, FBXL19 and NFKBIA in subjects of European ethnicity and HLA-C, IL12B, LCE3D, ERAP1, TNIP1, PTTG1, CSMD1, GJB2, SERPINB8 and ZNF816A in subjects of Chinese ethnicity. These associations provide us with a model for the pathogenesis of psoriasis involving skin barrier function, innate and adaptive immunity. Gene-gene and gene-environmental interaction effects have also been demonstrated. However, loci identified to date do not fully account for the high heritability of psoriasis and PsA, and therefore many genetic as well as environmental factors and interaction effects remain to be determined. This article reviews the current status of genetic studies in psoriasis and PsA.
Kapsokalyvas, Dimitrios; Cicchi, Riccardo; Bruscino, Nicola; Alfieri, Domenico; Massi, Daniela; Lotti, Torello; Pavone, Francesco S.
Psoriasis is an autoimmune disease of the skin characterized by hyperkeratosis, hyperproliferation of the epidermis, inflammatory cell accumulation and increased dilatation of dermal papillary blood vessels. Cases of psoriasis were investigated in vivo with optical means in order to evaluate the potential of in vivo optical biopsy. A Polarization Multispectral Dermoscope was employed for the macroscopic observation. Features such as the 'dotted' blood vessels pattern was observed with high contrast. The average size of dot vessels in Psoriasis was measured to be 974 μm2 which is much higher compared to healthy skin. High resolution image sections of the epidermis and the dermis were produced with a custom made Multiphoton Microscope. Imaging extended from the surface of the lesion down to the papillary dermis, at a depth of 200 μm. In the epidermis, a characteristic morphology of the stratum corneum found only in Psoriasis was revealed. Additionally, the cytoplasmic area of the cells in the stratum spinosum layer was found to be smaller than normal. In the dermis the morphological features were more pronounced, where the elongated dermal papillae dominated the papillary layer. Their length exceeds 100μm, which is a far greater value compared to that of healthy skin. These in vivo observations are consistent with the ex vivo histopathological observations, supporting both the applicability and potentiality of multispectral dermoscopy and multiphoton microscopy in the field of in vivo optical investigation and biopsy of skin.
Tselios, Konstantinos; Yap, Kristy Su-Ying; Pakchotanon, Rattapol; Polachek, Ari; Su, Jiandong; Urowitz, Murray B; Gladman, Dafna D
The coexistence of psoriasis with systemic lupus erythematosus (SLE) has been reported in limited case series, raising hypotheses about shared pathogenetic mechanisms. Nevertheless, important differences regarding treatment do exist. The aim of the present study was to determine the prevalence and characteristics of psoriasis in a defined cohort of lupus patients. Patients with psoriasis were retrieved from the University of Toronto Lupus Clinic from its inception in 1970 up to 2015. Charts were hand-searched to collect information concerning demographic, clinical, and therapeutic variables. Patients were matched with non-psoriasis lupus patients to identify the impact of supervening psoriasis on lupus activity, damage accrual, and venous thromboembolic (VTEs) and cardiovascular events (CVEs). Psoriasis was diagnosed in 63 patients (49 females, 14 males) for a prevalence of 3.46% (63/1823). The male-to-female ratio was significantly higher in non-psoriasis patients (0.286 vs. 0.138, p = 0.017). Plaque psoriasis was the most prominent type (55/63, 87.3%) whereas three patients had pustular disease; one had psoriatic arthritis. Nine patients (14.3%) were administered systemic treatment with methotrexate (n = 5), azathioprine (n = 1), ustekinumab (n = 3), and etanercept (n = 1). Psoriasis was definitely deteriorated by hydroxychloroquine in one patient. There was no significant impact of psoriasis on disease activity, damage accrual, VTEs, and CVEs. The prevalence of psoriasis was twice as high as that of the general Canadian population in this lupus cohort. Plaque psoriasis was the most prominent subtype, and topical treatment was adequate in the majority of patients. Supervening psoriasis had no significant impact on lupus activity and damage accrual.
Rajagopalan, Murlidhar; Mital, Asit
The biologics currently in use for psoriasis in India are etanercept, infliximab and recently introduced itolizumab and secukinumab. Biosimilars, expected to play a significant role in psoriasis management in future, have also been available for the last few years. Patients with psoriasis may be considered eligible to receive treatment with any of the licensed biologic interventions when they fulfill the eligibility criteria. The decision to proceed with treatment must be made in collaboration with the patient and include a careful assessment of the associated risks and benefits. Etanercept is indicated in moderate to severe psoriasis and moderate to severe psoriatic arthritis with a dose of 25 mg or 50 mg twice weekly. Methotrexate may be recommended as co-medication in certain clinical circumstances, e.g., where it is required for associated arthropathy, or to improve efficacy. Infliximab is indicated in severe psoriasis and moderate to severe psoriatic arthritis. Infliximab therapy should be initiated at a dose of 5 mg/kg at weeks 0, 2 and 6 and disease response assessed at 3 months. In patients who respond, subsequent infusions (5 mg/kg) should be given at 8-week intervals to maintain disease control although long-term data are available only up to 1 year. Interrupted therapy should be avoided given the associated increased risk of infusion reactions and poorer disease control. Itolizumab is indicated in moderate to severe plaque psoriasis. It is given in a dose of 1.6mg/kg iv infusions every 2 weeks for 12 weeks initially and then 1.6mg/kg every 4 weeks up to 24 weeks. Long term data are unavailable. Secukinumab is indicated in moderate to severe plaque psoriasis and psoriatic arthritis. An initial loading dosing regimen of 300 mg secukinumab should be given by subcutaneous injection at weeks 0, 1, 2 and 3 followed by maintenance dose of 300 mg every 4 weeks starting at week 4. To exclude tuberculosis (TB) before anti TNF alfa therapy and therapy with
Rajagopalan, Murlidhar; Mital, Asit
The biologics currently in use for psoriasis in India are etanercept, infliximab and recently introduced itolizumab and secukinumab. Biosimilars, expected to play a significant role in psoriasis management in future, have also been available for the last few years. Patients with psoriasis may be considered eligible to receive treatment with any of the licensed biologic interventions when they fulfill the eligibility criteria. The decision to proceed with treatment must be made in collaboration with the patient and include a careful assessment of the associated risks and benefits. Etanercept is indicated in moderate to severe psoriasis and moderate to severe psoriatic arthritis with a dose of 25 mg or 50 mg twice weekly. Methotrexate may be recommended as co-medication in certain clinical circumstances, e.g., where it is required for associated arthropathy, or to improve efficacy. Infliximab is indicated in severe psoriasis and moderate to severe psoriatic arthritis. Infliximab therapy should be initiated at a dose of 5 mg/kg at weeks 0, 2 and 6 and disease response assessed at 3 months. In patients who respond, subsequent infusions (5 mg/kg) should be given at 8-week intervals to maintain disease control although long-term data are available only up to 1 year. Interrupted therapy should be avoided given the associated increased risk of infusion reactions and poorer disease control. Itolizumab is indicated in moderate to severe plaque psoriasis. It is given in a dose of 1.6mg/kg iv infusions every 2 weeks for 12 weeks initially and then 1.6mg/kg every 4 weeks up to 24 weeks. Long term data are unavailable. Secukinumab is indicated in moderate to severe plaque psoriasis and psoriatic arthritis. An initial loading dosing regimen of 300 mg secukinumab should be given by subcutaneous injection at weeks 0, 1, 2 and 3 followed by maintenance dose of 300 mg every 4 weeks starting at week 4. To exclude tuberculosis (TB) before anti TNF alfa therapy and therapy with
Wrone-Smith, T; Nickoloff, B J
Establishing direct and causal relationships among the confederacy of activated cell types present in psoriasis has been hampered by lack of an animal model. Within psoriatic plaques there are hyperplastic keratinocytes, infiltrating immunocytes, and activated endothelial cells. The purpose of this study was to determine if psoriasis is primarily a disorder of keratinocytes or the immune system. Using a newly developed experimental system in which full-thickness human skin is orthotopically transferred onto severe combined immunodeficient mice, autologous immunocytes were injected into dermis, and the resultant phenotype characterized by clinical, histologic, and immunophenotypic analyses. Engraftment of samples included both uninvolved/ symptomless (PN) skin removed from patients with psoriasis elsewhere, or from healthy individuals with no skin disease (NN skin). In 10 different experiments involving 6 different psoriasis patients, every PN skin was converted to a full-fledged psoriatic plaque skin by injection of autologous blood-derived immunocytes. In all but one psoriatic patient, the immunocytes required preactivation with IL-2 and superantigens to convert PN skin into psoriatic plaque skin. In every case, resultant plaques were characterized by visible presence of flaking and thickened skin, loss of the granular cell layer, prominent elongation of rete pegs with a dermal angiogenic tissue reaction, and infiltration within the epidermis by T cells. Lesional skin displayed 20 different antigenic determinants of the psoriatic phenotype. None of the four NN skin samples injected with autologous immunocytes converted to psoriatic plaques. We conclude that psoriasis is caused primarily by the ability of pathogenetic blood-derived immunocytes to induce secondary activation and disordered growth of endogenous cutaneous cells including keratinocytes and vascular endothelium.
Wrone-Smith, T; Nickoloff, B J
Establishing direct and causal relationships among the confederacy of activated cell types present in psoriasis has been hampered by lack of an animal model. Within psoriatic plaques there are hyperplastic keratinocytes, infiltrating immunocytes, and activated endothelial cells. The purpose of this study was to determine if psoriasis is primarily a disorder of keratinocytes or the immune system. Using a newly developed experimental system in which full-thickness human skin is orthotopically transferred onto severe combined immunodeficient mice, autologous immunocytes were injected into dermis, and the resultant phenotype characterized by clinical, histologic, and immunophenotypic analyses. Engraftment of samples included both uninvolved/ symptomless (PN) skin removed from patients with psoriasis elsewhere, or from healthy individuals with no skin disease (NN skin). In 10 different experiments involving 6 different psoriasis patients, every PN skin was converted to a full-fledged psoriatic plaque skin by injection of autologous blood-derived immunocytes. In all but one psoriatic patient, the immunocytes required preactivation with IL-2 and superantigens to convert PN skin into psoriatic plaque skin. In every case, resultant plaques were characterized by visible presence of flaking and thickened skin, loss of the granular cell layer, prominent elongation of rete pegs with a dermal angiogenic tissue reaction, and infiltration within the epidermis by T cells. Lesional skin displayed 20 different antigenic determinants of the psoriatic phenotype. None of the four NN skin samples injected with autologous immunocytes converted to psoriatic plaques. We conclude that psoriasis is caused primarily by the ability of pathogenetic blood-derived immunocytes to induce secondary activation and disordered growth of endogenous cutaneous cells including keratinocytes and vascular endothelium. PMID:8878440
El-wahed Gaber, Mohamed Abd; El-Halim Kandil, Mona Abd; El-Farargy, Shawki Mahmoud; Galbet, Doaa Abd Elmoniem
Background: Psoriasis is a common inflammatory skin disease characterized by abnormal keratinocyte proliferation and differentiation. Beta-catenin participates in intercellular adhesion. Catenins are proteins found in complexes with cadherin cell adhesion molecules of cells. The role of catenin in regulating keratinocyte stem cell differentiation and hair follicle morphogenesis has been extensively reported. Aims and Objectives: is to study β-catenin expression in lesional and non-lesional psoriatic skin to throw light upon its possible role in the pathogenesis of psoriasis. Materials and Methods: Biopsies were taken from 20 patients with psoriasis vulgaris and from 10 normal controls. The distribution of Beta catenin was investigated using polycolonal rabbits B-catenin antibody-1 by immunohistochemical method. Results: In this study membranous β-catenin expression was significantly demonstrated in the control group then the non-lesional areas in comparison to the lesional areas (P < 0.001). Nuclear β-catenin staining expression was significantly more demonstrated in lesional and non-lesional areas in comparison to the control cases (P < 0.001). Conclusions: The down regulation of membranous β-catenin expression in lesional psoriatic skin might reflect a useful phenotypic marker of hyperprolifration of keratinocytes in psoriasis. Moreover, the mild down regulation of membranous β-catenin expression in non lesional psoriatic skin may provide clues about incipient structural abnormalities in the pathogenesis of psoriasis, providing an early diagnostic indicator for evolution to a generalized form of the disease. Nuclear β-catenin expression was not found in the control group but was demonstrated in lesional and moderately in non-lesional reflecting its role in kerationcyte proliferation. PMID:25657910
Matsushita, Y; Shimada, Y; Kawara, S; Takehara, K; Sato, S
Psoriasis is believed to be a T cell-mediated autoimmune disease, but also exhibits autoantibody production. Calpastatin is an endogenous inhibitor of calpain, a ubiquitous protease that regulates inflammatory processes. Anti-calpastatin autoantibody was first identified as an autoantibody specific to rheumatoid arthritis, but has been also detected in other autoimmune diseases. In this study, we examined the presence and levels of anti-calpastatin antibody in 77 psoriasis patients by enzyme-linked immunosorbent assay. Compared with normal controls, psoriasis patients exhibited significantly elevated IgG anti-calpastatin antibody levels that were similar to those found in rheumatoid arthritis patients. Remarkably, IgG anti-calpastatin autoantibody in sera from psoriasis patients inhibited calpastatin activity. Calpain II expression was up-regulated in psoriasis skin lesions compared with normal skin while calpastatin expression was normal. The results of this study reveal the presence of anti-calpastatin autoantibody in psoriasis. PMID:15654835
Łakuta, Patryk; Marcinkiewicz, Kamil; Bergler-Czop, Beata; Brzezińska-Wcisło, Ligia
This study examined the relationship between psoriasis and depression, proposing a multiple mediation model to analyse the relationship. A total of 193 patients with psoriasis aged 20-67 years completed the Beck Depression Inventory, the Stigmatization Scale, the Appearance Schemas Inventory-Revised, and the Body Emotions Scale. The Body Surface Area index was used to assess severity of psoriasis. Serial multiple mediation analysis revealed that experiences of stigmatization, maladaptive beliefs about appearance and its salience to one's self-evaluation, and negative emotional attitudes towards the body, jointly, sequentially mediated the relationship between the presence of skin lesions of psoriasis and depressive symptoms. These results highlight the importance of the associations between stigmatization and cognitive and affective aspects of body image in relation to depression in patients with psoriasis. We suggest that prevention and intervention programs for psoriasis patients that target body image enhancement would be worthy of further research.
Jiang, Shan; Hinchliffe, Taylor E.; Wu, Tianfu
Psoriasis is one of the most prevalent autoimmune skin diseases. However, its etiology and pathogenesis are still unclear. Over the last decade, omics-based technologies have been extensively utilized for biomarker discovery. As a result, some promising markers for psoriasis have been identified at the genome, transcriptome, proteome, and metabolome level. These discoveries have provided new insights into the underlying molecular mechanisms and signaling pathways in psoriasis pathogenesis. More importantly, some of these markers may prove useful in the diagnosis of psoriasis and in the prediction of disease progression once they have been validated. In this review, we summarize the most recent findings in psoriasis biomarker discovery. In addition, we will discuss several emerging technologies and their potential for novel biomarker discovery and diagnostics for psoriasis. PMID:26362816
IL-17-driven pathways are active in the skin of patients with psoriasis. Kim et al. examined lesions from mild and moderate to severe psoriasis and found that differences in cutaneous disease severity may be the outcome of lapses in immunoregulatory mechanisms; because as much, if not more, T helper type 17-induced inflammation was seen in mild psoriasis, these patients may also benefit from anti-IL-17-targeted biologics.
Dreiher, Jacob; Weitzman, Dahlia; Davidovici, Batya; Shapiro, Jonathan; Cohen, Arnon D
Previous reports demonstrated an association between psoriasis and the metabolic syndrome. The aim of this study was to elucidate the association between psoriasis and dyslipidaemia. A cross-sectional study was performed utilizing a population-based database. Psoriasis patients were compared with enrollees without psoriasis regarding the prevalence of dyslipidaemia and lipid levels. Comparison of lipid levels was performed on a "low-risk" subset of subjects without diabetes, hypertension and cardiovascular disease. The study included 10,669 psoriasis patients and 22,996 subjects without psoriasis. The prevalence of dyslipidaemia was significantly higher in psoriasis patients (odds ratio (OR) = 1.48, 95% confidence interval (CI) 1.40-1.55). The association remained significant after controlling for confounders (OR = 1.19, 95% CI 1.12-1.26, p < 0.001). In multivariate analysis of the "low-risk" subset, triglyceride levels were higher in psoriasis patients and high-density lipoprotein cholesterol levels were lower. This study supports previous reports of an association between psoriasis and lipid abnormalities.
Langley, R; Krueger, G; Griffiths, C
Psoriasis is a common chronic, recurrent, immune mediated disease of the skin and joints. It can have a significant negative impact on the physical, emotional, and, psychosocial wellbeing of affected patients. Psoriasis is found worldwide but the prevalence varies among different ethnic groups. It has a strong genetic component but environmental factors such as infections can play an important role in the presentation of disease. There are several clinical cutaneous manifestations of psoriasis but most commonly the disease presents as chronic, symmetrical, erythematous, scaling papules and plaques. The epidemiology, clinical features, and impact on quality of life of psoriasis are reviewed. PMID:15708928
Chandran, Nisha S; Greaves, Malcolm; Gao, Fei; Lim, Laurence; Cheng, Bob C L
There is little published data on the incidence of eye disease in Asian patients with psoriasis. We determined the frequency of ocular complications in Singaporean Asian patients with chronic plaque psoriasis and related these to extent and severity of psoriasis, family history, treatment and presence of arthritis. A cross-sectional prevalence investigation was carried out in 100 patients who received a comprehensive eye examination. Psoriasis extent and severity was graded by the Lattice System Physician's Global Assessment (LS-PGA). Two patients (four eyes) had uveitis, one of whom had psoriatic arthritis (2% incidence). Presence or absence of uveitis correlated with mean LS-PGA scores. Sixty-three patients had cataract unrelated to previous steroid or phototherapy treatment; in younger (<50 years) patients they were commoner than in those with higher (>5) LS-PGA scores. Three eyes in two patients (2% prevalence) had glaucomatous optic neuropathy unrelated to previous treatment, and comparable with expected population frequency. These findings, although limited by lack of data from a comparable control population, suggest that eye complications are common in Asian patients with psoriasis and eye symptoms should be elicited during history taking. Besides signs and symptoms of eye disease, an LS-PGA score of more than 5 should prompt referral for ophthalmological examination.
Bracke, S; Desmet, E; Guerrero-Aspizua, S; Tjabringa, S G; Schalkwijk, J; Van Gele, M; Carretero, M; Lambert, J
Diseases of the skin are amenable to RNAi-based therapies and targeting key components in the pathophysiology of psoriasis using RNAi may represent a successful new therapeutic strategy. We aimed to develop a straightforward and highly reproducible in vitro psoriasis model useful to study the effects of gene knockdown by RNAi and to identify new targets for topical RNAi therapeutics. We evaluated the use of keratinocytes derived from psoriatic plaques and normal human keratinocytes (NHKs). To induce a psoriatic phenotype in NHKs, combinations of pro-inflammatory cytokines (IL-1α, IL-17A, IL-6 and TNF-α) were tested. The model based on NHK met our needs of a reliable and predictive preclinical model, and this model was further selected for gene expression analyses, comprising a panel of 55 psoriasis-associated genes and five micro-RNAs (miRNAs). Gene silencing studies were conducted by using small interfering RNAs (siRNAs) and miRNA inhibitors directed against potential target genes such as CAMP and DEFB4 and miRNAs such as miR-203. We describe a robust and highly reproducible in vitro psoriasis model that recapitulates expression of a large panel of genes and miRNAs relevant to the pathogenesis of psoriasis. Furthermore, we show that our model is a powerful first step model system for testing and screening RNAi-based therapeutics.
Chong, Benjamin F.; Wong, Henry K.
The pathogenesis of various inflammatory cutaneous diseases such as psoriasis, atopic dermatitis and mycosis fungoides relies greatly on the abnormal function of T cells. Fundamental knowledge of the role of T cells in the cutaneous immune response has led to the development and production of biologic molecules designed to block T cell function at various steps, specifically activation (i.e. alefacept, efalizumab), trafficking into inflamed skin (i.e. efalizumab) and effector function under cytokine control (i.e. etanercept, infliximab, adalimumab, and anti-IL-12 antibody). We review the immune abnormalities and the role of T cells in psoriasis, and the recent biologic therapies, which share the common mission to hinder T cell activity in inflammatory diseases. An advantage from the preciseness of these biologic therapies is the potential limit of non-specific and potentially devastating organ toxicity, which commonly plagues other systemic therapies. PMID:17317321
Cengiz, Fatma Pelin; Emiroglu, Nazan; Bahali, Anil Gulsel; Ozkaya, Dilek Biyik; Su, Ozlem; Onsun, Nahide
Background: There is limited data about the relationship between psoriasis and melanocytic lesions and melanoma. Immunologic pathways which were implicated in psoriasis induce a reduction in the number of melanocytic nevi. Aims and Objectives: To investigate the number of melanocytic nevi in psoriatic patients compared with controls and its relationship with disease severity and type of treatment. Methods: We performed a prospective study in 100 psoriatic patients and 100 controls. Clinical data were recorded for all participants. Results: As compared with controls, patients had overall fewer nevi congenital nevi. Among psoriatic patients, biologic agents and disease severity did not correlate with the number of nevi. Conclusions: Psoriatic patients have fewer nevi than controls. Frequency of nevi in psoriatic patients is not related to treatment and disease severity. PMID:27904187
Padhi, Tanmay; Garima
Metabolic syndrome (Met S) is a clustering of risk factors comprising of abdominal obesity, dyslipidemia, elevated blood pressure, and abnormal glucose tolerance. The prevalence of Met S has been increasing in the last few years throughout the world. Psoriasis has consistently been associated with Met S as well as its various components. However, the association is no longer limited to psoriasis alone. Various dermatological conditions such as lichen planus, androgenetic alopecia, systemic lupus erythematosus, skin tags, acanthosis nigricans, and even cutaneous malignancies have also been found to be associated with this syndrome. Though chronic inflammation is thought to be the bridging link, the role of oxidative stress and endocrine abnormalities has recently been proposed in bringing them together. PMID:23919003
Veale, D; Ritchlin, C; FitzGerald, O
Psoriatic arthritis (PsA) is characterised by several unique clinical features that differentiate it from rheumatoid arthritis (RA). Attempts to identify immunopathological mechanisms, some shared with psoriasis, that underlie these differences from RA have been most challenging. Recent research studies, however, highlight novel findings in PsA at the molecular, cellular, and tissue levels that form the basis for a new understanding of this relatively common form of inflammatory arthritis. In particular, the availability of new, biological antitumour necrosis factor α therapies have allowed further insight into the immunopathology of psoriasis and PsA. This brief review focuses on immunohistological studies in psoriatic skin, PsA synovium, and bone to demonstrate how these data advance our knowledge of disease pathogenesis. PMID:15708930
Harden, Jamie L; Krueger, James G; Bowcock, Anne M
Psoriasis vulgaris is a common, chronic inflammatory skin disease with a complex etiology involving genetic risk factors and environmental triggers. Here we describe the many known genetic predispositions of psoriasis with respect to immune genes and their encoded pathways in psoriasis susceptibility. These genes span an array of functions that involve antigen presentation (HLA-Cw6, ERAP1, ERAP2, MICA), the IL-23 axis (IL12Bp40, IL23Ap19, IL23R, JAK2, TYK2), T-cell development and T-cells polarization (RUNX1, RUNX3, STAT3, TAGAP, IL4, IL13), innate immunity (CARD14, c-REL, TRAF3IP2, DDX58, IFIH1), and negative regulators of immune responses (TNIP1, TNFAIP3, NFKBIA, ZC3H12C, IL36RN, SOCS1). The contribution of some of these gene products to psoriatic disease has also been revealed in recent years through targeting of key immune components, such as the Th17/IL-23 axis which has been highly successful in disease treatment. However, many of the genetic findings involve immune genes with less clear roles in psoriasis pathogenesis. This is particularly the case for those genes involved in innate immunity and negative regulation of immune specific pathways. It is possible that risk alleles of these genes decrease the threshold for the initial activation of the innate immune response. This could then lead to the onslaught of the pathogenic adaptive immune response known to be active in psoriatic skin. However, precisely how these various genes affect immunobiology need to be determined and some are speculated upon in this review. These novel genetic findings also open opportunities to explore novel therapeutic targets and potentially the development of personalized medicine, as well as discover new biology of human skin disease.
Kelley, Nicola Louise
In summary, this patient has had a very positive experience with his UVB phototheapy treatment. The flaking of the skin has stopped which has made him less conscious in social situations and he is much more comfortable around other people. Being able to observe the improvement in his psoriasis through photography has increased the patient’s confidence and he hopes that the improvement in his condition will continue.
Van de Velde, Vanessa; Tidman, Michael J
There is no standard definition regarding the severity of psoriasis, and a number of factors should be considered, including the extent and stability of skin disease, involvement of joints, response to treatment, and impact on quality of life. Erythrodermic psoriasis and pustular psoriasis are severe conditions and the patient may be systemically unwell and febrile. NICE recommends that four key areas should be evaluated and recorded when assessing patients: severity, using the static Physician's Global Assessment (sPGA); disease impact on physical, psychological and social wellbeing using the Dermatology Life Quality Index (DLQI); the presence of psoriatic arthritis; and comorbidities. Ideally, patients should be assessed annually for psoriatic arthritis: the Psoriasis Epidemiology Screening Tool is a validated tool to screen for psoriatic arthritis in primary and secondary care. Patients with severe psoriasis should undergo cardiovascular risk assessment at presentation and every five years, or more frequently if indicated. Referral to secondary care should be made for patients with any type of psoriasis with poor response to topical therapy (after 2 or 3 months according to SIGN) and for extensive psoriasis. Cases where the psoriasis is having a significant physical or psychological impact on an individual's quality of life warrant early referral, as do those where the diagnosis is uncertain. Patients with generalised pustular psoriasis or erythroderma should be referred urgently for same-day specialist input. Patients with acute guttate psoriasis who may require phototherapy should also be referred. Children and adolescents with any type of psoriasis should be referred to a specialist at initial presentation.
Koch, Manja; Baurecht, Hansjörg; Ried, Janina S; Rodriguez, Elke; Schlesinger, Sabrina; Volks, Natalie; Gieger, Christian; Rückert, Ina-Maria; Heinrich, Luise; Willenborg, Christina; Smith, Catherine; Peters, Annette; Thorand, Barbara; Koenig, Wolfgang; Lamina, Claudia; Jansen, Henning; Kronenberg, Florian; Seissler, Jochen; Thiery, Joachim; Rathmann, Wolfgang; Schunkert, Heribert; Erdmann, Jeanette; Barker, Jonathan; Nair, Rajan P; Tsoi, Lam C; Elder, James T; Mrowietz, Ulrich; Weichenthal, Michael; Mucha, Sören; Schreiber, Stefan; Franke, Andre; Schmitt, Jochen; Lieb, Wolfgang; Weidinger, Stephan
Psoriasis has been linked to cardiometabolic diseases, but epidemiological findings are inconsistent. We investigated the association between psoriasis and cardiometabolic outcomes in a German cross-sectional study (n=4,185) and a prospective cohort of German Health Insurance beneficiaries (n=1,811,098). A potential genetic overlap was explored using genome-wide data from >22,000 coronary artery disease and >4,000 psoriasis cases, and with a dense genotyping study of cardiometabolic risk loci on 927 psoriasis cases and 3,717 controls. After controlling for major confounders, in the cross-sectional analysis psoriasis was significantly associated with type 2 diabetes (T2D, adjusted odds ratio (OR)=2.36; 95% confidence interval CI=1.26-4.41) and myocardial infarction (MI, OR=2.26; 95% CI=1.03-4.96). In the longitudinal study, psoriasis slightly increased the risk for incident T2D (adjusted relative risk (RR)=1.11; 95% CI=1.08-1.14) and MI (RR=1.14; 95% CI=1.06-1.22), with highest risk increments in systemically treated psoriasis, which accounted for 11 and 17 excess cases of T2D and MI per 10,000 person-years. Except for weak signals from within the major histocompatibility complex, there was no evidence of genetic risk loci shared between psoriasis and cardiometabolic traits. Our findings suggest that psoriasis, in particular severe psoriasis, increases the risk for T2D and MI, and that the genetic architecture of psoriasis and cardiometabolic traits is largely distinct.
Sarkar, Rashmi; Chugh, Shikha; Bansal, Shivani
Psoriasis generally does not affect survival but has significant detrimental effect on quality of life (QOL), which may be comparable to that of ischemic heart disease, diabetes, depression, and cancer. The foremost important thing in the management of psoriasis is counseling of the patient. The clinician needs to be empathetic and spend adequate time with the patient and educating the patient about psoriasis. Clinicians should make it clear to the patient that the primary goal of treatment is control of the disease rather than cure. Eating a balanced and low glycemic diet could be an important adjuvant factor in the prevention and treatment of moderate nonpustular psoriasis. Obese people are more likely to have severe psoriasis and psoriatic arthritis than people with an average body mass index. Dietary supplementation with oily fish, rich in n-3 fatty acids, in psoriasis had shown mixed results in trials. Promising results have been documented for parenteral application of n-3 fatty acid, but not with oral supplementation. Increased smoking or alcohol abuse increases the risk of developing psoriasis and may influence disease severity, and hence must be avoided. Soaking in warm water with bath oil can be done in extensive psoriasis for hydration and emollient effect, and bland soaps or soap substitutes should be used; antiseptics should be avoided as they may irritate the skin. Relatively small, localized patches of psoriasis may improve with occlusion, i.e., waterproof adhesive dressings. The use of emollients is an internationally accepted standard adjunctive to the treatment of psoriasis. Dermatology Life Quality Index is a psychometrically sound and responsive measure of psoriasis-specific outcomes and most comprehensively captures the impact of clinical signs and symptoms on patient's well-being. PMID:27990382
Koch, Manja; Baurecht, Hansjörg; Ried, Janina S.; Rodriguez, Elke; Schlesinger, Sabrina; Volks, Natalie; Gieger, Christian; Rückert, Ina-Maria; Heinrich, Luise; Willenborg, Christina; Smith, Catherine; Peters, Annette; Thorand, Barbara; Koenig, Wolfgang; Lamina, Claudia; Jansen, Henning; Kronenberg, Florian; Seissler, Jochen; Thiery, Joachim; Rathmann, Wolfgang; Schunkert, Heribert; Erdmann, Jeanette; Barker, Jonathan; Nair, Rajan P; Tsoi, Lam C; Elder, James T; Mrowietz, Ulrich; Weichenthal, Michael; Mucha, Sören; Schreiber, Stefan; Franke, Andre; Schmitt, Jochen; Lieb, Wolfgang; Weidinger, Stephan
Psoriasis has been linked to cardiometabolic diseases, but epidemiological findings are inconsistent. We investigated the association between psoriasis and cardiometabolic outcomes in a German cross-sectional study (n=4.185) and a prospective cohort of German Health Insurance beneficiaries (n=1.811.098). A potential genetic overlap was explored using genome-wide data from >22.000 coronary artery disease (CAD) and >4.000 psoriasis cases, and with a dense genotyping study of cardiometabolic risk loci on 927 psoriasis cases and 3.717 controls. Controlling for major confounders, in the cross-sectional analysis psoriasis was significantly associated with type 2 diabetes (T2D, adjusted odd’s ratio OR=2.36; 95% confidence interval CI=1.26–4.41) and myocardial infarction (MI, OR=2.26, 95% CI=1.03–4.96). In the longitudinal study, psoriasis slightly increased the risk for incident T2D (adjusted relative risk RR=1.11; 95%CI=1.08–1.14) and MI (RR=1.14; 95%CI=1.06–1.22), with highest risk increments in systemically treated psoriasis, which accounted for 11 and 17 excess cases of T2D and MI per 10,000 person-years. Except for weak signals from within the MHC, there was no evidence for genetic risk loci shared between psoriasis and cardiometabolic traits. Our findings suggest that psoriasis, in particular severe psoriasis, increases risk for T2D and MI, and that the genetic architecture of psoriasis and cardiometabolic traits is largely distinct. PMID:25599394
Umair, Ayesha; Babaker, Zynab; SN, Azzeghaiby; Gazal, Giath; Sarraj, Faysal
The aim this article is to investigate the link between geographic tongue and psoriasis skin disease. Our review paper of the literature will handle strict study about the relation between geographic tongue and psoriasis. Our search has identified only limited studies available in English written literature starting from 2006-2013 using pubMed – indexed for MEDLINE. The result of this review suggests that geographic tongue may be an oral manifestation of psoriasis.There is no clear evidence in literature about association with gender and aetiology except one study which shows that benign migratory glossitis is more prevalent in young, nonsmoker and atopic or allergic individuals. Treatment for oral lesions is not standardized. A geographic tongue is significantly more frequent in psoriatic patients but only a limited data is available to date to strongly validate the association between these two entities.We recommend the general practitioner to have a good understanding about the clinical presentation, pathogenesis, diagnosis and treatment of this lesion. Psoriatic patients should be encouraged to undergo routine dental checkups. PMID:25584342
Psoriasis is a chronic inflammatory skin disease with a significant number of patients suffering from additional joint involvement and other co-morbidities. The precise pathomechanisms of this disease are still unknown. But based on recent findings a picture emerges putting a new subset of inflammatory T cells, so-called Th17 T cells, into the centre of psoriasis pathogenesis. These cells secrete interleukin (IL)-17 and a further set of so-called Th17 cytokines such as IL-21 and IL-22, the latter of which appears to significantly contribute to the epidermal changes observed in this disease. Differentiation and maintenance of Th17 cells depends on IL-23 and transforming growth factor (TGF)-beta, secreted by activated monocytes or macrophages within the dermal compartment. In recent years, a plethora of new treatment approaches was introduced using antibodies or small molecule inhibitors specifically targeting inflammatory cytokines, cellular receptors or signalling mechanisms. Based on current results from large clinical trials, a more individualized treatment for affected patients may be achieved in the near future. In this review, we summarize the current knowledge about treatment of psoriasis with biological agents targeting inflammatory mechanisms.
Sundarrajan, Sudharsana; Arumugam, Mohanapriya
Increasing epidemiological studies in patients with psoriasis report the frequent occurrence of one or more associated disorders. Psoriasis is associated with multiple comorbidities including autoimmune disease, neurological disorders, cardiometabolic diseases and inflammatory-bowel disease. An integrated system biology approach is utilized to decipher the molecular alliance of psoriasis with its comorbidities. An unbiased integrative network medicine methodology is adopted for the investigation of diseasome, biological process and pathways of five most common psoriasis associated comorbidities. A significant overlap was observed between genes acting in similar direction in psoriasis and its comorbidities proving the mandatory occurrence of either one of its comorbidities. The biological processes involved in inflammatory response and cell signaling formed a common basis between psoriasis and its associated comorbidities. The pathway analysis revealed the presence of few common pathways such as angiogenesis and few uncommon pathways which includes CCKR signaling map and gonadotrophin-realising hormone receptor pathway overlapping in all the comorbidities. The work shed light on few common genes and pathways that were previously overlooked. These fruitful targets may serve as a starting point for diagnosis and/or treatment of psoriasis comorbidities. The current research provides an evidence for the existence of shared component hypothesis between psoriasis and its comorbidities. PMID:26966903
MARINA, ELENA MIHAELA; BOTAR-JID, CAROLINA; BOLBOACA, SORANA DANIELA; ROMAN, IULIA IOANA; SENILA, CORINA SIMONA; MIHU, CARMEN MIHAELA; TATARU, DUMITRU ALEXANDRU
Background and aim Nail manifestations are often an overlooked aspect in psoriatic disease, cutaneous and joint involvement being far more often reported and investigated. The reported prevalence of nail changes varies in literature, specific fingernail clinical features having different degrees of occurrence. The aim of this study was to describe specific clinical patterns of fingernail alterations in adult patients with plaque-type psoriasis in a university hospital in the North-West of Romania. Methods Clinical data of 35 patients with fingernail psoriasis were collected and analyzed. Psoriasis Area and Severity Index (PASI) and Nail Psoriasis Severity Index (NAPSI) scores were used to quantify disease extension in each patient. Results PASI score proved linearly correlated with NAPSI score (p<0.05). The age of onset of fingernail psoriasis was positively correlated with age of onset cutaneous psoriasis (p<0.0001). Furthermore, the duration of cutaneous involvement and NAPSI proved significantly related (p<0.05). The third fingernail in the right hand and first fingernail in the left hand were in most of the cases severely affected. The most common observed nail pattern was pitting, followed by salmon patches and subungual hyperkeratosis. Conclusion Important nail changes appear even in moderate forms of cutaneous psoriasis. Particular localization of specific fingernail psoriasis pattern enables the possibility of detecting early stage disease. PMID:28246493
Bilgiç, Özlem; Sivrikaya, Abdullah; Toker, Aysun; Ünlü, Ali; Altınyazar, Cevdet
Tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) has been implicated in the pathogenesis of a variety of inflammatory disorders and autoimmune diseases. However, studies conducted on the relationship of TWEAK and psoriasis patients are limited. In this study, we aimed to explore the serum levels of TWEAK and investigated whether TWEAK levels are associated with clinical variables and expression of other well-known psoriasis-related cytokines including IL-6, IL-23 and TNF-α. Forty-five patients with chronic plaque psoriasis and 43 controls were enrolled in this study. The severity of psoriasis was assessed by the Psoriasis Area and Severity Index (PASI). Serum levels of cytokines were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits. The mean TWEAK, IL-6, IL-23, and TN-α levels were significantly higher in psoriasis patients than in control subjects. However, there were no significant correlations between the psoriasis severity, the illness duration and serum cytokine levels. This study shows that TWEAK may be associated with the pathogenesis of psoriasis, like TNF-α, IL-6, and IL-23.
Sundarrajan, Sudharsana; Arumugam, Mohanapriya
Increasing epidemiological studies in patients with psoriasis report the frequent occurrence of one or more associated disorders. Psoriasis is associated with multiple comorbidities including autoimmune disease, neurological disorders, cardiometabolic diseases and inflammatory-bowel disease. An integrated system biology approach is utilized to decipher the molecular alliance of psoriasis with its comorbidities. An unbiased integrative network medicine methodology is adopted for the investigation of diseasome, biological process and pathways of five most common psoriasis associated comorbidities. A significant overlap was observed between genes acting in similar direction in psoriasis and its comorbidities proving the mandatory occurrence of either one of its comorbidities. The biological processes involved in inflammatory response and cell signaling formed a common basis between psoriasis and its associated comorbidities. The pathway analysis revealed the presence of few common pathways such as angiogenesis and few uncommon pathways which includes CCKR signaling map and gonadotrophin-realising hormone receptor pathway overlapping in all the comorbidities. The work shed light on few common genes and pathways that were previously overlooked. These fruitful targets may serve as a starting point for diagnosis and/or treatment of psoriasis comorbidities. The current research provides an evidence for the existence of shared component hypothesis between psoriasis and its comorbidities.
Kondo, Rogerio Nabor; Araújo, Fernanda Mendes; Pereira, Allamanda Moura; Lopes, Vivian Cristina Holanda; Martins, Ligia Márcia Mario
Impetigo herpetiformis is a rare dermatosis of pregnancy with typical onset during the last trimester of pregnancy and rapid resolution in the postpartum period. Clinically and histologically, it is consistent with pustular psoriasis. This similarity has led some authors to name the disease "the pustular psoriasis of pregnancy". We report the case of a patient who developed impetigo herpetiformis in two successive pregnancies.
Kaplan, Mariana J
Psoriasis is associated to an increased risk of cardiovascular (CV) complications. Overall, the pathogenic mechanisms involved in premature CV complications in psoriasis appear to be complex and multifactorial, with traditional and nontraditional risk factors possibly contributing to the increased risk. Based on what is known about the pathogenesis of psoriasis and extrapolating the current knowledge on CV complications in other inflammatory diseases, studies are needed to investigate if appropriate control of the inflammatory, immunologic and metabolic disturbances present in psoriasis can prevent the development of this potentially lethal complication. It is clear that there is a great need for heightened awareness of the increased risk for vascular damage in patients with psoriasis. It is also crucial to closely monitor patients with psoriasis for CV risk factors including obesity, hypertension, diabetes, and hyperlipidemia. Whether treatment regimens that effectively manage systemic inflammation will lead to prevention of CV complications in psoriasis needs to be investigated. Clearly, studies should focus on establishing the exact mechanisms that determine CV risk in psoriasis so that appropriate preventive strategies and treatment guidelines can be established. PMID:19337536
... seen in psoriasis, is associated with cardiovascular disease, diabetes, and obesity. "We are looking beyond psoriasis as a cosmetic disease, at all its potential effects," says Mehta. "Our participants are ... developing heart disease or diabetes, Donahue can't be sure and admits to ...
Chalmers, Robert J G
Psoriasis is a complex disease. Dermatologists have not documented psoriasis severity, except in clinical trials; doing so requires tools for assessing psoriasis and an understanding of what changes in those assessments mean in terms of outcome. Two psoriasis assessment tools have dominated: The Psoriasis Area and Severity Index and the Dermatology Life Quality Index. There are advantages and disadvantages to each. Newer instruments may not be more suitable for documenting psoriasis. There may be benefits in terms of patient ownership of disease management from using self-assessment tools for documenting severity, for example, the Self-assessment version of the Simplified Psoriasis Index.
Oram, Yasemin; Akkaya, A. Deniz
The lifetime incidence of nail involvement in psoriatic patients is estimated to be 80–90%, and the nails can be affected in 10% to 55% of psoriatic patients. Psoriasis may also solely involve the nails, without any other skin findings, in which the treatment can be more challenging. Nail psoriasis may lead to considerable impairment in quality of life due to aesthetic concerns and more importantly limitations in daily activities resulting from the associated pain, which may be overlooked by the physicians. Several topical and systemic treatment modalities, as well as radiation and light systems, have been used in the treatment of nail psoriasis. In the last decade, the introduction of biologic agents and the utilization of laser systems have brought a new insight into the treatment of nail psoriasis. This paper focuses on the recent advances, as well as the conventional methods, in treating nail psoriasis in adults and children, in reference to an extensive literature search. PMID:23762032
Wagner, Erwin F; Schonthaler, Helia B; Guinea-Viniegra, Juan; Tschachler, Erwin
Psoriasis is a common inflammatory skin disease of unknown etiology, for which there is no cure. This heterogeneous, cutaneous, inflammatory disorder is clinically characterized by prominent epidermal hyperplasia and a distinct inflammatory infiltrate. Crosstalk between immunocytes and keratinocytes, which results in the production of cytokines, chemokines and growth factors, is thought to mediate the disease. Given that psoriasis is only observed in humans, numerous genetic approaches to model the disease in mice have been undertaken. In this Review, we describe and critically assess the mouse models and transplantation experiments that have contributed to the discovery of novel disease-relevant pathways in psoriasis. Research performed using improved mouse models, combined with studies employing human cells, xenografts and patient material, will be key to our understanding of why such distinctive patterns of inflammation develop in patients with psoriasis. Indeed, a combination of genetic and immunological investigations will be necessary to develop both improved drugs for the treatment of psoriasis and novel curative strategies.
Zisova, L; Valtchev, V; Sotiriou, E; Gospodinov, D; Mateev, G
1-3% of human population is affected by psoriasis. Nail disorders are reported in 10-80% of patients with psoriasis. Nail deformations vary according to their degree of severity but are mainly represented by pitting, Beau's lines, hyperkeratosis, onycholysis, leuconychia or oil drops. Onychomycosis is a fungal infection of the nails, caused by dermatophytes, yeast and moulds. In this study, 228 patients with psoriasis aged between 18 and 72 were examined (48 - from Plovdiv, Bulgaria; 145 - from Pleven, Bulgaria and 35 - from Thessaloniki, Greece); 145 of them were male and 83 of them were female. The examination of the nail material was performed via direct microscopy with 20% KOH and nail samples plated out on Sabouraud agar methodology. The severity of the nail disorders was determined according to the Nail Psoriasis Severity Index (NAPSI). Positive mycological cultures were obtained from 62% of the patients with psoriasis (52%- Plovdiv, Bulgaria; 70%- Pleven, Bulgaria and 43%- Thessaloniki, Greece). In 67% of the cases, the infection was caused by dermatophytes, in 24% by yeast, in 6% by moulds and in 3% by a combination of causes. All patients with psoriasis were identified with high levels of NAPSI, whereas the ones with isolated Candida had even higher levels. Seventeen percentage of the patients have been treated with methotrexate, 6% have been diagnosed with diabetes and 22% have been reported with onychomycosis and tinea pedis within the family. An increased prevalence of onychomycosis among the patients with psoriasis was found. Dystrophic nails in psoriasis patients are more predisposed to fungal infections. The mycological examination of all psoriasis patients with nail deformations is considered obligatory because of the great number of psoriasis patients diagnosed with onychomycosis.
Dogan, Sibel; Atakan, Nilgün; Kurne, Asli; Karabudak, Rana
Psoriasis was recently accepted as an autoimmune T cell-mediated disease. Various autoimmune disease associations for psoriasis have been defined, including multiple sclerosis, a model autoimmune demyelinating neurologic disorder. In this study, the familial frequency of psoriasis in a Turkish multiple sclerosis cohort was investigated, and a higher frequency of psoriasis was found, supporting the presence of a complex background of autoimmunity underlying psoriasis.
Kwon, Hyuck Hoon; Na, Sun Jae; Jo, Seoung Jin; Youn, Jai Il
Few epidemiological studies of pediatric patients with moderate to severe psoriasis have been available despite there being no approved systemic therapy for these patients. The aim of the present study was to elucidate clinical features of pediatric psoriasis in a tertiary referral psoriasis clinic. We analyzed the clinical data of 358 patients under 18 years of age referred to our clinic from other private clinics and medical centers. Our data showed a male :female ratio of 1.06:1 and a peak age of onset of 10-11 years. Of the patients, 32.4% had a positive family history. The most prevalent phenotype was plaque type (67.3%) and the mean Psoriasis Area and Severity Index score was 17.2 ± 12.7. The most frequently affected body part was the trunk (69.5%), followed by the legs (65.3%). Exposure to sunlight and summer season improved psoriatic lesions, while stress and winter season aggravated the clinical course. Only 26.0% of patients received systemic therapy or phototherapy during the therapeutic course. Oral acitretin (11.2%) was most frequently used followed by ultraviolet B phototherapy (7.3%). The childhood group (<13 years) showed higher prevalence of guttate and generalized pustular phenotypes and more severe clinical course compared with the adolescent group (13-18 years). In conclusion, our patients showed distinctive features in clinical phenotypes, disease severity and affected body parts compared with previous reports. We also found that clinical application of systemic therapies were limited considering the severe disease state of our patients, demanding a need for more research on treatment of pediatric psoriasis.
Reich, K; Mrowietz, U; Radtke, M A; Thaci, D; Rustenbach, S J; Spehr, C; Augustin, M
The German Psoriasis Registry PsoBest was conducted in 2008 in order to investigate the long-term outcomes and safety of systemic treatments for moderate-to-severe psoriasis. Safety analysis of antipsoriatic drugs with special focus on serious adverse events (SAE) for infections, malignancies and major cardiac events (MACE) was done. Nationwide non-interventional patient treatment registry conducted in 251 active dermatology centers. Until June 2012, n = 2444 patients [40 % female; mean age 47.3 (SD 14.1) years; mean duration of disease 18.2 (SD 14.7) years] were recruited, including n = 1791 patients (3842 patient years) with conventional systemic drugs and n = 908 (3442 patient years) with biological drugs. Mean PASI (Psoriasis Area and Severity Index) at inclusion was 14.7, mean DLQI (Dermatology Life Quality Index) 11.1, mean BMI (Body Mass Index) 28.2. The overall rate of SAE per 100 patient years were 1.3 (SD 0.9) per 100 patient years in conventional systemic and 1.5 (SD 1.2) in biologics (p > 0.5, no significant difference). The rates per 100 patient years for single severe adverse events were as follows (systemic/biologics): serious infections, 0.33/0.65 [CI (confidence interval) 0.13-0.54/0.35-0.98]; MACE, 0.56/0.77 (CI 0.29-0.97/0.41-1.31); malignancies (except non-melanoma skin cancer), 0.46/0.49 (CI 0.22-0.84/0.21-0.97). There were no significant differences between single drugs in any of the safety parameters. The conventional systemic and biologic drugs for psoriasis show satisfying safety under routine psoriasis care in Germany with respect to infections, MACE and malignancies.
Medvedev, Boris A.; Tuchin, Valery V.; Yaroslavsky, Ilya V.
In order to optimize laser PUVA psoriasis treatment we develop the mathematical model of the dynamics of cell processes within epidermis. We consider epidermis as a structure consisting of N cell monolayers. There are four kinds of cells that correspond to four epidermal strata. The different kinds of cells can exist within a given monolayer. We assume that the following cell processes take place: division, death and transition from one stratum to the following. Discrete transition of cells from stratum j to j + 1 approximates to real differentiation.
Harden, Jamie L; Lewis, Steven M; Pierson, Katherine C; Suárez-Fariñas, Mayte; Lentini, Tim; Ortenzio, Francesca S; Zaba, Lisa C; Goldbach-Mansky, Raphaela; Bowcock, Anne M; Lowes, Michelle A
Mutations in the caspase recruitment domain, family member 14 (CARD14) gene have recently been described in psoriasis patients, and explain the psoriasis susceptibility locus 2 (PSORS2). CARD14 is a scaffolding protein that regulates NF-κB activation, and psoriasis-associated CARD14 mutations lead to enhanced NF-κB signaling. CARD14 is expressed mainly in epidermal keratinocytes, but also in unidentified dermal cells. In this manuscript, the identity of the dermal cell types expressing CARD14, as well the potential functional consequence of overactive CARD14 in these dermal cell types, was determined. Using two-color immunofluorescence, dermal CARD14 did not co-localize with T-cells, dendritic cells, or macrophages. However, dermal CARD14 did highly co-localize with CD31(+) endothelial cells (ECs). CARD14 was also expressed non-dermal endothelial cells, such as aortic endothelial cells, which may indicate a role of CARD14(+)ECs in the systemic inflammation and cardiovascular comorbidities associated with psoriasis. Additionally, phosphorylated NF-κB was found in psoriatic CARD14(+) CD31(+) ECs, demonstrating this pathway is active in dermal ECs in psoriasis. Transfection of dermal ECs with psoriasis-associated CARD14 mutations resulted in increased expression of several chemokines, including CXCL10, IL-8, and CCL2. These results provide preliminary evidence that CARD14 expression in ECs may contribute to psoriasis through increased expression of chemokines and facilitating recruitment of immune cells into skin.
Ryan, Caitriona; Korman, Neil J; Gelfand, Joel M; Lim, Henry W; Elmets, Craig A; Feldman, Steven R; Gottlieb, Alice B; Koo, John Y M; Lebwohl, Mark; Leonardi, Craig L; Van Voorhees, Abby S; Bhushan, Reva; Menter, Alan
Over the past 2 decades, considerable progress has been made to further elucidate the complex pathogenesis of psoriasis, facilitating the development of a new armamentarium of more effective, targeted therapies. Despite these important advances, substantial deficits remain in our understanding of psoriasis and its treatment, necessitating further research in many areas. In the sixth section of the American Academy of Dermatology Psoriasis Guidelines of Care, gaps in research and care were identified. We discuss the most important gaps in research that currently exist and make suggestions for studies that should be performed to address these deficits. These encompass both basic science and clinical research studies, including large, prospective epidemiologic studies to determine the true prevalence and natural history of psoriasis; further molecular studies in patients with psoriatic and psoriatic arthritis to understand the function of psoriasis susceptibility genes and to identify novel therapeutic targets; studies to examine the role of environmental factors in the development of psoriasis; further investigation of the relationship between psoriasis and cardiometabolic disease; studies that examine the role of adjunctive therapies such as psychological interventions in appropriate patient groups; and finally, studies to identify biomarkers of disease severity and treatment response to optimize patient therapy.
Ma, Guoli; He, Bei; Yang, Wenming; Shu, Chang
This paper proposes an interactive psoriasis lesion segmentation algorithm based on Gaussian Mixture Model (GMM). Psoriasis is an incurable skin disease and affects large population in the world. PASI (Psoriasis Area and Severity Index) is the gold standard utilized by dermatologists to monitor the severity of psoriasis. Computer aid methods of calculating PASI are more objective and accurate than human visual assessment. Psoriasis lesion segmentation is the basis of the whole calculating. This segmentation is different from the common foreground/background segmentation problems. Our algorithm is inspired by GrabCut and consists of three main stages. First, skin area is extracted from the background scene by transforming the RGB values into the YCbCr color space. Second, a rough segmentation of normal skin and psoriasis lesion is given. This is an initial segmentation given by thresholding a single gaussian model and the thresholds are adjustable, which enables user interaction. Third, two GMMs, one for the initial normal skin and one for psoriasis lesion, are built to refine the segmentation. Experimental results demonstrate the effectiveness of the proposed algorithm.
Gisondi, Paolo; Del Giglio, Micol; Girolomoni, Giampiero
Psoriasis is an immune-mediated inflammatory skin disease frequently associated with metabolic disorders, including diabetes, dyslipidaemia and metabolic syndrome. Moreover, a growing number of studies confirm the association between psoriasis and obesity. It has been found that obesity, as measured by body mass index >30 kg/m(2), can double the risk of incident psoriasis. A positive correlation between different measures of adiposity and the severity of psoriasis has also been reported. Epidemiologic studies have also provided robust evidence confirming the association between obesity and psoriatic arthritis. Genetic, metabolic and environmental factors are all likely to contribute to these associations. Adipose tissue is an active endocrine and paracrine organ that has a key role in lipid and glucose metabolism as well as inflammation. Fat tissue is traditionally distributed into two main compartments with different metabolic characteristics, i.e. the subcutaneous and visceral adipose tissue. Particular attention has been devoted to visceral adiposity because of its contribution to inflammation and atherosclerosis. The association between psoriasis and obesity should be properly considered when choosing a systemic treatment, because it could exert negative effects on metabolic parameters, including liver enzymes, serum lipids and renal function. Obesity may increase the risk of liver and renal toxicity from methotrexate and cyclosporine. Moreover, obesity can compromise the effectiveness of systemic treatments for psoriasis (conventional and biological therapies). Dermatologists are also expected to promote a healthy lifestyle and weight loss for obese patients because they could improve metabolic parameters and responsiveness to psoriasis therapies.
Farshchian, Mahmoud; Ansar, Akram; Sobhan, Mohammadreza
Background Psoriasis is a common chronic inflammatory skin disease. There is overwhelming evidence on the higher risk of cardiovascular diseases in patients with psoriasis as a result of hyperlipidemia, which is more common in these patients. Objectives The aim of this study was to elucidate the association between the cardiovascular risk factors and psoriasis. Methods In a cross-sectional study, 55 patients with psoriasis and 55 matched (sex and age) controls were entered the study at the Department of Dermatology between March 2011 and March 2013. Blood samples were obtained following 14 hours fasting status and serum levels of triglyceride, cholesterol, high-density lipoprotein, and low-density lipoprotein were determined using standard laboratory methods, and other variables such as sex, age, smoking, alcohol consumption, and the type of disease were recorded. Results Our findings showed that levels of triglyceride, low-density lipoprotein, and smoking were significantly higher in psoriatic patients when compared with controls, whereas the level of high-density lipoprotein and cholesterol was not significantly different between two groups. Body mass index of psoriatic patients was not significantly higher than controls. Patients with psoriasis also had an increased prevalence of hypertension. Conclusion Our findings further verify lipid abnormalities in psoriatic patients. Psoriasis is associated with higher rate of hypertension, which may be resulted in increasing the risk of cardiovascular diseases in these patients. Thus, serum lipid profile and blood pressure in all patients with psoriasis, regardless of disease severity, deserve consideration to be checked. PMID:26300652
Burden-Teh, E; Thomas, K S; Ratib, S; Grindlay, D; Adaji, E; Murphy, R
Psoriasis is an inflammatory noncommunicable skin disease that affects both adults and children. At present, the epidemiology and natural history of psoriasis are not widely understood. This scoping review aimed to map the existing literature on the epidemiology of childhood psoriasis, identify research gaps for future studies and provide a comprehensive, clinically useful review. Search strategies were developed for Ovid Medline, Ovid Embase, Google Scholar and hand searching. In total, 131 articles met the inclusion criteria and were mapped; 107 articles were included for data extraction. Over the last 25 years there has been a dramatic increase in the volume of published observational epidemiological studies on childhood psoriasis. The majority were case series or cross-sectional studies, concentrated in Europe, Asia and North America. The prevalence of childhood psoriasis was found to be higher in European countries, older children and girls. Up to 48·8% of children had a family history of psoriasis in a first-degree relative. The most frequent subtype was plaque psoriasis and the most common initial sites of presentation were the scalp, limbs and trunk. Specific genetic differences have been found between child-onset and adult-onset populations. Case-control and cohort studies investigating risk factors for psoriasis onset, comorbidities and long-term health outcomes were extremely limited. The choice of study design and heterogeneity in methodology limit the validity and generalizability of the information, consistency of the results, and comparability of the studies. Well-designed epidemiological studies are needed to provide precise and consistent information about the frequency and clinical presentation, risk factors, associated diseases and long-term outcomes in childhood psoriasis.
Deng, Yaxiong; Chang, Christopher; Lu, Qianjin
Psoriasis is a chronic inflammatory autoimmune disease characterized by an excessively aberrant hyperproliferation of keratinocytes. The pathogenesis of psoriasis is complex and the exact mechanism remains elusive. However, psoriasis is thought to result from a combination of genetic, epigenetic, and environmental influences. Recent studies have identified that epigenetic factors including dysregulated DNA methylation levels, abnormal histone modification and microRNAs expressions are involved in the development of psoriasis. The interplay of immune cells and cytokines is another critical factor in the pathogenesis of psoriasis. These factors or pathways include Th1/Th2 homeostasis, the Th17/Treg balance and the IL-23/Th17 axis. Th17 is believed particularly important in psoriasis due to its pro-inflammatory effects and its involvement in an integrated inflammatory loop with dendritic cells and keratinocytes, contributing to an overproduction of antimicrobial peptides, inflammatory cytokines, and chemokines that leads to amplification of the immune response. In addition, other pathways and signaling molecules have been found to be involved, including Th9, Th22, regulatory T cells, γδ T cells, CD8(+) T cells, and their related cytokines. Understanding the pathogenesis of psoriasis will allow us to develop increasingly efficient targeted treatment by blocking relevant inflammatory signaling pathways and molecules. There is no cure for psoriasis at the present time, and much of the treatment involves managing the symptoms. The biologics, while lacking the adverse effects associated with some of the traditional medications such as corticosteroids and methotrexate, have their own set of side effects, which may include reactivation of latent infections. Significant challenges remain in developing safe and efficacious novel targeted therapies that depend on a better understanding of the immunological dysfunction in psoriasis.
Wang, Y; Da, G; Yu, Y; Han, J; Li, H
Psoriasis vulgaris is an autoimmune chronic inflammatory skin disease, but its association with other typical autoimmune disease such as systemic lupus erythematosus has only occasionally been reported. We presented a 25-year-old female who developed systemic lupus erythematosus associated with psoriasis vulgaris. Her conditions were in good control after she got administration of prednisolone (5 mg/day) and Tripterygium Wilfordii Hook (20 mg/day). It is necessary to integrate past history and physical examination to diagnose coincident SLE and psoriasis, and combined treatment with prednisolone and Tripterygium Wilfordii Hook proves effective.
Constantin, M M; Poenaru, E; Constantin, T; Poenaru, C; Purcarea, V L; Mateescu, B R
An inflammatory, proliferative condition with chronic evolution and systemic response, psoriasis, is positioned today among the most common inflammatory skin diseases affecting the Caucasian population worldwide. With a significant incidence, psoriasis has been increasingly defined as a disease with a major impact on the patient's life and the society to which he/she belongs. This paper conducts an analysis of the currently available therapies for the treatment of moderate and severe psoriasis, therapies with biological agents obtained through sophisticated genetic engineering technologies. Recent research and the increasing interest in therapeutic methods as complete and efficient as possible make us optimistic and confident in the future.
Psoriasis skin lesions are characterized by dramatic changes in the transcriptome, reflecting altered activity of multiple signalling pathways in resident and infiltrating cells. miRNAs are small non-coding RNAs that have a large impact on cellular functions by regulating multiple genes simultaneously, and they have been shown to play key roles in skin homoeostasis and inflammation. In this commentary to the review article "MicroRNAs in Psoriasis: Immunological Functions and Potential Biomarkers" by Liu et al., the role of miRNAs in psoriasis and their diagnostic and therapeutic potential are discussed and remaining unanswered questions are highlighted.
Berki, Dorottya M; Liu, Lu; Choon, Siew-Eng; Burden, A David; Griffiths, Christopher E M; Navarini, Alexander A; Tan, Eugene S; Irvine, Alan D; Ranki, Annamari; Ogo, Takeshi; Petrof, Gabriela; Mahil, Satveer K; Duckworth, Michael; Allen, Michael H; Vito, Pasquale; Trembath, Richard C; McGrath, John; Smith, Catherine H; Capon, Francesca; Barker, Jonathan N
Caspase recruitment family member 14 (CARD14, also known as CARMA2), is a scaffold protein that mediates NF-κB signal transduction in skin keratinocytes. Gain-of-function CARD14 mutations have been documented in familial forms of psoriasis vulgaris (PV) and pityriasis rubra pilaris (PRP). More recent investigations have also implicated CARD14 in the pathogenesis of pustular psoriasis. Follow-up studies, however, have been limited, so that it is not clear to what extent CARD14 alleles account for the above conditions. Here, we sought to address this question by carrying out a systematic CARD14 analysis in an extended patient cohort (n=416). We observed no disease alleles in subjects with familial PV (n=159), erythrodermic psoriasis (n=23), acral pustular psoriasis (n=100), or sporadic PRP (n=29). Conversely, our analysis of 105 individuals with generalized pustular psoriasis (GPP) identified a low-frequency variant (p.Asp176His) that causes constitutive CARD14 oligomerization and shows a significant association with GPP in Asian populations (P=8.4×10(-5); odds ratio=6.4). These data indicate that the analysis of CARD14 mutations could help stratify pustular psoriasis cohorts but would be mostly uninformative in the context of psoriasis and sporadic PRP.
Huang, Kun; Chen, Aijun; Zhang, Xuemei; Song, Zhixin; Xu, Hongmei; Cao, Ju; Yin, Yibing
Progranulin (PGRN) is a multi-functional protein known to be involved in inflammation. Recent studies have found that PGRN has dual roles in inflammation and exerts anti-inflammatory and pro-inflammatory function in different diseases. However, the role of PGRN in psoriasis has not been fully elucidated. Here, we detected preferential expression of PGRN in human psoriatic lesions and serum. Moreover, serum PGRN/tumour necrosis factor-α ratio was negatively correlated with disease severity. To investigate the role of PGRN in the pathogenesis of psoriasis, we used wild-type (WT) and PGRN(-/-) mice in a model of 12-O-tetradecanoylphorbol 13-acetate (TPA) -induced psoriasis-like inflammation. We demonstrated that PGRN expression was dramatically enhanced in the psoriasis-like lesions of TPA-treated WT mice, in accordance with human psoriatic lesions. Surprisingly, PGRN(-/-) mice were more sensitive to the development of TPA-induced psoriasis-like inflammation. The mechanism underlying this increased sensitivity of PGRN(-/-) mice to TPA-induced psoriasis-like inflammation was impaired differentiation of regulatory T cells in lymph nodes and decreased recruitment of these cells in the affected skin, which results in more severe inflammation. Hence, in WT mice, PGRN promotes differentiation and recruitment of regulatory T cells at the site of inflammation, which protects the skin from an exaggerated psoriasis-like inflammatory response.
Perez, Juan J
Psoriasis is one of the most prevalent immune-mediated illness worldwide. The disease can still only be managed rather than cured, so treatments are aimed at clearing skin lesions and preventing their recurrence. Several treatments are available depending on the extent of the psoriatic lesion. Among the topical treatments corticostereoids, vitamin D3 analogs and retinoids are commonly used. However, these treatments may have adverse effects in the long term. Conversely, systemic conventional treatments include immunosuppresors such as cyclosporin or methotrexate associated with high toxicity levels. Biologicals are alternative therapeutical agents introduced in the last 10 years. These include fusion proteins or monoclonal antibodies designed to inhibit the action of specific cytokines or to prevent T-lymphocyte activation. However, due to recent knowledge on the etiology of the disease, diverse new small molecules have appeared as promising alternatives for the treatment of psoriasis. Among them, inhibitors of JAK3, inhibitors of PDE 4 and amygdalin analogs. The latter are promising small molecules presently in preclinical studies which are the object of the present report.
Puig, L; Julià, A; Marsal, S
Psoriasis vulgaris and psoriatic arthritis are interrelated disorders with an important genetic component. While linkage studies have identified several candidate loci and genes, only recent technological advances and extensive genome-wide association studies have provided robust evidence of associations between psoriasis and several genes inside and outside the major histocompatibility complex. Most of these genes can be incorporated into an integrated pathogenic model of psoriatic disease comprising distinct signaling networks affecting skin barrier function (LCE3, DEFB4, GJB2), innate immune responses involving nuclear factor-κB signaling (TNFAIP3, TNIP1, NFKBIA, REL, FBXL19, TYK2, NOS2, CARD14), and adaptive immune responses involving CD8 T cells and interleukin 23 (IL-23)/IL-17-mediated lymphocyte signaling (HLA-C, IL12B, IL23R, IL23A, TRAF3IP2, ERAP1). A better understanding of the potential gene/gene and gene/environment interactions and of the functions of altered transcripts will undoubtedly have nosologic, therapeutic and prognostic implications.
Estrada-Aguilar, Lorena; Amaya-Guerra, Mario; Gómez-Flores, Minerva; Guevara-Sanginés, Esther; Jurado-Santacruz, Fermín; Lopeztello-Santillán, Adriana; Maldonado-García, César; Rivera-Gómez, Mónica; Rodríguez-Martínez, Norma; Vega-González, Luis
Psoriasis is a chronic inflammatory disease with a worldwide prevalence between 6 and 39% in moderate to severe forms. In European countries like Germany and England was identified that only one third of patients with moderate to severe forms will receive systemic management, this fact motivated to integrate into Europe an international consensus on treatment goals with the aim of providing support to the dermatologist by algorithms that serve as a therapeutic guide that allows you to gain control short and long term effects of this disease. The European group met to develop the definitions of severity of psoriasis, treatment goals for moderate to severe disease, and optimization options and / or therapeutic transition than a paper published in 2011 was obtained. In Mexico a working group of experts on biological therapy (GTEB), made up of 10 members and an extended group of 150 dermatologists' voters in the country for the purpose of issuing Mexico's position on the proposals of the European group was formed. In this document the findings of the Working Group of Experts on Biological Therapy in Mexico are listed.
Creamer, D.; Allen, M.; Sousa, A.; Poston, R.; Barker, J.
Considerable evidence indicates that microvascular changes observed in psoriasis are a result of vascular proliferation. A critical step in the sequence of events leading to neovascularization involves interactions between endothelial cells and extracellular matrix proteins mediated in part by the integrin family of adhesion molecules. A number of endothelial integrins have been shown to participate in neovascularization, including members of the beta 1, beta 3, and beta 4 subfamilies. To investigate the role of these integrins in psoriasis, specimens of lesional and nonlesional skin were taken from 10 patients with active, untreated plaque disease. Vascular endothelium was labeled with monoclonal antibodies specific for alpha 2, alpha 5, alpha 6, beta 1, av beta 3, and beta 4 integrins. The use of image analysis permitted quantification of immunoperoxidase staining and comparison of endothelial labeling in lesional and nonlesional skin. There was a significant increase in endothelial staining of av beta 3 integrin in lesional compared with nonlesional skin, both in superficial and deep vasculature. In contrast, there was a significant decrease in endothelial beta 4 staining in lesional compared with nonlesional superficial dermal vessels, alpha 2, alpha 5, alpha 6, and beta 1 staining showed no significant difference between the two groups. These results demonstrate an important role of av beta 3 and beta 4 integrins in the microvascular changes of psoriatic lesions. Images Figure 1 Figure 3 PMID:7495291
Al-Mutairi, Nawaf; Shabaan, Dalia
Psoriasis is a chronic inflammatory disease that has been associated with an increased incidence of insulin resistance and diabetes mellitus (DM). Tumor necrosis factor (TNF) α inhibitors and IL-6 blockers, which are routinely used for the treatment of psoriasis, have been positively associated with insulin sensitivity. The aim of this study was to assess the effects of treatment with TNF-α inhibitors on insulin sensitivity in psoriatic patients with type 2 DM. This study confirms a beneficial effect of anti-TNF-α agents on insulin resistance and insulin sensitivity in psoriasis patients with type 2 DM.
Kim, Grace K.
Psoriasis is a commonly encountered dermatosis with a variety of internal and external paradoxical factors contributing to the clinical course of the disease. There are several drugs described in the literature that have been associated with the initiation, exacerbation, and aggravation of psoriasis. Understanding the pathophysiology can provide clues to treatment and management of drug-induced and drug-aggravated psoriasis, which may be indistinguishable from idiopathic psoriasis. The clinical manifestations of drug-associated psoriasis can range from plaque-type psoriasis to severe erythroderma, thus warranting astute and sustained clinical observation. PMID:20725536
Boza, Juliana Catucci; Basra, Mohammad K A; Vanin, Rafaela Caminha; Carvalho, Renata Rosa; Weber, Magda Blessmann; Cestari, Tania Ferreira
Psoriasis Family Index is a quality of life instrument for family members of patients with psoriasis developed in English. The aims of this study were to translate the Psoriasis Family Index into Brazilian Portuguese, culturally adapt it and verify its reliability and validity. The study followed these two steps: 1) Translation, linguistic and cultural adaptation, 2) Validation. The translated Psoriasis Family Index showed high internal consistency and high test-retest reliability, confirming its reproducibility. The Portuguese version of the Psoriasis Family Index was validated for our population and can be recommended as a reliable instrument to assess the QoL of family members and partners of patients with psoriasis.
Raposo, Inês; Torres, Tiago
Palmoplantar psoriasis and palmoplantar pustulosis are chronic skin diseases with a large impact on patient quality of life. They are frequently refractory to treatment, being generally described as a therapeutic challenge. This article aims to review the definitions of palmoplantar psoriasis and palmoplantar pustulosis, highlighting the similarities and differences in terms of epidemiology, clinical presentation, genetics, histopathology, and pathogenesis, as well as treatment options for both entities. Classical management of mild to moderate palmoplantar pustulosis and palmoplantar psoriasis relies on use of potent topical corticosteroids, phototherapy, and/or acitretin. Nevertheless, these drugs have proven to be insufficient in long-term control of extensive disease. Biologic therapy-namely, anti-interleukin-17 agents and phosphodiesterase type 4 inhibitors-has recently shown promising results in the treatment of palmoplantar psoriasis. Knowledge of the pathophysiologic pathways of both entities is of utmost importance and may, in the future, allow development of molecularly targeted therapeutics.
Dyring-Andersen, Beatrice; Skov, Lone; Zachariae, Claus
Psoriasis is a multifactorial chronic inflammatory skin disease of unknown etiology. Knowledge of the pathophysiology of psoriasis has evolved and identified IL-17 as a key pro-inflammatory mediator in psoriasis creating new medical avenues. Several agents targeting IL-17 or its receptor are in clinical trials for the treatment of moderate-to-severe psoriasis. This review focuses on the biological rationale and the results of clinical trials with ixekizumab, a humanized IgG4 monoclonal antibody. The currently available Phase I to III data indicate that ixekizumab is a well-tolerated promising drug, although long-term data of efficacy and safety are needed before ixekizumab and other IL-17 targeting therapeutics can find their place in clinical practice.
Farber, Eugene M.
Prevalence of psoriasis in Caucasians is estimated as 2 to 3 percent. Sound epidemiologic studies on a worldwide basis are needed to secure accurate prevalence rates for comparative purposes. Utilizing Stanford's psoriasis life histories records, the genetics of psoriasis has been explored by various means: statistical census data, pedigree analysis, and twin studies. This research suggests a multifactorial pattern of inheritance for psoriasis, implying that both genetic and environmental components are responsible for the manifestation of the disease. At present it is not possible to point to any single causative factor. Some of the suggested areas for research include study of uninvolved skin, growth control in the psoriatic lesion, viral causes, immunological aspects, and lipid metabolism. ImagesFigure 1.Figure 2.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6.Figure 7.Figure 9.Figure 10.Figure 11.Figure 11.Figure 12. PMID:5578103
Wahl, Astrid K; Robinson, Hilde S; Langeland, Eva; Larsen, Marie H; Krogstad, Anne-Lene; Moum, Torbjørn
Knowledge of illness perception may aid the identification of groups of patients with a higher risk of coping poorly with the demands of their illness. This study aims to investigate associations between illness perception, clinical characteristics, patient knowledge, quality of life and subjective health in persons with psoriasis. The present study was based on cross-sectional data from patients awaiting climate therapy in Gran Canaria. We included 254 eligible patients (74%) who completed a questionnaire including the revised Illness Perception Questionnaire, the Psoriasis Knowledge Questionnaire, and the Dermatological Life Quality Index. Disease severity was measured using the Psoriasis Area and Severity Index. Several statistically significant associations between clinical characteristics, knowledge and various illness perception dimensions were found. Illness perception was also significantly related to disease-specific quality of life and subjective health. These findings contradict previous findings, which suggested that objective disease factors are not relevant to illness perception in psoriasis.
Abstract Psoriasis is a chronic, autoimmune, and complex genetic disorder that affects 23% of the European population. The symptoms of Psoriatic skin are inflammation, raised and scaly lesions. microRNA, which is short, nonprotein-coding, regulatory RNAs, plays critical roles in psoriasis. microRNA participates in nearly all biological processes, such as cell differentiation, development and metabolism. Recent researches reveal that multitudinous novel microRNAs have been identified in skin. Some of these substantial novel microRNAs play as a class of posttranscriptional gene regulator in skin disease, such as psoriasis. In order to insight into microRNAs biological functions and verify microRNAs biomarker, we review diverse references about characterization, profiling and subtype of microRNAs. Here we will share our opinions about how and which microRNAs are as regulatory in psoriasis.
Krishnan, Ravi S; Hsu, Sylvia
Infliximab is a chimeric, murine-human, monoclonal antibody against tumor necrosis alpha which has shown great efficacy in the treatment of psoriasis. Serum sickness, which is an immune complex mediated syndrome consisting of a cutaneous eruption, fever, arthritis, edema, and lymphadenopathy, has been described in several patients receiving infliximab for the treatment of Crohn's disease. However, to our knowledge, this type of reaction has not been well described in a patient treated with infliximab for psoriasis. We describe a patient who developed serum sickness while receiving infliximab for psoriasis and discuss the pathogenesis, diagnosis, and treatment of serum sickness. We believe that with the increasing use of infliximab for psoriasis, more cases of serum sickness will occur. Therefore, awareness of this adverse effect is essential.
... https://medlineplus.gov/news/fullstory_163780.html Can Depression Up Odds for Arthritis Linked to Psoriasis? Mood ... 24, 2017 FRIDAY, Feb. 24, 2017 (HealthDay News) -- Depression in people with the chronic inflammatory skin disease ...
Kurian, A; Barankin, B
Topical therapy forms the cornerstone of treatment in the management of psoriasis. It plays a significant role as monotherapy in mild to moderate psoriasis, and it is used predominantly as adjunctive therapy in moderate to severe forms of the disease. Over the past decade, the topical treatment of psoriasis has evolved from the age-old applications, such as coal tar, to the more cosmetically acceptable and efficacious options containing topical corticosteroids, vitamin D analogues, and combined agents. With the advent of topical therapies in tailored vehicles and sophisticated delivery modes, the outlook for effectively managing psoriasis with topical approaches appears promising. To ensure therapeutic success, patient education about the disease, treatment options, proper administration, and adverse effects is essential, which will alleviate the common problem of poor patient adherence and promote more optimal clinical outcomes.
Nagar, Hemant K; Srivastava, Amit K; Srivastava, Rajnish; Ranawat, Mahendra S
The aim of present study was to determine the effect of newly formulated gels and suspensions of extractive Phytoconstituents of Woodfordia fructicosa flowers and Gardenia gummifera leaves by using UV Radiation induced psoriasis in rats. Both plants are traditionally claimed to be useful in treatment of number of skin diseases. However, there are no established scientific reports for their potential in psoriasis. Formulated Gels and Suspensions of ethanolic extract of both plants were tested for acute dermal and oral toxicity study respectively. The results of acute dermal toxicity at concentration 1% w/w and oral toxicity at dose 1000mg/kg showed that the gels and suspensions were safe. Psoriasis was induced in Wistar rats by espousing 10% area of total body by UV radiations. Anti-psoriatic activity was performed by applying 0.1% gel and orally at a dose 100mg/kg body weight in rats. Severity Index, histological study and biochemical estimation were analyzed. The results of our studies showed that the test formulations (Gels and Suspensions) of both plant extracts exhibited potential effect in anti-psoriatic activity.
Horton, Daniel B.; Scott, Frank I.; Haynes, Kevin; Putt, Mary E.; Rose, Carlos D.; Lewis, James D.; Strom, Brian L.
IMPORTANCE Antibiotics disrupt human microbiota and have been associated with several pediatric autoimmune diseases. Psoriasis activity has been linked to group A streptococcal and viral infections. OBJECTIVE To determine whether antibiotic exposure and infections are independently associated with incident psoriasis in children. DESIGN, SETTING, AND PARTICIPANTS This nested case-control study used data from the Health Improvement Network database, a population-representative electronic health records database from the United Kingdom, from June 27, 1994, through January 15, 2013. Data were analyzed from September 17, 2014, through August 12, 2015. Children aged 1 to 15 years with newly diagnosed psoriasis (n = 845) were compared with age- and sex-matched controls (n = 8450) randomly chosen at the time of psoriasis diagnosis from general practices with at least one case, excluding children with immunodeficiency, inflammatory bowel disease, and juvenile arthritis. EXPOSURES Systemic antibacterial prescriptions and infections of the skin and other sites within 2 years before psoriasis diagnosis. MAIN OUTCOMES AND MEASURES Incident psoriasis as determined by validated diagnostic codes. The association of antibiotic exposure and infections with incident psoriasis was determined by conditional logistic regression, adjusting for confounders. RESULTS After adjusting for matching, country, socioeconomic deprivation, outpatient visits, and infections within the past 2 years, antibiotic exposure in the last 2 years was weakly associated with incident psoriasis (adjusted odds ratio [aOR], 1.2; 95% CI, 1.0–1.5). The associations for infections of skin (aOR, 1.5; 95% CI, 1.2–1.7) and other sites (aOR, 1.3; 95% CI, 1.1–1.6) were similar. Untreated nonskin infections (aOR, 1.5; 95% CI, 1.3–1.8) but not antibiotic-treated nonskin infections (aOR, 1.1; 95% CI, 0.9–1.4) were associated with psoriasis. Results were similar when using a lifetime exposure window. Different
Jankovic, Slavenka; Raznatovic, Milena; Marinkovic, Jelena; Jankovic, Janko; Maksimovic, Natasa
A case-control study of 110 consecutive psoriatic outpatients and 200 unmatched controls was carried out in order to analyze the association of psoriasis with smoking habits, alcohol consumption, family history of psoriasis and stressful life events. Stressful life events were assessed with Paykel's Interview for Recent Life Events, a semi-structured interview covering 63 life events. According to our results, the risk of psoriasis is higher in urban dwellers (odds ratio [OR] = 3.61; 95% confidence interval [CI] = 0.99-13.18), patients who were divorced (OR = 5.69; 95% CI = 2.26-14.34) and those exposed to environmental tobacco smoke at home (OR = 2.29; 95% CI = 1.12-4.67). Alcohol consumption (OR = 2.55; 95% CI = 1.26-5.17), family history of psoriasis (OR = 33.96; 95% CI = 14.14-81.57) and change in work conditions (OR = 8.34; 95% CI = 1.86-37.43) are also risk factors for psoriasis. Separate analyses for men and women showed that the risk of developing psoriasis was stronger in men with a family history of psoriasis (OR = 30.39; 95% CI = 6.72-137.42) than in women (OR = 16.99; 95% CI = 7.21-40.07). The effect of environmental tobacco smoke at home was found only in women (OR = 2.44; 95% CI = 1.26-4.73). Future well-designed epidemiological studies need to be performed in order to determine whether lifestyle factors and stress could be risk factors triggering or aggravating psoriasis.
Barth, J; Pinzer, B
22 patients suffering from exanthematic psoriasis were irradiated with the UV-lamps UVS 65-2 (Narva, Brand-Erbisdorf) or TL-01 (Philips Company, Eindhoven, Niederlande) respectively. The latter one emits a narrow-band UV-spectrum at 311 nm which seems to be most suitable for the treatment of psoriasis. On our condition the clearing rate was higher and the cumulative irradiation dose was significantly lower with the TL-01 lamp.
Torres-Hernández, Marcela; López-García, Sonia; Pedroza-Escobar, David; Escamilla-Tilch, Mónica
Introducción: la alexitimia consiste en la carencia de representaciones mentales de las emociones que conduce a una capacidad limitada para comprender y regular estas, y que puede contribuir en el desarrollo o mantenimiento de una enfermedad psicosomática. El objetivo de este estudio fue demostrar que la alexitimia es una característica que se presenta más frecuentemente en pacientes con psoriasis y que la coexistencia de alexitimia-psoriasis se asocia, como rasgo, a niveles altos de ansiedad. Métodos: la escala de alexitimia de Toronto-20 (TAS- 20) y el inventario de ansiedad estado-rasgo (IDARE) se aplicaron a 16 pacientes con psoriasis de la consulta externa de Dermatología del Hospital de Especialidades del Centro Médico Nacional Siglo XXI y se compararon con 25 individuos control. Resultados: de los pacientes con psoriasis, 25 % presentaron alexitimia, mientras que en el grupo control fue un 8 % (p = 0.002). Se observó correlación entre las puntuaciones de la TSA-20 y del IDARE-rasgo (r = 0.6957, p < 0.0001). Conclusiones: la alexitimia se presenta con mayor frecuencia en individuos con psoriasis que en la población en general y los niveles de ansiedad como rasgo en individuos con psoriasis son similares, independientemente de la presencia de alexitimia.
de Carvalho, André Vicente Esteves; Romiti, Ricardo; Souza, Cacilda da Silva; Paschoal, Renato Soriani; Milman, Laura de Mattos; Meneghello, Luana Pizarro
During the last decade, different studies have converged to evidence the high prevalence of comorbidities in subjects with psoriasis. Although a causal relation has not been fully elucidated, genetic relation, inflammatory pathways and/or common environmental factors appear to be underlying the development of psoriasis and the metabolic comorbidities. The concept of psoriasis as a systemic disease directed the attention of the scientific community in order to investigate the extent to which therapeutic interventions influence the onset and evolution of the most prevalent comorbidities in patients with psoriasis. This study presents scientific evidence of the influence of immunobiological treatments for psoriasis available in Brazil (infliximab, adalimumab, etanercept and ustekinumab) on the main comorbidities related to psoriasis. It highlights the importance of the inflammatory burden on the clinical outcome of patients, not only on disease activity, but also on the comorbidities. In this sense, systemic treatments, whether immunobiologicals or classic, can play a critical role to effectively control the inflammatory burden in psoriatic patients. PMID:28099601
Guinea-Viniegra, Juan; Jiménez, María; Schonthaler, Helia B; Navarro, Raquel; Delgado, Yolanda; Concha-Garzón, María José; Tschachler, Erwin; Obad, Susanna; Daudén, Esteban; Wagner, Erwin F
Psoriasis is a common inflammatory skin disease with limited treatment options that is characterized by a complex interplay between keratinocytes, immune cells, and inflammatory mediators. MicroRNAs (miRNAs) are regulators of gene expression and play critical roles in many human diseases. A number of miRNAs have been described to be up-regulated in psoriasis, but their causal contribution to disease development has not been demonstrated. We confirm that miR-21 expression is increased in epidermal lesions of patients with psoriasis and that this leads to reduced epidermal TIMP-3 (tissue inhibitor of matrix metalloproteinase 3) expression and activation of TACE (tumor necrosis factor-α-converting enzyme)/ADAM17 (a disintegrin and metalloproteinase 17). Using patient-derived skin samples and mouse models of psoriasis, we demonstrate that increased miR-21 may be a consequence of impaired transcriptional activity of Jun/activating protein 1 (AP-1), leading to activation of the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (Stat3) pathway. Inhibition of miR-21 by locked nucleic acid (LNA)-modified anti-miR-21 compounds ameliorated disease pathology in patient-derived psoriatic skin xenotransplants in mice and in a psoriasis-like mouse model. Targeting miR-21 may represent a potential therapeutic option for the treatment of psoriasis.
He, Xiaoqin; Shen, Chuanbin; Lu, Qiumin; Li, Jiong; Wei, Yuquan; He, Li; Bai, Ruizhen; Zheng, Jie; Luan, Ning; Zhang, Zhiye; Rong, Mingqiang; Lai, Ren
Psoriasis is histologically characterized by keratinocytes (KC) hyperproliferation, inflammation, and increased angiogenesis, but the pathological factor responsible for these symptoms is unknown. Here, a neuroendocrine peptide (prokineticin 2, PK2), is highly expressed in human and mouse psoriatic skins but no significant change in other autoimmune diseases, suggesting that PK2 is a psoriasis-specific factor. Bacterial products significantly up-regulated PK2, implying that infection induces PK2 over-expression. PK2 promoted KC and macrophage to produce interleukin-1 (IL-1), the central player of inflammation and psoriasis, which acts on adjacent fibroblast to induce inflammatory cascades and KC hyperproliferation. IL-1 feeds back on macrophages to induce PK2 production to perpetuate PK2-IL-1 positive feedback loop. PK2 also promoted angiogenesis, another psoriatic symptom. In mouse models, PK2 over-expression aggravated psoriasis while its knock-down inhibited pathological development. The results indicate that PK2 over-production perpetuates psoriatic symptoms by creating PK-2-IL-1 vicious loop. PK2 is a central player in psoriasis and a promising psoriasis-specific target.
Prieto-Pérez, Rocío; Cabaleiro, Teresa; Daudén, Esteban; Ochoa, Dolores; Roman, Manuel; Abad-Santos, Francisco
Psoriasis is a chronic inflammatory disease of the skin. The causes of psoriasis are unknown, although family and twin studies have shown genetic factors to play a key role in its development. The many genes associated with psoriasis and the immune response include TNFα, IL23, and IL12. Advances in knowledge of the pathogenesis of psoriasis have enabled the development of new drugs that target cytokines (e.g., etanercept, adalimumab, and infliximab, which target TNFα, and ustekinumab, which targets the p40 subunit of IL23 and IL12). These drugs have improved the safety and efficacy of treatment in comparison with previous therapies. However, not all patients respond equally to treatment, possibly owing to interindividual genetic variability. In this review, we describe the genes associated with psoriasis and the immune response, the biological drugs used to treat chronic severe plaque psoriasis, new drugs in phase II and III trials, and current knowledge on the implications of pharmacogenomics in predicting response to these treatments. PMID:24069534
Patel, Mital; Liu, Stephanie W; Qureshi, Abrar; Merola, Joseph F
Psoriasis is a chronic inflammatory disease that encompasses a large spectrum of clinically distinct subtypes. Although chronic plaque psoriasis is reported as the most common form of psoriatic skin disease, there is growing evidence that other variants including scalp, nail, inverse, and palmoplantar psoriasis are prevalent, undertreated, and associated with significant impairment in quality of life. Currently, the Psoriasis Area and Severity Index (PASI) is the standard to assess psoriasis severity as well as response to treatment; however, the PASI has several limitations. In response to this need and as a complementary objective measure to the PASI, we created the Brigham Scalp Nail Inverse Palmoplantar Psoriasis Composite Index (B-SNIPI), based on patient-surveyed, patient-reported outcomes equally weighted with physician assessment of disease activity. Herein we summarize the B-SNIPI as presented at the 2013 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).
Parrish, J.A.; Jaenicke, K.F.
Using a monochromator the action spectrum for ultraviolet phototherapy of psoriasis was determined for radiation between 254 and 313 nm and compared to the action spectrum for erythema of uninvolved adjacent skin. Daily exposures of different doses of 254, 280, 290, 296, 300, 304 and 313 nm radiation were observed. Wavelengths of 254, 280, 290 nm were erythemogenic but not therapeutic even at 10 to 50 times the minimal erythema dose. At the other wavelengths studied, the 2 action spectra were similar. In general, fixed daily doses cleared at lower cumulative dose than did incrementally increased daily doses. The small number of suberythemogenic exposure doses required suggests that monochromatic radiation may have advantages over broadband sources.
Puig, Lluis; Kirby, Brian; Mallbris, Lotus; Strohal, Robert
Psoriasis is increasingly associated with a range of co-morbid diseases and risk factors. Patients with co-morbidities are more likely to need hospitalisation for non-dermatological conditions, and incur greater total costs than those without co-morbidities. A literature review was conducted on two of the most common co-morbidities of psoriasis (cardiovascular (CV) and psychological co-morbidities), to establish their incidence and impact and to raise awareness of unanswered questions and highlight knowledge gaps. A large number of small controlled or cross-sectional studies report increased prevalence of cardiometabolic and psychological co-morbidities in psoriasis patients. A number of large cohort studies documented the incidence of various cardiometabolic co-morbidities. Severe psoriasis is associated with increased mortality, and the most common cause of death is CV disease. Studies on the management of co-morbidities and their impact on psoriasis treatment are scarce. Many questions on the co-morbidities of psoriasis remain to be answered.
Palijan, Tija Zarković; Kovacević, Drazen; Koić, Elvira; Ruzić, Klementina; Dervinja, Fahri
Psoriasis, as same as other skin diseases, has an influence on many spheres of patient's life. It influences the mental image the patients have of themselves and it indirectly shapes their personality traits as well as it defines the quality of their lives. The purpose of the study was to examine the impact of psoriasis on the quality of life and gender differences in the quality of life and explore presence of neurotic symptoms among persons suffering from psoriasis in comparison to general population. During the treatment of persons suffering from psoriasis at the special hospital Naftalan in Ivanić Grad personality questionnaire and Quality of life scale were administered to 61 participants (m = 25; f = 36). Our results showed few gender differences in the satisfaction with specific life domains, but only differences in the satisfaction with sexual life could be related to the different effects psoriasis has on the quality of life of men and women. Our participants experience more anxiety and depression symptoms as well phobic fears in comparison to general population. Found genders differences in the presence and intensity of anxiety symptoms closely resemble those documented in the general population therefore aren't typical for people suffering from psoriasis.
Morhenn, V.B.; Nelson, T.E.; Gruol, D.L.
Background Psoriasis shares many features with wound healing, a process that involves switching keratinocytes from growth to differentiation. Ca2+ is known to regulate this process. The N-methyl-D-aspartate receptor (NMDAR), an ionotropic glutamate receptor found on keratinocytes, is expressed abnormally in psoriasis in vivo. Objectives The goals of this study are to determine whether the rate of healing in the skin of psoriatic individuals differs from that observed in normal skin and whether the keratinocyte hyperproliferation found in psoriasis correlates with expression of specific NMDAR subunits. Methods Three mm punch biopsies were performed on the skin of normal, as well as, involved and uninvolved skin of subjects with psoriasis. On day 0, as well as, on day 6 after the biopsy, photographs were taken and the size of the wounds determined using ImageJ. Using immunohistochemistry, the biopsy material was stained for NMDAR and its subunits. Results Involved and uninvolved skin of individuals with psoriasis shows significantly more rapid healing than normal. The NR2C subunit of NMDAR is down-regulated in the basal cell layer of involved and uninvolved epidermis of psoriatic subjects compared to controls. By contrast, cells in the basal cell layer of the uninvolved epidermis showed a significantly greater percent strong staining for NR2D compared to those cells in normal epidermis. Conclusions Wound healing is significantly accelerated in psoriasis compared to normal. Immunohistochemistry showed that the relative intensity of strong immunostaining for subunits of the NMDAR is altered in the basal cell layer in psoriatic skin compared to normal controls. We suggest that these alterations may contribute to the increased rate of wound healing in psoriasis. PMID:23819987
Godoy, Ana Leonor Pardo Campos; Rocha, Adriana; da Silva Souza, Cacilda; Lanchote, Vera Lucia
Psoriasis is a chronic inflammatory disease associated with several comorbidities, including depression. Previous studies have shown that inflammatory diseases downregulate the expression and suppress activity of CYP isoforms. Venlafaxine (VLX) is an antidepressant metabolized mainly by CYP2D6 to O-desmethylvenlafaxine (ODV), CYP3A to N-desmethylvenlafaxine (NDV), and CYP2D6 and CYP3A to N,O-didesmethylvenlafaxine (DDV). This study evaluated the influence of psoriasis on the enantioselective pharmacokinetics of VLX. Psoriasis patients (n = 13) and healthy volunteers (n = 11) phenotyped as CYP2D6 extensive (EM) or poor metabolizers (n = 1) received a single oral dose of 150 mg racemic VLX. Plasma concentrations of TNF-α, IFN-γ, IL-6, IL-8, and IL-17 cytokines were higher in EM psoriasis patients when compared with healthy volunteers. IL-6 plasma concentrations varied from 0.4 to 12.9 pg/mL (mean, 2.1 pg/mL) in healthy volunteers and from 0.4 to 29.3 pg/mL (mean, 4.2 pg/mL) in psoriatic patients. VLX pharmacokinetics are enantioselective in healthy volunteers and psoriasis patients phenotyped as EM. Higher AUC values for the (S)-VLX, (S)-NDV, and (S)-DDV enantiomers were observed in healthy volunteers, whereas higher AUC values for (S)-VLX and (R)-ODV were found in psoriasis patients phenotyped as EM. Psoriasis does not alter the pharmacokinetics of the VLX enantiomers probably because of the low levels of IL-6 plasma concentrations.
Ben-Amitai, Dan; David, Michael
Climatotherapy at the Dead Sea is highly effective and safe for the treatment of psoriasis vulgaris in adults. We examine the efficacy and safety of climatotherapy at the Dead Sea in children with psoriasis vulgaris. More than 75% improvement in the Psoriasis Area and Severity Index was noted in 35.3% of the patients. None of the patients had side effects.
Prieto-Pérez, Rocío; Solano-López, Guillermo; Cabaleiro, Teresa; Román, Manuel; Ochoa, Dolores; Talegón, María; Baniandrés, Ofelia; López-Estebaranz, José Luis; de la Cueva, Pablo; Daudén, Esteban; Abad-Santos, Francisco
Psoriasis is a chronic skin disease in which genetics play a major role. Although many genome-wide association studies have been performed in psoriasis, knowledge of the age at onset remains limited. Therefore, we analyzed 173 single-nucleotide polymorphisms in genes associated with psoriasis and other autoimmune diseases in patients with moderate-to-severe plaque psoriasis type I (early-onset, <40 years) or type II (late-onset, ≥40 years) and healthy controls. Moreover, we performed a comparison between patients with type I psoriasis and patients with type II psoriasis. Our comparison of a stratified population with type I psoriasis (n = 155) and healthy controls (N = 197) is the first to reveal a relationship between the CLMN, FBXL19, CCL4L, C17orf51, TYK2, IL13, SLC22A4, CDKAL1, and HLA-B/MICA genes. When we compared type I psoriasis with type II psoriasis (N = 36), we found a significant association between age at onset and the genes PSORS6, TNF-α, FCGR2A, TNFR1, CD226, HLA-C, TNFAIP3, and CCHCR1. Moreover, we replicated the association between rs12191877 (HLA-C) and type I psoriasis and between type I and type II psoriasis. Our findings highlight the role of genetics in age of onset of psoriasis.
Efficacy and safety of ixekizumab treatment for Japanese patients with moderate to severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis: Results from a 52-week, open-label, phase 3 study (UNCOVER-J).
Saeki, Hidehisa; Nakagawa, Hidemi; Nakajo, Ko; Ishii, Taeko; Morisaki, Yoji; Aoki, Takehiro; Cameron, Gregory S; Osuntokun, Olawale O
Psoriasis, a chronic, immune-mediated skin disease characterized by red, scaly plaques, affects approximately 0.3% of the population in Japan. The aim of this open-label study was to evaluate the long-term efficacy and safety of ixekizumab, a humanized, anti-interleukin-17A monoclonal antibody, in Japanese patients with plaque psoriasis (n = 78, including 11 psoriatic arthritis), erythrodermic psoriasis (n = 8) and generalized pustular psoriasis (n = 5). Ixekizumab was administrated s.c. at baseline (week 0, 160 mg), from weeks 2 to 12 (80 mg every 2 weeks), and from weeks 16 to 52 (80 mg every 4 weeks). At week 52, 92.3% of patients with plaque psoriasis achieved Psoriasis Area and Severity Index (PASI) 75, 80.8% achieved PASI 90, 48.7% achieved PASI 100, and 52.6% had remission of plaques (by static Physician Global Assessment, sPGA ). Difficult to treat areas of psoriasis (nail or scalp) also responded to ixekizumab. All patients with psoriatic arthritis who were assessed (5/5) achieved an American College of Rheumatology 20 response. Most patients with erythrodermic psoriasis or generalized pustular psoriasis responded to ixekizumab and the clinical outcome was maintained over 52 weeks (75% and 60% of patients achieved sPGA [0, 1] at week 52, respectively). Mostly mild or moderate treatment-emergent adverse events were reported by 79 of 91 patients; the most common were nasopharyngitis, eczema, seborrheic dermatitis, urticaria and injection site reactions. In conclusion, 52-week ixekizumab treatment was efficacious and well tolerated in Japanese patients with plaque psoriasis. Efficacy was also observed in patients with erythrodermic psoriasis, generalized pustular psoriasis and psoriatic arthritis.
Egeberg, Alexander; Khalid, Usman; Gislason, Gunnar Hilmar; Mallbris, Lotus; Skov, Lone; Hansen, Peter Riis
Study Objectives: Psoriasis and sleep apnea are associated with significant morbidity and mortality. Although both diseases have been linked with systemic inflammation, studies on their potential bidirectional association are lacking. We investigate the potential association between psoriasis and sleep apnea. Methods: All Danish citizens age 18 y or older between January 1, 1997 and December 31, 2011 (n = 5,522,190) were linked at individual level in nationwide registries. Incidence rates (IRs) per 10,000 person-years were calculated and incidence rate ratios (IRRs) adjusted for age, sex, socioeconomic status, smoking history, alcohol abuse, medication, and comorbidity were estimated by Poisson regression. Results: There were 53,290, 6,885, 6,348, and 39,908 incident cases of mild psoriasis, severe psoriasis, psoriatic arthritis, and sleep apnea, respectively. IRRs (95% confidence interval) for sleep apnea were 1.30 (1.17–1.44), 1.65 (1.23–2.22), and 1.75 (1.35–2.26) in subjects with mild and severe psoriasis, and psoriatic arthritis, and IRRs for mild and severe psoriasis, and psoriatic arthritis in sleep apnea without continuous positive airway pressure (CPAP) therapy were 1.62 (1.41–1.86), 2.04 (1.47–2.82), and 1.94 (1.34–2.79), respectively. In patients with sleep apnea and CPAP therapy (i.e., severe sleep apnea) the IRRs were 1.82 (1.43–2.33), 3.27 (2.03–5.27), and 5.59 (3.74–8.37), respectively. Conclusions: Psoriasis was associated with increased risk of sleep apnea, and sleep apnea was associated with increased risk of psoriasis. The clinical significance of this bidirectional relationship warrants further study. Citation: Egeberg A, Khalid U, Gislason GH, Mallbris L, Skov L, Hansen PR. Psoriasis and sleep apnea: a Danish nationwide cohort study. J Clin Sleep Med 2016;12(5):663–671. PMID:26715401
Perera, Gayathri K; Ainali, Chrysanthi; Semenova, Ekaterina; Hundhausen, Christian; Barinaga, Guillermo; Kassen, Deepika; Williams, Andrew E; Mirza, Muddassar M; Balazs, Mercedesz; Wang, Xiaoting; Rodriguez, Robert Sanchez; Alendar, Andrej; Barker, Jonathan; Tsoka, Sophia; Ouyang, Wenjun; Nestle, Frank O
Cytokines are critical checkpoints of inflammation. The treatment of human autoimmune disease has been revolutionized by targeting inflammatory cytokines as key drivers of disease pathogenesis. Despite this, there exist numerous pitfalls when translating preclinical data into the clinic. We developed an integrative biology approach combining human disease transcriptome data sets with clinically relevant in vivo models in an attempt to bridge this translational gap. We chose interleukin-22 (IL-22) as a model cytokine because of its potentially important proinflammatory role in epithelial tissues. Injection of IL-22 into normal human skin grafts produced marked inflammatory skin changes resembling human psoriasis. Injection of anti-IL-22 monoclonal antibody in a human xenotransplant model of psoriasis, developed specifically to test potential therapeutic candidates, efficiently blocked skin inflammation. Bioinformatic analysis integrating both the IL-22 and anti-IL-22 cytokine transcriptomes and mapping them onto a psoriasis disease gene coexpression network identified key cytokine-dependent hub genes. Using knockout mice and small-molecule blockade, we show that one of these hub genes, the so far unexplored serine/threonine kinase PIM1, is a critical checkpoint for human skin inflammation and potential future therapeutic target in psoriasis. Using in silico integration of human data sets and biological models, we were able to identify a new target in the treatment of psoriasis.
Torres, Tiago; Filipe, Paulo
Psoriasis is a chronic, immune-mediated inflammatory disease that affects up to 1-3% of the general population. An advanced understanding of the immune-pathogenesis of psoriasis has led to the development of new drugs that refine existing treatments or target novel molecular and immunologic pathways. IL-17 and Th17 cells play an important role in the pathogenesis of several autoimmune and immune-mediated disorders, including psoriasis. IL-17A, a pro-inflammatory cytokine, is produced by Th17 cells along with other effector cytokines, such as IL-17F an IL-22, but it is also expressed by other cells of the innate immune system, including mast cells, neutrophils or dendritic cells, that are found in psoriatic lesions. For this reason IL-17 has emerged as an attractive therapeutic target. Agents that inhibit IL-17 are in development and preliminary clinical results are promising, confirming the importance of IL-17 in psoriasis pathophysiology. Their selective intervention in the immune system makes them an attractive therapeutic approach to autoimmune diseases, particularly psoriasis, being possible that in the near future these novel therapies could be a valid alternative for currently available biologic agents.
Connor, Cody J; Liu, Vincent; Fiedorowicz, Jess G
Psoriasis is a chronic, immune-mediated skin condition with a high rate of psychiatric comorbidity, which often goes unrecognized. Beyond the negative consequences of mood disorders like depression and anxiety on patient quality of life, evidence suggests that these conditions can worsen the severity of psoriatic disease. The mechanisms behind this relationship are not entirely understood, but inflammation seems to be a key feature linking psoriasis with mood disorders, and physiologic modulators of this inflammation, including the hypothalamic-pituitary-adrenal axis and sympathetic nervous system, demonstrate changes with psychopathology that may be contributory. Cyclical disruptions in the secretion of the sleep hormone, melatonin, are also observed in both depression and psoriasis, and with well-recognized anti-inflammatory and antioxidant activity, this aberration may represent a shared contributor to both conditions as well as common comorbidities like diabetes and cardiovascular disease. While understanding the complexities of the biological mechanisms at play will be key in optimizing the management of patients with comorbid psoriasis and depression/anxiety, one thing is certain: recognition of psychiatric comorbidity is an imperative first step in effectively treating these patients as a whole. Evidence that improvement in mood decreases psoriasis severity underscores how psychological awareness can be critical to clinicians in their practice.
Aldahan, Adam S.; Chen, Lucy L.; Fertig, Raymond M.; Holmes, Jon; Shah, Vidhi V.; Mlacker, Stephanie; Hsu, Vincent M.; Nouri, Keyvan; Tosti, Antonella
Background Nail psoriasis is a painful and disfiguring nail disease that often leads to invasive biopsies. Dermoscopy of the hyponychium can be useful in the diagnosis showing twisted coiled vessels. Structural features of nail psoriasis have been described with optical coherence tomography (OCT). Objectives To investigate vascular features of nail psoriasis using dynamic OCT. Methods This was an observational, prospective, controlled study in which psoriasis patients with psoriatic nail changes and healthy control patients underwent OCT imaging of the distal nail plate and proximal nail fold. Vertical and horizontal OCT images were analyzed to describe structural and vascular features and to quantify blood flow at depth. Results Sixteen psoriatic nails and 16 control nails were included. Psoriatic nails had significantly increased blood flow in the proximal nail fold at depths of 0.72 mm (p = 0.035) and 0.76 mm (p = 0.027). Nail thickness was significantly greater in psoriatic nails compared to control nails (p = 0.0016). Compared to control nails, psoriatic nails had dilated, disorganized blood vessels superficially in the proximal nail fold. Limitations The main limitation of our study is the relatively small sample size. Conclusions OCT can identify structural and vascular features specific to nail psoriasis. PMID:28232916
Zibert, John R; Skov, Lone; Thyssen, Jacob P; Jacobsen, Grete K; Grigorian, Mariam
The S100A4 protein is reported as a pivotal player in the tumor microenvironment with a metastasis-promoting function. Moreover, the upregulation of S100A4 is found in other non-malignant human disorders as cardiac and pulmonary systems and rheumatoid arthritis. In this study, we investigated the expression and significance of S100A4 in psoriasis. We found significant upregulation of S100A4 in the dermis of psoriatic skin compared with normal skin. This pattern of S100A4 expression differs considerably from that of other S100 proteins, S100A7 and S100A8/9, with predominant expression in the epidermis of psoriasis. Furthermore, we revealed a massive release of the biologically active forms of S100A4 from psoriatic skin. Interestingly, we found stabilization (increase) of p53 in the basal layer of epidermis in close proximity to cells expressing S100A4. To examine the possible implication of S100A4 in the pathogenesis of psoriasis, we analyzed the effect of S100A4 blocking antibodies in a human psoriasis xenograft SCID mouse model and observed a significant reduction of the epidermal thickness and impairment in cell proliferation and dermal vascularization. In conclusion, we showed strong upregulation and release of S100A4 in the upper dermis of psoriatic skin and found evidence indicating that S100A4 might actively contribute to the pathogenesis of psoriasis.
Nestle, Frank O; Conrad, Curdin; Tun-Kyi, Adrian; Homey, Bernhard; Gombert, Michael; Boyman, Onur; Burg, Günter; Liu, Yong-Jun; Gilliet, Michel
Psoriasis is one of the most common T cell-mediated autoimmune diseases in humans. Although a role for the innate immune system in driving the autoimmune T cell cascade has been proposed, its nature remains elusive. We show that plasmacytoid predendritic cells (PDCs), the natural interferon (IFN)-alpha-producing cells, infiltrate the skin of psoriatic patients and become activated to produce IFN-alpha early during disease formation. In a xenograft model of human psoriasis, we demonstrate that blocking IFN-alpha signaling or inhibiting the ability of PDCs to produce IFN-alpha prevented the T cell-dependent development of psoriasis. Furthermore, IFN-alpha reconstitution experiments demonstrated that PDC-derived IFN-alpha is essential to drive the development of psoriasis in vivo. These findings uncover a novel innate immune pathway for triggering a common human autoimmune disease and suggest that PDCs and PDC-derived IFN-alpha represent potential early targets for the treatment of psoriasis.
Kuijpers, A L; van Baar, H M; van Gasselt, M W; van de Kerkhof, P C
Scalp psoriasis is associated with hair loss and an increased telogen/anagen ratio. Topical treatment of scalp psoriasis (with corticosteroids, dithranol or tar) results in decreased scaling, induration and erythema of the plaques. Calcipotriol is effective in the treatment of psoriasis vulgaris. However, the potent growth-inhibiting potential of this compound might theoretically induce hair loss. A study was designed to find out to what extent calcipotriol treatment modulates the percentage of anagen and telogen hair during treatment of scalp psoriasis. A group of 26 patients participated in a placebo-controlled dose-finding study on the efficacy of calcipotriol in scalp psoriasis. Hair plucks before and after treatment were taken. The telogen/anagen ratio remained unaffected during 6 weeks of calcipotriol treatment. No correlation was demonstrated between efficacy of treatment and quantification of telogen/anagen ratio. It can be concluded that the growth-inhibiting potential of calcipotriol is not reflected in the in vivo hair growth pattern during calcipotriol treatment.
Antonyan, Albert S.; Porto, Dennis A.; Gomez-Roberts, Hunter; Alhousseini, Ali
Introduction. Kaposi varicelliform eruption (KVE) is a widespread cutaneous viral infection, most commonly herpes simplex virus, which affects patients with underlying dermatosis. When KVE occurs in a patient with a history of psoriasis, it is referred to as psoriasis herpeticum, a rare subtype of KVE with only a handful of cases reported in the literature. To the authors' knowledge, we report for the first time a case of psoriasis herpeticum in pregnancy. Case Presentation. A 23-year-old woman in her third pregnancy presented at 26-week gestation with a 10-year history of psoriasis. Cutaneous examination revealed diffuse psoriatic plaques with scattered ~1 cm erosions. Punch biopsy of the skin revealed herpes simplex virus (HSV) infection within a psoriatic plaque, necessitating dermatological treatment. The patient experienced premature rupture of membranes at 37-week gestation. Pelvic exam showed no evidence of herpetic lesions. After labor augmentation, the patient delivered a healthy female infant with no evidence of HSV infection. Discussion. Psoriasis herpeticum is a rare and potentially devastating complication of an underlying dermatosis. With a paucity of data available to guide pregnancy-specific issues, the general management of this condition is controversial and requires a multidisciplinary care approach. Concerns for systemic infection in the mother and vertical transmission to the neonate are of critical importance. PMID:27840756
Zamirska, Aleksandra; Reich, Adam; Berny-Moreno, Joanna; Salomon, Joanna; Szepietowski, Jacek C
Approximately 80% of psoriatic individuals experience pruritus, of varying intensity. This study evaluated the frequency of vulvar itching and burning and its influence on well-being in women with psoriasis. A total of 93 women were included in the study. Psoriasis severity was assessed according to the Psoriasis Area and Severity Index, the intensity of vulvar discomfort by visual analogue scale and depressive symptoms by Beck's Depression Inventory. On admission 41 (44.1%) women experienced vulvar discomfort, 18 (19.4%) itching, 10 (10.8%) burning and 13 (14.0%) both itching and burning sensations. Psoriatic lesions on the vulva were found in 22 (23.7%) women. No significant correlation was found between burning or itching intensity and global psoriasis severity (r = 0.19, p = 0.26). Patients with vulvar discomfort had psoriatic lesions on the vulva more often than women without discomfort (43.6% vs. 8.2%, p < 0.001). In addition, patients with vulvar discomfort more frequently demonstrated depressive symptoms (p < 0.05). We conclude that vulvar discomfort is an important clinical problem in women with psoriasis and should be taken into consideration during treatment.
Wolf, Joel; Ferris, Laura Korb
The IL-36 family of cytokines and receptors seems to play a role in the pathogenesis of both pustular psoriasis, and the much more common variant, plaque-type psoriasis. Human skin biopsies from patients with psoriasis show overexpression of IL-36 and mice that lack the inhibitory IL-36 receptor (IL-36Ra) antagonist develop psoriasis, suggesting that signaling through the IL-36R may drive the skin lesions of psoriasis. Currently, no drugs targeting IL-36 are used in the treatment of psoriasis. The patent WO2013074569 describes an antibody to the IL-36R that is proposed as a potential therapy for psoriasis.
Casper, U; Seiffert, K; Dippel, E; Zouboulis, C C
Lesions of the oral mucosa are frequently described in association with psoriasis, particularly in the pustular type. Controversy surrounds the question whether mucosal lesions can be considered as oral manifestation of psoriasis. Two patients presented with concurrent pustular psoriasis and mucosal lesions with the characteristic picture of geographic tongue. Histopathology of the mucosa showed typical features of psoriasis such as marked acanthosis, clubbing of the rete ridges, focal parakeratosis and neutrophilic infiltrates. There was parallel improvement of the skin and the mucosal lesions with systemic retinoid treatment. On the basis of the histopathological features and the clinical course we favour the hypothesis that geographic tongue is an oral manifestation of pustular psoriasis.
Soboleva, A G; Mezentsev, A V; Bruskin, S A
Psoriasis is a chronic autoimmune skin disorder. Experimental models of psoriasis can be used to study the disease in controlled conditions. Moreover, the experimental models allow to study a certain aspect of the pathological process. Although none of the multiple mouse models reproduces the human disease precisely, lab animals as model systems can be very helpful because of two reasons. First, introduction of new mutations into animal genome allows to reveal the new genes that may play a certain role in pathogenesis of the disease. Second, the experiments that are carried on the lab animals can be used for testing the new drugs and selection of the most efficient chemical agents from a variety of the proposed experimental preparations. The aim of this paper was to summarize the data on the lab animals that serve as experimental models of psoriasis.
Lin, Yin-Ku; Yen, Hung-Rong; Wong, Wen-Rou; Yang, Sien-Hung; Pang, Jong-Hwei Su
The treatment of psoriasis in children is still an intractable problem and demands a long-term therapy with prolonged efficacy that is free from serious adverse events. Many modes of therapy are currently in use but the disease is often resistant to treatment owing to the unacceptable toxicity that leads to poor compliance. Therefore, to develop an alternative treatment is indispensable. Traditional Chinese medicine has been documented for over 1000 years to provide various effective treatments for inflammatory skin diseases. Herein, we report an 8-year-old boy with recalcitrant pediatric psoriasis who, after multiple treatment failures with conventional antipsoriatic medications, showed remarkable clinical improvement with 8 weeks of topical treatment with Indigo naturalis composite ointment. Remission has lasted for over 2 years until now. Our patient's response suggests that topical Indigo naturalis composite ointment may provide a safe and effective alternative treatment for pediatric psoriasis.
Uva, Luís; Miguel, Diana; Pinheiro, Catarina; Antunes, Joana; Cruz, Diogo; Ferreira, João; Filipe, Paulo
Psoriasis is a lifelong, chronic, and immune-mediated systemic disease, which affects approximately 1–3% of the Caucasian population. The different presentations of psoriasis require different approaches to treatment and appropriate prescriptions according to disease severity. The use of topical therapy remains a key component of the management of almost all psoriasis patients, and while mild disease is commonly treated only with topical agents, the use of topical therapy as adjuvant therapy in moderate-to-severe disease may also be helpful. This paper focuses on the cutaneous mechanisms of action of corticosteroids and on the currently available topical treatments, taking into account adverse effects, bioavailability, new combination treatments, and strategies to improve the safety of corticosteroids. It is established that the treatment choice should be tailored to match the individual patient's needs and his/her expectations, prescribing to each patient the most suitable vehicle. PMID:23213332
Conrad, Curdin; Nestle, Frank O
Psoriasis is a chronic inflammatory skin disorder characterized by accelerated growth and altered differentiation of keratinocytes and angiogenesis with marked ectasia of blood vessels. It develops through interactions between the skin and immune system mediated by T cells, dendritic cells, and inflammatory cytokines. The understanding of the cellular and molecular alterations underlying the disease has advanced, yet the majority of factors leading to the initiation and maintenance of disease remain elusive. Researchers have attempted to reproduce psoriasis in genetically modified and xenotransplantation mouse models to gain insight into its pathogenesis, and they are beginning to use these models to test new therapeutic agents and define mechanisms of action. Every mouse model has strengths and weaknesses, with room for improvement. Still, these models will accelerate knowledge of psoriasis pathogenesis and aid in the development of new therapeutics.
Armstrong, April W.; Aldredge, Lakshi; Yamauchi, Paul S.
Psoriasis is a common inflammatory disease with significant comorbidities, whose management can be challenging given the variety of treatment options. It is critical for nurse practitioners, physician assistants, general practitioners, and dermatology trainees to have useful information about the treatment and monitoring of patients with psoriasis. Although certain aspects of care apply to all patients, each therapeutic agent has its own nuances in terms of assessments, dosing, and monitoring. The most appropriate treatment is based not only on disease severity but also on comorbid conditions and concomitant medications. These practitioners are vital in facilitating patient care by thorough understanding of systemic agents, selection criteria, dosing, and recommended monitoring. This article provides high-yield practical pearls on managing patients with moderate to severe psoriasis. It includes case-based discussions illustrating considerations for special populations, such as pregnant women, children, and patients with comorbidities (eg, human immunodeficiency virus infection, hepatitis C, hepatitis B, and history of malignancy). PMID:26712930
Migliari, Dante A; Penha, S S; Marques, M M; Matthews, R W
This paper discusses the difficulties in making a definitive diagnosis of oral psoriasis based upon clinical and histological evidence only. A young black male presented with multiple lesions showing erosions, fissures, and yellowish scales on the vermilion borders of both lips. He also had erythematous-erosive areas on the gingivae, a fissured tongue showing greyish areas on its ventral surface, whitish lesions and longitudinal sulci in the hard palate with lacelike lesions on the soft palate. Biopsies from the lower lip, gingiva and soft palate showed hyperkeratosis, spongiosis, acanthosis, and elongation of rete ridges. In addition, collections intraepithelial micro-abscesses of Munro were observed. These findings are consistent with oral psoriasis. Typical cutaneous lesions and a family history of psoriasis were absent.
Giardina, Emiliano; Sinibaldi, Cecilia; Novelli, Giuseppe
Psoriasis [OMIM*177900] is a common, chronic and papulosquamous inflammatory skin disease affecting approximately 2% of Caucasian. However, this disorder is rare among Japanese, Eskimos, West Africans and North American blacks and very uncommon in North American and South American natives. The causes for these variations are likely to be both genetic and environmental. Population-based studies and twin studies indicate that psoriasis is a heritable disease with a polygenic mode of inheritance with variable penetrance. Independent genome-wide scans have suggested the involvement of a large number of chromosomal regions (loci), and many candidate genes have been proposed. We discuss genetic approaches to the disease, results and interpretations of relevant studies, as well as future perspectives. Understanding the genetic basis of psoriasis will represent a major advance in our understanding of the disease and will reveal novel disease-specific biologic pathways.
Szabó, Kornélia; Bata-Csörgő, Zsuzsanna; Dallos, Attila; Bebes, Attila; Francziszti, László; Dobozy, Attila; Kemény, Lajos; Széll, Márta
The non-involved, healthy-looking skin of psoriatic patients displays inherent characteristics that make it prone to develop typical psoriatic symptoms. Our primary aim was to identify genes and proteins that are differentially regulated in the non-involved psoriatic and the normal epidermis, and to discover regulatory networks responsible for these differences. A cDNA microarray experiment was performed to compare the gene expression profiles of 4 healthy and 4 psoriatic non-involved epidermis samples in response to T-cell lymphokine induction in organotypic cultures. We identified 61 annotated genes and another 11 expressed transcripts that were differentially regulated in the psoriatic tissues. Bioinformatics analysis suggested that the regulation of cell morphology, development and cell death is abnormal, and that the metabolism of small molecules and lipids is differentially regulated in psoriatic epidermis. Our results indicate that one of the early steps of psoriasis pathogenesis may be the abnormal regulation of IL-23A and IL-1B genes in psoriatic keratinocytes.
Thorleifsdottir, Ragna H; Eysteinsdóttir, Jenna H; Olafsson, Jón H; Sigurdsson, Martin I; Johnston, Andrew; Valdimarsson, Helgi; Sigurgeirsson, Bardur
Streptococcal throat infections are known to trigger or exacerbate psoriasis, and several studies support the benefit of tonsillectomy. To evaluate the potential of tonsillectomy as a treatment, we used a retrospective study-specific questionnaire to assess the proportion of psoriasis patients with sore throat-associated psoriasis exacerbations. Our survey sampled 275 psoriasis patients. Of patients with plaque psoriasis, 42% reported sore throat-associated psoriasis exacerbations, and of patients with confirmed streptococcal infections, 72% reported aggravation. Notably, women and patients with early onset psoriasis were more likely to report psoriasis exacerbation after a sore throat (p < 0.001, p = 0.046, respectively). Other psoriasis aggravation factors were more common in patients with sore throat-associated exacerbations (p < 0.01). Of tonsillectomized patients, 49% reported subsequent improvement and had more frequent sore throat-associated aggravation of psoriasis than patients who did not improve after tonsillectomy (p = 0.015). These findings suggest a closer association between sore throats, streptococcal throat infections and plaque psoriasis than reported previously.
Rigopoulos, Dimitris; Gregoriou, Stamatis; Katrinaki, Aimilia; Korfitis, Chrysovalantis; Larios, Giorgos; Stamou, Christos; Mourellou, Olympia; Petridis, Athanasios; Rallis, Efstathios; Sotiriadis, Dimitris; Katsambas, Andreas D; Antoniou, Christina
Psoriasis is a chronic inflammatory skin disease with important socioeconomic consequences. Data on psoriasis prevalence in Greece is scarce and circumstantially reported. The aim of this study was the recording of psoriatic patients' demographic data, clinical characteristics of the disease, and exacerbating factors. Seven hundred and eighty four patients were enrolled in 6 centres (4 in Athens and 2 in Thessaloniki) in a multicenter epidemiologic prospective study. The mean age of patients was 43.2 (standard deviation, SD 17.44) years (median 42 years), while the men: women ratio was 1.8:1. Additionally, 35% of patients reported a positive family history of psoriasis. The mean age of patients at the first episode of psoriasis was 31.3 (SD 16.39) years (median 28 years). Psoriasis vulgaris was the most common form of psoriasis in the population participating in this study. Flares of psoriasis occurred 2.6 times per year on average. The patients considered stress as the main cause for psoriasis exacerbation. Most frequent target points of psoriasis included elbows, legs, scalp and knees. The most common symptoms reported were scaling, and itching. On average, patients visited dermatologists 2.4 times per year for issues related to psoriasis. This study provides epidemiological information regarding psoriasis in Greece. Results of this survey could assist in delineation of patient profiles, and improve communication between doctors and patients.
Thorleifsdottir, Ragna H.; Eysteinsdottir, Jenna H.; Olafsson, Jon H.; Sigurdsson, Martin I.; Johnston, Andrew; Valdimarsson, Helgi; Sigurgeirsson, Bardur
Streptococcal throat infections are known to trigger or exacerbate psoriasis, and several studies support the benefit of tonsillectomy. To evaluate the potential of tonsillectomy as a treatment, we used a retrospective study-specific questionnaire to assess the proportion of psoriasis patients with sore throat-associated psoriasis exacerbations. Our survey sampled 275 psoriasis patients. 42% of patients with plaque psoriasis reported sore throat-associated psoriasis exacerbations, and 72% of patients with confirmed streptococcal infections reported aggravation. Notably, women and early onset psoriasis patients were more likely to report psoriasis exacerbation after a sore throat (p<0.001, p=0.046 respectively). Other psoriasis aggravation factors were more common in patients with sore throat-associated exacerbations (p<0.01). 49% of tonsillectomized patients reported subsequent improvement and had more frequent sore throat-associated aggravation of psoriasis than patients who did not improve after tonsillectomy (p=0.015). These findings suggest a closer association between sore throats, streptococcal throat infections and plaque psoriasis than previously reported. PMID:26984718
Armstrong, April W; Bukhalo, Michael; Blauvelt, Andrew
Many of the molecular pathways associated with psoriasis pathogenesis are also involved in host defense mechanisms that protect against common pathogens. Candida can stimulate the production of cytokines that trigger or exacerbate psoriasis, and many systemic psoriasis treatments may put patients at increased risk for developing oral, cutaneous, and genitourinary candidiasis. Therefore, dermatologists should regularly screen patients with psoriasis for signs of Candida infection, and take steps to effectively treat these infections to prevent worsening of psoriasis symptoms. This review provides an overview of candidiasis epidemiology in patients with psoriasis, followed by a primer on the diagnosis and treatment of superficial Candida infections, with specific guidance for patients with psoriasis. Candidiasis in patients with psoriasis typically responds to topical or oral antifungal therapy. While biologic agents used to treat moderate-to-severe psoriasis, such as tumor necrosis factor-α inhibitors and interleukin-17 inhibitors, are known to increase patients' risk of developing localized candidiasis, the overall risk of infection is low, and candidiasis can be effectively managed in most patients while receiving systemic psoriasis therapies. Thus, the development of candidiasis does not usually necessitate changes to psoriasis treatment regimens.
Mesquita, Priscila Miranda Diogo; Diogo Filho, Augusto; Jorge, Miguel Tanus; Berbert, Alceu Luiz Camargo Villela; Mantese, Sônia Antunes de Oliveira; Rodrigues, José Joaquim
BACKGROUND Psoriasis is a chronic inflammatory disease that affects the skin and joints and has a multifactorial etiology. Recently, it has been suggested that Helicobacter pylori infection may contribute as a trigger for the development of the disease. OBJECTIVES To determine the prevalence of H. pylori seropositivity in patients with psoriasis and to evaluate the relation between disease severity and H. pylori infection. METHODS H. pylori infection was assessed in psoriatic patients and controls by using H. pylori IgG quantitative enzyme immunoassay (ELISA test). The patients were classified according to the severity of the disease (PASI score). RESULTS One hundred and twenty six patients with psoriasis (73 females and 53 males); mean age 50.48 years; 65 patients (51.59%) had severe psoriasis, 40 (31.75%) moderate psoriasis and 21 (16.67%) mild psoriasis. Twenty one healthy volunteers included as a control group, mean age of 41.05 years, 13 females and 8 males. One hundred and eleven patients with psoriasis tested serologically, 80 (72.07%) were seropositive compared with 7 positive volunteers (33.33%; P=0.002). Forty-nine (75.38%) patients with severe psoriasis were positive, 25 (62.50%) with moderate psoriasis were positive and 6 (28.57%) with mild psoriasis were positive (P=0.045). Study limitations: none. CONCLUSIONS H. pylori infection influences the development of psoriasis and severity of the disease. PMID:28225957
Okamoto, F; Sato, T; Umebayashi, Y; Ohtsuka, F; Hommura, S
We evaluated aqueous humor protein concentration in psoriasis using a laser flare-cell meter, which can quantify aqueous flare precisely and objectively. Psoriatic severity was evaluated on the basis of psoriasis area and severity index (PASI) score. Aqueous flare was measured in 40 eyes of 20 psoriasis patients (sixteen psoriasis vulgaris, three guttate psoriasis, and one psoriatic arthritis) and 28 eyes of 14 normal controls. Aqueous flare value was significantly higher in psoriatic patients than in normal controls (p < 0.01). There was no difference between psoriasis vulgaris and the other types of psoriasis. Aqueous flare value was higher in patients with psoriatic history longer than 10 years than in those with less than 10 years (p < 0.05), and also higher in patients with severe psoriasis (PASI score > 10) than in those with mild psoriasis (PASI score < 10) (p < 0.05). But no statistically significant differences in aqueous flare value were found among cyclosporin, etretinate, and psoralen ultra violet A therapies. These findings strongly suggest that patients suffering from psoriasis have slight damage of the blood-aqueous barrier even if they have no ocular symptoms, and that the degree of blood-aqueous barrier damage increases with time and severity of psoriasis.
Ladoyanni, E; Nambi, R
Interferon-alpha can exacerbate existing psoriasis and induce de novo psoriasis and psoriatic arthritits. The exact underlying mechanism is not very well understood. It is not a contraindication to treat patients with pre-existing psoriasis with interferon-alpha. In these patients interferon-alpha should be used with care and only if the potential benefits justify the potential risk. Control of psoriasis prior to initiation of interferon-alpha and simultaneous antipsoriatic therapy while on interferon-alpha are essential. We would like to report a 61-year-old male patient with stable psoriasis for over 20 years, who experienced exacerbation of his psoriasis after receiving interferon-alpha for chronic myeloid leukemia. The association between the interferon-alpha therapy and the exacerbation of his psoriasis was only recognized on rechallenge at the stage he was referred to our department.
Bakry, Ola Ahmed; El Hefnawy, Sally; Mariee, Alaa Hassan; El Gendy, Yara
Background: Psoriasis is a common chronic, relapsing, immune-mediated disease involving skin and joints of genetically predisposed individuals. Oxidative stress has been found to play many important roles in cellular damage and loss of function in a number of tissues and organs and is believed to contribute to the pathogenesis of a variety of diseases. Urinary biopyrrin levels have gained attention as an indicator of oxidative stress. Aim and Objective: To measure urinary biopyrrins excretion as a marker of oxidative stress in psoriasis. Patients and Methods: This case–control study was carried out on 85 subjects; 55 cases with chronic plaque psoriasis and 30 age, gender and body mass index-matched normal subjects as a control group. Urinary biopyrrin levels were measured using enzyme immunoassay. Results: There was a highly significant difference between cases and controls regarding urinary biopyrrins level (P < 0.001). There was significant positive correlation between biopyrrins level and both the age of cases (r = 0.28, P = 0.01) and psoriasis area and severity index score (r = 0.99, P < 0.001). Conclusion: Urinary biopyrrins are increased in patients with psoriasis, and the level is correlated with disease severity. Further large-scale studies involving different ages and different clinical varieties of the disease are needed to expand and validate current findings. The clinical usefulness of antioxidants in psoriasis treatment needs to be evaluated in future research. Furthermore, the value of biopyrrins as biomarkers for monitoring response to therapy needs to be evaluated. PMID:27057016
Vincent, Nitha; Ramya, Devi D; Vedha, Hari BN
Psoriasis is a lifelong condition which is caused by the negative signals produced by immune system, which leads to hyper proliferation and other inflammatory reactions on the skin. In this case, keratinocytes which are the outermost layer of skin possess shortened life cycle and results in the alteration of desquamation process where the cytokines will come out through lesions of affected patients and as a result, scaling marks appears on the skin. These conditions may negatively affect the patient’s quality of life and lead to psychosocial stress. Psoriasis can be categorized as mild, moderate and severe conditions. Mild psoriasis leads to the formation of rashes, and when it becomes moderate, the skin turns into scaly. In severe conditions, red patches may be present on skin surface and becomes itchy. Topical therapy continues to be one of the pillars for psoriasis management. Drug molecules with target effect on the skin tissues and other inflammations should be selected for the treatment of psoriasis. Most of the existing drugs lead to systemic intoxication and dryness when applied in higher dose. Different scientific approaches for topical delivery are being explored by researches including emollient, modified gelling system, transdermal delivery, spray, nanogels, hydrogels, micro/nano emulsion, liposomes, nano capsules etc. These topical dosage forms are evaluated for various physico chemical properties such as drug content, viscosity, pH, extrudability, spreadability, toxicity, irritancy, permeability and drug release mechanism. This review paper focus attention to the impact of these formulation approaches on various anti-psoriasis drugs for their successful treatment. PMID:25386329
Luan, Chao; Chen, Xu; Hu, Yu; Hao, Zhimin; Osland, Jared M.; Chen, Xundi; Gerber, Skyler D.; Chen, Min; Gu, Heng; Yuan, Rong
Nuclear receptor interacting protein 1 (NRIP1, also known as RIP140) is a co-regulator for various transcriptional factors and nuclear receptors, and has been shown to take part in many biological and pathological processes, such as regulating mammary gland development and inflammatory response. The aim of this study is to investigate the expression of NRIP1 and to explore its roles in the pathogenesis of psoriasis. Thirty active psoriasis patients and 16 healthy volunteers were enrolled for this study. qRT-PCR analyses found that both NRIP1 and RelA/p65 were elevated in psoriatic lesions compared to psoriatic non-lesions and normal controls, and also overexpressed in peripheral blood mononuclear cell (PBMCs) of psoriasis patients. Suppression of NRIP1 in HaCaT cells could significantly inhibit cell growth and induce apoptosis, and the suppression of NRIP1 in CD4+ T cells isolated from psoriasis patients could downregulate the expression of RelA/p65 and decrease the secretion of IL-17. Furthermore, in Nrip1 knockout mice, IMQ-induced inflammation of skin was delayed and the RelA/p65 expression in lesions was reduced. In conclusion, our data suggests that NRIP1 is overexpressed both in skin and PBMCs of psoriasis patients and may be involved in the abnormal proliferation and apoptosis of keratinocytes, as well as the immune reaction through the regulation of RelA/p65. Therefore, NRIP1 may be a potential therapeutic target for psoriasis. PMID:27708240
Bakry, Ola Ahmed
Introduction Psoriasis is a common skin disorder characterized by erythaematosquamous papules and plaques. It is known to be associated with stressful and depressive disorders. Serotonin is a neurotransmitter that plays a role in the pathogenesis of inflammatory skin disorders. Aim To evaluate the role of serotonin in pathogenesis of psoriasis. Materials and Methods Using standard immunohistochemical techniques, 24 biopsies from patients with chronic plaque psoriasis were examined together with 12 biopsies from age and gender-matched healthy subjects as a control group. Results Both the percentage of positive cells (p=0.018) and H-score values (p=0.015) of serotonin expression were significantly higher in psoriasis compared to normal skin. H score of serotonin expression was significantly higher in cases with totally absent Granular Cell Layer (GCL) as opposed to those with thin/focally absent GCL (p=0.011), and in cases with moderate/strong epidermal inflammation compared to cases with mild inflammation (p=0.035). No significant correlation was detected between H score of cases and age, disease duration or Psoriasis Area and Severity Index (PASI) score. Conclusion Serotonin might play a role in development of psoriasis through its role as a growth factor promoting keratinocyte proliferation, and as mediator of inflammation and stimulant of T cell activation. It recruits T cells to sites of cutaneous inflammation and potentiate macrophage accessory function for T cell activation. Its expression is not related to the disease severity. Future large-scaled research on population of different ethnicities including other disease variants is needed. The use of serotonin receptor antagonists and serotonin reuptake inhibitors may be evaluated on wide-based studies to put the current observation into action. PMID:27891342
Shin, Dongyun; Kim, Hee Joo; Kim, Dae Suk; Kim, Soo Min; Park, Jin Su; Park, Yong-Beom; Lee, Min-Geol
The prevalence and clinical features of psoriatic arthritis (PsA) in psoriasis patients vary widely in different countries, and studies on Korean population are rarely reported. The aim of this study was to investigate the clinical features of PsA in a Korean population of patients with psoriasis by using psoriatic arthritis screening questionnaires. A cross-sectional observational study was conducted, and consecutive psoriatic patients were evaluated for PsA by using two kinds of psoriatic arthritis screening questionnaires: Psoriatic Arthritis Screening and Evaluation tool (PASE) and Psoriasis Epidemiology Screening Tool (PEST). Psoriatic patients with higher score in screening questionnaires were referred to rheumatologist for confirmative diagnosis of PsA. Among 196 psoriasis patients screened by PASE and PEST, total prevalence of PsA was 11.2 % (n = 22/196) with 59.1 % of the cases being newly diagnosed. Compared with patients without PsA, patients with PsA had more extensive psoriasis, higher frequency of pustular and inverse type of psoriasis, and lower frequency of plaque type of psoriasis. Spondylitis was the most common manifestation pattern, followed by polyarthritis, oligoarthritis, predominant distal interphalangeal arthritis, and arthritis mutilans. Our findings are consistent with a low prevalence of PsA among patients with psoriasis in Asia. We also confirm a spondylitis as the most common pattern of PsA in Korea. PsA screening questionnaires can be a simple and useful tool to screen PsA in patients with psoriasis.
Shenenberger, Donald W
Psoriasis, a T-cell-mediated disorder, affects 1% to 3% of the world's population. The characteristic lesions occur in many different forms, can cause significant discomfort and social distress, and in some instances, lead to dehydration and metabolic derangement. A chronic, unpredictable course and the necessity of periodically switching drugs or classes of drugs make psoriasis frustrating to treat. However, topical and systemic drug therapies and phototherapy can help minimize the exacerbations and prolong remissions. In this article, Dr Shenenberger outlines treatment approaches and discusses research into the use of immunomodulatory agents.
Schmuth, Matthias; Blunder, Stefan; Dubrac, Sandrine; Gruber, Robert; Moosbrugger-Martinz, Verena
Several skin disorders are associated with impaired skin barrier function. Primary dysfunction is caused by monogenic defects in key components of the epidermis (for example ichthyoses). Secondary barrier impairment occurs in inflammatory dermatoses marked by disturbed epidermal homeostasis (eczema, psoriasis, etc.). In these disorders, inflammation impedes the synthesis or maintenance of skin barrier components. Recent evidence suggests a combination of primary and secondary barrier dysfunction in atopic dermatitis and, to a lesser extent, also in psoriasis. In the future, subtypes of atopic dermatitis may likely be defined, in which one or the other is prevalent.
Appell, M L; Sherertz, E F
Three members of a family with numerous ectodermal abnormalities are described. These anomalies primarily include patchy alopecia beginning in childhood, premature cataracts, widespread keratosis pilaris, and psoriasis. The alopecia and premature cataracts appear to follow an autosomal dominant inheritance pattern with incomplete penetrance and appear to be linked. Psoriasis also occurs in several members of this family and probably represents a separate but possibly related genodermatosis. This kindred has features of both keratosis follicularis spinulosa decalvans and ichthyosis follicularis, and the disorder seems to fit into the group of follicular hyperkeratosis disorders.
Vakirlis, Efstratios; Kastanis, Athanasios; Ioannides, Demetrios
Psoriasis is one of the most common skin diseases. The mainstay of treatment for the vast majority of patients is topical therapy. A rising first-line treatment modality for psoriasis vulgaris is the two-compound ointment containing calcipotriol 50 μg/g plus betamethasone dipropionate 0.5 mg/g (Dovobet®, Daivobet®, Taclonex®), which combines a vitamin D analog and a corticosteroid. This innovative formulation preserves the activity and bioavailability of the two components and many clinical studies have demonstrated that it has a greater efficacy, tolerability, and a rapid onset of action compared with its individual ingredients or tacalcitol. PMID:18728704
Carrascosa, J M; López-Estebaranz, J L; Carretero, G; Daudén, E; Ferrándiz, C; Vidal, D; Belinchón, I; Sánchez-Regaña, M; Puig, L
Novel treatment strategies and new information concerning the management of moderate to severe psoriasis justify a reassessment of the role of the classic therapies in this setting. This consensus statement evaluates narrowband UV-B therapy, which is currently considered the phototherapy option of choice in psoriasis because of its risk-to-benefit ratio. The role of excimer laser and photodynamic therapies are also discussed. These targeted therapies are still only available in a small number of centers in Spain and are used principally in the treatment of localized and recalcitrant forms of psoriasis. We discuss the efficacy and safety of phototherapy as well as treatment regimens, combination therapy, and clinical considerations relating to the characteristics of the patient or the disease.
Weidemann, Anja K; Crawshaw, Ania A; Byrne, Emily; Young, Helen S
Psoriasis is a common inflammatory autoimmune condition in which environmental factors and genetic predisposition contribute to the development of disease in susceptible individuals. Angiogenesis is known to be a key pathogenic feature of psoriasis. Local and systemic elevation of vascular endothelial growth factor (VEGF)-A has been demonstrated in the skin and plasma of patients with psoriasis and is known to correlate with improvement following some traditional psoriasis treatments. A number of VEGF inhibitors are licensed for the treatment of malignancies and eye disease and isolated case reports suggest that some individuals with psoriasis may improve when exposed to these agents. The small number of cases and lack of unified reporting measures makes it difficult to draw generalizations and underline the heterogeneity of psoriasis as a disease entity. Though not yet licensed for the treatment of psoriasis in humans, experimental data supports the potential of VEGF inhibitors to influence relevant aspects of human cell biology (such as endothelial cell differentiation) and to improve animal models of skin disease. Given the multi-factorial nature of psoriasis it is unlikely that VEGF inhibitors will be effective in all patients, however they have the potential to be a valuable addition to the therapeutic arsenal in selected cases. Current VEGF inhibitors in clinical use are associated with a number of potentially serious side effects including hypertension, left ventricular dysfunction, and gastrointestinal perforation. Such risks require careful consideration in psoriasis populations particularly in light of growing concerns linking psoriasis to increased cardiovascular risk. PMID:24101875
Cardoso, Pablo Ramon Gualberto; Lima, Emerson Vasconcelos de Andrade; Lima, Mariana Modesto de Andrade; Rêgo, Moacyr Jesus Barreto de Melo; Marques, Claudia Diniz Lopes; Pitta, Ivan da Rocha; Duarte, Angela Luzia Branco Pinto; Pitta, Maira Galdino da Rocha
Psoriasis is a common, enigmatic, and recurrent disease. The precise etiology and pathogenesis of psoriasis are still unclear. Psoriasis has been treated as an inflammatory disorder related to an underlying Th1/Th17-dominated immune response. Interleukins are involved in the development of psoriasis lesions through Th-17-associated inflammation. Th1 and Th17 cytokines are found in skin lesions and in the peripheral blood of psoriasis patients. We sought to analyze serum levels of IL-1-β, IL-8, IL-9, IL-27, IL-29, IL-35, IFN-γ, TNF and TGF-β in patients with psoriasis and healthy control volunteers. Blood samples were collected from fifty-three patients with psoriasis and thirty-five healthy controls. Serum cytokines concentrations were determined using an enzyme-linked immunosorbent assay. Serum IL-8, IL-9, IL-27, IL-29 and TNF levels were statistically significant in psoriasis patients. Detectable serum IL-9 levels were found in 47 patients of the 53 in the psoriasis group. Interleukins-8, 27, 29 and TNF levels measured in the serum of psoriasis patients were slightly elevated as compared to healthy controls in a weakly significant way. On the other hand, there were highly significant differences in IL-9 levels between the two groups.
Fan, Tingting; Wang, Shaowen; Yu, Linjiang; Yi, Huqiang; Liu, Ruiling; Geng, Wenwen; Wan, Xiaochun; Ma, Yifan; Cai, Lintao; Chen, Youhai H; Ruan, Qingguo
Psoriasis is a chronic inflammatory disorder of the skin. Accumulating evidence indicates that the Rel gene, a member of the NF-κB family, is a risk factor for the disease. We sought to investigate whether psoriasis can be prevented by directly targeting the Rel gene transcript, i.e., the c-Rel mRNA. Using chemically-modified c-Rel specific siRNA (siRel) and poly(ethylene glycol)-b-poly(l-lysine)-b-poly(l-leucine) (PEG-PLL-PLLeu) micelles, we successfully knocked down the expression of c-Rel, and showed that the expression of cytokine IL-23, a direct target of c-Rel that can drive the development of IL-17-producing T cells, was markedly inhibited. More importantly, treating mice with siRel not only prevented but also ameliorated imiquimod (IMQ)-induced psoriasis. Mechanistic studies showed that siRel treatment down-regulated the expression of multiple inflammatory cytokines. Taken together, these results indicate that the susceptibility gene Rel can be targeted to treat and prevent psoriasis.
Skarmoutsou, Evangelia; Trovato, Chiara; Granata, Mariagrazia; Rossi, Giulio A; Mosca, Ambra; Longo, Valentina; Gangemi, Pietro; Pettinato, Maurizio; D'Amico, Fabio; Mazzarino, Maria Clorinda
Psoriasis is a chronic inflammatory skin disease, characterized by hyperproliferation of keratinocytes and by skin infiltration of activated T cells. To date, the pathophysiology of psoriasis has not yet been fully elucidated. The Notch pathway plays a determinant role in cell fate determination, proliferation, differentiation, immune cell development and function. Many biological agents, used in the treatment of psoriasis, include TFN-α inhibitors, such as etanercept, adalimumab, and anti IL-12/IL-23 p40 antibody, such as ustekinumab. This study aimed to determine mRNA expression levels by real-time RT-PCR, and protein expression levels, analysed by Western blot and immunohistochemistry, of some components of the Notch pathway, such as NOTCH1, NOTCH2, JAGGED1, and HES1 after biological treatments in psoriatic patients. mRNA and protein levels of NOTCH1, NOTCH2, JAGGED1 and HES1 were upregulated in skin samples from untreated psoriatic patients compared with normal controls. Biological therapy showed to downregulate differently the protein expression levels of the molecules under study. Our study suggests that Notch pathway components might be a potential therapeutic target against psoriasis.
Guenther, Lyn C
Although biologics are very efficacious as monotherapy in patients with psoriasis, combination treatment with traditional systemic and topical therapies may increase the speed of onset and enhance efficacy without significant additional toxicity. In contrast, in psoriatic arthritis, the addition of methotrexate to anti-tumour necrosis factor-alpha therapy does not enhance efficacy in either the skin or joints.
Nititham, Joanne; Gupta, Rashmi; Zeng, Xue; Hartogensis, Wendy; Nixon, Douglas F; Deeks, Steven G; Hecht, Frederick M; Liao, Wilson
Human evolution has resulted in selection for genetic polymorphisms beneficial in the defense against pathogens. However, such polymorphisms may have the potential to heighten the risk of autoimmune disease. Here, we investigated whether psoriasis-associated single nucleotide polymorphisms influence host control of HIV-1 infection. We studied psoriasis and viral immune response variants in three HIV-positive cohorts: (1) HIV-1 controllers and non-controllers in the Study of the Consequences of the Protease Inhibitor Era (SCOPE) cohort (n=366), (2) Individuals with primary HIV infection in the Options cohort (n=675), and (3) HIV-positive injection drug users from the Urban Health Study (UHS) (n=987). We found a strong association of two psoriasis MHC variants, rs9264942 and rs3021366, with both HIV-1 controller status and viral load, and identified another Class III MHC variant rs9368699 to be strongly associated with viral load. A number of genetic variants outside the MHC (SOX5, TLR9, SDC4, PROX1, IL12B, TLR4, MBL-2, TYK2, IFIH1) demonstrated nominal significance. Overall, our data suggest that several psoriasis variants within the MHC have a robust impact on HIV-1 control, while variants outside the MHC require further investigation.
Baumgardner, Jonathan M.; Hennings, David R.; Johnston, Thomas F., Jr.; Taylor, Eric
We present our research into a pulsed xenon lamp source for the treatment of psoriasis and other skin disorders. Various filtering techniques, lamp configurations, power supply configurations and delivery systems are discussed. Comparisons are made to existing treatment modalities. Cryogen cooling of the treatment site is discussed.
Generalized pustular psoriasis (GPP) is a rare form of childhood psoriasis, often requiring systemic therapy, which is challenging as there is a paucity of randomized controlled trials and standardized guidelines. Biologic agents have been used in adults and in pediatric plaque psoriasis, but evidence regarding their efficacy in pediatric GPP has slowly become available. The objective of this study is to summarize and compare the efficacy and safety of biologic agents, such as etanercept, infliximab, and adalimumab, in the treatment of pediatric GPP. A PubMed literature review was conducted and 12 studies met the inclusion criteria for analysis. After reviewing the efficacy of these drugs in pediatric GPP patients and their safety in the use of other pediatric conditions, etanercept was identified as a possible first-line biologic agent for pediatric psoriasis, including GPP, followed by infliximab and adalimumab. In conclusion, several case reports have documented the successful use of biologic agents in refractory cases of pediatric GPP, but clinical trials are needed to gain a better understanding of the efficacy and side effect profile in this population. PMID:27462478
Leovigildo, Érida Silva; David, Rose Ana Rios; Mendes, Andreia Santos
Background Psoriasis is a chronic dermatosis of unknown etiology with a tendency to relapse after treatment. The disease is frequently linked to psychological stress due to the embarrassment caused by the lesions. Objective To analyze the stress level presented by psoriasis patients followed at the Dermatology Service of a public hospital in Salvador, Bahia state, Brazil. Methods A cross-sectional study of a consecutive convenience sample composed of 60 participants. We used Lipp's Stress Symptoms Inventory for Adults to assess stress levels. The questionnaire identifies and classifies physical and psychological symptoms according to three stages of stress: alarming, resistance, and exhaustion. We also collected socio-demographic and clinical data that could be associated with psoriasis. Results 85% of the participants presented stress. Lipp's questionnaire results revealed that 48% were in the resistance stage and 37% in the exhaustion stage. Women presented higher levels of stress. Of the total 28 women, 64% were in exhaustion stage, 29% in the resistance stage, and only 7% presented no stress symptoms. Of the total 32 men, 44% were in resistance stage, 34% in exhaustion stage, and 22% presented no stress symptoms. Regarding physical and psychological symptoms, psychological symptomatology was prevalent (55%). Conclusions Based on the number of patients in exhaustion stage, we can conclude that stress levels of the participants were high regardless the type of psoriasis and treatment duration. PMID:27579739
Baeta, Isabela Guimarães Ribeiro; Bittencourt, Flávia Vasques; Gontijo, Bernardo; Goulart, Eugênio Marcos Andrade
BACKGROUND Psoriasis is a chronic inflammatory disease and its pathogenesis involves an interaction between genetic, environmental, and immunological factors. Recent studies have suggested that the chronic inflammatory nature of psoriasis may predispose to an association with other inflammatory diseases, especially cardiovascular diseases and metabolic disorders. OBJECTIVES To describe the demographic, clinical, epidemiological, and laboratory characteristics of a sample of psoriasis patients; to assess the prevalence of cardiovascular comorbidities in this group of patients; and to identify the cardiovascular risk profile using the Framingham risk score. METHODS We conducted a cross-sectional study involving the assessment of 190 patients. Participants underwent history and physical examination. They also completed a specific questionnaire about epidemiological data, past medical history, and comorbidities. The cardiovascular risk profile was calculated using the Framingham risk score. RESULTS Patients' mean age was 51.5 ± 14 years, and the predominant clinical presentation was plaque psoriasis (78.4%). We found an increased prevalence of systemic hypertension, type 2 diabetes, metabolic syndrome, and obesity. Increased waist circumference was also found in addition to a considerable prevalence of depression, smoking, and regular alcohol intake. Patients' cardiovascular risk was high according to the Framingham risk score, and 47.2% of patients had moderate or high risk of fatal and non-fatal coronary events in 10 years. CONCLUSIONS Patients had high prevalence of cardiovascular comorbidities, and high cardiovascular risk according to the Framingham risk score. Further epidemiological studies are needed in Brazil for validation of our results. PMID:25184912
Introduction Dermoscopy is a non-invasive imaging method that enables the evaluation of pigmented and non-pigmented skin lesions. More recently, dermoscopy has been recognized as an effective tool in the diagnosis of nail diseases. Aim To evaluate the dermoscopic features of nail psoriasis and to assess the relationship between these features and disease severity. Material and methods A total of 67 patients with clinically evident nail psoriasis (14 women, 53 men) were prospectively enrolled. Following a thorough clinical examination, patients were graded according to the Nail Psoriasis Severity Index and physician’s global assessment score. A dermoscopic examination of all fingernails and toenails was performed using a videodermatoscope. Mann-Whitney U and χ2 tests were used for statistical analysis, with a significance threshold of p < 0.05. Results The most frequently observed dermoscopic features were splinter haemorrhage (73.1%), pitting (58.2%), distal onycholysis (55.2%), dilated hyponychial capillaries (35.8%) and the pseudo-fiber sign (34.3%). The pseudo-fiber sign, dilated hyponychial capillaries, nail plate thickening and crumbling, subungual hyperkeratosis, transverse grooves, trachyonychia, pitting and salmon patches were positively associated with disease severity. Conclusions The pseudo-fiber sign described in this study appears to be a novel dermoscopic feature of nail psoriasis. We have demonstrated positive associations between a number of dermoscopic manifestations and disease severity. Further studies are required to support the present findings. PMID:28286468
Ungt. Dithranoli 0.075 and 0.1% L/W cum Spir. Picis lithanthrac. 5% is an alternative in the treatment of psoriasis vulgaris on the face region as shown by bilateral comparison studies with fluocinolone acetonide 0.025% (Flucinar cream).
Quaranta, Maria; Eyerich, Stefanie; Knapp, Bettina; Nasorri, Francesca; Scarponi, Claudia; Mattii, Martina; Garzorz, Natalie; Harlfinger, Anna T; Jaeger, Teresa; Grosber, Martine; Pennino, Davide; Mempel, Martin; Schnopp, Christina; Theis, Fabian J; Albanesi, Cristina; Cavani, Andrea; Schmidt-Weber, Carsten B; Ring, Johannes; Eyerich, Kilian
Psoriasis is characterized by an apoptosis-resistant and metabolic active epidermis, while a hallmark for allergic contact dermatitis (ACD) is T cell-induced keratinocyte apoptosis. Here, we induced ACD reactions in psoriasis patients sensitized to nickel (n = 14) to investigate underlying mechanisms of psoriasis and ACD simultaneously. All patients developed a clinically and histologically typical dermatitis upon nickel challenge even in close proximity to pre-existing psoriasis plaques. However, the ACD reaction was delayed as compared to non-psoriatic patients, with a maximum intensity after 7 days. Whole genome expression analysis revealed alterations in numerous pathways related to metabolism and proliferation in non-involved skin of psoriasis patients as compared to non-psoriatic individuals, indicating that even in clinically non-involved skin of psoriasis patients molecular events opposing contact dermatitis may occur. Immunohistochemical comparison of ACD reactions as well as in vitro secretion analysis of lesional T cells showed a higher Th17 and neutrophilic migration as well as epidermal proliferation in psoriasis, while ACD reactions were dominated by cytotoxic CD8+ T cells and a Th2 signature. Based on these findings, we hypothesized an ACD reaction directly on top of a pre-existing psoriasis plaque might influence the clinical course of psoriasis. We observed a strong clinical inflammation with a mixed psoriasis and eczema phenotype in histology. Surprisingly, the initial psoriasis plaque was unaltered after self-limitation of the ACD reaction. We conclude that sensitized psoriasis patients develop a typical, but delayed ACD reaction which might be relevant for patch test evaluation in clinical practice. Psoriasis and ACD are driven by distinct and independent immune mechanisms.
Background Psoriasis is a common chronic inflammatory disease of the skin. We sought to characterize and compare the cutaneous microbiota of psoriatic lesions (lesion group), unaffected contralateral skin from psoriatic patients (unaffected group), and similar skin loci in matched healthy controls (control group) in order to discern patterns that govern skin colonization and their relationship to clinical diagnosis. Results Using high-throughput 16S rRNA gene sequencing, we assayed the cutaneous bacterial communities of 51 matched triplets and characterized these samples using community data analysis techniques. Intragroup Unifrac β diversity revealed increasing diversity from control to unaffected to lesion specimens. Likewise, principal coordinates analysis (PCoA) revealed separation of the lesion samples from unaffected and control along the first axis, suggesting that psoriasis is a major contributor to the observed diversity. The taxonomic richness and evenness decreased in both lesion and unaffected communities compared to control. These differences are explained by the combined increased abundance of the four major skin-associated genera (Corynebacterium, Propionibacterium, Staphylococcus, and Streptococcus), which present a potentially useful predictor for clinical skin type. Psoriasis samples also showed significant univariate decreases in relative abundances and strong classification performance of Cupriavidus, Flavisolibacter, Methylobacterium, and Schlegelella genera versus controls. The cutaneous microbiota separated into two distinct clusters, which we call cutaneotypes: (1) Proteobacteria-associated microbiota, and (2) Firmicutes-associated and Actinobacteria-associated microbiota. Cutaneotype 2 is enriched in lesion specimens compared to control (odds ratio 3.52 (95% CI 1.44 to 8.98), P <0.01). Conclusions Our results indicate that psoriasis induces physiological changes both at the lesion site and at the systemic level, which select for specific
Elfatoiki, Fatima Zahra; El Azhari, Mohamed; El Kettani, Assiya; Serhier, Zineb; Othmani, Mohamed Bennani; Timinouni, Mohamed; Benchikhi, Hakima; Chiheb, Soumiya; Fellah, Hassan
Psoriatic lesions are rarely complicated by recurrent infections. The aim of our study is to determine skin colonisation and nasal carriage of Staphylococcus aureus in patients with psoriasis and in healthy persons. Patients and methods: a comparative study that include 33 patients with psoriasis and 33 healthy persons. Samples were taken from lesional and non lesional psoriatic skin and from healthy skin of control group. For S. aureus nasal carriage, we used sterile cotton tipped swabs. Out of165 samples (66 skin samples and 33 nasal swabs), 26 S. Aureus strains were isolated in 26 persons, 57.69% in the control group and 42.3% in the psoriasisgroup. S. aureus skin colonization was found in one case (3%) inlesional psoriatic skin vs 9 cases (27.3%) in control skin OR=0.08 IC 95% (0.01-0.70) p=0.02 and in 12,1% in non lesional soriatic skin vs 27, 3% in control skin (p =0,13). This colonization was less important in lesional psoriatic skin (3%) than in non lesional psoriatic skin (12.1%) p= 0.20. Nasal screening identified (7/33) 21, 21% S. aureus carriers in psoriasis group and in control group. Our results are in consensus withliterature findings. They have confirmed the importance of antimicrobial peptides in Innateimmunity of human skin. These peptides are normally produced bykeratinocytes in response to inflammatory stimuli such as psoriasis. Their high expression in psoriasis skin reduces the risk of skin infection and skin colonization with S. Aureus. PMID:27200138
Background: Although various therapies used for the treatment of psoriasis are able to produce remission, yet relapses, a common problem, remains frequent. It was observed that treatment with intermittent high dose (IHD) and continuous low dose (CLD) azathioprine can produce prolonged and durable remission in psoriasis. Aims: To see the long term effect of azathioprine pulse therapy (APT) in psoriasis. Methods: Ten patients with psoriasis who has completed more than 5 years in remission with azathioprine pulse therapy are being taken in the study. They were given IHD azathioprine (500 mg on 3 consecutive days which is repeated every month) with CLD azathioprine (100 mg orally) daily in between IHD. The entire treatment schedule was divided into four phases. During phase I, treatment with IHD and CLD azathioprine was started and continued till complete clearance of lesions after which, patients proceeded to Phase II. In phase II, they continued to get treatment with IHD and CLD. After continued remission for a period of nine months, they entered into phase III, when the treatment with IHD was stopped, but CLD continued. If there was no recurrence after nine months of phase III treatment, CLD was also withdrawn, and patients were followed-up without any treatment (Phase IV). Results: All 10 patients completed treatment and are in remission for more than five years without any treatment. Conclusions: Out of 60 patients in phase IV, 10 patients were in continuous remission for more than five years, after all treatment had been stopped. Thus, azathioprine pulse therapy regimen produces prolonged remission in psoriasis. PMID:26288403
Kvist, Peter H; Svensson, Lars; Hagberg, Oskar; Hoffmann, Vibeke; Kemp, Kaare; Røpke, Mads A
The aim of the present study was to compare the effects of Daivobet and calcipotriol on clinical score and biomarker responses in a modified version of the Scholtz-Dumas psoriasis plaque assay. Furthermore, it was the aim to compare the effects of calcipotriol and betamethasone in the murine psoriasis xenograft model. Twenty four patients with psoriasis were treated topically once daily for three weeks, whereas the grafted mice were treated for four weeks. Clinical responses were scored twice weekly and biopsies were taken at the end of each study to analyse for skin biomarkers by histology and immunohistochemistry. The results clearly demonstrate effects on both clinical signs and biomarkers. In the patient study the total clinical score was reduced significantly with both Daivobet and calcipotriol. Both treatments reduced epidermal thickness, Ki-67 and cytokeratin 16 expression. T cell infiltration was significantly reduced by Daivobet but only marginally by calcipotriol. Both treatments showed strong effects on the epidermal psoriatic phenotype.Results from the xenograft model essentially showed the same results. However differences were observed when investigating subtypes of T cells.The study demonstrates the feasibility of obtaining robust biomarker data in the psoriasis plaque test that correlate well with those obtained in other clinical studies. Furthermore, the biomarker data from the plaque test correlate with biopsy data from the grafted mice.
Jiang, Long; Liu, Lu; Cheng, Yuyan; Lin, Yan; Shen, Changbing; Zhu, Caihong; Yang, Sen; Yin, Xianyong; Zhang, Xuejun
Missing heritability is a common problem in genome-wide association studies in complex diseases/traits. To quantify the unbiased heritability estimate, we applied the phenotype correlation-genotype correlation regression in psoriasis genome-wide association data in Han Chinese which comprises 1139 cases and 1132 controls. We estimated that 45.7% heritability of psoriasis in Han Chinese were captured by common variants (s.e.=12.5%), which reinforced that the majority of psoriasis heritability can be covered by common variants in genome-wide association data (68.2%). The results provided evidence that the heritability covered by psoriasis genome-wide genotyping data was probably underestimated in previous restricted maximum likelihood method. Our study highlights the broad role of common variants in the etiology of psoriasis and sheds light on the possibility to identify more common variants of small effect by increasing the sample size in psoriasis genome-wide association studies.
Psoriasis is an immune-mediated chronic inflammatory skin disease with a complex etiology. The proinflammatory cytokine IL-17A is known to play key role in the pathogenesis of psoriasis, and recently anti-IL-17A antibodies have been approved for psoriasis treatment. Here, we discuss our recent findings demonstrating that IκBζ, a transcriptional co-activator, plays a crucial role in the development of psoriasis by mediating IL-17A-driven effects. These findings have significant implications as they uncover a novel crucial regulatory mechanism involved in psoriasis development, and identify IκBζ as a possible future target in the treatment of psoriasis and other IL-17A-driven diseases.
Na, Sun Jae; Jo, Seong Jin; Youn, Jai Il
Psoriasis is a chronic relapsing disorder which shows variable clinical features. The long-term clinical study with many patients is important to elucidate the epidemiologic characteristics and clinical features of psoriasis. The purpose of this study was to analyze the epidemiologic characteristics and clinical features of psoriasis in Korean patients. Epidemiologic and clinic data and assessments for severity of extent and activity of psoriasis were collected from the medical records of 5084 patients, who had been newly diagnosed with psoriasis in the Psoriasis Clinic of Seoul National University Hospital between 1982 and 2012. The sex ratio of the psoriasis patients was 1.2:1 (male 54.6%, female 45.4%). The peak age of onset in males was 20s, while it was the teenage years in females. A total of 63.5% of patients developed psoriasis before 30 years of age. Family history of psoriasis was observed in 26.0% of patients. Moderate to severe extent of involvement were more frequently observed in male patients and patients under 30 years of onset age than in females and patients 30 years or over of onset age, respectively. Moderate to severe disease activity were also more frequently presented in male patients, but not in patients under 30 years of onset age. The most common morphological type was nummular (56.7%), followed by large plaque (28.5%) and guttate (8.5%). Nail involvement accompanied in 26.4% of patients. We demonstrated the epidemiologic and clinical characteristics of psoriasis in Korean patients.
Paek, So Yeon; Thompson, Jordan M; Qureshi, Abrar A; Merola, Joseph F; Husni, M Elaine
Outcome measures for psoriasis severity are complex because of the heterogeneous presentation of the disease. At the 2015 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members introduced the Comprehensive Assessment of the Psoriasis Patient (CAPP), a novel disease severity measure to more accurately assess the full burden of plaque psoriasis and subtypes, including inverse, scalp, nail, palmoplantar, and genital psoriasis. The CAPP is based on a 5-point physician's global assessment for 7 psoriasis phenotypes and incorporates visual analog scale-based, patient-derived, patient-reported outcomes. By quantifying disease effects of plaque psoriasis, 6 other psoriasis subtypes, as well as quality of life and daily function, the CAPP survey identifies a subset of psoriasis patients with moderate to severe psoriasis that would not be considered moderate to severe when assessed by the Psoriasis Area and Severity Index. The current version of CAPP is focused entirely on psoriasis. Feedback from our industry colleagues and collaborators has suggested that a psoriatic arthritis (PsA) measure may be important to include in the CAPP. At the 2015 GRAPPA meeting, we administered a survey to 106 GRAPPA members to determine whether a PsA measure should be included. A majority (74%) of respondents across all professions agreed that the CAPP should include a measure of PsA. Although responses varied widely on how PsA should be measured, a majority of the respondents reported that presence of PsA in both peripheral and axial joint assessment was important.
Shin, Dongyun; Kim, Dae Suk; Kim, Sung Hee; Je, Jung Hwan; Kim, Hee Ju; Young Kim, Do; Kim, Soo Min; Lee, Min-Geol
Follicular helper T (Tfh) cells are recently characterized subset of helper T cells, which are initially found in the germinal centers of B cell follicles. The major role of Tfh cells is helping B cell activation and antibody production during humoral immunity. Recently, blood Tfh cells were shown to be associated with autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, bullous pemphigoid and psoriasis. There is only one study which investigated Tfh cells in psoriasis patients. Therefore, in this study, we evaluated and analyzed blood Tfh cells in Korean patients with psoriasis. A total of 28 psoriasis patients and 16 healthy controls were enrolled. The frequency and absolute number of CXCR5(+)PD-1(+) Tfh cells were decreased in patients with psoriasis compared to healthy controls. CD4(+)CXCR5(+) T cells and CXCR5(+)ICOS(+) Tfh cells did not show differences. The frequency and absolute number of CXCR5(+)PD-1(+) Tfh cells in psoriasis patients negatively correlated with erythrocyte sedimentation rate and positively correlated with disease duration. The absolute number of CXCR5(+)ICOS(+) Tfh cells also showed positive correlation with disease duration. However, the subpopulations of Tfh cells did not correlate with Psoriasis Area and Severity Index. Serum interleukin-21 level was significantly increased in psoriasis patients compared to healthy controls, however, its level did not correlate with clinical and experimental parameters of psoriasis patients. These findings suggest the decreased function of Tfh cells in psoriasis, which could result in attenuated B cell immune responses in the pathogenesis of psoriasis. However, further investigations are necessary to confirm the function of Tfh cells in psoriasis vulgaris.
Liu, Junlian; Chen, Wei; Zhou, Jinlian; Liu, Jianjun; Zhang, Jianzhong
Psoriasis is a chronic inflammatory skin disease that is characterized by erythematous, sharply demarcated papules and plaques covered by scales. Extramammary Paget disease (EMPD) is a uncommon neoplastic condition of apocrine gland-bearing skin and its occurrence in combination with psoriasis is very rare. We report an interesting case of a 61-year-old male with extensive psoriasis presented with penoscrotal EMPD, which was confirmed by histopathological stain.
Wang, Ting-Shun; Chiu, Hsien-Yi; Hong, Jin-Bong; Chan, Chih-Chieh; Lin, Sung-Jan; Tsai, Tsen-Fang
Different studies have reported various values for the percentage of patients with IL36RN mutations, and it has also been reported that the sites of these mutations differ among different ethnicities. The current study was a cross-sectional study conducted to investigate the risk factors predicting IL36RN mutation in Chinese patients with different clinical features of pustular psoriasis. 57 Han Chinese patients, including 32 with generalized pustular psoriasis, 14 with palmoplantar pustulosis, 9 with plaque-type psoriasis with pustules, and 2 with erythrodermic psoriasis, were enrolled between March 2013 and July 2014. Blood samples were collected, genomic DNA was extracted from leukocytes, and polymerase chain reaction (PCR)-based Sanger sequencing was used to analyze the coding exons and flanking introns of the IL36RN gene. The patients with generalized pustular psoriasis exhibited the highest IL36RN mutation rate (75 %) among the aforementioned patient types, with the subgroup consisting of those patients who had features of acrodermatitis continua of Hallopeau exhibiting the highest c.115+6T>C mutation rate (93.8 %). In addition, early onset, ever generalized pustular psoriasis (more than two attacks), ever acrodermatitis continua of Hallopeau, inverse psoriasis, and a family history of pustular psoriasis were associated with IL36RN mutation. The c.115+6T>C mutation was the most common and the most important variant in all subtypes of pustular psoriasis with IL36RN mutations among our sample of Chinese patients.
Treadwell, Patricia A
This article has addressed some of the recent discoveries in pathogenesis and treatment options of 4 papulosquamous disorders: atopic dermatitis, psoriasis, seborrheic dermatitis, and nickel contact dermatitis.
Barrea, Luigi; Savanelli, Maria Cristina; Di Somma, Carolina; Napolitano, Maddalena; Megna, Matteo; Colao, Annamaria; Savastano, Silvia
Psoriasis is a chronic immune-mediated inflammatory skin disease. Psoriasis lesions are characterized by hyper-proliferation of epidermal keratinocytes associated with inflammatory cellular infiltrate in both dermis and epidermis. The epidermis is the natural source of vitamin D synthesis by sunlight action. Recently, a role for vitamin D in the pathogenesis of different skin diseases, including psoriasis, has been reported. Indeed, significant associations between low vitamin D status and psoriasis have been systematically observed. Due to its role in proliferation and maturation of keratinocytes, vitamin D has become an important local therapeutic option in the treatment of psoriasis. To date, the successful treatment based on adequate dietary intake of vitamin D or oral vitamin D supplementation in psoriasis represent an unmet clinical need and the evidence of its beneficial effects remains still controversial. This information is important either for Dermatologists and Nutritionists to increases the knowledge on the possible bi-directional relationships between low vitamin D status and psoriasis and on the potential usefulness of vitamin D in psoriasis with the aim not only to reduce its clinical severity, but also for delineating the risk profile for co-morbidities cardiac risk factors that may result from psoriasis. In the current review, we analyzed the possible bi-directional links between psoriatic disease and vitamin D.
Tanigawa, Hiroki; Miyata, Keishi; Tian, Zhe; Aoi, Jun; Kadomatsu, Tsuyoshi; Fukushima, Satoshi; Ogata, Aki; Takeda, Naoki; Zhao, Jiabin; Zhu, Shunshun; Terada, Kazutoyo; Endo, Motoyoshi; Morinaga, Jun; Sugizaki, Taichi; Sato, Michio; Morioka, Masaki Suimye; Manabe, Ichiro; Mashimo, Youichi; Hata, Akira; Taketomi, Yoshitaka; Yamamoto, Kei; Murakami, Makoto; Araki, Kimi; Jinnin, Masatoshi; Ihn, Hironobu; Oike, Yuichi
Psoriasis is a chronic inflammatory skin disease marked by aberrant tissue repair. Mutant mice modeling psoriasis skin characteristics have provided useful information relevant to molecular mechanisms and could serve to evaluate therapeutic strategies. Here, we found that epidermal ANGPTL6 expression was markedly induced during tissue repair in mice. Analysis of mice overexpressing ANGPTL6 in keratinocytes (K14-Angptl6 Tg mice) revealed that epidermal ANGPTL6 activity promotes aberrant epidermal barrier function due to hyperproliferation of prematurely differentiated keratinocytes. Moreover, skin tissues of K14-Angptl6 Tg mice showed aberrantly activated skin tissue inflammation seen in psoriasis. Levels of the proteins S100A9, recently proposed as therapeutic targets for psoriasis, also increased in skin tissue of K14-Angptl6 Tg mice, but psoriasis-like inflammatory phenotypes in those mice were not rescued by S100A9 deletion. This finding suggests that decreasing S100A9 levels may not ameliorate all cases of psoriasis and that diverse mechanisms underlie the condition. Finally, we observed enhanced levels of epidermal ANGPTL6 in tissue specimens from some psoriasis patients. We conclude that the K14-Angptl6 Tg mouse is useful to investigate psoriasis pathogenesis and for preclinical testing of new therapeutics. Our study also suggests that ANGPTL6 activation in keratinocytes enhances psoriasis susceptibility. PMID:27698489
Barrea, Luigi; Nappi, Francesca; Di Somma, Carolina; Savanelli, Maria Cristina; Falco, Andrea; Balato, Anna; Balato, Nicola; Savastano, Silvia
Psoriasis is a common, chronic, immune-mediated skin disease with systemic pro-inflammatory activation, where both environmental and genetic factors contribute to its pathogenesis. Among the risk factors for psoriasis, evidence is accumulating that nutrition plays a major role, per se, in psoriasis pathogenesis. In particular, body weight, nutrition, and diet may exacerbate the clinical manifestations, or even trigger the disease. Understanding the epidemiological relationship between obesity and psoriasis is also important for delineating the risk profile for the obesity-related comorbidities commonly found among psoriatic patients. Moreover, obesity can affect both drug’s pharmacokinetics and pharmacodynamics. Additionally, the overall beneficial effects on the obesity-associated comorbidities, clinical recommendations to reduce weight and to adopt a healthy lifestyle could improve the psoriasis severity, particularly in those patients with moderate to severe disease, thus exerting additional therapeutic effects in the conventional treatment in obese patients with psoriasis. Education regarding modifiable environmental factors is essential in the treatment of this disease and represents one of the primary interventions that can affect the prognosis of patients with psoriasis. The goal is to make psoriatic patients and health care providers aware of beneficial dietary interventions. The aim of this review is to assess the relevance of the environmental factors as modifiable risk factors in psoriasis pathogenesis, with particular regard to the involvement of obesity and nutrition in the management of psoriasis, providing also specific nutrition recommendations. PMID:27455297
Smith, RhLl; Warren, RB; Eyre, S; Ke, X; Young, HS; Allen, M; Strachan, D; McArdle, W; Gittins, MP; Barker, JNWN; Griffiths, CEM; Worthington, J
Background Psoriasis, a chronic inflammatory skin disease, affects approximately 2% of the population worldwide. Although the aetiology of psoriasis is poorly understood, patients with disease of early onset (Type I, age of onset ≤ 40 years) usually have a strong genetic component to the disease. Objectives The purpose of this study was to investigate the role of the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene region in susceptibility to Type I psoriasis. Patients and methods Thirteen single nucleotide polymorphisms (SNPs) mapping to the PTPN22 region were genotyped in 647 patients with Type I psoriasis and 566 normal controls. Results The rs2476601 (R620W) SNP, widely associated with other inflammatory autoimmune diseases, showed no evidence of association with susceptibility to Type I psoriasis. Two SNPs (rs1217414 and rs3789604) demonstrated significant association with Type I psoriasis and were subsequently genotyped in a further 253 unrelated patients and 2024 normal controls. rs1217414 and rs3789604 were also significantly associated with Type I psoriasis in the combined datasets (P = 0·003 and P = 0·0002, respectively); furthermore carriage of both risk alleles was also significantly associated (P = 0·002). Conclusions This study demonstrates evidence of association of two SNPs (rs1217414 and rs3789604) in the PTPN22 region with Type I psoriasis, providing evidence for a role of this gene in Type I psoriasis that is not conferred by the R620W variant previously associated with a number of inflammatory diseases. PMID:18341666
Inani, Kawtar; Meziane, Mariame; Mernissi, Fatimazahra
Le psoriasis est une maladie inflammatoire chronique, son traitement peut être local ou général. Le méthotrexate (MTX) est parmi les traitements systémiques du psoriasis modéré à sévère. Le but de notre étude est d’évaluer la place du MTX dans le traitement du psoriasis dans notre contexte marocain. C'est une étude rétrospective menée au service de dermatologie du CHU HASSAN II FES de 2010 à 2013. 46 patients ont répondus aux critères d'inclusions. Il s'agissait de patients de sexe masculin dans 58,7% des cas, de sujets âgés entre 18 et 45 ans dans 45,7% des cas. Le psoriasis vulgaire était la forme la plus répondue (76,1%), 56,5% avaient une surface corporelle(SC) atteinte comprise entre 25 et 50%, L’évolution était marquée par une rémission complète dans 50% des cas. Le MTX a été utilisé depuis plus de 40 ans dans le traitement du psoriasis modéré à sévère. Dans notre série le recours au MTX était nécessaire et ceci après échec d'autres thérapeutiques. Son efficacité a été constatée chez 50% des patients, avec peu d'effets secondaires. Le MTX est une molécule de référence dans le traitement du psoriasis modéré à sévère, avec un meilleur rapport coût/bénéfice/risque. PMID:25709742
Randeberg, Lise L.; Hernandez-Palacios, Julio; Lilleeng, Mila; Nilsen, Lill Tove; Krogstad, Anne-Lene
Psoriasis is a common autoimmune disease with inflammatory symptoms affecting skin and joints. One way of dealing with psoriasis is by controlled solar UV exposure treatment. However, this treatment should be optimized to get the best possible treatment effect and to limit negative side effects such as erythema and an increased risk of skin cancer. In this study 24 patients at Valle Marina Treatment Center in Gran Canaria were monitored throughout a treatment period of three weeks starting at the beginning of November. The total UV dose to the location was monitored by UV-meters placed on the roof of the treatment centere, and the patients wore individual film dosimeters throughout the treatment period. Skin parameters were accessed by reflection spectroscopy (400-850nm). This paper presents preliminary findings from the skin measurements in the visible part of the spectrum, such as blood oxygenation, erythema and melanin indexes. Reflection spectroscopy was found to be a good tool for such treatment monitoring.
Pagliarello, C; Fabrizi, G; Cortelazzi, C; Boccaletti, V; Feliciani, C; Di Nuzzo, S
Psoriasis is a common inflammatory dermatosis that may be seen in infants, children, and adolescents. The clinical presentation and course may be quite variable, and while patients with mild disease are often easily managed, those with recalcitrant or more severe disease often present a therapeutic dilemma given the number of therapies available and the relative lack of data on the efficacy and safety of use of these therapies in children. Diagnosis in children can be more difficult, but family history may be helpful. Moreover, sometimes clinical pattern of pediatric psoriasis is very different from its adult counterpart or it could manifests in association with atopic dermatitis, and for these reason it is possibly misdiagnosed and under recognized. We therefore focus on diagnostic patterns and effective treatments of this challenging disease.
It is known that inflammatory and immune responses protect us from the invasion of micro-organisms and eliminate "wastes" from the injured sites, but they may also be responsible for significant tissue damage. Adenosine, as a purine nucleoside, which is produced in inflamed or injured sites, fulfills its role in limiting tissue damage. Although, it may have a pleiotropic effect, which signals it with a proinflammatory state in certain situations, it can be considered a potent anti-inflammatory mediator. The effects of adenosine, which acts through its receptors on T cell, on mast cell and macrophages, on endothelial cells, on neutrophils and dendritic cells, as they indicate TNF-alpha and cytokines, show that this mediator has a central role in the pathogenesis of psoriasis. The way it acts in psoriasis will be reviewed in this study. PMID:26734868
López-Estebaranz, Jose Luis; Sánchez-Carazo, Jose Luis; Sulleiro, Sara
Psoriasis is a chronic inflammatory skin disease whose clinical characteristics vary from patient to patient. We aimed to analyze how comorbidities and quality of life (QoL, as per the Dermatology Life Quality Index [DLQI]) may be affected by a family history of psoriasis and by age. The ARIZONA study was a multicenter, cross-sectional study in 1022 adult patients diagnosed with moderate to severe psoriasis at least 6 months prior to inclusion. The severity of psoriasis and the proportion of patients with comorbidities were not affected by the presence of a family history. The regression analysis revealed that the presence of a family history of psoriasis was associated with the effect on the patient's QoL (P = 0.002), regardless of disease severity. The mean DLQI total score varied significantly across age groups (5.1 ± 5.3 for the 18-30-year group, 5.7 ± 6.5 for the 31-60-year group and 3.8 ± 5.1 for the >60-year group; P = 0.001). In conclusion, the presence of a family history of psoriasis appears to disrupt QoL in patients with moderate to severe psoriasis, but it hardly affected the prevalence of comorbid conditions. The effect of age on QoL was particularly noticeable in younger patients, highlighting its negative impact. As expected, older patients appeared to be burdened with a higher number of comorbidities than their younger counterparts.
Chen, Tao; Fu, Li-Xin; Zhang, Li-Wen; Yin, Bin; Zhou, Pei-Mei; Cao, Na; Lu, Yong-Hong
Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders, characterized by hyperproliferation of keratinocytes, dilation and growth of dermal capillary vasculature, and cellular infiltration of T cells, dendritic cells (DCs), and neutrophils. Paeoniflorin (PF), the principal component of total glucosides of paeony (TGP), displays anti-inflammatory and antioxidant properties in several animal models. In this study, we investigated the anti-inflammatory effects and mechanisms of PF in imiquimod (IMQ)-induced psoriasis-like mouse model. The effects of PF on inflammatory cytokine expression in peripheral blood mononuclear cells (PBMCs) from patients with psoriasis vulgaris were also observed. Our results indicated that PF effectively attenuated the clinical and histopathologic changes in IMQ-induced psoriasis-like mouse model. Furthermore, PF reduced the infiltration of T cells, CD11c(+)DCs, and neutrophils in lesional skin. In addition, PF also significantly decreased the mRNA expression of inflammatory cytokines, such as IL-17, INF-γ, IL-6, and TNF-α, in IMQ-induced psoriasis-like mouse model and PBMCs from patients with psoriasis vulgaris. Hence, our data suggest that PF can inhibit leukocyte infiltration and decrease the expression of inflammatory cytokines such as IL-17, INF-γ, IL-6, and TNF-α. PF might be a candidate drug for the treatment of psoriasis.
Zweegers, J; de Jong, E M G J; Nijsten, T E C; de Bes, J; te Booij, M; Borgonjen, R J; van Cranenburgh, O D; van Deutekom, H; van Everdingen, J J E; de Groot, M; Van Hees, C L M; Hulshuizen, H; Koek, M B G; de Korte, W J A; de Korte, J; Lecluse, L L A; Pasch, M C; Poblete-Gutiérrez, P A; Prens, E P; Seyger, M M B; Thio, H B; Torcque, L A; de Vries, A C Q; van de Kerkhof, P C M; Spuls, Ph I
This document provides a summary of the Dutch S3-guidelines on the treatment of psoriasis. These guidelines were finalized in December 2011 and contain unique chapters on the treatment of psoriasis of the face and flexures, childhood psoriasis as well as the patient's perspective on treatment. They also cover the topical treatment of psoriasis, photo(chemo)therapy, conventional systemic therapy and biological therapy.
Wald, Jenna M; Klufas, Daniel M; Strober, Bruce E
Palmoplantar psoriasis is a chronic debilitating type of psoriasis. Treatment options for this disease are poorly studied. This chart review evaluated the use of methotrexate alone and in combination with 7 other systemic therapies in 48 patients with palmoplantar psoriasis. The findings demonstrate that methotrexate is a relatively well-tolerated and effective treatment for palmoplantar psoriasis, amenable as either monotherapy or in combination with other systemic agents.
Schön, M P
Research into the pathogenesis of psoriasis has been hampered by the lack of an animal disease resembling this common human skin disorder. Over the past few years, however, various rodent models that mirror aspects of the psoriatic phenotype and pathogenesis have become available. Here, the most prominent models are compared with human psoriasis and potential uses for psoriasis research are reviewed. Asebia (ab), flaky skin (fsn), and chronic proliferative dermatitis (cpd) are spontaneous mouse mutations with psoriasiform skin alterations of unclear pathogenesis. Transgenic mice with cutaneous overexpression of cytokines, such as interferon-gamma, interleukin-1alpha, keratinocyte growth factor, transforming growth factor-alpha, interferon-6, vascular endothelial growth factor, or bone morphogenic protein-6, are valuable tools for studying in vivo effects of individual cytokines in the pathogenesis of psoriasiform features. Psoriasiform lesions also were seen in beta2-integrin hypomorphic mice backcrossed to the PL/J strain and in beta1-integrin transgenic mice. A T cell-based immunopathogenesis of psoriasiform features was shown in a form of graft-versus-host disease in scid/scid mice reconstituted with CD4+/CD45RB(hi) T lymphocytes as well as in HLA-B27/hbeta2m transgenic rats, demonstrating that dysregulated T cells can induce psoriasiform skin alterations without a primary epithelial abnormality. Finally, xenotransplantation models using human skin grafted on to immunodeficient mice are attractive, as different cell types and some environmental factors leading to psoriasiform features may be studied in human tissue. Overall, although there is no animal model imitating psoriasis completely, many aspects of this common human skin disorder are mirrored in the currently available models and psoriatic plaques can be created in xenotransplantation models.
Kang, Di; Li, Bowen; Luo, Lei; Jiang, Wenbing; Lu, Qiumin; Rong, Mingqing; Lai, Ren
Curcumin is an active herbal ingredient possessing surprisingly wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity. Recently, it has been reported to exhibit inhibitory activity on potassium channel subtype Kv1.3. As Kv1.3 channels are mainly expressed in T cells and play a key role in psoriasis, the effects of curcumin were investigated on inflammatory factors secretion in T cells and psoriasis developed in keratin (K) 14-vascular endothelial growth factor (VEGF) transgenic mouse model. Results showed that, 10 μM of curcumin significantly inhibited secretion of inflammatory factors including interleukin (IL)-17,IL-22, IFN-γ, IL-2, IL-8 and TNF-α in T cells by 30-60% in vitro. Notably, more than 50% of T cells proliferation was inhibited by application of 100 μM curcumin. Compared with severe psoriatic symptoms observed in the negative control mice, all psoriasis indexes including ear redness, weight, thickness and lymph node weight were significantly improved by oral application of curcumin in treatment mouse group. Histological examination indicated that curcumin had anti-inflammatory function in the experimental animals. More than 50% level of inflammatory factors including TNF-α, IFN-γ, IL-2, IL-12, IL-22 and IL-23 in mouse serum was decreased by curcumin treatment as well as cyclosporine. Compared with renal fibrosis observed in the mouse group treated by cyclosporine, no obvious side effect in mouse kidney was found after treated by curcumin. Taken together, curcumin, with high efficacy and safety, has a great potential to treat psoriasis.
Psoriasis is a systemic, immune-mediated disorder, characterized by inflammatory skin and joint manifestations. A range of co-morbidities is associated with psoriasis, including metabolic diseases, such as diabetes, and psychological disorders. Although the systemic nature of psoriasis often remains unrecognized, the inflammatory processes involved may be associated with the development of co-morbidities, which, themselves, have a significant impact on the patient's health and quality of life. The relative risks of myocardial infarction (MI) and stroke are increased in patients with psoriasis compared with the general population. These are especially seen in younger patients with more severe disease, and are believed to contribute to the 3- to 4-year reduction in life expectancy among patients with severe psoriasis. The recent results of large studies indicate that the increased cardiovascular (CV) risk is at least partially attributable to psoriasis and independent of the presence of metabolic co-morbidities. The possible interplay between psoriasis and CV disease is complex. Metabolic diseases such as obesity and diabetes have overlapping genetic predispositions with psoriasis. Both conditions are likely to also interact at a functional level because obesity and the up-regulation of pro-inflammatory mediators in psoriasis appear to influence adipocyte homoeostasis, inducing non-professional immune functions. This may perpetuate psoriatic inflammation, displaying similarities to the immunopathogenesis of atherosclerosis. Finally, the disturbed adipokine profile and inflammation associated with psoriasis enhances insulin resistance, causing subsequent endothelial dysfunction, atherosclerosis and eventual coronary events. The differential contribution of psoriasis and uncontrolled classical CV risk factors to the increased CV risk seen in psoriasis patients is not clear. Successful treatment with methotrexate appears to lower the rates of MI in patients with
Tey, Hong Liang; Ee, Hock Leong; Tan, Andy S L; Theng, Thiam Seng; Wong, Su Ni; Khoo, Shih Wee
The aim of this study was to determine if the following characteristics were associated with the presence of psoriatic arthritis in a sample of psoriasis patients: race, family history of psoriasis and psoriatic arthritis, age of onset of psoriasis, smoking, alcohol consumption and the maximum body surface area (BSA) affected by psoriasis. This was a case-control study involving 400 psoriasis patients who attended the Psoriasis and Photo-medicine clinic in the National Skin Center of Singapore over a 1-year period. Cases were psoriasis patients with psoriatic arthritis while controls were psoriasis patients without psoriatic arthritis. The diagnosis of psoriatic arthritis was made by rheumatologists and participants completed a self-administered standardized questionnaire. The maximum BSA involved was determined from the case notes. Psoriatic arthritis was not significantly associated with sex, race, age of onset of psoriasis, a family history of psoriasis, smoking and alcohol consumption but was significantly associated with a family history of psoriatic arthritis (P < 0.001) and the maximum body surface involved (P = 0.05). Using multivariate analysis to control for variables, the presence of psoriatic arthritis was significantly associated with a family history of psoriatic arthritis (odds ratio [OR] = 20.5; 95% confidence interval [CI] = 2.49-169.10) and the maximum BSA involved (OR = 2.52; 95% CI = 1.33-4.75). Indian psoriatic patients were more likely to have psoriatic arthritis compared to the other races. A family history of psoriatic arthritis and a greater maximum body surface involved may be associated with having psoriatic arthritis in this study population of psoriasis patients.
Aydın, Ersin; Tekeli, Hakan; Karabacak, Ercan; Altunay, İlknur Kıvanç; Aydın, Çigdem; Çerman, Aslı Aksu; Altundağ, Aytuğ; Salihoğlu, Murat; Çayönü, Melih
It is well known that psoriasis is not only limited to skin, but a systemic autoimmune disease with various comorbidities. Olfactory dysfunction, one of as a common but lesser known symptom of patients with autoimmune diseases, often presents with smell loss. The aim of this study was to assess the olfactory functions in patients with psoriasis and to compare with healthy controls. A total of 50 patients with psoriasis and 43 control subjects were included to the study. The clinical severity of psoriasis was calculated by psoriasis area and severity index (PASI). Patients were classified into two groups according to PASI score as mild (PASI ≤10) and moderate-severe (PASI >10). Olfactory function was evaluated with "Sniffin'Sticks" test. Total test scores (max. 48 points) of threshold, discrimination, and identification (TDI) were classified as normal olfaction = normosmia (>30.3 points), decreased olfaction = hyposmia (16.5-30.3 points) and loss of olfaction = anosmia (<16.5 points). Psoriasis patients had significantly lower smell scores compared with healthy controls (p < 0.001). Of the 50 psoriasis patients, 40 (80 %) were hyposmic. We found negative correlation between TDI and PASI (r = -0.34, p = 0.014). The TDI scores of the patients with moderate-severe psoriasis (PASI score >10) were found to be significantly lower than the patients with mild psoriasis (PASI ≤10) (p < 0.001). Olfactory dysfunction in patients with psoriasis could be thought as a comorbidity as in other inflammatory disorders. Physicians should be aware of olfactory impairment when evaluating psoriasis patients in their clinical practice.
Shidara, Kumi; Soejima, Makoto; Shiseki, Mariko; Ohta, Syuji; Nishinarita, Makoto
A 49-years-old female admitted to our hospital because of skin eruptions on the extremities in 1985. She had suffered from polyarthralgia, skin eruptions since 1983. Physical examinations revealed discoid lesion, central nervous system involvement, and polyarthritis. Laboratory tests revealed leukopenia, thrombocytopenia, and hypocomplementemia. Antinuclear antibody, ant-DNA antibody, LE test were positive. From these findings, she was diagnosed as systemic lupus erythematosus (SLE). She developed lupus peritonitis in 1990 and 1994, which was successfully treated by steroid pulse therapy. Since then, the activity of SLE was in good control under administration of prednisolone 10 mg/day. Chilblain lupus was seen from 1993, Raynaud's phenomenon from 1996, and she further developed subcutaneous induration on her chest, back and upper extremities in 1999. Skin biopsy findings were compatible with lupus panniculitis. In 2002, erythematous patches with scales were observed on her right hand and left knee, and these skin lesions were histologically diagnosed as psoriasis vulgaris. An autoimmune response similar to SLE is speculated in psoriasis. We describe a rare case of SLE with various skin lesions including psoriasis vulgaris.
Schön, Michael P; Broekaert, Sigrid M C; Erpenbeck, Luise
Notwithstanding their prominent presence in psoriatic skin, the functional role of neutrophilic granulocytes still remains somewhat enigmatic. Sparked by exciting scientific discoveries regarding neutrophil functions within the last years, the interest in these short-lived cells of the innate immune system has been boosted recently. While it had been known for some time that neutrophils produce and respond to a number of inflammatory mediators, recent research has linked neutrophils with the pathogenic functions of IL-17, possibly in conjunction with the formation of NETs (neutrophil extracellular traps). Antipsoriatic therapies exert their effects, at least in part, through interference with neutrophils. Neutrophils also appear to connect psoriasis with comorbid diseases. However, directly tampering with neutrophil functions is not trivial as evinced by the failure of therapeutic approaches targeting redundantly regulated cellular communication networks. It has also become apparent that neutrophils link important pathogenic functions of the innate and the adaptive immune system and that they are intricately involved in regulatory networks underlying the pathophysiology of psoriasis. In order to advocate intensified research into the role of this interesting cell population, we here highlight some features of neutrophils and put them into perspective with our current view of the pathophysiology of psoriasis.
Soler, David C; McCormick, Thomas S
Traditionally, myeloid-derived suppressor cells (MDSC) have been studied in regard to their increased numbers of circulating cells in cancer patients. Recent research efforts have also increased awareness of MDSC in non-malignant inflammatory diseases, including asthma, inflammatory bowel disease, and arthritis. Psoriasis can now be added to the growing list of inflammatory disorders with an MDSC component. Cao et al. report increased numbers of monocytic myeloid-derived suppressor cells (Mo-MDSC) in psoriasis patients and examine the implication of dysregulated Mo-MDSC function. Cao et al. describe psoriatic Mo-MDSC that produce increased IL-23, IL-1b, and CCL4 cytokines compared to Mo-MDSC from healthy controls. These results complement previous research demonstrating psoriatic Mo-MDSC are unable to suppress autologous and heterologous CD8 T-cell proliferations, display decreased expression levels of PD-1 as well as PD-L1, and fail to produce effective immuno-competent regulatory T cells (Tregs). Cao et al. also identify the unique expression of the surface protein DC-HIL on psoriatic Mo-MDSC. The expanded population of DC-HIL(+) Mo-MDSC in psoriasis patients, however, display inferior suppressive capabilities compared to DC-HIL(+) Mo-MDSC found in melanoma patients, suggesting contextual signaling as a potential contributing factor to Mo-MDSC function.
Papp, Kim A
Effective treatment with etanercept results from a congregation of immunological signaling and modulating roles played by tumor necrosis factor-alpha (TNF-alpha), a pervasive member of the TNF super-family of cytokines participating in numerous immunologic and metabolic functions. Macrophages, lymphocytes and other cells produce TNF as part of the deregulated immune response resulting in psoriasis or other chronic inflammatory disorders. Tumor necrosis factor is also produced by macrophages and lymphocytes responding to foreign antigens as a primary response to potential infection. Interference with cytokine signaling by etanercept yields therapeutic response. At the same time, interference with cytokine signaling by etanercept exposes patients to potential adverse events. While the efficacy of etanercept for the treatment of psoriasis is evident, the risks of treatment continue to be defined. Of the potential serious adverse events, response to infection is the best characterized in terms of physiology, incidence, and management. Rare but serious events: activation of latent tuberculosis, multiple sclerosis, lymphoma, and others, have been observed but have questionable or yet to be defined association with therapeutic uses of etanercept. The safe use of etanercept for the treatment of psoriasis requires an appreciation of potential adverse events as well as screening and monitoring strategies designed to manage patient risk PMID:18360633
O'Connell, M.-L.; O'Connor, W.; Ramsay, B.; Guihen, E.; Ho, W. L.; Leahy, M. J.
Optical coherence tomography (OCT) has been used as part of a ground breaking translational study to shed some light on one of the worlds most prevalent autoimmune diseases; psoriasis. The work successfully integrates the fields of optical imaging, biochemistry and dermatology in conducting a dermal microdialysis (DMD) trial for quantitative histamine assessment amongst a group of psoriasis sufferers. The DMD process involves temporary insertion of microscopic hollow tubes into a layer of skin to measure the levels of histamine and other important biological molecules in psoriasis. For comparison purposes, DMD catheters were implanted into healthy, peri-lesional and lesional skin regions. The catheters' entry and exit points and their precise locations in the epidermal layer of the skin were confirmed using OCT thus obtaining high resolution, wide-field images of the affected skin as well as catheter placement whilst local microdialysis enabled a tissue chemistry profile to be obtained from these three skin regions including histamine, a local immune system activator known to contribute towards itch and inflammation. Together these tools offer a synergistic approach in the clinical assessment of the disease. In addition, OCT delivered a non-invasive and rapid method for analyzing the affected skin architecture.
Sarıcaoglu, Hayriye; Oz, Arife; Turan, Hakan
Psoriasis is a common, chronic disease which affects nearly 3% of the population. The lifetime incidence of nail involvement increases up to 80-90% for psoriatic patients. Nail psoriasis is considered a significant social problem. Many topical agents have been used for psoriatic nails with various side effects and some benefits; management is currently inconclusive. Methotrexate (MTX) is a folic acid analog, which irreversibly binds to dehydrofolate reductase and blocks deoxyribonucleic acid synthesis. It is considered a potential treatment option for rapidly growing cells and has an anti-inflammatory effect through inhibition of the polyamine pathway in autoimmune diseases. Intralesional MTX has been used successfully for various indications. We present a case successfully treated with low-dose intralesional MTX with no observed side effects in a 26-year-old female psoriatic patient suffering from nail dystrophy. In contrast, conventional topical and systemic therapies have various side effects, which limit their use. We conclude that intralesional MTX injection seems to be a safe and effective treatment option for nail psoriasis; however, large controlled studies are needed.
Kapsokalyvas, Dimitrios; Cicchi, Riccardo; Bruscino, Nicola; Alfieri, Domenico; Massi, Daniela; Lotti, Torello; Pavone, Francesco S.
Psoriasis is an autoimmune disease of the skin characterized by hyperkeratosis, hyperproliferation of the epidermis, inflammatory cell accumulation and increased dilatation of dermal papillary blood vessels. Cases of psoriasis were investigated in vivo with optical means in order to evaluate the potential of in vivo optical biopsy. A Polarization Multispectral Dermoscope was employed for the macroscopic observation. Features such as the 'dotted' blood vessels pattern was observed with high contrast. High resolution image sections of the epidermis and the dermis were produced with a custom made Multiphoton Microscope. Imaging extended from the surface of the lesion down to the papillary dermis, at a depth of 200 μm. In the epidermis, a characteristic morphology of the stratum corneum found only in Psoriasis was revealed. Additionally, the cytoplasmic area of the cells in the stratum spinosum layer was found to be smaller than normal. In the dermis the morphological features were more pronounced, where the elongated dermal papillae dominated the papillary layer. Their length exceeds 100μm, which is a far greater value compared to that of healthy skin. These in vivo observations are consistent with the ex vivo histopathological observations, supporting both the applicability and potentiality of multispectral dermoscopy and multiphoton microscopy in the field of in vivo optical investigation and biopsy of skin.
... dandruff, seborrheic dermatitis, or psoriasis. 358.750 Section 358.750 Food and Drugs FOOD AND DRUG... Dermatitis, and Psoriasis § 358.750 Labeling of drug products for the control of dandruff, seborrheic dermatitis, or psoriasis. (a) Statement of identity. The labeling of the product contains the...
... dandruff, seborrheic dermatitis, or psoriasis. 358.750 Section 358.750 Food and Drugs FOOD AND DRUG... Dermatitis, and Psoriasis § 358.750 Labeling of drug products for the control of dandruff, seborrheic dermatitis, or psoriasis. (a) Statement of identity. The labeling of the product contains the...
... dandruff, seborrheic dermatitis, or psoriasis. 358.750 Section 358.750 Food and Drugs FOOD AND DRUG... Dermatitis, and Psoriasis § 358.750 Labeling of drug products for the control of dandruff, seborrheic dermatitis, or psoriasis. (a) Statement of identity. The labeling of the product contains the...
İnci, Sinan; Aksan, Gökhan; Nar, Gökay; Yüksel, Esra Pancar; Ocal, Hande Serra; Çapraz, Mustafa; Yüksel, Serkan; Şahin, Mahmut
Introduction The arrhythmia potential has not been investigated adequately in psoriatic patients. In this study, we assessed the ventricular repolarization dispersion, using the Tp-e interval and the Tp-e/QT ratio, and investigated the association with inflammation. Material and methods Seventy-one psoriasis vulgaris patients and 70 age- and gender-matched healthy individuals were enrolled in the study. The severity of the disease was calculated using Psoriasis Area and Severity Index scoring. The QTd was defined as the difference between the maximum and minimum QT intervals. The Tp-e interval was defined as the interval from the peak of the T wave to the end of the T wave. The Tp-e interval was corrected for heart rate. The Tp-e/QT ratio was calculated using these measurements. Results There were no significant differences between the groups with respect to basal clinical and laboratory characteristics (p > 0.05). The Tp-e interval, the corrected Tp-e interval (cTp-e) and the Tp-e/QT ratio were also significantly higher in psoriasis patients compared to the control group (78.5 ±8.0 ms vs. 71.4 ±7.6 ms, p < 0.001, 86.3 ±13.2 ms vs. 77.6 ±9.0 ms, p < 0.001 and 0.21 ±0.02 vs. 0.19 ±0.02, p < 0.001 respectively). A significant correlation was detected between the cTp-e time and the Tp-e/QT ratio and the PASI score in the group of psoriatic patients (r = 0.51, p < 0.001; r = 0.59, p < 0.001, respectively). Conclusions In our study, we detected a significant increase in the Tp-e interval and the Tp-e/QT ratio in patients with psoriasis vulgaris. The Tp-e interval and the Tp-e/QT ratio may be predictors for ventricular arrhythmias in patients with psoriasis vulgaris. PMID:27904512
Gutknecht, Mandy; Krensel, Magdalene; Augustin, Matthias
In the course of the chronic skin disease psoriasis, where a variety of treatment interventions is available, a strong growth of health economic studies comparing treatment costs and benefits can be noticed. The objective was to identify health economic evaluations of psoriasis treatments that have been published to date. Of particular interest were the mostly used analysis and outcome parameters, the compared treatments, and the question, if available health economic studies may be used to perform a meta-analysis of qualitative findings. A systematic literature search using PubMed Medline, Ovid Medline, and Cochrane Library was performed for articles, published and available until mid of January 2016. Among the key words were the terms "psoriasis" and "cost-effectiveness". The search resulted in 318 articles without duplicates. Thereof 60 health economic analyses in psoriasis management were identified. Most of these are cost-effectiveness evaluations (45). The clinical parameter PASI (Psoriasis Area Severity Index) is the most often used cost-effectiveness outcome (33) followed by the Dermatology Life Quality Index (DLQI) (6). In case of cost-utility analyses, QALYs (quality-adjusted life-years) were mostly generated with the help of EuroQol five dimensions questionnaire (EQ-5D) (12), which was partly based on PASI and DLQI values. The majority of health economic studies is focusing on the direct medical and non-medical costs without consideration of productivity losses. Almost 70 % of 60 publications were conducted in Europe. Overall, most considered systemic treatments were the biological agents etanercept (36), adalimumab (27), and infliximab (26) followed by ustekinumab (17) and phototherapy (incl. UV-B, PUVA/psoralen combined with UV-A) (14). Comparisons including only topical treatments mostly focused on vitamin D treatment (14), corticosteroids (13), and coal tar products (6) followed by dithranol (5) and tazarotene (4). Given the setting, compared
Nguyen, Catherine M; Beroukhim, Kourosh; Danesh, Melissa J; Babikian, Aline; Koo, John; Leon, Argentina
Introduction Chronic skin conditions have been well reported to affect a patient’s quality of life on multiple dimensions, including the psychosocial domain. Psychosocial is defined as the interrelation of social factors with an individual’s thoughts and behavior. The assessment of the psychosocial impact of skin disease on a patient can help direct the dermatologists’ treatment goals. To evaluate the psychosocial impact of skin disease, we conducted a review of the literature on three skin conditions with onsets at various stages of life: acne, vitiligo, and psoriasis. Methods A PubMed search was conducted in March 2015 using the terms “psychosocial” AND “acne”, “psychosocial” AND “vitiligo”, and “psychosocial” AND “psoriasis”. The results were limited to articles published in English in the past 5 years studying patients of all ages. Results and their references were evaluated for relevance according to their discussion of psychosocial qualities in their patients and the validity of psychosocial assessments. The search for acne yielded 51 results, and eleven were found to be relevant; vitiligo yielded 30 results with ten found to be relevant; and psoriasis yielded 70 results with seven found to be relevant. Results According to the articles evaluated, 19.2% of adolescent patients with acne were affected in their personal and social lives. Social phobia was present in 45% of patients with acne compared to 18% of control subjects. Race and sex played a role in self-consciousness and social perceptions of the disease. Vitiligo negatively affected marriage potential and caused relationship problems in >50% of patients. Psoriasis negatively affected multiple domains of life, including work, relationships, and social activities. Anxiety and depression affected not only psoriasis patients but also their cohabitants; up to 88% of cohabitants had an impaired quality of life. Conclusion Though all three skin conditions resulted in an increase
Pariser, David; Schenkel, Brad; Carter, Chureen; Farahi, Kamyar; Brown, T. Michelle; Ellis, Charles N.
Abstract Background: Moderate to severe plaque psoriasis (with or without psoriatic arthritis) places significant burden on patients’ lives. Objective: Explore and document patients’ experiences of living with psoriasis, including symptoms, treatments, impact on daily lives and patient-reported functioning. Methods: In a US-based, non-interventional study, narrative interviews were conducted at baseline and again within 16 weeks. In interviews, patients with moderate to severe psoriasis indicated symptoms, ranked symptoms according to level of bother and indicated areas of their lives affected by psoriasis. Transcripts of interviews were coded for themes. Measurements of psoriasis severity including BSA, PGA and PASI were recorded. Results: Symptoms reported most frequently included flaking/scaling (non-scalp areas), itching/scratching and rash, while the most bothersome symptoms were itching/scratching, flaking/scaling (non-scalp areas) and skin pain. Frequently reported impact areas were social and emotional. Conclusion: Broad-reaching interviews with patients with psoriasis show that these patients suffer in many aspects of their lives and in ways not indicated by typical psoriasis severity measures. Patients with psoriatic arthritis reported symptoms and disease-related complications at higher rates than those without arthritis. Physicians’ explorations of the effect of psoriasis on patients’ life events could aid in managing these patients. PMID:26138406
Hu, Zhengmao; Xiong, Zhimin; Xu, Xiaojuan; Li, Fangfang; Lu, Lina; Li, Wei; Su, Juan; Liu, Yalan; Liu, Deyuan; Xie, Zhiguo; Peng, Yu; Kuang, Yehong; Wu, Lisha; Zhang, Jianglin; Pan, Qian; Tang, Beisha; Chen, Xiang; Xia, Kun
Loss-of-function mutations in filaggrin gene (FLG; OMIM #135940) have been reported to cause the semi-dominant keratinizing disorders such as ichthyosis vulgaris (IV; OMIM #146700) and atopic dermatitis (AD; OMIM #605803). Recent linkage analysis and immunohistochemical studies suggest the possible contribution of FLG to psoriatic susceptibility. However, no susceptibility variant in FLG gene associated with psoriasis (OMIM #177900) has been identified. In this study, we identified a non-sense mutation of FLG (p.K4022X) in a Chinese psoriasis/IV coexisting family. The homozygous p.K4022X mutation was detected in a psoriasis patient, whereas the heterozygous p.K4022X mutation was identified in two IV patients and four apparently normal family members. We also genotyped p.K4022X variant in 441 sporadic Chinese psoriasis patients and found homozygous mutation in two patients, while no homozygous variant was found in 500 control individuals. After sequencing the entire coding region of FLG gene in 441 psoriasis patients, we identified another five mutations (p.R826X, p.W2583X, c.7945delA, c.3321delA and p.Q2417X). Although all six FLG mutations as a whole was not significantly associated with psoriasis (P = 0.105), mutation p.K4022X was significantly associated with psoriasis (P < 0.05). Our data thus indicates an association of FLG with psoriasis in Chinese population.
Johnston, Andrew; Gudjonsson, Johann E
IL-22 targets our external epithelial barriers, bolstering our defenses, and has long been implicated in the pathogenesis of psoriasis. Nikamo and colleagues (2014) identify a haplotype in the IL22 promoter with a strong association to juvenile-onset psoriasis and demonstrate that this risk variant is associated with increased IL-22 production by T cells. We explore the implications of this work.
Nottrott, Markus; Hardes, Jendrik; Winkelmann, Winfried; Gosheger, Georg
Extraskeletal mesenchymal chondrosarcoma is extremely rare and, in combination with psoriasis, it has never been described before. We report a case of wide resection of an extraskeletal chondrosarcoma of the thigh and reconstruction with a femoral megaprosthesis in a patient with psoriasis vulgaris. Special emphasis has been laid to postoperative wound healing in psoriatic skin which did not show any problems. PMID:18414591
Nottrott, Markus; Hardes, Jendrik; Winkelmann, Winfried; Gosheger, Georg
Extraskeletal mesenchymal chondrosarcoma is extremely rare and, in combination with psoriasis, it has never been described before. We report a case of wide resection of an extraskeletal chondrosarcoma of the thigh and reconstruction with a femoral megaprosthesis in a patient with psoriasis vulgaris. Special emphasis has been laid to postoperative wound healing in psoriatic skin which did not show any problems.
Guo, Ren; Li, Fang-Fang; Chen, Ming-Liang; Ya, Ming-Zhu; He, Hui-Lan; Li, Dai
Calcitonin gene related protein (CGRP) is increased in both lesional and non-lesional psoriasis. The role of CGRP in the pathogenesis of psoriasis vulgaris is still not clear. We designed to determine the CGRP-I (or CALCA), II (or CALCB) gene expression and morbidity and CALCA T-692C single-nucleotide polymorphism (SNP). Peripheral blood mononuclear cells (PBMCs) and plasma samples were collected, and CGRP level and CGRP-I, II mRNA expression were measured in psoriasis patients and healthy controls. The CALCA T-692C genetic polymorphism in psoriasis and control subjects was also compared. A higher expression of CGRP-I, II mRNA in PBMCs in psoriasis patients. The plasma CGRP level in psoriasis patients was also higher than that in healthy subjects. SNP analysis showed carriers of the T-692C allele were over-represented in non-drinking Patients. The plasma CGRP level was higher in alcohol-drinking patients with TT genotype than that with TC genotype. The plasma CGRP level is increased in psoriasis patients and CALCA T-692C polymorphism TT genotype is a factor for the affectability in alcohol-drinking Psoriasis vulgaris patients.
Hirotsu, Camila; Rydlewski, Mariana; Araújo, Mariana Silva; Tufik, Sergio; Andersen, Monica Levy
Up to 80% of people develop a cutaneous condition closely connected to their exposure to stressful life events. Psoriasis is a chronic recurrent inflammatory skin disorder with multifactorial etiology, including genetic background, environmental factors, and immune system disturbances with a strong cytokine component. Moreover, psoriasis is variably associated with sleep disturbance and sleep deprivation. This study evaluated the influence of sleep loss in the context of an animal model of psoriasis by measuring cytokine and stress-related hormone levels. Male adult Balb/C mice with or without psoriasis were subjected to 48 h of selective paradoxical sleep deprivation (PSD). Sleep deprivation potentiated the activities of kallikrein-5 and kallikrein-7 in the skin of psoriatic groups. Also, mice with psoriasis had significant increases in specific pro-inflammatory cytokines (IL-1β, IL-6 and IL-12) and decreases in the anti-inflammatory cytokine (IL-10) after PSD, which were normalized after 48 h of sleep rebound. Linear regression showed that IL-2, IL-6 and IL-12 levels predicted 66% of corticosterone levels, which were selectively increased in psoriasis mice subject to PSD. Kallikrein-5 was also correlated with pro-inflammatory cytokines, explaining 58% of IL-6 and IL-12 variability. These data suggest that sleep deprivation plays an important role in the exacerbation of psoriasis through modulation of the immune system in the epidermal barrier. Thus, sleep loss should be considered a risk factor for the development of psoriasis. PMID:23226485
Piérard-Franchimont, C; Henry, F; Szepetiuk, G; Piérard, G E
Psoriasis is primarily a chronic inflammatory skin disease burdened by some comorbidities including psoriatic alopecia, arthropathies, Crohn's disease, the metabolic syndrome and some cardiovascular involvement. During the past years, several biologicals corresponding to monoclonal antibodies were offered to treat psoriasis refractory to other potent conventional treatments. We review the effects of biologicals, in particular adalimumab (Humira), on psoriatic comorbidities.
Hobbs, Ryan P; Smith, Susan H; Getsios, Spiro
Unchecked inflammation, impaired keratinocyte differentiation, and heightened host defense responses typify psoriasis. Lambert et al. make clever use of psoriasis patient genetics and whole transcriptome RNA-Seq analysis to implicate Act1 in these seemingly variegated processes by keeping IL-17 receptor signaling in check while supporting differentiation and limiting innate immune responses in human keratinocytes.
Lin, Yan; Zhao, Pan; Shen, Changbing; Shen, Songke; Zheng, Xiaodong; Zuo, Xianbo; Yang, Sen; Zhang, Xuejun; Yin, Xianyong
Many common variants have been found associated with the risk of psoriasis, but the underlying mechanism is still largely unknown, mostly owing to the difficulty in dissecting the mechanism of each variant using representative cell type and tissue in biological experiments. We applied an integrative method SNPsea which has been developed by investigators in Broad, to identify the most relevant cell types, tissues, and pathways to psoriasis by assessing the condition specificity affected by psoriasis genome-wide association studies-implicated genes. We employed this software on 89 single-nucleotide polymorphisms with genome-wide significance in Han Chinese and Caucasian populations. We found significant evidence for peripheral blood CD56 + NK cells (P = 1.30 × 10(-7)), Langerhans cells (P = 4.96 × 10(-6)) and CD14+ monocytes (P < 4.80 × 10(-5)) in psoriasis. We suggested that the DNase I hypersensitivity sites in CD14+ cells were active in psoriasis (P = 2.20 × 10(-16)). In addition, we discovered that biotic stimulus response, cytokine production and NF-κB pathways were significantly activated in psoriasis (P < 1.00 × 10(-5)). In conclusion, we found several innate immune cells and immune pathways in psoriasis that will help guide biological experiments for psoriasis risk variants in future.
Kim, Kyung Eun; Houh, Younkyung; Park, Hyun Jeong; Cho, Daeho
Psoriasis is a common skin disease accompanied by chronic inflammation. In previous studies, erythroid differentiation regulator 1 (ERDR1) was shown to have a negative correlation with proinflammatory cytokine IL-18. However, the role of ERDR1 in the inflammatory skin disease psoriasis has not been evaluated. In this study, to investigate the role of ERDR1 in psoriasis, recombinant ERDR1 was injected intraperitoneally into a psoriasis mouse model. Recombinant ERDR1 (rERDR1) significantly alleviated the symptoms of psoriasis-like skin inflammation and reduced the mRNA of various psoriasis-related markers, including keratin 14, S100A8, and Th17-related cytokines IL-17 and IL-22, suggesting that rERDR1 exerts therapeutic effects on psoriasis via the regulation of Th17 functions. Additionally, the expression of CCL20, a well-known Th17 attracting chemokine, was determined. CCL20 expression significantly decreased in the rERDR1-injected group compared with the vehicle (PBS)-injected group. CCR6 expression in the psoriatic lesional skin was also decreased by rERDR1 administration, implying the inhibition of CCR6-expressing Th17 cell chemotaxis via the downregulation of CCL20. Taken together, this study provides the first evidence that ERDR1 may be a potential therapeutic target for psoriasis.
Wahlstroem, J.; Swanbeck, G.; Inerot, A.
Information on psoriasis among parents and siblings in 14,008 families has been collected. On the basis of this material, evidence for monogenetic autosomal recessive inheritance of psoriasis has recently been presented. Indications from more than one type of non-pustular psoriasis has been obtained from the population genetic data. Molecular genetic linkage analysis of psoriasis to a number of polymorphic genetic markers for a large number of families has been made. It is apparent that there is genetic heterogeneity in a psoriasis population with regard to psoriasis genes. Using the computer program Linkage 5.0 and a formula for heterogeneity, a lodscore over 3.0 for one locus has been obtained. This locus has further been confirmed by several other markers in the vicinity. The locus found is linked to slightly over half of the families, indicating that there are more genetically independent types of psoriasis. The age at onset of those families that are apparently linked to this locus have a slightly higher age at onset than those not linked to that locus but with a considerable overlap. In spite of close coverage of the whole chromosomes number 6 and 17, no linkage has been found in this regions. This indicates that neither the HLA region nor the region earlier found to be involved in one family with psoriasis are primarily involved in our families.
Augustin, M; Eissing, L; Langenbruch, A; Enk, A; Luger, T; Maaßen, D; Mrowietz, U; Reich, K; Reusch, M; Strömer, K; Thaçi, D; von Kiedrowski, R; Radtke, M A
In 2005, the first national psoriasis survey in Germany revealed large deficits in health care particularly in patients with moderate to severe disease. The consecutive goal was to improve health care for psoriasis countrywide. For this, a large-scale national program was initiated starting with a comprehensive analysis of structures and processes of care for psoriasis. Patient burden, economic impact and barriers to care were systematically analyzed. In order to optimize routine care, a S3 guideline, a set of outcomes measures and treatment goals, were developed. Implementation was enforced by the German Psoriasis Networks (PsoNet) connecting the most dedicated dermatologists. The annual National Conference on Health Care in Psoriasis established in 2009 consented National Health Care Goals in Psoriasis 2010-2015 and defined a set of quality indicators, which are monitored on a regular basis. Currently 28 regional networks including more than 800 dermatologists are active. Between 2005 and 2014 7 out of 8 quality indicators have markedly improved, and regional disparities were resolved. e.g., mean PASI (Psoriasis Area Severity Index) dropped from 11.4 to 8.1 and DLQI (Dermatology Life Quality Index) from 8.6 to 5.9. A decade of experience indicates that a coordinated nationwide psoriasis program based on goal orientation can contribute to better quality of care and optimized outcomes.
Callis Duffin, Kristina; Mease, Philip J
Investigators use several physical examination measures to assess clinical features and severity of psoriasis and psoriatic arthritis (PsA) in clinical trials, clinical registries, and clinical practice; however, no relevant training modules are widely available to teach and standardize the performance of these measures. At a GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) meeting adjacent to the 2009 International Federation of Psoriasis Associations in Stockholm, members were updated on the development status of online training videos of psoriasis and PsA examination measures. Dermatology assessment modules include the Psoriasis Area and Severity Index, the Static Physician Global Assessment, body surface area, the original and modified Nail Psoriasis Severity Index, the Palmar-Plantar Pustular Psoriasis Area and Severity Index, and the Psoriasis Scalp Severity Index. Rheumatology modules include assessment of tender and swollen joint counts used in the American College of Rheumatology criteria, Disease Activity Score, and other composite arthritis scores; enthesitis assessment used in various enthesitis scoring systems; dactylitis; and spine disease. Each module will include background information for each measure, diagrams and photographs to emphasize teaching points, demonstration video of examination where applicable, and an optional examination at the end. Future plans include evaluating the modules for their influence on interrater and intrarater reliability and development of additional modules.
Hunter, H J A; Griffiths, C E M; Kleyn, C E
It is widely accepted that psychosocial stress can result from the daily strains of living with a diagnosis of psoriasis. There is now an evolving body of work to suggest that psychosocial stress may also play a role in the exacerbation of psoriasis. We discuss the historical evidence supporting a temporal relationship between psychosocial stress and the exacerbation of psoriasis. The underlying pathophysiological mechanisms by which this occurs are largely unknown, but current evidence points towards a role for nerve-related factors, namely their interaction with mast cells and the potentiation of neurogenic inflammation in this regard. It is also likely that the physiological stress response in patients with psoriasis differs from that in healthy individuals, as evidenced by alterations in the hypothalamic-pituitary-adrenal axis and sympathetic-adrenal-medullary system function. Psychological stress results in a redistribution of leucocytes with increased trafficking of inflammatory cells into the skin, which may exacerbate psoriasis. Langerhans cells play a role in the stress response of normal skin; their function in the stress response of patients with psoriasis is open to speculation. We discuss the influence of stress reactivity in patients with psoriasis and the impact of stress reduction strategies in the management of psoriasis. Finally, we suggest potentially fruitful areas for future research.
Pradhan, Madhulika; Singh, Deependra; Singh, Manju Rawat
Psoriasis is an autoimmune disorder of the skin with relapsing episodes of inflammation and hyperkeratosis. Numerous approaches have been explored to treat this dreadful disease using different antipsoriatic drugs with different modes of action and routes of administration. But, till date there is no cure for psoriasis due to lack of an ideal carrier for safe and effective delivery of antipsoriatic drugs. Constant progression in the development of newer formulations utilizing colloidal drug delivery systems has led to effective treatment of psoriasis. Colloidal carriers include vesicular and particulate systems like liposome, transferosome, niosomes, ethosomes, solid lipid nanoparticles, microspheres, micelles, dendrimers etc. have gained unique position as drug cargoes. Present review is an attempt to contemplate on psoriasis in terms of pathogenesis, role of cytokines, major hindrances in psoriasis treatment, currently available treatment options pertaining to mode of action, pharmacokinetics, marketed products, side effects of individual antipsoriatic drugs and recent developments in the delivery of various antipsoriatic drugs through novel colloidal drug carriers.
Wei, Kai-Che; Lai, Ping-Chin
Severe forms of psoriasis that are refractory to conventional therapies are often difficult to manage. The mammalian target of rapamycin (mTOR) inhibitors potentially have versatile effects toward putative psoriatic pathologic pathways. Therefore, mTOR inhibitors may offer a range of new therapeutic options for patients with psoriasis. We describe a 55-year-old male renal transplant patient with refractory psoriasis. We adjusted his antirejection regimen and put him on everolimus (Certican(®); Novartis, Basel, Switzerland; a semisynthetic macrolide, belonging to the mTOR inhibitors family) with low-dose tacrolimus. This combination regimen maintained his graft function and successfully controlled his psoriasis. His skin lesions never recurred in the next 18 months. To our knowledge, this is the first report showing that the combination of everolimus and tacrolimus could be used to treat recalcitrant psoriasis. The relative benefit-risk profiles of such therapies worth further investigation.
Psoriasis is a common, chronic, relapsing/remitting, immune-mediated skin disease that causes itchy skin with silvery scales. It is characterized by thickened red erythematous plaques covered with silvery scales. Biological therapies have been recently introduced for patients with psoriasis in India. The biological therapies contain protein biomolecules which can be employed to target specific immune or genetic mediator of a pathophysiological process. Here, we share our clinical experience of managing 20 patients with moderate to severe psoriasis by itolizumab a humanized IgG1 monoclonal antibody. Eighteen patients achieved Psoriasis Area and Severity Index (PASI) 75 response after receiving 10 infusion of itolizumab (at the completion of treatment). Out of 18 patients 4 patients had achieved PASI 95 response and 10 patients had achieved PASI 90 response. There was no adverse event reported during the treatment period. Itolizumab was found effective and safe in the treatment of moderate to severe psoriasis patients.
Psoriasis is a common, chronic, relapsing/remitting, immune-mediated skin disease that causes itchy skin with silvery scales. It is characterized by thickened red erythematous plaques covered with silvery scales. Biological therapies have been recently introduced for patients with psoriasis in India. The biological therapies contain protein biomolecules which can be employed to target specific immune or genetic mediator of a pathophysiological process. Here, we share our clinical experience of managing 20 patients with moderate to severe psoriasis by itolizumab a humanized IgG1 monoclonal antibody. Eighteen patients achieved Psoriasis Area and Severity Index (PASI) 75 response after receiving 10 infusion of itolizumab (at the completion of treatment). Out of 18 patients 4 patients had achieved PASI 95 response and 10 patients had achieved PASI 90 response. There was no adverse event reported during the treatment period. Itolizumab was found effective and safe in the treatment of moderate to severe psoriasis patients. PMID:28050487
Mahé, Emmanuel; Beauchet, Alain; Reguiai, Ziad; Maccari, François; Ruer-Mulard, Mireille; Chaby, Guillaume; Guyadec, Thierry Le; Estève, Eric; Goujon-Henry, Catherine; Parier, Josiane; Barthelemy, Hugues; Bégon, Edouard; Steiner, Henri-Georges; Bénéton, Nathalie; Boyé, Thierry; Mery-Bossard, Laure; Schmutz, Jean-Luc; Bravard, Pierre; Resopso, Michèle-Léa Sigal
Psoriasis has major physical, psychological, and social impacts: its management should not be restricted by individual financial considerations in Western countries as these have well-structured health systems and social/insurance coverage. We investigated if the socioeconomic characteristics of patients were associated with severity of psoriasis and access to healthcare. In a cross-sectional study, we included 903 patients with psoriasis that were consulting for the first time. We showed that low educational level was associated with severity of disease in multivariate analyses. Moreover, patients of lower class and lower educational level, with severe psoriasis, had seen fewer physicians and had less frequently received a systemic treatment. Thus, physicians need to be vigilante of patients with a low socioeconomic status. Both low socioeconomic status and less access to dermatologists are associated with clinical severity of psoriasis at a first consultation.
Ariza, Maria-Eugenia; Williams, Marshall V; Wong, Henry K
Psoriasis vulgaris is a chronic, immune-mediated inflammatory skin disease associated with complex genetic susceptibility. Although the hallmark of psoriasis is characterized by cutaneous inflammation and keratinocyte hyperproliferation, recent studies show that the pathologic features observed in psoriasis arises as a result of innate and adaptive immune activation in genetically prone individuals. Studies focused on the microenvironment in the skin of psoriasis lesions have revealed novel cellular and cytokine abnormalities of the immune system. One pathway important is the role of the T(H)17/IL-17 dysregulation. The recent development of biologics that target the IL-17 cytokine pathway has confirmed the importance of T(H)17 and IL-17 homeostasis in the skin and yielded potent therapies in the treatment of psoriasis, and potentially other autoimmune diseases.
Mavropoulos, Athanasios; Rigopoulou, Eirini I.; Liaskos, Christos; Bogdanos, Dimitrios P.; Sakkas, Lazaros I.
The pathogenetic mechanisms responsible for the induction of immune-mediated disorders, such as psoriasis, remain not well characterized. Molecular signaling pathways are not well described in psoriasis, as well as psoriatic arthritis, which is seen in up to 40% of patients with psoriasis. Signaling pathway defects have long been hypothesized to participate in the pathology of psoriasis, yet their implication in the altered psoriatic gene expression still remains unclear. Emerging data suggest a potential pathogenic role for mitogen activated protein kinases p38 (p38 MAPK) extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK) in the development of psoriasis. The data are still limited, though, for psoriatic arthritis. This review discusses the current data suggesting a crucial role for p38 MAPK in the pathogenesis of these disorders. PMID:24151518
Fu, Lisa Wenyang; Vender, Ronald
The novel discovery of the systemic role of vitamin D in the modulation of the immune system especially the Type 1 helper T cell (Th1) pathway reveals its potential for treating Th1 inflammatory diseases. Psoriasis has been recently established to be a systemic disease centered on inflammation and involvement of cytokines of the Th1 pathway. There is an increased prevalence of metabolic syndrome in patients with psoriasis. Metabolic syndrome also involves a proinflammatory state. This paper proposes the idea of the potential use of oral vitamin D to treat psoriasis and metabolic syndrome concurrently. We propose there is merit in more clinical trials investigating the use of vitamin D to treat both psoriasis and metabolic syndrome through its anti-inflammatory effects. On application to psoriasis management and prognosis, the goal is to decrease the risk for cardiovascular disease and decrease disease morbidity and mortality.
There is increasing awareness that psoriasis is more than "skin deep." Several recent reviews focused on biomarkers have indicated the systemic dimension of psoriasis and the comorbidity that psoriasis shares with other chronic inflammatory diseases. Of emerging significance is the relationship to cardiovascular disease, which contributes substantially to patients' increased mortality. This article examines currently available evidence favoring the concept of a causal link between psoriasis and cardiovascular disease, and summarizes a report represented at the 2010 Annual Meeting of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis).
Armstrong, April W.; Lin, Steven W.; Chambers, Cynthia J.; Sockolov, Mary E.; Chin, David L.
Background Epidemiologic studies have provided new insights into the association between psoriasis and cardiovascular diseases. Previous population studies have examined hypertension frequency in psoriasis patients. However, the relationship between severity of hypertension and psoriasis has not been characterized. Objective We sought to investigate whether patients with psoriasis have more difficult-to-manage hypertension compared to non-psoriatic hypertensive patients. Approach We performed a case-control study using the University of California Davis electronic medical records. The cases were defined as patients diagnosed with both psoriasis and hypertension, and controls were defined as patients with hypertension and without psoriasis. In this identified population, 835 cases were matched on age, sex, and body mass index (BMI) to 2418 control patients. Key Results Treatment with multiple anti-hypertensives was significantly associated with the presence of psoriasis using univariate (p<0.0001) and multivariable analysis, after adjusting for diabetes, hyperlipidemia, and race (p<0.0001). Compared to hypertensive patients without psoriasis, psoriasis patients with hypertension were 5 times more likely to be on a monotherapy antihypertensive regimen (95% CI 3.607.05), 9.5 times more likely to be on dual antihypertensive therapy (95% CI 6.68–13.65), 16.5 times more likely to be on triple antihypertensive regimen (95% CI 11.01–24.84), and 19.9 times more likely to be on quadruple therapy or centrally-acting agent (95% CI 10.58–37.33) in multivariable analysis after adjusting for traditional cardiac risk factors. Conclusions Psoriasis patients appear to have more difficult-to-control hypertension compared to non-psoriatic, hypertensive patients. PMID:21479272
Lee, Y H; Song, G G
The aim of this study was to explore whether vascular endothelial growth factor (VEGF) polymorphisms confer susceptibility to psoriasis. Meta-analyses were conducted to examine the associations between the +405 C/G, -460 C/T, -1154 A/G, and -2578 A/C polymorphisms of VEGF and psoriasis using allele contrast and recessive, dominant, and additive models. Seven studies on VEGF polymorphisms and psoriasis involving 1956 subjects (psoriasis patients 665, controls 1291) were included in this meta-analysis. We observed no association between psoriasis and the VEGF +405 C allele in all study subjects (odds ratio = 0.984, 95% confidence interval = 0.754-1.285, P = 0.906), but stratification by ethnicity indicated a significant association between the VEGF +405 C allele and psoriasis in Asians (odds ratio = 0.762, 95% confidence interval = 0.628-0.923, P = 0.005). In addition, we observed a significant association between the VEGF -460 C allele and psoriasis in Europeans (odds ratio = 0.807, 95% confidence interval = 0.672-0.968, P = 0.021). Meta-analyses of the -1154 A/G polymorphism also revealed a significant association with psoriasis in Europeans. However, the VEGF -2578 A/C polymorphism showed no association in all subjects or in Europeans or Asians. This meta-analysis suggests the VEGF +405 C/G polymorphism confers susceptibility to psoriasis in Asians, and that the -460 C/T and -1154 A/G polymorphisms confer susceptibility to psoriasis in Europeans.
Batycka-Baran, Aleksandra; Besgen, Petra; Wolf, Ronald; Szepietowski, Jacek C; Prinz, Joerg C
Psoriasis is a common, chronic immune-mediated inflammatory disease. The inflammatory process in psoriasis has systemic effects and may influence the development of psoriatic comorbidities. The systemic action of phototherapy in patients with psoriasis has been so far poorly elucidated. We aimed to investigate the expression of genes encoding selected psoriasis-related cytokines in peripheral blood mononuclear cells (PBMCs) isolated from patients with psoriasis before and after treatment with phototherapy. 17 patients with mild to moderate plaque psoriasis were treated with narrow band-UVB (NB-UVB), 8 patients with moderate to severe plaque psoriasis with bath-psoralen-ultraviolet A therapy (PUVA). PBMCs were isolated by Ficoll gradient density centrifugation. Expression of genes encoding TNF-α, IL-17A, IL-6, IL-1 β, INF-γ, and IL-10 in PBMCs of patients with psoriasis before and after phototherapy was analyzed with quantitative RT-PCR. Treatment with NB-UVB therapy led to a significant decrease in IL-17A, TNF-α, and IL-6 mRNA levels in PBMCs (p=0.003; p=0.042; p=0.019, respectively). Following treatment with bath-PUVA therapy, we observed a significant decrease in TNF-α and IL-6 mRNA levels in PBMCs (p=0.031, p=0.035, respectively). Treatment with phototherapy in patients with psoriasis may affect systemic inflammation by downregulation of the expression of genes encoding proinflammatory cytokines in PBMCs, implicated in the development of psoriasis and psoriatic comorbidities.
Kim, Dae Suk; Shin, Dongyun; Lee, Min Seok; Kim, Hee Ju; Kim, Do Young; Kim, Soo Min; Lee, Min-Geol
The objective of this retrospective study is to assess neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as inflammatory markers in patients with psoriasis and psoriatic arthritis (PsA). A hundred and eleven psoriasis patients and 25 PsA patients were compared with 94 healthy controls. Demographic, clinical and laboratory information were collected and analyzed. NLR and PLR were calculated. White blood cell (WBC), neutrophils, eosinophils and NLR were increased in psoriasis patients compared with controls. WBC, neutrophils, NLR, monocytes, platelets and PLR were increased in PsA patients compared with both controls and psoriasis patients. Erythrocyte sedimentation rate (ESR) and C-reactive protein were significantly higher in PsA patients compared with psoriasis patients. Among psoriasis patients, Psoriasis Area and Severity Index (PASI) score correlated positively with platelets, NLR and PLR. These parameters were all significantly higher in moderate to severe psoriasis patients (PASI ≥ 10) compared with mild patients (PASI < 10). Elevated platelets, NLR and PLR were significantly associated with the increased PASI scores in multivariate analysis. NLR, PLR and ESR were statistically significant predictors for the presence of PsA in psoriasis patients. NLR was the strongest predictor (odds ratio = 3.351, P = 0.005). In conclusion, elevated NLR and PLR were significantly associated with psoriasis and PsA. Both NLR and PLR were strong predictors for the presence of PsA among psoriasis patients.
Puig, L; Bordas, X; Carrascosa, J M; Daudén, E; Ferrándiz, C; Hernanz, J M; López-Estebaranz, J L; Moreno, J C; Sánchez-Carazo, J L; Vanaclocha, F; Vázquez-Veiga, H
The treatment of psoriasis has been revolutionized by the introduction of biologic agents; these agents achieve skin clearance and long-term improvement without the risk of toxicity that has limited use of the classic systemic treatments. The role of systemic treatment in the management of psoriasis is being reviewed on the basis of a large volume of scientific evidence on the efficacy and safety of biologic agents, and new therapeutic goals and strategies are being devised for patients with moderate-to-severe psoriasis. This has led to the need to establish severity criteria that will provide the rationale for the indication of the different systemic agents currently available for the treatment of moderate-to-severe psoriasis, as well as therapeutic goals, efficacy measures, therapeutic strategies, screening protocols, and choice of treatment based on the risk-benefit ratio of the different agents. These criteria must be established through consensus by experienced dermatologists and based on available scientific evidence. The present document reflects the consensus of the Spanish Psoriasis Group on these different issues in the management of moderate-to-severe psoriasis.
Harada, Yukinori; Yamamoto, Hiroaki; Sato, Midori; Kodaira, Mutsuki; Kono, Tsunesuke
Adalimumab is commonly used to treat autoimmune diseases with few reported hematological adverse reactions. We herein describe the case of an 85-year-old Japanese man with plaque psoriasis who developed autoimmune hemolytic anemia (AIHA) after 3 years of adalimumab treatment. The patient suddenly developed hematuria and dyspnea on exertion while receiving adalimumab treatment. Laboratory data showed low hemoglobin levels and slightly increased reticulocyte counts, while direct and indirect antiglobulin tests were positive. The patient was diagnosed with AIHA which resolved after replacing the adalimumab treatment with prednisolone therapy. The findings from this case indicate that AIHA may be caused by long-term adalimumab treatment.
Souza, Claudia Fernanda Dias; Suarez, Olga Milena Zarco; da Silva, Talita Fonseca Medeiros; Gorenstein, Ana Carolina Lourenço Araújo; Quintella, Leonardo Pereira; Avelleira, João Carlos Regazzi
Methotrexate is one of the most used drugs in the treatment of psoriasis with indication of systemic therapy. Cutaneous and mucous side effects are described by pharmacological characteristics of the drug itself or due to overdose. We report the case of a patient with ulcerations in oral mucosa and psoriatic plaques after incorrect use of Methotrexate. Prescribed in a weekly dose, it was used continuously for 10 days and without simultaneous intake of folic acid. It is important to ensure correct comprehension of the prescription. PMID:27438211
Hall, R.P.; Peck, G.L.; Lawley, T.J.
The sera of 21 patients with psoriasis were examined for the presence of IgA-containing circulating immune complexes (CIC) using the Raji IgA radioimmunoassay. In addition, the Raji IgG radioimmunoassay and 125I-Clq binding assay were used to detect IgG- and IgM-containing CIC. Twenty-five patients with other hyperkeratotic skin disorders were studied as controls. Patients were studied before institution of systemic therapy with etretinate (20 patients) or 13-cis-retinoic acid (1 patient). In addition, sera of 15 of the patients treated with etretinate were studied before, during, and after therapy. The extent of pretreatment disease involvement as well as response to therapy were evaluated in a blinded fashion. Fourteen of 21 (67%) patients with psoriasis had evidence of IgA-containing CIC at some time during the course of their disease, as compared to only 1 of 25 patients with other hyperkeratotic skin disorders. In contrast, only 2 of 19 (11%) had evidence of IgG-containing CIC using the Raji IgG assay, and only 1 of 19 (5%) had evidence of IgG- or IgM-containing CIC using the 125I-Clq binding assay. A positive correlation was found between the extent of pretreatment disease involvement and the level of IgA-containing CIC by linear regression analysis (p . 0.01). There was, however, no correlation between clinical improvement and the presence or level of IgA-containing CIC in 15 patients followed during therapy. Sucrose density gradient analysis of the IgA-containing CIC found in 2 of these patients demonstrated IgA-containing CIC in the 9S to 13S region. The finding of IgA-containing CIC in a significant number of patients with psoriasis and the relative absence of IgG- or IgM-containing CIC suggest that IgA-containing CIC may play a role in psoriasis.
da Silva, Suze Aparecida; Magalhães, Renata Ferreira; Torres, Rafael Augusto Tamasauskas; de Oliveira, Raquel Diana; Velho, Paulo Eduardo Neves Ferreira
Clobetasol benefits to control psoriasis lesions are well defined, but there were not studies about its action when used in lacquer vehicle to control skin lesions. A double-blind study was conducted with 40 patients that utilized clobetasol 0.05% in one hemibody and just the vehicle in the other hemibody. Twenty of them used petrolatum as vehicle and the others used lacquer. An assessment was conducted using the clinical index PASI and a quality of life questionnaire (Dermatological Life Quality Index). There was no statistical difference between groups. There was a trend of favorable response particularly in the hemibody treated with clobetasol.
van de Kerkhof, Peter C M
Topical therapies are the mainstream treatment of psoriasis because most patients have mild disease. First-line treatments are vitamin D derivatives and corticosteroids. These treatments are usually given in combination schedules. For topical treatments the selection of the most appropriate vehicle is of major importance, thus improving adherence to the treatment, which frequently is impaired by the complexities of topical therapeutic choices. Evidence for efficacy and safety of topical treatments is readily available for vitamin D treatments and short-term treatment with corticosteroids. However, the scientific evidence for longer-term treatments is limited. Multiple new small molecules are in various stages of development and are reviewed.
Wang, Ying; Yang, Haoyu; Yuan, Weichang; Ren, Jingyi
Circulating T follicular helper (cTfh) cells are known to be involved in numerous immune-mediated diseases, but their pathological role in psoriasis is less fully investigated. Herein, we aimed to identify whether cTfh cells contributed to the pathogenesis of psoriasis. The frequency and function of cTfh cells were compared between patients with psoriasis vulgaris and healthy controls, and the infiltration of Tfh cells was detected between lesional and nonlesional skin tissues of psoriasis patients. Moreover, the dynamic change of cTfh cells before and after acitretin treatment was evaluated. Our results showed both increased frequency and activation (indicated by higher expression of ICOS, PD-1, HLA-DR, and Ki-67 and increased production of IL-21, IL-17, and IFN-γ) of cTfh cells in psoriasis patients. Compared with nonlesional skin tissues of psoriasis patients, the number of infiltrated Tfh cells was significantly increased in psoriasis lesions. In addition, positive correlations between the percentage of cTfh, functional markers on cTfh cells in peripheral blood and disease severity were noted. Furthermore, the frequency of cTfh cells and the levels of cytokines secreted by cTfh cells were all significantly decreased after 1-month treatment. PMID:27774460
Egeberg, Alexander; Mallbris, Lotus; Gislason, Gunnar Hilmar; Skov, Lone; Hansen, Peter Riis
Psoriasis and multiple sclerosis (MS) are inflammatory disorders with similarities in genetic risk variants and inflammatory pathways. Limited evidence is available on the relationship between the two diseases. We therefore investigated the risk of incident (new-onset) MS in patients with mild and severe psoriasis, respectively. All Danish citizens aged ≥ 18 years from 1 January 1997 to 31 December 2011 were identified by linkage of nationwide registries at the individual level. We estimated incidence rate ratios (IRRs) adjusted for age, gender, socioeconomic status, smoking, medication, comorbidity, and UV phototherapy by Poisson regression. There were 58,628 and 9,952 cases of mild and severe psoriasis, respectively, and 9,713 cases of MS. Incidence rates of MS per 10,000 person-years for the reference population, mild psoriasis, and severe psoriasis were 1.78, 3.22, and 4.55, respectively. Adjusted IRRs of MS were 1.84 (95% confidence interval [CI], 1.46-2.30) and 2.61 (95% CI, 1.44-4.74) in mild and severe psoriasis, respectively. Similar results were observed when adjustment for family history of MS was included in the analyses. Psoriasis may confer a disease severity-dependent risk of MS. Further studies are warranted to establish the mechanisms underlying this relationship and its potential clinical consequences.
Chang, C C; Gangaram, H B; Hussein, S H
The Malaysian Psoriasis Registry, established in 1998, is the first skin disease clinical registry in Malaysia. It aims to provide useful data on various aspects of psoriasis. Following an extensive revision of the registry form in 2007, a total of 509 psoriasis patients from 10 government dermatologic centres were reviewed in a three month pilot study. The onset of psoriasis was during the second to fourth decade of life in the majority of patients. There was no sexual and ethnic predilection. A positive family history was present in 21.2%, and more common in patients with younger disease onset. The main aggravating factors of psoriasis were stress, sunlight and infection. Plaque psoriasis was the commonest clinical type (80.9%). Joint disease was present in 17.3% of patients, among which mono-/oligoarticular type being the commonest. Nail changes occurred in 68%. More psoriasis patients were overweight and obese compared to the normal population. The mean Dermatologic Life Quality Index (DLQI) score was 8.08 +/- 6.29, and changes during subsequent follow-up may reflect therapeutic effectiveness. This study enabled evaluation of the revised registry form and helped in identifying shortcomings in the implementation of the registry.
Asahina, Akihiko; Torii, Hideshi; Ohtsuki, Mamitaro; Tokimoto, Toshimitsu; Hase, Hidenori; Tsuchiya, Tsuyoshi; Shinmura, Yasuhiko; Reyes Servin, Ofelia; Nakagawa, Hidemi
The safety and efficacy of adalimumab were evaluated over 24 weeks in Japanese patients with psoriasis in routine clinical practice. In this multicenter, observational, open-label, postmarketing study, primary efficacy measures included the Psoriasis Area and Severity Index (PASI) and the Dermatology Life Quality Index (DLQI) in all patients with psoriasis. In patients with psoriatic arthritis (PsA), the 28-joint Disease Activity Score (DAS28) and the visual analog scale (VAS) pain were also evaluated. Safety was assessed based on the frequency of adverse drug reactions (ADR). Among patients with psoriasis evaluated for efficacy (n = 604), significant improvements from baseline were observed in mean PASI and DLQI scores at weeks 16 and 24 (all P < 0.0001). Furthermore, in psoriasis patients without PsA, the PASI 75/90 response rates were 55.9%/28.4% at week 16 (n = 306) and 65.6%/43.3% at week 24 (n = 270), respectively. In patients with PsA evaluable for effectiveness, significant improvements from baseline were observed in PASI, DAS28 erythrocyte sedimentation rate, DAS28 C-reactive protein and VAS pain at weeks 16 and 24 (all P < 0.0001). ADR and serious ADR were reported by 26.1% and 3.3%, respectively, of 731 safety evaluable patients with psoriasis; no unexpected safety findings were noted. The safety profile and effectiveness of adalimumab for the treatment of psoriasis in a routine clinical setting were as expected in Japanese patients.
Demirel, Reha; Genc, Abdurrahman; Ucok, Kagan; Kacar, Seval Dogruk; Ozuguz, Pinar; Toktas, Muhsin; Sener, Umit; Karabacak, Hatice; Karaca, Semsettin
The aim of this study was to compare aerobic exercise capacity, daily physical activity, pulmonary functions, resting metabolic rate, and body composition parameters in patients with psoriasis and healthy controls. A total of 60 participants (30 [15 men, 15 women] patients with psoriasis, and 30 [15 men, 15 women] healthy controls) ranging in age from 22-57 were included in the study. Maximal aerobic capacity was determined by Astrand exercise protocol. Daily physical activity was measured with an accelerometer. Resting metabolic rate was determined with an indirect calorimeter. Pulmonary function tests were performed with a portable spirometer. Body composition was established with a bioelectric impedance analysis system. Skinfold thicknesses and body circumference measurements were carried out. Short Form 36 quality of life questionnaire was applied to all participants. In both genders, daily physical activity parameters were found to be higher in the psoriasis group compared to the control. Maximal aerobic capacity, resting metabolic rate, pulmonary function tests, body fatness, body fat distributions, and quality of life were not statistically different between patients with psoriasis and controls in males and females. We suggest that patients with psoriasis who do not have psoriatic arthritis or severe psoriasis are well in performing daily physical activities. In addition, we suggest that this lifestyle helped to prevent impairments of body fatness, body fat distributions, resting metabolic rate, pulmonary functions, and quality of life in patients with mild to moderate psoriasis.
Sun, Yue; Zhang, Jie; Zhou, Zhou; Wu, Pinru; Huo, Rongfen; Wang, Beiqing; Shen, Zhengyu; Li, Huidan; Zhai, Tianhang; Shen, Baihua; Chen, Xiangdong; Li, Ningli
Psoriasis is a common chronic skin disease characterized by epidermal hyperplasia and inflammation. The pathogenesis of psoriasis is multifactorial and is not fully understood. Here we demonstrate that CCN1 (also called Cyr61, which is short for cysteine-rich 61), an extracellular matrix protein that is also considered a pro-inflammatory factor, is highly expressed in the lesional skin of psoriasis patients, as well as in that of imiquimod (IMQ)- and IL-23-treated psoriasis-like mice. Then we show that blocking CCN1 function in vivo attenuates epidermal hyperplasia and inflammation in psoriasis-like mice. Further, in primary cultured normal human keratinocytes and HaCaT (human keratinocyte cell line) cells, CCN1 promotes keratinocyte activation, including the proliferation and expression of immune-related molecules. Finally, we observe that integrin α6β1 is the receptor of CCN1 in keratinocytes, and CCN1 stimulation activates the downstream phosphoinositide-3 kinase/Akt/NF-κB signaling pathway. Taken together, our findings reveal that CCN1 has a critical role in psoriasis pathogenesis. Moreover, as CCN1 is a secreted extracellular matrix (ECM) protein, our study also provides evidence that ECM, which is involved in psoriatic pathogenesis, could be a potent target for psoriasis treatment.
Psoriasis is a complex inflammatory disease that occurs in genetically susceptible individuals and presents with the development of erythematous scaly plaques on the skin. Interleukins (ILs) in the Th17 pathway play a pivotal role in the pathogenesis of psoriasis and have thus become targets for recent biologic drug development. Secukinumab is a human monoclonal IgG1k antibody that has been developed to target and block the actions of IL-17A. Secukinumab recently approved for use as first-line systemic therapy in a patient with moderate to severe psoriasis has been studied first in psoriasis before other diseases. Both Phase II and III clinical trials have demonstrated the effectiveness of secukinumab in the treatment of moderate-to-severe plaque psoriasis, and it has demonstrated superiority to other comparable biologics on the market, including the tumor necrosis factor inhibitor etanercept. Secukinumab has also shown superiority to ustekinumab, a relatively recent biologic introduced for the treatment of psoriasis. Besides demonstrating better efficacy compared to etanercept and ustekinumab, secukinumab has also demonstrated a greater impact of the quality of life of patients with a comparable safety profile. Secukinumab shows great promise in having a tremendous impact on the treatment of plaque psoriasis based on its ability to produce similar, if not better, clinical outcomes than other biologic antipsoriasis medications.
Jin, Yiguang; Zhang, Xiaohan; Zhang, Baolei; Kang, Hongxiang; Du, Lina; Li, Miao
Psoriasis is a chronic inflammatory skin disease affecting 2-5% of the population worldwide and it severely affects patient quality of life. In this study, an amphiphilic zinc phthalocyanine polymer conjugate (ZPB) was synthesized, in which zinc phthalocyanine (ZnPc) was conjugated with the poly(ethylene glycol) (PEG) chain of Brij 58. ZPB showed two maximum UV-vis absorption wavelengths, 348 nm and 678 nm. A monomolecular micelle of ZPB formed in water with a mean size of 25 nm and zeta potential of -15 mV. The nanostructures aggregated into cloudy precipitates, which were easily dispersed. The nanostructure showed the shell-core structure with the ZnPc segments as the core and the PEG chains as the shell. The anti-psoriasis effect of the ZPB nanostructure was explored using a guinea pig psoriasis model. After comparing the anti-psoriasis effects of saline, light alone, ZPB alone, and the combination of light and ZPB, the combination of light and ZPB showed the best photodynamic therapy of psoriasis based on the light excitation of the photosensitizer ZPB and the psoriasis was nearly cured according to the histopathological investigation. The ZPB nanostructure is a promising anti-psoriasis nanomedicine based on photodynamic therapy.
Park, Ji-Hye; Park, Young Joon; Kim, Sue Kyoung; Kwon, Ji Eun; Kang, Hee Young; Lee, Eun-So; Choi, Jee Ho
Background The differential diagnosis of psoriasis and seborrheic dermatitis can be difficult when both conditions are localized to the scalp without the involvement of other skin sites. Objective We aimed to evaluate the histopathological differences between psoriasis and seborrheic dermatitis on the scalp and identify favorable criteria for their differential diagnosis. Methods We evaluated 15 cases of psoriasis and 20 cases of seborrheic dermatitis of the scalp that had been clinicopathologically diagnosed. Skin biopsy sections stained with H&E were examined. Additional immunohistochemistry was performed, including Ki-67, keratin 10, caspase-5, and GLUT-1. Results On histopathological examination, mounds of parakeratosis with neutrophils, spongiform micropustules of Kogoj, and clubbed and evenly elongated rete ridges were significantly more frequently observed in psoriasis. Follicular plugging, shoulder parakeratosis and prominent lymphocytic exocytosis were significantly more common in seborrheic dermatitis. Moreover, significantly higher mitotic figures were observed in psoriatic lesions than in seborrheic dermatitis. Immunohistochemistry did not show any difference between psoriasis and seborrheic dermatitis. Conclusion Histopathological features favoring psoriasis include mounds of parakeratosis with neutrophils, spongiform micropustules of Kogoj, clubbed and evenly elongated rete ridges, and increased mitotic figures (≥6/high-powered field). Features indicating seborrheic dermatitis are follicular plugging, shoulder parakeratosis and prominent lymphocytic exocytosis. Immunohistochemistry was not helpful in differentiating psoriasis from seborrheic dermatitis. PMID:27489423
Ungprasert, Patompong; Wijarnpreecha, Karn; Kittanamongkolchai, Wonngarm
Background and Objectives: The possible association between psoriasis and celiac disease (CD) has long been observed, but epidemiologic studies attempting to characterize this association have yielded inconclusive results. This meta-analysis was conducted with the aims to summarize all available data. Methods: We conducted a systematic review and meta-analysis of observational studies that reported relative risk, hazard ratio, odds ratio (OR), or standardized incidence ratio with 95% confidence interval (CI) comparing the risk of CD in patients with psoriasis versus participants without psoriasis. Pooled risk ratio and 95% CI were calculated using random-effect, generic inverse-variance methods of DerSimonian and Laird. Results: Four retrospective cohort studies with 12,912 cases of psoriasis and 24,739 comparators were included in this meta-analysis. The pooled analysis demonstrated a significantly higher risk of CD among patients with psoriasis compared with participants without psoriasis with the pooled OR of 3.09 (95% CI, 1.92–4.97). Limitations: Most primary studies reported unadjusted estimated effect, raising a concern over confounders. Conclusions: Our meta-analysis demonstrated an approximately 3-fold increased risk of CD among patients with psoriasis. PMID:28216724
Wu, Dongze; Shi, Deshun; Yang, Li; Zhu, Xiaoliang
Several studies have evaluated the associations between methylenetetrahydrofolate reductase (MTHFR) C677T and psoriasis. However, the results remain inconclusive. The objective of the present study was to conduct a qualitative and quantitative meta-analysis investigating the associations between MTHFR C677T and psoriasis. A published work search of PubMed, Embase, Web of Science and Chinese National Knowledge Infrastructure database were conducted to identify all publications concerning MTHFR C677T polymorphism and psoriasis on 1 October 2014. The principal outcome measure for evaluating the strength of the association was crude odds ratios along with their corresponding 95% confidence intervals. Data were extracted and statistical analyses were implemented using STATA version 12.0 software. A total of 1179 psoriatic cases and 937 controls from five case-control studies concentrating on the association between MTHFR C677T polymorphism and psoriasis were included in this qualitative meta-analysis. Pooled analysis revealed that there is no association between this polymorphism and susceptibility to psoriasis in dominant, recessive, allele and additive models under a random-effect model. However, a marginal significant association was found in the overdominant model under fixed-effect model. Subgroup analysis of ethnicity demonstrated that there is no association between MTHFR C677T polymorphism and either Asian or European psoriatic patients. In conclusion, MTHFR C677T polymorphism, qualitatively, is not a genetic factor for the pathogenesis of psoriasis but could quantitatively reflect the severity of psoriasis to some extent.
Kouris, Anargyros; Christodoulou, Christos; Stefanaki, Christina; Livaditis, Miltiadis; Tsatovidou, Revekka; Kouskoukis, Constantinos; Petridis, Athanasios; Kontochristopoulos, George
BACKGROUND Psoriasis is a common, long-term skin disease associated with high levels of psychological distress and a considerable adverse impact on life. The effects of psoriasis, beyond skin affliction, are seldom recognized and often undertreated. OBJECTIVE The aim of the study is to evaluate the quality of life, anxiety and depression, self-esteem and loneliness in patients with psoriasis. METHODS Eighty-four patients with psoriasis were enrolled in the study. The quality of life, depression and anxiety, loneliness and self-esteem of the patient were assessed using the Dermatology Life Quality Index, Hospital Anxiety and Depression Scale, the UCLA loneliness Scale (UCLA-Version 3) and Rosenberg's Self-esteem Scale, respectively. RESULTS The Dermatology Quality of Life Index score among psoriasis patients was 12.61 ± 4.88. They had statistically significantly higher scores according to the Hospital Anxiety and Depression Scale -anxiety subscale (p=0.032)-compared with healthy volunteers. Moreover, a statistically significant difference was found between the two groups concerning the UCLA-scale (p=0.033) and RSES-scale (p<0.0001). Female patients presented with lower self-esteem than male patients. CONCLUSION Psoriasis is a distressing, recurrent disorder that significantly impairs quality of life. Therefore, the recognition and future management of psoriasis may require the involvement of multi-disciplinary teams to manage the physical, psychological and social aspects of the condition, as is the case for systemic, long-term conditions. PMID:26734865
Aldredge, Lakshi M.; Young, Melodie S.
ABSTRACT Psoriasis is a chronic, immune-mediated disease characterized by itchy, scaly, and often painful plaques in the skin. Psoriasis can have significant psychosocial burdens and increased risks for numerous comorbidities, including diabetes, hypertension, and cardiovascular disease, particularly in patients with moderate-to-severe disease. Dermatology nurse practitioners and physician assistants are an important part of the healthcare team, contributing to all aspects of psoriasis management. This review reinforces the unique aspects of care that nurse practitioners and physician assistants provide to patients with psoriasis, such as facilitating conversations about managing disease, setting appropriate expectations, and considering treatment options, including when treatment response or tolerability is suboptimal. The importance of relationship building is stressed. Patient management topics discussed include helpful tips about assessing treatment options, initiating biologic therapy, optimizing patient adherence, and managing comorbidities. Also reviewed are how to deal with common barriers including lack of knowledge about psoriasis or making healthy lifestyle changes, fear of injections or side effect risks, lack of health insurance, and concerns about treatment costs. Overall, by forming meaningful relationships and engaging patients in their psoriasis care, nurse practitioners and physician assistants can help to optimize clinical efficacy outcomes and consistently manage moderate-to-severe psoriasis and its comorbidities over the patient’s life course. PMID:27004085
Ganzetti, Giulia; Campanati, Anna; Offidani, Annamaria
Psoriasis is a chronic inflammatory immune-mediated skin diseases which is frequently associated to comorbidities. Non-alcoholic fatty liver disease (NAFLD) is defined as an excessive accumulation of triglycerides in hepatocytes and includes a wide spectrum of liver conditions ranging from relatively benign steatosis to non-alcoholic steatohepatitis with fatty infiltration and lobular inflammation and to cirrhosis and end-stage liver disease. Actually, psoriasis is considered a systemic diseases associated to comorbidities, as metabolic syndrome and NAFLD is seen the hepatic manifestation of the metabolic syndrome. The possible link between psoriasis, obesity and metabolic syndrome, which are known risk factors for NAFLD has been recently documented focusing in the crucial role of the adipose tissue in the development of the inflammatory background sharing by the above entities. According to recent data, patients with psoriasis show a greater prevalence of NAFLD and metabolic syndrome than the general population. Moreover, patients with NAFLD and psoriasis are at higher risk of severe liver fibrosis than those with NAFLD and without psoriasis. The link between these pathological conditions appears to be a chronic low-grade inflammatory status. The aim of this review is to focus on the multiple aspects linking NAFLD and psoriasis, only apparently far diseases. PMID:25848461
Yin, Xianyong; Wineinger, Nathan E.; Wang, Kai; Yue, Weihua; Norgren, Nina; Wang, Ling; Yao, Weiyi; Jiang, Xiaoyun; Wu, Bo; Cui, Yong; Shen, Changbing; Cheng, Hui; Zhou, Fusheng; Chen, Gang; Zuo, Xianbo; Zheng, Xiaodong; Fan, Xing; Wang, Hongyan; Wang, Lifang; Lee, Jimmy; Lam, Max; Tai, E. Shyong; Zhang, Zheng; Huang, Qiong; Sun, Liangdan; Xu, Jinhua; Yang, Sen; Wilhelmsen, Kirk C.; Liu, Jianjun; Schork, Nicholas J.; Zhang, Xuejun
Background Previous studies have shown that individuals with schizophrenia have a greater risk for psoriasis than a typical person. This suggests that there might be a shared genetic etiology between the 2 conditions. We aimed to characterize the potential shared genetic susceptibility between schizophrenia and psoriasis using genome-wide marker genotype data. Methods We obtained genetic data on individuals with psoriasis, schizophrenia and control individuals. We applied a marker-based coheritability estimation procedure, polygenic score analysis, a gene set enrichment test and a least absolute shrinkage and selection operator regression model to estimate the potential shared genetic etiology between the 2 diseases. We validated the results in independent schizophrenia and psoriasis cohorts from Singapore. Results We included 1139 individuals with psoriasis, 744 with schizophrenia and 1678 controls in our analysis, and we validated the results in independent cohorts, including 441 individuals with psoriasis (and 2420 controls) and 1630 with schizophrenia (and 1860 controls). We estimated that a large fraction of schizophrenia and psoriasis risk could be attributed to common variants (h2SNP = 29% ± 5.0%, p = 2.00 × 10−8), with a coheritability estimate between the traits of 21%. We identified 5 variants within the human leukocyte antigen (HLA) gene region, which were most likely to be associated with both diseases and collectively conferred a significant risk effect (odds ratio of highest risk quartile = 6.03, p < 2.00 × 10−16). We discovered that variants contributing most to the shared heritable component between psoriasis and schizophrenia were enriched in antigen processing and cell endoplasmic reticulum. Limitations Our sample size was relatively small. The findings of 5 HLA gene variants were complicated by the complex structure in the HLA region. Conclusion We found evidence for a shared genetic etiology between schizophrenia and psoriasis. The
Cheuk, Stanley; Wikén, Maria; Blomqvist, Lennart; Nylén, Susanne; Talme, Toomas; Ståhle, Mona; Eidsmo, Liv
Psoriasis is a common and chronic inflammatory skin disease in which T cells play a key role. Effective treatment heals the skin without scarring, but typically psoriasis recurs in previously affected areas. A pathogenic memory within the skin has been proposed, but the nature of such site-specific disease memory is unknown. Tissue-resident memory T (TRM) cells have been ascribed a role in immunity after resolved viral skin infections. Because of their localization in the epidermal compartment of the skin, TRM may contribute to tissue pathology during psoriasis. In this study, we investigated whether resolved psoriasis lesions contain TRM cells with the ability to maintain and potentially drive recurrent disease. Three common and effective therapies, narrowband-UVB treatment and long-term biologic treatment systemically inhibiting TNF-α or IL-12/23 signaling were studied. Epidermal T cells were highly activated in psoriasis and a high proportion of CD8 T cells expressed TRM markers. In resolved psoriasis, a population of cutaneous lymphocyte-associated Ag, CCR6, CD103, and IL-23R expressing epidermal CD8 T cells was highly enriched. Epidermal CD8 T cells expressing the TRM marker CD103 responded to ex vivo stimulation with IL-17A production and epidermal CD4 T cells responded with IL-22 production after as long as 6 y of TNF-α inhibition. Our data suggest that epidermal TRM cells are retained in resolved psoriasis and that these cells are capable of producing cytokines with a critical role in psoriasis pathogenesis. We provide a potential mechanism for a site-specific T cell-driven disease memory in psoriasis.
Iraji, Fariba; Tajmirriahi, Nabet; Siadat, Amir Hossein; Momeni, Iman; Nilforoushzadeh, Mohammad Ali
Background: Psoriasis is a common dermatologic disorder, with fluctuating response to treatment. Considering the proven immunomodulatory effects of oral simvastatin in psoriasis, this trial study was enrolled to determine whether the topical form has also antipsoriatic effects. Vitamin D analogs known to be effective and are considered the first line of therapy in mild to moderate cases. In this study, the efficacy of topical calcipotriol 0.005% ointment (as a standard method of treatment for psoriasis) versus combination of calcipotriol plus topical simvastatin is compared in the treatment of psoriasis. Materials and Methods: A total of 80 subjects with symmetric psoriasis who had body surface involvement up to 20% were divided randomly into 2 groups. Group A were treated with calcipotriol 0.005% ointment twice daily and Group B with calcipotriol 0.005% ointment twice daily and simvastatin 3% ointment twice daily for 12 weeks. The results were evaluated by a Blind Dermatologist using psoriasis area severity index (PASI) score at baseline, 4th, 8th and 12th week of treatment. In a similar way, a subjective assessment performed by patients based on photo-evaluation at the end of the study. Results: Despite a continuous reduction in PASI score in both groups, according to both physician (P = 0.603) and patient (P = 0.243) assessment topical simvastatin was not statistically more effective than conventional treatment of psoriasis at the end of the study. Conclusion: This study indicates that topical simvastatin is not associated with significant impacts in the treatment of psoriasis as compared to oral form. This study indicates that psoriasis is a systemic disorder with variable skin manifestations. PMID:24592364
Altunay, Zeynep Tülay; Ilkit, Macit; Denli, Yaşargül
The data about the prevalence of onychomycosis in patients with psoriasis is contradictory. In this study, we investigated the prevalence of onychomycosis and tinea pedis in patients with psoriasis compared to control group. A total of 60 patients with psoriasis (27 male, 33 female; mean age: 40.8 +/- 17.6 years) and 60 subjects without psoriasis (27 male, 33 female; mean age: 42.8 +/- 17.3 years) who were admitted to dermatology outpatient clinics of our hospital were included to the study. Scrapings from both normal and abnormal toenails as well as toewebs were examined using microscopy and fungal culture. Foot dermatomycosis was diagnosed in 6 (5 onychomycosis and 1 tinea pedis) patients with psoriasis (10%) and in 8 (5 onychomycosis and 3 tinea pedis) control subjects (13.3%) (p > 0.05). The only dermatophyte fungi isolated in both patients with psoriasis and control group were Trichophyton rubrum (75%) and Trichophyton interdigitale (25%). Onychomycosis was more predominant in male psoriatic patients (p = 0.01). Both distero-lateral subungual onychomycosis (DLSO) and total dystrophic onychomycosis were detected in patients with psoriasis, however, DLSO, was the only clinical type in the control group. Pitting is the most typical lesions in nails in patients with psoriasis (p = 0.04). The use of common showers play a role in transmission of foot dermatomycosis (p = 0.04). In this study, psoriasis was not found as a risk factor for onychomycosis. However, onychomycosis is a major problem in psoriatic nails, and mycological methods would be useful in differential diagnosis. Since dermatomycosis is still an important public health problem, it may be controlled by education of the patient about proper foot hygiene and avoiding walking barefooted in shower areas.
Fonseca, Gabriela Poglia; Werner, Betina; Seidel, Gabriela; Staub, Henrique Luiz
BACKGROUND The nail involvement in psoriasis is related to psoriatic arthritis and may represent a predictor of the disease. OBJECTIVES To analyze, through nail clipping, clinically normal and dystrophic nails of patients with cutaneous psoriasis and psoriatic arthritis. METHODS This is a cross-sectional multicenter study, conducted between August 2011 and March 2012. Patients were divided into four groups: patients with cutaneous psoriasis and onychodystrophy, patients with cutaneous psoriasis and clinically normal nails, patients with psoriatic arthritis and onychodystrophy and patients with psoriatic arthritis and clinically normal nails. We calculated NAPSI (Nail Psoriasis Severity Index) of the nail with more clinically noticeable change. After collection and preparation of the nail clipping, the following microscopic parameters were evaluated: thickness of the nail plate and subungual region, presence or absence of parakeratosis, serous lakes, blood, and fungi. RESULTS There were more layers of parakeratosis (p=0.001) and a greater thickness of the subungual region in patients with cutaneous psoriasis and onychodystrophy (p=0.002). Serous lakes were also more present in the same group (p=0.008) and in patients with psoriatic arthritis and normal nails (p=0.047). The other microscopic parameters showed no significant difference between normal and dystrophic nails or between patients with psoriatic arthritis or cutaneous psoriasis. STUDY LIMITATIONS Small sample size and use of medications. CONCLUSIONS Nail clipping is a simple and quick method to assess the nails of patients with nail psoriasis although does not demonstrate difference between those with joint changes or exclusively cutaneous psoriasis. PMID:28225951
Bowcock, A.; Tomfohrde, J.; Barnes, R.
Psoriasis is a chronic inflammatory dermatosis that affects approximately 2% of the population. A gene for psoriasis susceptibility was localized to the distal region of human chromosome 17q as a result of a genome wide linkage-analysis with polymorphic microsatellites and eight multiply affected psoriasis kindreds. With one large kindred a maximum two-point lod score with D17S784 was 5.70 at 15% recombination. Heterogeneity testing indicated that psoriasis susceptibility in 50% of the families was linked to distal 17q. Susceptibility to psoriasis has repeatedly been found to be associated with HLA-Cw6 and associated HLA alleles. We therefore genotyped the families for loci within and flanking HLA; these included PCR assays for susceptibility alleles. By lod score analysis no evidence of linkage of psoriasis susceptibility to HLA was detected. The distribution of HLA-Cw6 and HLA-Class II alleles showed that HLA-Cw6 was frequent among patients, particularly in 4 of the 5 unlinked families. All affected members of two of these unlinked families carried HLA-Cw6 (empirical P values of 0.027 and 0.004). In 2 other families 4 of 6 and 6 of 7 had HLA-Cw6. In some of these families, an inability to detect linkage to HLA may have been due to the occurrence of multiple haplotypes carrying the psoriasis associated allele, HLA-Cw6. Contrasting with these findings, we observed a lack of association between HLA-Cw6 and psoriasis in the 3 families in which 17q markers were linked to susceptibility. The ability to detect linkage to 17q confirms that some forms of familial psoriasis are due to molecular defects at a single major genetic locus other than HLA.
Crincoli, Vito; Di Comite, Mariasevera; Di Bisceglie, Maria Beatrice; Fatone, Laura; Favia, Gianfranco
AIMS: Psoriasis is a chronic, remitting and relapsing inflammatory disorder, involving the skin, nails, scalp and mucous membranes, that impairs patients' quality of life to varying degrees. Psoriatic arthritis is a chronic seronegative, inflammatory arthritis, usually preceded by psoriasis. Temporomandibular disorders is a generic term referred to clinical conditions involving the jaw muscles and temporomandibular joint. The aim of this study was to assess symptoms and signs of temporomandibular disorders in psoriasis patients with and without psoriatic arthritis. METHODS: The study group included 112 patients (56 men, 56 women; median age 49.7±12 years) with psoriasis, 25 of them were affected by psoriatic arthritis. A group of 112 subjects without psoriasis (56 men, 56 women; median age 47.7±17 years) served as controls. Signs and symptoms of temporomandibular disorders were evaluated according to the standardized Research Diagnostic Criteria for Temporomandibular Disorders. Psoriasis patients were subgrouped according to the presence/absence of psoriatic arthritis and by gender, to assess the prevalence of traditional symptoms and signs of temporomandibular disorders. RESULTS: Patients with psoriasis, and to an even greater extent those with psoriatic arthritis, were more frequently affected by symptoms and signs of temporomandibular disorders, including an internal temporomandibular joint opening derangement than healthy subjects. A statistically significant increase in symptoms of temporomandibular disorders, in opening derangement, bruxism and sounds of temporomandibular joint was found in patients with psoriatic arthritis as compared with psoriasis patients without arthritis and controls. CONCLUSIONS: psoriasis seems to play a role in temporomandibular joint disorders, causing an increase in orofacial pain and an altered chewing function. PMID:26019683
Gånemo, Agneta; Wahlgren, Carl-Fredrik; Svensson, Åke
Psoriasis is a common, chronic disease and in one-third of the patients it begins during the first 2 decades of life. The burdens of psoriasis are many, and some can be assessed with quality of life questionnaires. The aim was to investigate the impact of childhood psoriasis on quality of life in children and their parents and to correlate certain clinical findings with quality of life. Forty-five Swedish children (4-16 years, 28 girls) with psoriasis, and their parents, were investigated with the validated questionnaires Children's Dermatology Life Quality Index (5-16 years, n = 42), The Infant's Dermatitis Quality of Life Index (4 years, n = 3), and Dermatitis Family Impact (n = 45), the two latter with the word eczema replaced by psoriasis. Clinical examination was performed, and psoriasis severity was scored with Psoriasis Area and Severity Index. Chronic plaque psoriasis was the most common clinical type (87%). Four of the children had joint complaints. Ninety-three percent had pruritus the preceding 3 days. Ninety-three percent were receiving treatment. Median Psoriasis Area and Severity Index score was 3.3 (range 0.5-12.3). Median score for the Infant's Dermatitis Quality of Life Index was 4.0 (range 2-12), for Children's Dermatology Life Quality Index 4.0 (0-24), and for Dermatitis Family Impact questionnaire 4.0 (0-25). No significant gender difference existed. The Children's Dermatology Life Quality Index scores were higher for younger (5-8 yrs) than older (9-16 yrs) children and higher for those with joint complaints. The Dermatitis family impact scores correlated significantly with Children's Dermatology Life Quality Index and Psoriasis Area and Severity Index scores, but the Children's Dermatology Life Quality Index did not correlate with Psoriasis Area and Severity Index. The Visual Analog Scale and quality of life scores were significantly correlated. Psoriasis in children affects quality of life in the subjects and their parents. Joint complaints
Globe, Denise; Bayliss, Martha S; Harrison, David J
Background The objective of this qualitative study was to better understand the impact of psoriasis symptoms using a 3-part process: 1) develop a disease model for psoriasis to identify the most important concepts relevant to psoriasis patients; 2) conduct interviews with dermatologists to identify key areas of clinical concern; and 3) explore psoriasis patients' perceptions of the impact of psoriasis. Methods A disease model was developed from a review of the published literature and later revised based on the findings of clinician interviews and patient focus groups. To confirm the clinical relevance of the concepts identified in the disease model, 5 dermatologists were selected and interviewed one-on-one. They were asked to rate major psoriasis symptoms according to importance and bothersomeness level to patients on separate scales of 1 to 10. Results of clinician interviews were used to develop interview guides for patient focus groups. To identify important domains of psoriasis, 39 patients participated in 5 separate concept elicitation focus groups. Four focus groups included patients with severe psoriasis (n = 31) and one included patients with mild psoriasis (n = 8). Patients were asked to describe their current psoriasis symptoms and to rate them on a scale of 1 to 10, according to importance, severity, and troublesomeness. An average mean rating was calculated for each symptom throughout all focus groups. Results Clinicians most frequently mentioned itch (n = 5), psoriatic arthritis or "joint pains" (n = 4), flaking (n = 4), and pain (n = 3) as primary physical symptoms of psoriasis. Three clinicians gave a rating of 10 for the importance of itch; two clinicians gave ratings of 8 and 7 for importance. The majority of patients rated itch as the most important (31/39), most severe (31/39), and most troublesome (24/39) symptom and noted that itch negatively impacted daily activities (eg, concentration, sleep, ability to attend work or school), as well as
Callis Duffin, Kristina; Armstrong, April W; Mease, Philip J
The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has developed online videos intended to provide training on the most commonly used physical examination measures for psoriasis and psoriatic arthritis (PsA). At the 2012 GRAPPA annual meeting, attendees were updated on the development, availability, use, and validation of these video modules. To date, 1300 users from 45 different countries have used the Psoriasis Area and Severity Index (PASI) module at least once. Results were presented from a recently completed study of pre- and post-video scoring of the PASI by experienced and naive physicians and patient assessors. Future modifications of the video collection were also discussed.
Prans, Ele; Kingo, Külli; Traks, Tanel; Silm, Helgi; Vasar, Eero; Kõks, Sulev
Psoriasis vulgaris (PsV) is a frequent, chronically relapsing, immune-mediated systemic disease with characteristic skin changes. IL22 is a cytokine of IL10 family, with significant proliferative effect on different cell lines. Copy number variations (CNV) have been discovered to have phenotypic consequences and are associated with various types of diseases. In the work presented here we analyzed the copy number variations in IL22 gene of exon1 and exon5. Our results showed that the IL22 gene exon1 was significantly associated with psoriasis severity (P<0.0001). However, the association between IL22 gene exon5 copy numbers and psoriasis was not detected.
Rojo Suárez, Natalia; Jiménez Gallo, David; Arjona Aguilera, Cintia; Espinosa Rosso, Raúl; Linares Barrios, Mario
Inverse psoriasis is characterized by the development of erythematous shiny plaques at intertriginous areas of the body. It has a prevalence of 2% worldwide. The usefulness of levodopa in psoriasis was discovered in 1970 but nowadays it is not a standard therapy for this condition. A 74-year-old woman was diagnosed with Parkinson's disease subsequent to the development of extensive inverse psoriasis. The skin lesions were resistant to classical topical and systemic medications. Treatment with levodopa was initiated in order to treat her neurological problem and progressive remission of the skin lesions was noted. We highlight the role of dopamine in the pathophysiology of this dermatosis.
Secrest, Aaron M.; Matinrazm, Ali
Objective: To determine which factors (i.e., cost, efficacy, safety, and method of delivery) influence choice of psoriasis treatment by patients and how patients obtain information regarding treatment options. Design: Anonymous survey. Setting: Specialty Psoriasis Clinic at an academic dermatology department over a six-month period. Participants: Convenience sample of 40 psoriasis patients. Measurements: Participant demographics, psoriasis treatment history, sources of information about treatment options, factors influencing treatment choices, and knowledge of treatment costs. Results: The mean (±SD) patient age and duration of psoriasis was 50 (±17) and 19 (±17) years, respectively. Factors influencing patient’s choice of psoriasis treatment were, in order of importance: efficacy (90% very important), safety/side effects (65%), patient’s own cost (53%), then total treatment cost (46%), frequency of use (37%), and method of medication delivery (i.e., topical, oral, or injection; 17%). Eighty percent of patients reported not knowing the total cost of any psoriasis treatments. The patient’s dermatologist was identified as both the most important (90%) and the most influential (75%) source of information for selecting psoriasis treatments, with the internet being the second most important source. Conclusion: Patients, in large measure, are unaware of the costs for different psoriasis treatments. Efficacy, safety, and out-of-pocket costs are the most important factors to patients in deciding on a psoriasis treatment. PMID:25584135
Hu, Stephen Chu-Sung; Yu, Hsin-Su; Yen, Feng-Lin; Lin, Chi-Ling; Chen, Gwo-Shing; Lan, Cheng-Che E.
Neutrophil extracellular traps (NETs) have been implicated in the development of certain immune-mediated diseases, but their role in psoriasis has not been clearly defined. Human β-defensin-2 (HBD-2) is an important antimicrobial peptide overexpressed in psoriasis epidermis. We evaluated whether the amount of NETs is increased in psoriasis and determined the effect of NETs on HBD-2 production in epidermal keratinocytes. Using fluorescent microscopy, we found that patients with psoriasis (n = 48) had higher amount of NETotic cells in their peripheral blood compared to healthy controls (n = 48) and patients with eczema (n = 35). Psoriasis sera showed increased ability to induce NET formation in control neutrophils but normal NET degradation ability. The amount of NETs in the peripheral blood correlated with psoriasis disease severity. NETosis was also observed in the majority (18 of 20) of psoriasis skin specimens. Furthermore, NETs induced HBD-2 mRNA and protein production in keratinocytes, and immunohistochemical analysis confirmed strong expression of HBD-2 in psoriasis lesional skin. In summary, NET formation is increased in peripheral blood and lesional skin of psoriasis patients and correlates with disease severity. Additionally, NET-induced HBD-2 production may provide a novel mechanism for the decreased susceptibility of psoriasis plaques to microbial infections. PMID:27493143
Kim, Jaehwan; Oh, Chil-Hwan; Jeon, Jiehyun; Baek, Yoosang; Ahn, Jaewoo; Kim, Dong Joo; Lee, Hyun-Soo; Correa da Rosa, Joel; Suárez-Fariñas, Mayte; Lowes, Michelle A; Krueger, James G
Psoriasis is present in all racial groups, but in varying frequencies and severity. Considering that small plaque psoriasis is specific to the Asian population and severe psoriasis is more predominant in the Western population, we defined Asian small and intermediate plaque psoriasis as psoriasis subtypes and compared their molecular signatures with the classic subtype of Western large plaque psoriasis. Two different characteristics of psoriatic spreading-vertical growth and radial expansion-were contrasted between subtypes, and genomic data were correlated to histologic and clinical measurements. Compared with Western large plaque psoriasis, Asian small plaque psoriasis revealed limited psoriasis spreading, but IL-17A and IL-17-regulated proinflammatory cytokines were highly expressed. Paradoxically, IL-17A and IL-17-regulated proinflammatory cytokines were lower in Western large plaque psoriasis, whereas T cells and dendritic cells in total psoriatic skin area were exponentially increased. Negative immune regulators, such as CD69 and FAS, were decreased in both Western large plaque psoriasis and psoriasis with accompanying arthritis or obesity, and their expression was correlated with psoriasis severity index. Based on the disease subtype comparisons, we propose that dysregulation of T-cell expansion enabled by downregulation of immune negative regulators is the main mechanism for development of large plaque psoriasis subtypes.
Mazzuoccolo, Luis D; Marciano, Sebastián; Echeverría, Cristina M
The ECHO® (Extension for Community Healthcare Outcomes) project is a model of distance medical education. Its mission is to expand knowledge and evaluate the results of this action, both in the training of human resources in healthcare and in the accomplishment of the best medical practices in the community target. It is developed through case presentation videoconferencing, between experts in chronic and complex diseases and physicians, with the aim of reducing the healthcare asymmetries between large urban centers and peripherals areas. We have implemented this telementoring for dermatologists and residents who treat patients with psoriasis. After 10 sessions, a survey was conducted to evaluate the educational attainment of the participants. A significant improvement was found in their abilities to determine the severity of psoriasis, screening for arthritis, assessment of the patient before beginning systemic treatment and appropriate follow-up under different systemic therapies. ECHO replication model helped improve the skills of the participants in the management of this disease, and reduced professional isolation.
Nguyen, Catherine M; Liao, Wilson
Genomic imprinting is a genetic process where only one allele of a particular gene is expressed in a parent-of-origin dependent manner. Epigenetic changes in the DNA, such as methylation or acetylation of histones, are primarily thought to be responsible for silencing of the imprinted allele. Recently, global CpG methylation changes have been identified in psoriatic skin in comparison to normal skin, particularly near genes known to be upregulated in psoriasis such as KYNU, OAS2, and SERPINB3. Furthermore, imprinting has been associated with multi-chromosomal human disease, including diabetes and multiple sclerosis. This paper is the first to review the clinical and genetic evidence that exists in the literature for the association between imprinting and general skin disorders, including atopic dermatitis and psoriatic disease. Atopy was found to have evidence of imprinting on chromosomes 6, 11, 14, and 13. The β subunit of the IgE receptor on chromosome 11q12-13 may be imprinted. Psoriatic disease may be related to imprinting effects on chromosome 6 for psoriasis and 16 for psoriatic arthritis.
Diani, Marco; Altomare, Gianfranco; Reali, Eva
According to the current view the histological features of psoriasis arise as a consequence of the interplay between T cells, dendritic cells and keratinocytes giving rise to a self-perpetuating loop that amplifies and sustains inflammation in lesional skin. In particular, myeloid dendritic cell secretion of IL-23 and IL-12 activates IL-17-producing T cells, Th22 and Th1 cells, leading to the production of inflammatory cytokines such as IL-17, IFN-γ, TNF and IL-22. These cytokines mediate effects on keratinocytes thus establishing the inflammatory loop. Unlike psoriasis the immunopathogenic features of psoriatic arthritis are poorly characterized and there is a gap in the knowledge of the pathogenic link between inflammatory T cell responses arising in the skin and the development of joint inflammation. Here we review the knowledge accumulated over the years from the early evidence of autoreactive CD8 T cells that was studied mainly in the years 1990s and 2000s to the recent findings of the role of Th17, Tc17 cells and γδ T cells in psoriatic disease pathogenesis. The review will also focus on common and distinguishing features of T cell responses in psoriatic plaques and in synovial fluid of patients with psoriatic arthritis. The integration of this information could help to distinguish the role played by T cells in the initiation phase of the disease from the role of T cells as downstream effectors sustaining inflammation in psoriatic plaques and potentially leading to disease manifestation in distant joints.
Mastrolonardo, Mario; Picardi, Angelo; Alicino, Dario; Bellomo, Antonello; Pasquini, Paolo
A defective response of psoriatic skin to beta-adrenergic stimulation has been implicated in the pathophysiology of psoriasis. A psychophysiological study was planned to investigate whether the beta-adrenergic receptor hyporesponsiveness found in psoriatic skin can also be detected in other systems. Twenty-five psoriatic patients and 50 healthy controls were submitted to a standardized stressful procedure (mental arithmetic and the Stroop Colour-Word Naming Test) to trigger the activation of the sympathetic nervous system, and their haemodynamic responses were compared. While there were no differences between groups in perceived stress, a blunted increase in heart rate and a sharper increase in diastolic blood pressure was observed in psoriasis patients compared with controls. The psychophysiological reaction pattern observed in psoriatic patients might be explained by lower reactivity of heart beta1-adrenergic receptors and arteriolar walls beta2-adrenergic receptors. While this study suggests that beta-adrenergic receptor hyporesponsiveness might have a systemic expression in psoriatic patients, it needs support from future studies exploring beta-adrenergic function in psoriatic patients more directly.
Daudén, E; Puig, L; Ferrándiz, C; Sánchez-Carazo, J L; Hernanz-Hermosa, J M
Psoriasis is a highly prevalent disease with a major impact on quality of life; therefore, appropriate patient management is mandatory. Given that many issues in psoriasis are controversial and not clearly defined by evidence-based medicine, management of psoriasis is very variable. Expert consensus can generate practical guidelines for optimization of patient care. Much has changed since 2009, when the Consensus Document on the Evaluation and Treatment of Moderate to Severe Psoriasis was published by the Spanish Psoriasis Group (GEP) of the Spanish Academy of Dermatology and Venereology (AEDV). The objective of the present consensus document is to provide the dermatologist with updated recommendations for the evaluation and treatment of patients with moderate-to-severe plaque psoriasis. All active members of the GEP of the AEDV were invited to participate in the survey. The final group comprised 46 members from various areas of Spain and with substantial experience in managing psoriasis. A 3-round Delphi process was used to reach consensus. Consistent agreement and consistent disagreement (consensus) required the achievement of at least two of the following three criteria: Criterion 1, which was based on the position occupied by the mean on a scale of 1-9 and an SD <2; Criterion 2, which was based on the median and interquartile range (IQR) on a scale of 1-9; Criterion 3, which considered the percentage of the voting experts on a scale of 1-9. The items studied were definition of severity, therapeutic objectives, indications for systemic treatment and biologic therapy, induction and maintenance periods, therapeutic failure, loss of response, relapse and rebound, continuous and intermittent therapy, screening of patients before treatment, adherence to therapy, follow-up of treatment outcome, combination of drugs, transitioning and associated comorbidities. Consistent agreement or disagreement (consensus) was achieved for 198 items (agreement, 3 criteria 146 items
Oostveen, Annet M; Bergboer, Judith G M; van de Kerkhof, Peter C M; Zeeuwen, Patrick L J M; de Jong, Elke M G J; Schalkwijk, Joost; Seyger, Marieke M B
This study aims to investigate associations between observed clinical parameters and known genetic risk factors of psoriasis in a well-defined prospective cohort of paediatric patients with plaque psoriasis (n = 151). Significant associations were found for paediatric-onset psoriasis with ERAP1 (p = 0.002), IL23R (p = 0.01), LCE3C_LCE3B-del (p = 0.00049) and HLA-C*06 (p = 3.15 × 10(-30)). Psoriasis severity was associated with the single nucleotide polymorphisms tagging IFIH1 and ERAP1 (p < 0.05). An onset before 10 years of age was associated with IL12B (p = 0.02). Nail psoriasis was more often seen in HLA-C*06-negative patients (p = 0.008). Remarkably, family history is clearly not associated with HLA-C*06 in this specific group. The large proportion of patients with a positive family history in HLA-C*06 negative patients (and the lack of correlation between the two) indicates that other genes, either alone or interaction between two or more genes, may have significant effects on heritability.
Menter, A.; Korman, N.J.; Elmets, C.A.; Feldman, S.R.; Gelfand, J.M.; Gordon, K.B.; Gottlieb, A.; Koo, J.Y.M.; Lebwohl, M.; Lim, H.W.; Van Voorhees, A.S.; Beutner, K.R.; Bhushan, R.
Psoriasis is a common, chronic, inflammatory, multi-system disease with predominantly skin and joint manifestations affecting approximately 2% of the Population. In this third of 6 sections of the guidelines of care for psoriasis, we discuss the use of topical medications for the treatment of psoriasis. The majority of patients with psoriasis have limited disease (<5% body surface area involvement) and can be treated with topical agents, which generally provide a high efficacy-to-safety ratio. Topical agents may also be used adjunctively for patients with more extensive psoriasis undergoing therapy with either ultraviolet light, systemic or biologic medications. However, the use of topical agents as monotherapy in the setting of extensive disease or in the setting of limited, but recalcitrant, disease is not routinely recommended. Treatment should be tailored to meet individual patients' needs. We will discuss the efficacy and safety of as well as offer recommendations for the use of topical corticosteroids, vitamin D analogues, tazarotene, tacrolimus, pimecrolimus, emollients, salicylic acid, anthralin, coal tar, as well as combination therapy.
Gisondi, Paolo; Girolomoni, Giampiero
Chronic plaque psoriasis presents clinically as an inflammatory disease of the skin, which is often associated with comorbidities and responsible for a poor quality of life. It can widely vary among patients because of different age of onset, type of symptoms, areas of involvement, and disease severity. The choice of the treatment of psoriasis should be personalized according to the specific needs of the patients. Apremilast is a well-tolerated and effective phosphodiesterase type 4 inhibitor that is indicated for the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis. In this article, the pharmacological, clinical, and safety aspects of apremilast are reviewed. Based on these data, apremilast could be indicated for patients with a Psoriasis Area and Severity Index score <10 but with a significant impact on quality of life and seems to be an appropriate treatment for elderly patients also. PMID:27307707
Ghaffari, Javad; Abedian- Kenari, Saeed; Ghasemi, Maryam; Gohardehi, Farzad
Background: Hyper IgE syndrome (HIES) is a rare primary immune deficiency, described as Job`s syndrome characterized by increased serum levels of IgE, eczema, recurrent cutaneous and pulmonary infections. In this paper, we presented a case of Hyper IgE syndrome. Case Presentation: A 16-year-old Iranian boy presented with a one year history of skin lesions in knees and elbows was diagnosed of psoriasis disease. He had a history of recurrent infections including otitis media, pneumonia, diarrea and skin infection. Laboratory results showed increased level of total IgE and normal in other immunoglobulin. Histologic finding showed hyperkeratosis, parakeratosis of acanthotic epidermis with regular elongation of rete ridges diagnose psoriasis disorder. Conclusion: In conclusion, this is the first case of hyper IgE patient with psoriasis disorder. We addressed the important laboratory findings and actual theories explaining possible association between hyper IgE immunoglobulinemia and psoriasis disorder. PMID:24009971
McKenzie, Roddie C; Oda, Yuko; Szepietowski, Jacek C; Behne, Martin J; Mauro, Theodora
A positive association between intake of calcium channel blockers and psoriasis has been observed recently. Intake of blockers of voltage-gated calcium ion channels is associated with outbreaks of psoriasis after a latent period in patients with and without a previous family history of psoriasis. This suggests that interfering with calcium influx may trigger psoriasis. Calcium influx also occurs via cyclic guanosine monophosphate-gated channels; human keratinocytes contain functional and non-functional (splice variants) versions of these channels. We show here that keratinocytes and skin from psoriatic individuals express higher levels of mRNA encoding a non-functional cyclic guanosine monophosphate-gated calcium channel and that high expression of the splice variant by transfection of cells in culture leads to loss of protein expression for the functional cyclic guanosine monophosphate-gated Ca2+ channels.
Nimmannitya, Kulsupa; Tateishi, Chiharu; Mizukami, Yukari; Hamamoto, Kae; Yamada, Shinsuke; Goto, Hitoshi; Okada, Shigeki; Tsuruta, Daisuke
Psoriasis is a common chronic inflammatory skin disease but psoriasis patients with renal impairment undergoing dialysis are not frequently seen. Furthermore, the published work contains little information on the treatment with biologic drugs of patients with end-stage renal disease. We describe a 57-year-old man with refractory plaque-type psoriasis and end-stage renal disease due to polycystic kidney disease undergoing hemodialysis. He had tried topical medications and ultraviolet therapy for many years and was then treated with ustekinumab (an interleukin-12 and interleukin-23 blocker), which resulted in good clinical response along with stable renal function. After a few years of therapy, no side-effects have been observed. Our experience with this patient expands the spectrum of ustekinumab to include psoriasis patients with renal failure undergoing hemodialysis.
Errichetti, Enzo; Stinco, Giuseppe
Clinical differentiation between palmar psoriasis and chronic hand eczema may sometimes be a diagnostic challenge; in such cases histopathological analysis helps to differentiate the two conditions. In the present study, palmar psoriasis and chronic hand eczema were investigated using dermoscopy and the significance of specific dermoscopic features was assessed in order to improve their non-invasive differentiation. Ten patients with biopsy-proven palmar psoriasis and 11 patients with biopsy-proven chronic hand eczema were included in the study. We found that the presence of diffuse white scales was significant in palmar psoriasis whereas the presence of yellowish scales, brownish-orange dots/globules and yellowish-orange crusts was significant in chronic hand eczema.
Garzorz, Natalie; Eyerich, Kilian
Chronic inflammatory skin diseases such as psoriasis and eczema are a major medical challenge. Development of highly specific therapies for both conditions is opposed by the lack of translation of basic knowledge into biomarkers for clinical use. Furthermore, to distinguish psoriasis from eczema might be difficult occasionally, but specific and costly therapies would not be efficient in misdiagnosed patients. In the era of high-throughput 'omics'-technologies, comparing the molecular signature of psoriasis and eczema is a promising approach to gain insight into their complex pathogeneses and develop new diagnostic and therapeutic strategies. Investigating patients affected by both psoriasis and eczema simultaneously, we recently constructed a disease classifier consisting of only two genes (NOS2 and CCL27) that reliably predicts the correct diagnosis even in clinically unclear cases. When such easy-to-handle approaches are combined with individual therapeutic response, we might reach the ultimate goal of personalized medicine in inflammatory skin diseases in near future.
Ceovic, Romana; Mance, Marko; Bukvic Mokos, Zrinka; Svetec, Maja; Kostovic, Kresimir; Stulhofer Buzina, Daska
Psoriasis is one of the most prevalent immune mediated skin diseases worldwide. Despite the large prevalence in both men and women, the pathogenesis of this disease has not yet been fully clarified. Nowadays, it is believed that psoriasis is most likely a T helper Th1/Th17 induced inflammatory disease. Stressful life situations are known to cause flare-ups and psoriasis activity may be linked to stress from major life events. We know that stress greatly affects both the hormone and immune systems and that there are many different hormonal phases throughout a woman's lifetime. The severity of psoriasis may fluctuate or be influenced by each phase and this relationship can be seen as disease frequency seems to peak during puberty, postpartum, and menopause when hormone levels fall, while symptoms improve during pregnancy, a state when hormone levels are increased.
Sampogna, Francesca; Tabolli, Stefano; Abeni, Damiano
Psychosocial problems are frequent among patients with psoriasis. The aim of this study was to analyse the prevalence of some specific psychosocial issues. These were evaluated in 936 patients using the emotions and functioning scales of the Skindex-29 questionnaire. The problems most frequently experienced were: shame, anger, worry, difficulties in daily activities and social life. All problems were associated with the severity of psoriasis and with depression or anxiety. Shame, worry and annoyance were more frequent in women than in men, and shame and anger were associated with a low level of education. Impairment in work/hobbies was significantly higher in patients with palmoplantar psoriasis and those with arthro-pathic psoriasis. In conclusion, clinicians could gain important insights about their patients by looking at the single items of a quality of life instrument, to identify patients with high levels of emotional and social problems, in order to improve quality of care.
Van Nuffel, Elien; Schmitt, Anja; Afonina, Inna S; Schulze-Osthoff, Klaus; Beyaert, Rudi; Hailfinger, Stephan
Mutations in caspase recruitment domain-containing protein 14(CARD14) have been linked to susceptibility to psoriasis. CARD14 is an intracellular scaffold protein that regulates proinflammatory gene expression. Recent studies have offered novel insights into the mechanisms of CARD14-mediated signaling in keratinocytes and the molecular impact of psoriasis-associated CARD14 mutations. CARD14 forms a signaling complex with BCL10 and the paracaspase MALT1, and this process is enhanced upon pathogenic CARD14 mutation, culminating in the activation of MALT1 protease activity and psoriasis-associated gene expression. This review summarizes the current knowledge of CARD14/MALT1-mediated signaling in keratinocytes and its therapeutic implications in psoriasis.
Tomfohrde, J.; Barnes, R.; Bowcock, A.; Fernandez-Vina, M.A.; Stastny, P.; Silverman, A.; Young, M.; Lory, D.; Morris, L.; Menter, A.
A gene involved in psoriasis susceptibility was localized to the distal region of human chromosomes 17q as a result of a genome-wide linkage analysis with polymorphic microsatellites and eight multiply affected psoriasis kindreds. In the family which showed the strongest evidence for linkage, the recombination fraction between a psoriasis susceptibility locus and D17S784 was 0.04 with a maximum two-point lod score of 5.33. There was also evidence for genetic heterogeneity and although none of the linked families showed any association with HLA-Cw6, two unlinked families showed weak levels of association. This study demonstrates that is some families, psoriasis susceptibility is due to variation at a single major genetic locus other than the human lymphocyte antigen locus. 28 refs., 2 figs., 1 tab.
Kim, Jaehwan; Krueger, James G
Psoriasis vulgaris, affecting the skin, is one of the most common organ-specific autoimmune diseases in humans. Until recently, psoriasis was treated by agents or approaches discovered largely through serendipity. Many of the available drugs were inherently quite toxic when used as continuous treatment for many years in this chronic disease. However, an increasing understanding of disease-specific immune pathways has spurred development of pathway-targeted therapeutics during the past decade. Psoriasis is now the most effectively treated human autoimmune disease, with high-level clinical improvements possible in ∼90% of patients using a new generation of drugs that selectively target the IL-23/Type 17 T cell axis. Thus, psoriasis is a model for the success of a translational-medicine approach based on cellular and molecular dissection of disease pathogenesis in humans.
Guerreiro de Moura, Carlos Antônio Gusmão; de Assis, Luiz Henrique; Góes, Paulo; Rosa, Fabiana; Nunes, Victor; Gusmão, Ítalo Magalhães; Cruz, Constança Margarida Sampaio
Psoriasis is an autoimmune disease triggered by different conditions in genetically susceptible people. It is characterized by variable cutaneous manifestations including localized or disseminated pustules. Generalized pustular psoriasis (GPP) has two main clinical forms: von Zumbusch psoriasis, characterized by severe erythrodermia and scaling skin after the resolution of pustules, and the annular form. GPP may also present severe extracutaneous manifestations including pneumonitis, heart failure and hepatitis. Old reports showed a relationship between hypoparathyroidism and hypocalcemia as triggers for GPP highlighting the importance of adequate workup of the patient and possible therapeutic changes in acute situations. Here, we present a case of severe von Zumbusch psoriasis with life-threatening complications triggered by severe hypocalcemia secondary to hypoparathyroidism successfully treated with aggressive calcium reposition. PMID:26955330
Gisondi, Paolo; Galvan, Arturo; Idolazzi, Luca; Girolomoni, Giampiero
Psoriasis is a chronic inflammatory skin disease affecting 2–3% of worldwide population. The extent of skin involvement is variable, ranging from a few localized plaques to generalized involvement. Moderate to severe psoriasis (>10% of body surface area) is frequently associated with psoriatic arthritis and metabolic diseases, like abdominal obesity, diabetes, non-alcoholic fatty liver disease, dyslipidemia, metabolic syndrome, and chronic kidney disease. A common genetic background as well as several acquired risk factors links psoriasis to comorbidities. From a clinical prespective, the understanding of the patients in the context of these comorbidities is very important to ensure that treatment is tailored to meet the individual patient needs. Indeed, some pharmacological treatments may negatively affect cardio-metabolic comorbidities, and have important interactions with drugs that are commonly used to treat them. Non-pharmacological intervention such as diet, smoking cessation, and physical exercise could both improve the response to treatments for psoriasis and reduce the cardiovascular risk. PMID:25654080
Milčić, Danijela; Janković, Slavenka; Vesić, Sonja; Milinković, Mirjana; Marinković, Jelena; Ćirković, Andja; Janković, Janko
BACKGROUND Emerging epidemiological evidence suggests independent associations between psoriasis and metabolic syndrome. Objectives: The aim of the study was to examine the prevalence of metabolic syndrome and its components in patients with psoriasis, and to assess which factors may predict metabolic syndrome in these patients. METHODS A hospital-based, cross-sectional study with 244 psoriatic patients and 163 control subjects with skin diseases other than psoriasis was conducted at the Clinic of Dermatovenerology, Clinical Center of Serbia, Belgrade, from October 2011 to October 2012. Metabolic syndrome was defined using the revised National Cholesterol Education Program Adult Treatment Panel III. Severity of psoriasis was measured by Psoriasis Area and Severity Index and Body Surface Area. RESULTS The adjusted odds ratios (ORs) and 95% confidence intervals (CI) for psoriasis patients vs. non-psoriasis patients were 2.66 (95% CI, 1.58-4.42) for metabolic syndrome, 3.81 (95% CI, 2.30-6.31) for hypertension, 2.29 (95% CI, 1.39-3.78) for central obesity, 1.92 (95% CI, 1.08-3.41) for hyperglycemia, 1.87 (95% CI 1.18-2.96) for low high-density lipoprotein cholesterol level, and 1.42 (95% CI, 0.87-1.04) for hypertrigliceridemia. We failed to find any statistically significant association between the metabolic syndrome and clinical severity of psoriasis. Later onset and longer duration of psoriasis were predicting factors for metabolic syndrome in our patients. Study limitations: The cross-sectional design of the study does not allow us to draw directional causal inferences concerning the association between psoriasis and metabolic syndrome. Factors such as diet, alcohol consumption or mental health, which have not been evaluated in this study, may be confounders in this relation. CONCLUSION A higher prevalence of metabolic syndrome and its components in patients with psoriasis than in controls, regardless of disease severity, emphasizes the need for early treatment and
Shlyankevich, Julia; Mehta, Nehal N.; Krueger, James G.; Strober, Bruce; Gudjonsson, Johann E.; Qureshi, Abrar A.; Tebbey, Paul W.; Kimball, Alexandra Boer
The International Psoriasis Council (IPC), a global non-profit organization dedicated to advancing psoriasis research and treatment, led an initiative to better define the association of various cardiometabolic comorbidities with psoriasis. In November 2013, a workshop was held in Boston, MA. By assembling a panel of global dermatology, immunology and cardiovascular experts, the objective was to better define the current status of the science that explains the association of psoriasis with various cardiometabolic-related comorbidities. IPC has played a historical role in associating psoriasis with various comorbidities by integrating multidisciplinary expertise to advance the scientific and clinical knowledge through publications and clinical trials. This report synthesizes the current understanding of psoriasis with various cardiometabolic risk factors by exploring the potential shared pathogenic mechanisms and genetic connectivity. PMID:25149424
Raychaudhuri, S P; Dutt, S; Raychaudhuri, S K; Sanyal, M; Farber, E M
Elucidation of the molecular and cellular mechanisms responsible for the pathogenesis of psoriasis had been significantly handicapped due to lack of an ideal animal model. To overcome this hurdle several investigators have developed a number of animal models for psoriasis. Recent establishment of the SCID-human skin chimeras with transplanted psoriasis plaques has opened new vistas to study the molecular complexities involved in psoriasis. This model also offers a unique opportunity to investigate various key biological events such as cell proliferation, angiogenesis, homing in of T cells in target tissues, neurogenic inflammation and cytokine/chemokine cascades involved in an inflammatory reaction. The SCID mouse model will be of immense help to target the cellular and molecular events associated with these pathogenic processes and develop novel drugs for psoriasis and other inflammatory diseases. In this article we have reviewed the prospects and the limitations of the SCID mouse model of psoriasis.
Aterido, Adrià; Julià, Antonio; Ferrándiz, Carlos; Puig, Lluís; Fonseca, Eduardo; Fernández-López, Emilia; Dauden, Esteban; Sánchez-Carazo, José Luís; López-Estebaranz, José Luís; Moreno-Ramírez, David; Vanaclocha, Francisco; Herrera, Enrique; de la Cueva, Pablo; Dand, Nick; Palau, Núria; Alonso, Arnald; López-Lasanta, María; Tortosa, Raül; García-Montero, Andrés; Codó, Laia; Gelpí, Josep Lluís; Bertranpetit, Jaume; Absher, Devin; Capon, Francesca; Myers, Richard M; Barker, Jonathan N; Marsal, Sara
Psoriasis is a chronic inflammatory disease with a complex genetic architecture. To date, the psoriasis heritability is only partially explained. However, there is increasing evidence that the missing heritability in psoriasis could be explained by multiple genetic variants of low effect size from common genetic pathways. The objective of this study was to identify new genetic variation associated with psoriasis risk at the pathway level. We genotyped 598,258 single nucleotide polymorphisms in a discovery cohort of 2,281 case-control individuals from Spain. We performed a genome-wide pathway analysis using 1,053 reference biological pathways. A total of 14 genetic pathways (PFDR ≤ 2.55 × 10(-2)) were found to be significantly associated with psoriasis risk. Using an independent validation cohort of 7,353 individuals from the UK, a total of 6 genetic pathways were significantly replicated (PFDR ≤ 3.46 × 10(-2)). We found genetic pathways that had not been previously associated with psoriasis risk such as retinol metabolism (Pcombined = 1.84 × 10(-4)), the transport of inorganic ions and amino acids (Pcombined = 1.57 × 10(-7)), and post-translational protein modification (Pcombined = 1.57 × 10(-7)). In the latter pathway, MGAT5 showed a strong network centrality, and its association with psoriasis risk was further validated in an additional case-control cohort of 3,429 individuals (P < 0.05). These findings provide insights into the biological mechanisms associated with psoriasis susceptibility.
Lajevardi, Vahideh; Ghiasi, Maryam; Goodarzi, Azadeh; Mohtasham, Sima; Ansari, Mahsa; Hedayat, Kosar; Nassiri, Farzad
Psoriasis is a chronic relapsing disorder that involves the skin, nails and joints. With regard to the role of the immune system in psoriasis, the current study compared serum IgE concentration in patients with psoriasis with control group. Current case-control study was conducted in Dermatology clinic of Razi hospital, Tehran University of medical sciences, Tehran, Iran in 2012. Fifty-eight patients with psoriasis e referred to the clinic were assigned as patient group and 58 healthy subjects with matched age and sex as a control group. Patient's history, family history and demographic characteristics such as age and sex, duration and severity of disease using PASI, were collected and entered into a form. Consent form was obtained from participants. Serum IgE concentrations of both study groups were measured by electrochemiluminescence assay in the laboratory A total number of 58 patients with psoriasis, mean age of 44.15 (19-76 years) and 58 controls with matched age and sex were studied. Mean average of serum IgE concentration in the control group was 115.13 versus 200/06 concentration in patients group (P=0.16). Serum IgE concentration in 22.4% of patients versus 17.2% in controls was greater than normal concentration (P=0.48). No significant correlation was between serum IgE concentration and disease severity using PASI (P=0.11, r=0.21), neither a significant correlation with disease duration, age and gender. According to the present study, serum IgE concentrations are not greater in patients with psoriasis. IgE concentration is also not associated with the severity of psoriasis based on the PASI score, therefore, the role of IgE in psoriasis can be considered insignificant as some previous studies indicate.
Kirschner, Nina; Poetzl, Claudia; von den Driesch, Peter; Wladykowski, Ewa; Moll, Ingrid; Behne, Martin J.; Brandner, Johanna M.
Psoriasis is an inflammatory skin disease characterized by hyperproliferation of keratinocytes, impaired barrier function, and pronounced infiltration of inflammatory cells. Tight junctions (TJs) are cell-cell junctions that form paracellular barriers for solutes and inflammatory cells. Altered localization of TJ proteins in the epidermis was described in plaque-type psoriasis. Here we show that localization of TJ proteins is already altered in early-stage psoriasis. Occludin, ZO-1, and claudin-4 are found in more layers than in normal epidermis, and claudin-1 and -7 are down-regulated in the basal and in the uppermost layers. In plaque-type psoriasis, the staining patterns of occludin and ZO-1 do not change, whereas the claudins are further down-regulated. Near transmigrating granulocytes, all TJ proteins except for junctional adhesion molecule-A are down-regulated. Treatment of cultured keratinocytes with interleukin-1β and tumor necrosis factor-α, which are present at elevated levels in psoriatic skin, results in an increase of transepithelial resistance at early time points and a decrease at later time points. Injection of interleukin-1β into an ex vivo skin model leads to an up-regulation of occludin and ZO-1, resembling TJ protein alteration in early psoriasis. Our results show for the first time that alteration of TJ proteins is an early event in psoriasis and is not the consequence of the more profound changes found in plaque-type psoriasis. Our data indicate that cytokines are involved in alterations of TJ proteins observed in psoriasis. PMID:19661441
Schons, Karen Regina Rosso; Beber, André Avelino Costa; Beck, Maristela de Oliveira; Monticielo, Odirlei André
BACKGROUND: Psoriasis is a disease of worldwide distribution with a prevalence of 1 to 3%. Nail psoriasis is estimated in 50% of patients with psoriasis, and in the presence of joint involvement, it can reach 80%. OBJECTIVE: To study the nail changes - and their clinical implications - presented by patients with psoriasis vulgaris under surveillance in a university hospital from the south of Brazil. METHODS: his cross-sectional study evaluated 65 adult patients from January 2012 to March 2013. Cutaneous severity was assessed according to the Psoriasis Area and Severity Index (PASI). The Nail Psoriasis Severity Index (NAPSI) was used to evaluate patient's nails. The diagnosis of psoriatic arthritis was established according to the Classification Criteria for Psoriatic Arthritis (CASPAR). RESULTS: The prevalence of NP was 46.1%. These patients had a median [interquartilic range (IQR)] NAPSI of 1 (0-15). A total of 63.3% of patients reported aesthetic discomfort or functional impairment related to their nails. Onycholysis was the most common feature (80%). When compared with patients without nail involvement, patients with NP had lower mean age at psoriasis onset [21 (18-41) vs. 43 (30-56) years, p=0,001]; longer disease duration [15.5 (10-24) vs. 6 (2-12) years, p=0.001]; higher PASI [9.2 (5-17) vs. 3.7 (2-10), p=0.044], higher frequency of psoriatic arthritis (43.3 vs. 3.7, p = 0.002) and more often reported family history of psoriasis (40% vs. 7.4%, p = 0.011). CONCLUSION: Onycholysis was the most frequent finding and most patients feel uncomfortable with the psoriatic nail changes that they experience. PMID:26131859
Chang, Ting; Sun, Linchao; Wang, Yan; Wang, Datai; Li, Wei; Li, Chunying; Gao, Tianwen; Liu, Yufeng; Wang, Gang
Psoriasis is now considered to be a chronic, immune-mediated and inflammatory skin disease. As the precise cause of psoriasis remains unknown, its treatment is challenging for dermatologists. Keratin 17 (K17), an intermediate filament protein, is highly expressed in psoriatic lesions, while not normally expressed in healthy epidermis. Studies have suggested that K17 plays a role in the pathogenesis of psoriasis. However, no study has been performed to determine the potential application of K17 down-regulation as a treatment option for psoriatic lesions. We hypothesized that anti-K17 interference may suppress the development and progression of psoriasis and potentially serve as a novel strategy for the treatment of psoriasis. Therefore, we down-regulated and silenced K17 gene expression in keratinocytes (KCs) using antisense and RNA interference (RNAi) techniques. We found that K17-specific antisense oligonucleotides (ASODN) or siRNAs inhibited proliferation and induced apoptosis in KCs as well as down-regulated K17 expression at both mRNA and protein levels. For our in vivo study, we constructed the SCID-hu xenogeneic transplantation psoriasis mouse model by grafting psoriatic lesions onto SCID mice and topically applied K17-specific ASODN and liposome-encapsulated siRNA to the grafts. We observed morphological and histological improvement in the treated psoriatic grafts. As a result, K17 mRNA and protein expression was significantly decreased in the grafts of the mouse model. Taken together, we conclude that anti-K17 therapy is an effective treatment option for psoriasis, and the K17 molecule, as a new target, may hold tremendous potential for the treatment of psoriasis in the future.
Dmitruck, Vadim S.; Sosnin, Edward A.; Obgol'tz, Irina A.
Clinical efficiency estimation of XeCl-excilamp application for psoriasis curing in comparison with other methods of phototherapy for has been carried out for the first time. Curing psoriasis by XeCl-excilamp assistance is shown to be an effective and present-date method. Such a phototherapy advantages suggested are the good tolerance, and absence of intact skin irradiation. The use of chemicals is no longer relevant, and the total doze of irradiation happens to be rather low.
Baş, Yalçın; Altunkaş, Fatih; Seçkin, Havva Yıldız; Takcı, Zennure; Arısoy, Arif; Karayakalı, Metin; Karaman, Kayıhan; Demir, Osman
Myocardial fibrosis causes the fragmentation of QRS complexes on electrocardiogram. We hypothesized that the frequency of fragmented QRS (fQRS) could be more common in patients with psoriasis vulgaris than in healthy control subjects. In this prospective study, 100 patients with psoriasis vulgaris who did not have any cardiovascular disease were compared with 50 healthy volunteers in control group. The Psoriasis Area Severity Index (PASI) was used for expressing the severity of psoriasis. Patients with psoriasis were categorized according to presence of fQRS in ECG [fQRS (+) group and fQRS (-) group]. Patients with psoriasis had higher frequency of fQRS, higher levels of C reactive protein (CRP) and sedimentation rate (ESR) than the control group (n = 49, 49 % vs. n = 3, 6 %, p < 0.001; 9.91 ± 17.86 vs. 3.59 ± 0.79 mg/dL, p = 0.014; 17.37 ± 17.40 vs. 5.66 ± 5.22 mm/h, p < 0.001, respectively). Within the patient group there was no statistically significant difference between fQRS (+) and fQRS (-) subgroups with regards to sex, disease duration, CRP, ESR, medications and PASI score. It was suggested that presence of fQRS in ECG may be related with myocardial fibrosis in patients with psoriasis who do not have cardiovascular disease. For this reason, in our opinion, fQRS could be used as a predictive marker for myocardial fibrosis in patients with psoriasis.
Introduction Psoriasis is a hyperproliferative disorder of the skin, and vitamin D analogs are widely used in its treatment. It is evident that ultraviolet radiation enables vitamin D3 (cholecalciferol) formation in the epidermis, and this product is further converted into the active metabolites 25-hydroxycholecalciferol and 1,25-hydroxycholecalciferol, which exert several important effects on the skin. The disruption in proper functioning of the skin which occurs in psoriasis leads to a loss of capacity for cutaneous synthesis of vitamin D3. In consequence, it activates a vicious circle that impairs homeostasis of the skin and results in a progressive decrease in the level of vitamin D in the whole human body. Aim To estimate the prevalence of vitamin D serum deficiency in patients with psoriasis and analyse the association of vitamin D food intake with clinical features. Material and methods Forty adults with psoriasis and 40 healthy subjects (control group) were recruited. Psoriasis plaques were diagnosed and evaluated by the PASI scale. Collected blood samples enabled measurement of serum vitamin D level by assessment with the immunoenzyme technique. Results The analysis with the Mann-Whitney U test revealed a statistically significant difference in 25-hydroxycholecalciferol level between healthy individuals and patients with psoriasis (p = 0.048). In both groups (control and psoriatic) the level of 25-hydroxycholecalciferol was seriously deficient (< 50 nmol/l). There was also a negative correlation of 25-hydroxycholecalciferol serum level with both PASI (r = –0.43) and the duration of psoriasis (r = –0.53). Conclusions It is necessary to bear in mind that not only the ingestion of food rich in vitamin D is necessary, but also the production of vitamin D with sun exposure. The quantity of 25-hydroxycholecalciferol is very important both in the general population and in patients with psoriasis, because these groups have a distinct metabolism. PMID:28035222
Torales-Cardeña, Azael; Martínez-Torres, Isaí; Rodríguez-Martínez, Sandra; Gómez-Chávez, Fernando; Cancino-Díaz, Juan C.; Vázquez-Sánchez, Ernesto A.; Cancino-Díaz, Mario E.
Psoriasis is a chronic inflammatory skin disease where the altered regulation in angiogenesis, inflammation, and proliferation of keratinocytes are the possible causes of the disease, and the transcription factor “hypoxia-inducible factor 1-alpha” (HIF-1α) is involved in the homeostasis of these three biological phenomena. In this review, the role of HIF-1α in the cross talk between the cytokines and cells of the immunological system involved in the pathogenesis of psoriasis is discussed. PMID:26136626
Stawczyk-Macieja, Marta; Szczerkowska-Dobosz, Aneta; Rębała, Krzysztof; Purzycka-Bohdan, Dorota
Psoriasis is a common inflammatory skin disease. It is known to be a complex condition with multifactorial mode of inheritance, however the associations between particular pathogenic pathways remain unclear. A novel report on the pathogenesis of psoriasis has recently included the genetic determination of the skin barrier dysfunction. In this paper, we focus on specific genetic variants associated with formation of the epidermal barrier and their role in the complex pathogenesis of the disease.
Background Genome-scale studies of psoriasis have been used to identify genes of potential relevance to disease mechanisms. For many identified genes, however, the cell type mediating disease activity is uncertain, which has limited our ability to design gene functional studies based on genomic findings. Methods We identified differentially expressed genes (DEGs) with altered expression in psoriasis lesions (n = 216 patients), as well as candidate genes near susceptibility loci from psoriasis GWAS studies. These gene sets were characterized based upon their expression across 10 cell types present in psoriasis lesions. Susceptibility-associated variation at intergenic (non-coding) loci was evaluated to identify sites of allele-specific transcription factor binding. Results Half of DEGs showed highest expression in skin cells, although the dominant cell type differed between psoriasis-increased DEGs (keratinocytes, 35%) and psoriasis-decreased DEGs (fibroblasts, 33%). In contrast, psoriasis GWAS candidates tended to have highest expression in immune cells (71%), with a significant fraction showing maximal expression in neutrophils (24%, P < 0.001). By identifying candidate cell types for genes near susceptibility loci, we could identify and prioritize SNPs at which susceptibility variants are predicted to influence transcription factor binding. This led to the identification of potentially causal (non-coding) SNPs for which susceptibility variants influence binding of AP-1, NF-κB, IRF1, STAT3 and STAT4. Conclusions These findings underscore the role of innate immunity in psoriasis and highlight neutrophils as a cell type linked with pathogenetic mechanisms. Assignment of candidate cell types to genes emerging from GWAS studies provides a first step towards functional analysis, and we have proposed an approach for generating hypotheses to explain GWAS hits at intergenic loci. PMID:24885462
Sato, Kenji; Takaishi, Mikiro; Tokuoka, Shota; Sano, Shigetoshi
TNF-α plays a crucial role in psoriasis; therefore, TNF inhibition has become a gold standard for the treatment of psoriasis. TNF-α is processed from a membrane-bound form by TNF-α converting enzyme (TACE) to soluble form, which exerts a number of biological activities. EGF receptor (EGFR) ligands, including heparin-binding EGF-like growth factor (HB-EGF), amphiregulin and transforming growth factor (TGF)-α are also TACE substrates and are psoriasis-associated growth factors. Vascular endothelial growth factor (VEGF), one of the downstream molecules of EGFR and TNF signaling, plays a key role in angiogenesis for developing psoriasis. In the present study, to assess the possible role of TACE in the pathogenesis of psoriasis, we investigated the involvement of TACE in TPA-induced psoriasis-like lesions in K5.Stat3C mice, which represent a mouse model of psoriasis. In this mouse model, TNF-α, amphiregulin, HB-EGF and TGF-α were significantly up-regulated in the skin lesions, similar to human psoriasis. Treatment of K5.Stat3C mice with TNF-α or EGFR inhibitors attenuated the skin lesions, suggesting the roles of TACE substrates in psoriasis. Furthermore, the skin lesions of K5.Stat3C mice showed down-regulation of tissue inhibitor of metalloproteinase-3, an endogenous inhibitor of TACE, and an increase in soluble TNF-α. A TACE inhibitor abrogated EGFR ligand-dependent keratinocyte proliferation and VEGF production in vitro, suggesting that TACE was involved in both epidermal hyperplasia and angiogenesis during psoriasis development. These results strongly suggest that TACE contributes to the development of psoriatic lesions through releasing two kinds of psoriasis mediators, TNF-α and EGFR ligands. Therefore, TACE could be a potential therapeutic target for the treatment of psoriasis.
Tong, Lana X; Wu, Shaowei; Li, Tricia; Qureshi, Abrar A; Giovannucci, Edward L; Cho, Eunyoung
Background Metabolic syndrome has been associated with both gallstones and psoriasis, suggesting a potential biological linkage between gallstones and psoriasis. However, the association between gallstones and psoriasis has not yet been studied. Objective To investigate the association between gallstones and psoriasis. Methods Design Prospective cohort study. Setting Nurses' Health Study II (1991-2005). Participants 89,230 women aged 25 to 42 years who were free of psoriasis at baseline and responded to a 2005 follow-up questionnaire regarding their diagnosis of psoriasis. Main Outcomes and Measures Relative risk (RR) of developing psoriasis or psoriatic arthritis (PsA), which were self-reported and validated by supplemental questionnaires. Results In this population of women, 2,206 participants had gallstones confirmed by a history of cholecystectomy at baseline. A total of 642 individuals had a diagnosis of incident psoriasis, of which 157 had concomitant PsA. After adjusting for known risk factors of psoriasis besides body mass index (BMI), a baseline history of cholecystectomy-confirmed gallstones was associated with increased risk of psoriasis (multivariate-adjusted RR = 2.20, 95% CI: 1.56, 3.10) and concomitant PsA (multivariate-adjusted RR = 4.41, 95% CI: 2.70, 7.18). After additionally adjusting for BMI, the fully-adjusted RRs associated with a history of cholecystectomy-confirmed gallstones were 1.70 (95% CI: 1.20,2.41) for psoriasis and 2.96 (95% CI: 1.80, 4.89) for PsA. Conclusions and Relevance Personal history of gallstones was associated with an increased risk of psoriasis and PsA, independent of obesity in a cohort of US women. PMID:25307342
Indhumathi, S; Rajappa, Medha; Chandrashekar, Laxmisha; Ananthanarayanan, P H; Thappa, D M; Negi, V S
Psoriasis is a multi-factorial heritable prototypical immune-mediated inflammatory disease, characterized by hyperproliferation of keratinocytes in the affected skin. There are no studies till date, to the best of our knowledge, about the association of HLA-C*06, the risk variant in the PSORS 1 susceptibility locus that confers the greatest risk for early onset of psoriasis, with the disease in South Indian Tamil patients with psoriasis. The present study was performed to determine the association of HLA-C*06 with psoriasis in the South Indian Tamil ethnic population. Three hundred and fifty-five cases of psoriasis and 360 healthy controls were included in this case-control study. Severity grading according to psoriasis area severity index (PASI) scoring was done in patients with psoriasis. PCR assays with sequence-specific primers (PCR-SSP) were used for specific detection of HLA-C*06. PCR with analysis of restriction fragment length polymorphism was used to distinguish between patients homozygous and heterozygous for HLA-C*06. We observed that those with the HLA-C*06-positive allele had a 3.5 times higher odds of having psoriasis compared to those without, [p < 0.0001, OR 3.5, 95 % CI (2.59-4.79)]. Among cases of psoriasis, it was noted that there was a significant association of HLA-C*06 positivity with female psoriatics [p = 0.006; OR 2.49 (1.28-4.87)] and early age of onset of psoriasis [p = 0.002; OR 2.04 (1.29-3.20)]. Our results suggest that the HLA-C*06 allele is positively associated with susceptibility to psoriasis, female gender and early onset of psoriasis in South Indian Tamils.
Atakan, Nilgün; Yazici, Ayça Cordan; Özarmağan, Güzin; İnalÖz, Hüseyin Serhat; Gürer, Mehmet Ali; Sabuncu, İlham; Kİremİtçİ, Ümmühan; Alper, Sibel; Aytekİn, Sema; Arican, Özer; Polat, Mualla; Doğan, Sibel; Aldİnç, Emre
Psoriasis is a common inflammatory disease that has a severe impact on quality of life. There is lack of data regarding epidemiological and clinical features of psoriasis patients in Turkey, a country with a population of 76 million. The aim of this study was to define the demographic and clinical characteristics, quality of life and treatment patterns of psoriasis patients in Turkey. A cross-sectional observational study was conducted at 40 centers, chosen from geographically diverse locations in Turkey. Patients diagnosed with psoriasis were assessed by investigators who were specialists of dermatology using standardized study questionnaire forms. Dermatology Life Quality Index (DLQI) and EuroQol-5 dimension (EQ-5D) forms were also filled out by each patient. 3971 psoriasis patients were included in this study. 24.2% of plaque psoriasis patients had moderate to severe psoriasis (Psoriasis Area and Severity Index, ≥10). Mean DLQI was 7.03 ± 6.02; quality of life was moderately, severely or very severely affected in 49.2% of patients. The most severely affected component of EQ-5D was anxiety/depression. Among all patients, 22.9% were not receiving any treatment, 39.8% were receiving only topical treatment, 11.5% were on phototherapy, 26.1%, were taking conventional systemic agents and 4.1% were on a biologic treatment. 31.3% of psoriasis patients with moderate to severe disease were treated with only topical agents and only 30.5% of moderate to severe psoriasis patients were receiving systemic therapy. Moderate to severe psoriasis has a considerable impact on quality of life. Treatment in Turkey of patients with moderate to severe psoriasis is insufficient.
Eskin-Schwartz, Marina; Basel-Vanagaite, Lina; David, Michael; Lagovsky, Irina; Ben-Amitai, Dan; Smirin-Yosef, Pola; Atzmony, Lihi; Hodak, Emmilia
Psoriasis is a multifactorial chronic inflammatory disease. Monogenic psoriasis has been described recently, including dominantly inherited plaque and generalized pustular types, related to activating mutations in the CARD14 gene. We describe here a family with CARD14-related psoriasis, exhibiting an extreme variability of clinical presentation (from mild plaque-type to generalized pustular psoriasis) and early disease onset. The affected family members harboured the c.349G>A [p.Gly117Ser] mutation in CARD14, which has not previously been linked to pustular psoriatic phenotype. Furthermore, most severely affected individuals carried 3 additional CARD14 coding region polymorphisms (rs2066964, rs34367357 and rs11652075), suggesting their possible effect on disease expression. Early-onset psoriasis co-segregated with the HLA-C*0602, indicating that HLA-C*0602 could potentially modulate the time of disease onset. In summary, this paper describes a family with CARD14-related psoriasis and discusses the possible influence of the specific haplotypes on intra-familial variation in the clinical phenotype of the disease.
Siow, K Y; Safdar, N A Mohd; Chong, K H; Chua, K B
A prospective clinical study of 181 patients with psoriasis seen in Seremban General Hospital showed the incidence of psoriasis among dermatology outpatients was 2.15%. A significantly higher proportion of male patients were affected, with a male to female ratio of 1.7:1. Within the racial groups; 63 were Malays, 37 Chinese, and 81 Indians. There was a significantly higher proportion of Indians affected as compared with the races. The mean age of patients in this study was 43.7 years old but the mean age of onset of psoriasis in these patients was 33.1 years old. Thirty-one (17.1%) patients gave a positive family history of psoriasis and the mean age of onset of psoriasis was lower (29.3 years old) for patients with a positive family history. Plaque psoriasis was the commonest type of clinical presentation with the scalp being the commonest site affected. Psoriatic arthropathy was seen in 35 (19.3%) patients. Ninety-five (52.5%) patients gave a positive history of factors exacerbating their pre-existing disease and stress was singled out as the most common exacerbating factor.
Bacaksiz, Ahmet; Erdogan, Ercan; Sonmez, Osman; Sevgili, Emrah; Tasal, Abdurrahman; Onsun, Nahide; Topukcu, Bugce; Kulaç, Beytullah; Uysal, Omer; Goktekin, Omer
Background Psoriasis vulgaris is one of the most prevalent chronic, inflammatory skin disorders. Patients with psoriasis have excess risk of essential hypertension. Masked hypertension (MH), defined as normal office blood pressure (BP) with elevated ambulatory BP (ABPM), has been drawing attention recently due to its association with increased risk of developing sustained hypertension, cardiovascular morbidity, and mortality. The aim of this study was to investigate the prevalence of MH in psoriatic patients. Material/Methods On hundred and ten middle-aged, normotensive, non-obese patients with psoriasis vulgaris and 110 age- and sex-matched normotensive controls were included in the study. ABPM was performed in all participants over a 24-h period. The clinical severity of the disease was determined according to current indexes. Results The prevalence of MH among subjects with psoriasis vulgaris was 31.8% and increased compared to control subjects (p<0.01). Predictors of MH in patients with psoriasis vulgaris were detected as male sex, smoking, obesity-related anthropometric measures, and disease activity. Male sex, waist circumference, and diffuse psoriatic involvement were detected as independent predictors of MH. Conclusions MH is prevalent in patients with psoriasis vulgaris. Assessment with ABPM and close follow-up for development of hypertension is reasonable. PMID:23800996
Zhang, L; Li, Y; Yang, X; Wei, J; Zhou, S; Zhao, Z; Cheng, J; Duan, H; Jia, T; Lei, Q; Huang, J; Feng, C
Psoriasis is one of the most common inflammatory skin conditions affecting both children and adults. Growing evidence indicates that T-helper 17 (Th17) cells and CD4(+) CD25(+) regulatory T (Treg) cells play an important role in the pathogenesis of psoriasis. However, the relationship between Th17 and Treg cells and their dynamic variations in paediatric psoriasis remain unclear. In this study, we found that both Th17 and FoxP3(+) Treg cells and the ratio of Th17 to Treg cell frequency in the peripheral circulation were increased in patients with paediatric psoriasis and were positively correlated with the disease severity. The function of Treg to suppress CD4(+) CD25(-) T cell proliferation and IFN-γ secretion was impaired during the onset of psoriasis. After disease remission, both the Th17 and Treg cell frequencies were decreased, and the suppressive function of the Treg cells was obviously restored. However, neither Treg cells from the disease onset nor those after remission can regulate IL-17 secretion by CD4(+) T cells. These findings will further our understanding of the associations between Th17 and Treg cells in paediatric psoriasis and their influence on disease severity.
Background Psoriasis is a chronic inflammatory skin disease with a genetic basis. Its ill-defined causes make it difficult to diagnose. This study aims to develop a diagnostic checklist for psoriasis classification in the context of traditional Chinese medicine. Methods A Delphi study was conducted with three rounds by a panel of 16 dermatology experts to develop a checklist for traditional Chinese medicine symptoms and signs of psoriasis. Dermatology experts in psoriasis research, nine in Yunnan and seven in Beijing, were selected as the expert panel. The initial list of symptoms and signs in psoriasis was developed by reviewing the literature retrieved from Chinese and English journals. Experts rated each item of the list on a 5-point Likert scale. The list was revised and re-evaluated in the same manner for a total of 3 rounds before it was finalized. Results One hundred and thirty items were extracted from the literature review. After three rounds of expert ratings, 96 items were retained with eight domains: color, type and shape of skin lesion, physical expression, tongue and coating, pulse, associated factors, and living environment. Intraclass correlation coefficient and Kappa statistics indicated an inter-rater agreement in the final checklist. Conclusion A checklist containing 96 items in 8 domains was developed for psoriasis diagnosis using traditional Chinese medicine symptoms and signs. PMID:23663296
Hanley, Tessa L; Yiu, Zenas ZN
Developments in the understanding of the immunopathogenesis of psoriasis have identified interleukin (IL)-17 as the key proinflammatory cytokine in the pathogenesis of plaque psoriasis, with the consequent development of drugs that target this cytokine or associated receptors. Ixekizumab is a subcutaneously administered humanized monoclonal antibody, which acts to neutralize IL-17A. This article reviews the role of IL-17 in the pathogenesis of psoriasis, the biological and pharmacokinetics of ixekizumab and the safety profile and the clinical efficacy of ixekizumab in Phase III clinical trials. Phase III clinical trials of ixekizumab have so far demonstrated excellent early clinical efficacy, with a comparable safety profile to the existing biologic therapies for psoriasis. To further assess its position in the treatment algorithm for psoriasis, a further head to head RCT with secukinumab could be established, alongside comparative effectiveness studies from observational research. In addition, trials are needed to assess its role in those with tumor necrosis factor inhibitors/ustekinumab resistant disease. However, it is clear that the IL-17 antagonists have changed the benchmark for clinical efficacy, and it is likely that ixekizumab along with the other IL-17 antagonists are set to achieve a new standard of care in the treatment of moderate to severe plaque psoriasis. PMID:28352182
Quaranta, Maria; Knapp, Bettina; Garzorz, Natalie; Mattii, Martina; Pullabhatla, Venu; Pennino, Davide; Andres, Christian; Traidl-Hoffmann, Claudia; Cavani, Andrea; Theis, Fabian J; Ring, Johannes; Schmidt-Weber, Carsten B; Eyerich, Stefanie; Eyerich, Kilian
Previous attempts to gain insight into the pathogenesis of psoriasis and eczema by comparing their molecular signatures were hampered by the high interindividual variability of those complex diseases. In patients affected by both psoriasis and nonatopic or atopic eczema simultaneously (n = 24), an intraindividual comparison of the molecular signatures of psoriasis and eczema identified genes and signaling pathways regulated in common and exclusive for each disease across all patients. Psoriasis-specific genes were important regulators of glucose and lipid metabolism, epidermal differentiation, as well as immune mediators of T helper 17 (TH17) responses, interleukin-10 (IL-10) family cytokines, and IL-36. Genes in eczema related to epidermal barrier, reduced innate immunity, increased IL-6, and a TH2 signature. Within eczema subtypes, a mutually exclusive regulation of epidermal differentiation genes was observed. Furthermore, only contact eczema was driven by inflammasome activation, apoptosis, and cellular adhesion. On the basis of this comprehensive picture of the pathogenesis of psoriasis and eczema, a disease classifier consisting of NOS2 and CCL27 was created. In an independent cohort of eczema (n = 28) and psoriasis patients (n = 25), respectively, this classifier diagnosed all patients correctly and also identified initially misdiagnosed or clinically undifferentiated patients.
Picciani, Bruna Lavinas Sayed; Domingos, Tábata Alves; Teixeira-Souza, Thays; dos Santos, Vanessa de Carla Batista; Gonzaga, Heron Fernando de Sousa; Cardoso-Oliveira, Juliana; Gripp, Alexandre Carlos; Dias, Eliane Pedra; Carneiro, Sueli
Geographic tongue is a chronic, inflammatory, and immune-mediated oral lesion of unknown etiology. It is characterized by serpiginous white areas around the atrophic mucosa, which alternation between activity, remission and reactivation at various locations gave the names benign migratory glossitis and wandering rash of the tongue. Psoriasis is a chronic inflammatory disease with frequent cutaneous involvement and an immunogenetic basis of great importance in clinical practice. The association between geographic tongue and psoriasis has been demonstrated in various studies, based on observation of its fundamental lesions, microscopic similarity between the two conditions and the presence of a common genetic marker, human leukocyte antigen (HLA) HLA-C*06. The difficulty however in accepting the diagnosis of geographic tongue as oral psoriasis is the fact that not all patients with geographic tongue present psoriasis. Some authors believe that the prevalence of geographic tongue would be much greater if psoriatic patients underwent thorough oral examination. This study aimed to develop a literature review performed between 1980 and 2014, in which consultation of theses, dissertations and selected scientific articles were conducted through search in Scielo and Bireme databases, from Medline and Lilacs sources, relating the common characteristics between geographic tongue and psoriasis. We observed that the frequency of oral lesions is relatively common, but to establish a correct diagnosis of oral psoriasis, immunohistochemical and genetic histopathological analyzes are necessary, thus highlighting the importance of oral examination in psoriatic patients and cutaneous examination in patients with geographic tongue. PMID:27579734
Papagrigoraki, Anastasia; Del Giglio, Micol; Cosma, Chiara; Maurelli, Martina; Girolomoni, Giampiero; Lapolla, Annunziata
Psoriasis is frequently associated with metabolic comorbidities. Advanced glycation end products (AGEs) are highly oxidant, biologically active compounds that accumulate in tissues in association with hyperglycaemia, hyperlipidaemia and oxidative stress. This is a cross-sectional case-control study involving 80 patients with mild/severe psoriasis and 80 controls matched for age, sex and body mass index (40 with severe eczema, 40 healthy individuals). Patients and healthy individuals with a smoking habit, diabetes, dyslipidaemia, hypercholesterolaemia, hypertension or who were under systemic treatment were excluded from the study. Skin AGEs were measured in normal-appearing skin by a standard fluorescence technique, and blood AGEs (total AGEs, pentosidine and AGEs receptor) by enzyme-linked immunosorbent assay. Levels of cutaneous AGEs (p < 0.04), serum AGEs (p < 0.03) and pentosidine (p < 0.05) were higher in patients with severe psoriasis. Cutaneous AGEs correlated well with serum AGEs (r = 0.93, p < 0.0001) and with Psoriasis Area and Severity Index score (r = 0.91, p < 0.0001). Receptor levels were lower (p < 0.001) in severe psoriasis, and inversely correlated with disease severity (r = -0.71, p < 0.0002). Patients with severe psoriasis have accumulation of skin and serum AGEs, independent of associated metabolic disorders.
Zuo, Xianbo; Sun, Liangdan; Yin, Xianyong; Gao, Jinping; Sheng, Yujun; Xu, Jinhua; Zhang, Jianzhong; He, Chundi; Qiu, Ying; Wen, Guangdong; Tian, Hongqing; Zheng, Xiaodong; Liu, Shengxiu; Wang, Wenjun; Li, Weiran; Cheng, Yuyan; Liu, Longdan; Chang, Yan; Wang, Zaixing; Li, Zenggang; Li, Longnian; Wu, Jianping; Fang, Ling; Shen, Changbing; Zhou, Fusheng; Liang, Bo; Chen, Gang; Li, Hui; Cui, Yong; Xu, Aie; Yang, Xueqin; Hao, Fei; Xu, Limin; Fan, Xing; Li, Yuzhen; Wu, Rina; Wang, Xiuli; Liu, Xiaoming; Zheng, Min; Song, Shunpeng; Ji, Bihua; Fang, Hong; Yu, Jianbin; Sun, Yongxin; Hui, Yan; Zhang, Furen; Yang, Rongya; Yang, Sen; Zhang, Xuejun
Genome-wide association studies (GWASs) have reproducibly associated ∼40 susceptibility loci with psoriasis. However, the missing heritability is evident and the contributions of coding variants have not yet been systematically evaluated. Here, we present a large-scale whole-exome array analysis for psoriasis consisting of 42,760 individuals. We discover 16 SNPs within 15 new genes/loci associated with psoriasis, including C1orf141, ZNF683, TMC6, AIM2, IL1RL1, CASR, SON, ZFYVE16, MTHFR, CCDC129, ZNF143, AP5B1, SYNE2, IFNGR2 and 3q26.2-q27 (P<5.00 × 10(-08)). In addition, we also replicate four known susceptibility loci TNIP1, NFKBIA, IL12B and LCE3D-LCE3E. These susceptibility variants identified in the current study collectively account for 1.9% of the psoriasis heritability. The variant within AIM2 is predicted to impact protein structure. Our findings increase the number of genetic risk factors for psoriasis and highlight new and plausible biological pathways in psoriasis.
Ando, Noriko; Nakamura, Yuki; Aoki, Rui; Ishimaru, Kayoko; Ogawa, Hideoki; Okumura, Ko; Shibata, Shigenobu; Shimada, Shinji; Nakao, Atsuhito
There are several reports suggesting that the pathophysiology of psoriasis may be associated with aberrant circadian rhythms. However, the mechanistic link between psoriasis and the circadian time-keeping system, "the circadian clock," remains unclear. This study determined whether the core circadian gene, Clock, had a regulatory role in the development of psoriasis. For this purpose, we compared the development of psoriasis-like skin inflammation induced by the Toll-like receptor 7 ligand imiquimod (IMQ) between wild-type mice and mice with a loss-of-function mutation of Clock. We also compared the development of IMQ-induced dermatitis between wild-type mice and mice with a loss-of-function mutation of Period2 (Per2), another key circadian gene that inhibits CLOCK activity. We found that Clock mutation ameliorated IMQ-induced dermatitis, whereas the Per2 mutation exaggerated IMQ-induced dermatitis, when compared with wild-type mice associated with decreased or increased IL-23 receptor (IL-23R) expression in γ/δ+ T cells, respectively. In addition, CLOCK directly bound to the promoter of IL-23R in γ/δ+ T cells, and IL-23R expression in the mouse skin was under circadian control. These findings suggest that Clock is a novel regulator of psoriasis-like skin inflammation in mice via direct modulation of IL-23R expression in γ/δ+ T cells, establishing a mechanistic link between psoriasis and the circadian clock.
Nyunt, Wint Wint Thu; Low, Wah Yun; Ismail, Rokiah; Sockalingam, Sargunan; Min, Aung Ko Ko
Psoriasis is a chronic dermatological disorder that has a negative impact on quality of life (QoL). This hospital-based cross-sectional study determined factors associated with health-related QoL (HRQoL) impairment in adult psoriasis patients. HRQoL was assessed using the Dermatology Life Quality Index (DLQI). Disease severity was assessed using the Psoriasis Area and Severity Index (PASI). A total of 223 patients, aged 18 to 83 years, were recruited. For 67 (30%) patients, psoriasis had very large to extremely large effect on their life (DLQI score = 11-30). The median DLQI score was 7 (interquartile range = 7). Factors significantly associated with severe impact on HRQoL (DLQI ≥ 10) were disease severity, single status, working status, sports activities, nail dystrophy, exposed area involvement, itch, disturbed sleep, stress, and infection. The factor predictive of severe impact of psoriasis on HRQoL was disease severity. A holistic approach in the management, including psychosocial issues, is absolutely crucial for the optimal care of psoriasis patients.
Cicora, Federico; Roberti, Javier
Organ transplant recipients may have skin diseases as a result of immunosuppression, but psoriasis is reported infrequently. This skin condition may be induced by immunosuppression imbalance. We present 2 cases of recurrent psoriasis in 2 kidney transplant patients with belatacept-based immunosuppressive regimens. Two years after transplant, upon suspicion of calcineurin inhibitor neurotoxicity in the first patient, tacrolimus was replaced with belatacept. The patient's neurological signs resolved but the patient presented with skin lesions compatible with psoriatic plaques, successfully treated with betamethasone dipropionate and hydrocortisone. The second patient had a history of obesity and dyslipidemia, left foot amputation, and psoriasis. He received a kidney transplant, and maintenance immunosuppression included prednisone, mycophenolate mofetil, and belatacept. At posttransplant month 15, the patient presented with cutaneous erythematosus, maculopapular, and desquamative lesions compatible with psoriasis, treated with betamethasone dipropionate. The belatacept-based immunosuppressive regimens were maintained and psoriasis resolved. Psoriasis is a potential complication in kidney recipients that may recur when belatacept is used and/or tacrolimus is withdrawn as it could have happened in the first patient. The characteristics of the second case may suggest that belatacept might not have been the inciting agent. Good results were obtained with topical treatment.
De Simone, Clara; Caldarola, Giacomo; Corbeddu, Marialuisa; Moro, Francesca; Tropea, Anna; Moretta, Gaia; Apa, Rosanna
Psoriasis is a common, chronic, relapsing immune-mediated inflammatory disease (IMID) of the skin. IMIDs are multifactorial diseases characterized by common molecular pathways leading to a systemic inflammation. Patients with an IMID are also at higher risk of developing co-morbidities, such as adverse pregnancy outcomes, than the general population. A higher rate of pregnancy complications have been seen in inflammatory bowel disease and rheumatoid arthritis. The data for psoriasis are inconsistent but it appears that women with moderate-to-severe psoriasis may also have an increased risk of poor pregnancy outcomes. The cause of this association is unknown, although it may be related to elevated proinflammatory cytokines such as IL-6 and TNF-α, the high prevalence of comorbidities and other unhealthy behaviours, or the high prevalence of polycystic ovary syndrome (PCOS). In a recent study, PCOS prevalence in a psoriatic cohort (n = 51) was higher than in non-psoriatic women (n = 102) (47% versus 11%), and women with PCOS and psoriasis had a greater probability of insulin resistance, hyperinsulinaemia, and dyslipidaemia as well as a more severe skin condition, than those with psoriasis alone. Further studies are necessary to clarify the impact of psoriasis on pregnancy and in particular if these effects are mediated by concomitant PCOS.
Kopp, I.; Augustin, M.; Banditt, K. B.; Boehncke, W. H.; Follmann, M.; Friedrich, M.; Huber, M.; Kahl, C.; Klaus, J.; Koza, J.; Kreiselmaier, I.; Mohr, J.; Mrowietz, U.; Ockenfels, H. M.; Orzechowski, H. D.; Prinz, J.; Reich, K.; Rosenbach, T.; Rosumeck, S.; Schlaeger, M.; Schmid-Ott, G.; Sebastian, M.; Streit, V.; Weberschock, T.; Rzany, B.
Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1–S126, 2006; or http://www.psoriasis-leitlinie.de). PMID:17497162
Picardi, A; Mazzotti, E; Gaetano, P; Cattaruzza, M S; Baliva, G; Melchi, C F; Biondi, M; Pasquini, P
The authors' aim was to investigate the role of stressful events, perceived social support, attachment security, and alexithymia in triggering exacerbations of diffuse plaque psoriasis. Inpatients experiencing a recent exacerbation of diffuse plaque psoriasis (N=33) were compared with inpatients with skin conditions believed to have a negligible psychosomatic component (N=73). Stressful events during the last year were assessed with Paykel's Interview for Recent Life Events. Attachment style, alexithymia, and perceived social support were assessed with the Experiences in Close Relationships questionnaire, the Toronto Alexithymia Scale, and the Multidimensional Scale of Perceived Social Support, respectively. Multiple logistic regression analysis was used to control for age, gender, education, marital status, and alcohol consumption. In relation to comparison subjects, the patients with psoriasis had lower perceived social support and higher attachment-related avoidance. Also, they were more likely to have high alexithymic characteristics. There were no differences between the patients with psoriasis and the comparison subjects in scores on the Experiences in Close Relationships anxiety scale, the total number of stressful events, and the number of undesirable, uncontrollable, or major events. Although caution should be applied in generalizing these findings to outpatients, this study suggests that alexithymia, attachment-related avoidance, and poor social support might increase susceptibility to exacerbations of diffuse plaque psoriasis, possibly through impaired emotional regulation. Several physiological mechanisms involving the neuroendocrine and the immune system might mediate the interplay between stress, personality, and diffuse plaque psoriasis.
Stawczyk-Macieja, Marta; Rębała, Krzysztof; Szczerkowska-Dobosz, Aneta; Wysocka, Joanna; Cybulska, Lidia; Kapińska, Ewa; Haraś, Agnieszka; Miniszewska, Paulina; Nowicki, Roman
Psoriasis genetic background depends on polygenic and multifactorial mode of inheritance. As in other complex disorders, the estimation of the disease risk based on individual genetic variants is impossible. For this reason, recent investigations have been focused on combinations of known psoriasis susceptibility markers in order to improve the disease risk evaluation. Our aim was to compare psoriasis genetic risk score (GRS) for five susceptibility loci involved in the immunological response (HLA-C, ERAP1, ZAP70) and in the skin barrier function (LCE3, CSTA) between patients with chronic plaque psoriasis (n = 148) and the control group (n = 146). A significantly higher number of predisposing alleles was observed in patients with psoriasis in comparison to healthy individuals (6.1 vs. 5.2, respectively; P = 8.8×10−7). The statistical significance was even more profound when GRS weighted by logarithm odds ratios was evaluated (P = 9.9×10−14). Our results demonstrate the developed panel of five susceptibility loci to be more efficient in predicting psoriasis risk in the Polish population and to possess higher sensitivity and specificity for the disease than any of the markers analyzed separately, including the most informative HLA-C*06 allele. PMID:27658291
Wu, Shaowei; Cho, Eunyoung; Li, Wenqing; Grodstein, Francine; Qureshi, Abrar A
Previous studies suggest that hormonal factors modulate the natural course of psoriasis in women. However, the association of hormonal factors with psoriasis risk has not been assessed using prospective data. We carried out a thorough prospective analysis on the topic in 163,763 women in the Nurses' Health Study I and II. Participants provided information on age at menarche, parity, menopause status, and exogenous hormone use (oral contraceptive and postmenopausal hormone therapy) over the follow-up. We ascertained 1,253 incident psoriasis cases over 2 million person-years. Psoriasis risk appeared to be higher in women with always irregular menstrual cycles in adulthood (multivariate-adjusted hazard ratio=1.32, 95% CI: 1.01-1.73, compared with regular cycles) and surgical menopause (hazard ratio=1.19, 95% CI: 1.01-1.40, compared with natural menopause). Hormone therapy had suggestive but insignificant associations with psoriasis risk. Our results suggest little evidence for hormonal factors and risk of psoriasis in women that need further investigation.
Tang, Tony Yuqi
Mono- or combine immunosuppressants are commonly used for psoriasis; however the side effect caused by potent systemic immunosuppressants frequently incurred; moreover the inflammation flares up shortly after immunosuppressants are discontinued. An alternative nonimmunosuppressive therapy was introduced to psoriasis subjects. A retrospective observational study consisted of 1583 psoriasis patients who were treated with Herose Psoria capsule 1440 mg three times daily at two clinical centres, one in China, the other in Singapore, from 1 January 2000 to 1 January 2011. Psoriasis lesion evolution was photographed at monthly visit, and efficacy and safety were assessed using psoriasis area severity index PASI score grading, renal and liver function testing, and adverse event reporting and supplemented by information obtained during targeted telephone interviews. The effectiveness of Herose on psoriasis was inversely associated to prior immunosuppressants exposure (r = 0.9154), significant improvements occurred in non-immunosuppressants subjects, and complete clearance was achieved in 8 months (87.5%, 14 of 16); the wavelike evolution of psoriatic lesion appeared in prior immunosuppressants subjects. PMID:22287957
Takahashi, Hidetoshi; Iinuma, Shin; Honma, Masaru; Iizuka, Hajime
Psoriasis is a chronic inflammatory skin disease, which may be associated with metabolic syndrome accompanied by cardio- and cerebrovascular diseases. We investigated the relation between serum C-reactive protein (CRP) and cardio- and cerebrovascular diseases in Japanese psoriasis vulgaris patients. Ninety-seven psoriasis vulgaris patients and 79 healthy controls were assessed for serum CRP levels by immunoturbidimetry. The data were analyzed in terms of Psoriasis Area and Severity Index (PASI) scores, and comorbidity of cardio- and cerebrovascular disease and metabolic syndrome. Serum CRP levels in psoriasis vulgaris patients were significantly higher than those of healthy controls. There was no significant difference between male and female CRP levels in either psoriasis or healthy controls. No correlation was detected between PASI scores and serum CRP levels, either. Psoriasis with cardio- and cerebrovascular disease showed significantly higher CRP levels compared with those without the diseases. Furthermore, psoriasis with metabolic syndrome showed significantly higher serum CRP levels than those without the metabolic syndrome. In conclusion, serum CRP level is increased in psoriasis, and may be a useful marker for the prediction of the future risk of cardio- and cerebrovascular disease.
Swindell, William R; Sarkar, Mrinal K; Liang, Yun; Xing, Xianying; Gudjonsson, Johann E
Transcriptome studies of psoriasis have identified robust changes in mRNA expression through large-scale analysis of patient cohorts. These studies, however, have analyzed all mRNA changes in aggregate, without distinguishing between disease-specific and nonspecific differentially expressed genes (DEGs). In this study, RNA-seq meta-analysis was used to identify (1) psoriasis-specific DEGs altered in few diseases besides psoriasis and (2) nonspecific DEGs similarly altered in many other skin conditions. We show that few cutaneous DEGs are psoriasis specific and that the two DEG classes differ in their cell type and cytokine associations. Psoriasis-specific DEGs are expressed by keratinocytes and induced by IL-17A, whereas nonspecific DEGs are expressed by inflammatory cells and induced by IFN-γ and tumor necrosis factor. Peripheral blood mononuclear cell-derived DEGs were more psoriasis specific than cutaneous DEGs. Nonetheless, peripheral blood mononuclear cell DEGs associated with major histocompatibility complex class I and natural killer cells were commonly downregulated in psoriasis and other autoimmune diseases (e.g., multiple sclerosis, sarcoidosis, and juvenile rheumatoid arthritis). These findings demonstrate "cross-disease" transcriptomics as an approach to gain insights into the cutaneous and noncutaneous psoriasis transcriptomes. This highlighted unique contributions of IL-17A to the cytokine network and uncovered a blood-based gene signature that links psoriasis to other diseases of autoimmunity.
Dalhoff, K; Faerber, P; Arnholdt, H; Sack, K; Strubelt, O
24 days after starting treatment of psoriasis with fumaric acid derivatives (0.8-1.0 g orally, plus unknown quantities locally) a 21-year-old woman developed acute oliguric renal failure with a rise of serum creatinine levels to 1094 mumol/l (12.4 mg/dl). Deterioration of renal function had been preceded by severe abdominal symptoms with nausea, vomiting and colicky pain. On admission to hospital she was dehydrated with hyponatraemia and hypokalaemia. There was glomerular microhaematuria, increased excretion of renal epithelia, and tubular proteinuria. Renal biopsy demonstrated acute tubular damage with vacuolization of proximal epithelia, dilated tubules and scattered necroses. After intermittent haemodialysis (13 courses over two weeks) renal function gradually recovered, as demonstrated at a follow-up examination four months after discharge.
Relhan, Vineet; Sinha, Surabhi; Khurana, Nita; Garg, Vijay K.
A 22 year old male psoriatic patient presented with multiple reddish scaly plaques all over body. After hematological and biochemical investigations the patient was started on oral methotrexate 15 mg weekly. PASI score at the start of treatment was 26.2. After 3 months PASI dropped to 11.5, the dose of methotrexate was tapered to 7.5mg weekly and the patient was maintained on this dose and kept under monthly follow up. Four months later, the patient presented with reddish to hyperpigmented raised firm nodules having a central crater over the healing plaques of psoriasis. Few lesions showed self resolution over a period of 6-12 weeks. Histopathology of the lesion confirmed it to be Keratoacanthoma. We believe the most likely etiologic factors for the multiple KAs in our patient could be a genetic susceptibility stimulated by multiple causes. PMID:23984234
Garber, Caren; Rosmarin, David; Nguyen, Bichchau; Goodarzi, Mahmoud; Shinagare, Shweta; Jessup, Chad; Madani, Abdulaziz; Au, Shiu-Chung; Hasanain, Afnan
Discrete papular lichen myxedematosus (DPLM), asubset of localized lichen myxedematosus, is a rarecutaneous mucinosis of unknown etiology. We reporta case of a 57-year-old woman with palmoplantarpsoriasis who developed DPLM 8 weeks after addingustekinumab to a long-term course of methotrexate.The patient had previously failed 2 prior tumor necrosisfactor (TNF) inhibitors, adalimumab and etanercept.This case demonstrates an association between TNFinhibitor and ustekinumab use in a psoriasis patientand localized lichen myxedematosus for the secondtime in the literature. The presented case is of interestbecause of the rare diagnosis of DPLM, especially inassociation with the start of the anti-IL 12/23 agentustekinumab. The appearance of DPLM in this settingsuggests a possible etiology for the disease.
Wcisło-Dziadecka, Dominika; Zbiciak-Nylec, Martyna; Brzezińska-Wcisło, Ligia; Mazurek, Urszula
Psoriasis is a chronic immunological skin disease and patients with this disorder typically experience a significant decrease in their quality of life. The disease is traditionally managed with topical and systemic agents (retinoids, ciclosporin A, methotrexate), but these treatment options are often long-term and their effects can be inconsistent and not ideal. The use of biological drugs in dermatological treatment is relatively new and began in the early 2000s. It should be noted that, in most countries, in order for biological treatment to be administered, specific criteria must be met. The current treatment options for psoriasis and psoriatic arthritis include tumour necrosis factor alpha (TNF-α) blockers, interleukin (IL)-12 and IL-23 inhibitors, T cell inhibitors and B cell inhibitors. These classes of biological drugs are characterised by protein structure as well as high molecular weight and their effectiveness is evaluated based on the Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) and the Dermatology Life Quality Index (DLQI). TNF-α antagonists are one such class of biological drugs which includes infliximad, etanercept and adalimumab. Infliximab is a chimeric protein that is administered via intravenous infusions as a monotherapy in psoriasis vulgaris. Etanercept is indicated for use in both psoriasis vulgaris and psoriatic arthritis and it is the only drug that can be used as a treatment for children under the age of 8 with psoriasis. The drug is administered subcutaneously. Finally, adalimumab is a fully human monoclonal antibody that neutralises both free and membrane-bound TNF-α and is used in the treatment of psoriasis vulgaris and psoriatic arthritis. This article reviews the latest research in the use of TNF-α for the treatment of moderate to severe psoriasis and psoriatic arthritis. The results of research in this field are promising and confirm the effectiveness and safety of biological drugs as dermatological treatments
Kragballe, K.; Reich, K.; Spuls, P.; Griffiths, C. E. M.; Nast, A.; Franke, J.; Antoniou, C.; Arenberger, P.; Balieva, F.; Bylaite, M.; Correia, O.; Daudén, E.; Gisondi, P.; Iversen, L.; Kemény, L.; Lahfa, M.; Nijsten, T.; Rantanen, T.; Reich, A.; Rosenbach, T.; Segaert, S.; Smith, C.; Talme, T.; Volc-Platzer, B.; Yawalkar, N.
Patients with moderate to severe psoriasis are undertreated. To solve this persistent problem, the consensus programme was performed to define goals for treatment of plaque psoriasis with systemic therapy and to improve patient care. An expert consensus meeting and a collaborative Delphi procedure were carried out. Nineteen dermatologists from different European countries met for a face-to-face discussion and defined items through a four-round Delphi process. Severity of plaque psoriasis was graded into mild and moderate to severe disease. Mild disease was defined as body surface area (BSA) ≤10 and psoriasis area and severity index (PASI) ≤10 and dermatology life quality index (DLQI) ≤10 and moderate to severe psoriasis as (BSA > 10 or PASI > 10) and DLQI > 10. Special clinical situations may change mild psoriasis to moderate to severe including involvement of visible areas or severe nail involvement. For systemic therapy of plaque psoriasis two treatment phases were defined: (1) induction phase as the treatment period until week 16; however, depending on the type of drug and dose regimen used, this phase may be extended until week 24 and (2) maintenance phase for all drugs was defined as the treatment period after the induction phase. For the definition of treatment goals in plaque psoriasis, the change of PASI from baseline until the time of evaluation (ΔPASI) and the absolute DLQI were used. After induction and during maintenance therapy, treatment can be continued if reduction in PASI is ≥75%. The treatment regimen should be modified if improvement of PASI is <50%. In a situation where the therapeutic response improved ≥50% but <75%, as assessed by PASI, therapy should be modified if the DLQI is >5 but can be continued if the DLQI is ≤5. This programme defines the severity of plaque psoriasis for the first time using a formal consensus of 19 European experts. In addition, treatment goals for moderate to severe disease were established
Sharma, Manju; Levenson, Corey; Clements, Ian; Castella, Paul; Gebauer, Kurt; Cox, Michael E.
Psoriasis, a chronic inflammatory skin disease marked by hyper proliferation and aberrant differentiation of keratinocytes, affects 2–3% of the world’s population. Research into the pathogenesis of psoriasis has been hampered by the lack of models that accurately reflect the biology of the psoriatic phenotype. We have previously reported that East Indian Sandalwood oil (EISO) has significant anti-inflammatory properties in skin models and hypothesized that EISO might provide therapeutic benefit to psoriasis patients due to its anti-inflammatory and anti-proliferative properties. Here we present interim results from an on-going proof-of-concept Phase 2 clinical trial in which topically applied EISO is demonstrating to be well tolerated and helpful in alleviating mild to moderate psoriasis symptoms. This led us to evaluate the ability of EISO to affect the psoriatic phenotype using MatTek Corporation reconstituted organotypic psoriatic and normal human skin models. EISO had no impact on the phenotype of the normal skin tissue model, however, EISO treatment of the psoriasis tissue model reverted psoriatic pathology as demonstrated by histologic characterization and expression of keratinocyte proliferation markers, Ki67 and psoriasin. These phenotypic affects correlated with suppressed production of ENA-78, IL-6, IL-8, MCP-1, GM-CSF, and IL-1β. Demonstration of the ability of EISO to abrogate these psoriasis symptoms in well-characterized in vitro psoriatic tissue models, supports the hypothesis that the clinically observed symptom alleviation is due to suppression of intrinsic tissue inflammation reactions in afflicted lesions. This study presents a systematic approach to further study the underlying mechanisms that cause psoriasis, and presents data supporting the potential of EISO as a new ethnobotanical therapeutic concept to help direct and accelerate the development of more effective therapies. PMID:28360856
Thom, Nicole; Ritchlin, Christopher T.; Zhang, Xiao; Reveille, John; Weisman, Michael H.
Objective To provide prevalence estimates for inflammatory back pain (IBP) and spondyloarthritis (SpA) in those subjects with psoriasis using 2009–2010 National Health and Nutrition Examination Survey (NHANES) data. Methods In the NHANES 2009–2010 sample set, 6,684 persons ages 20–69 years were screened for participation, and 5,103 answered questions regarding onset of back pain, location of pain, and functional limitations. Data set assembly and statistical analysis were performed using SASTM and SUDAAN software. SEs were estimated by Taylor series linearization. The equality of the prevalence estimates for selected variables was tested (univariately) at an alpha level of 0.05 using 2-sided Student’s t-test with appropriate degrees of freedom. Results A total of 148 persons had self-reported medically diagnosed psoriasis. The psoriasis group versus the nonpsoriasis group had a significantly higher prevalence of axial pain using the 3-month duration criterion (31.1% versus 18.9%; P = 0.04) and alternating buttock pain (7.2% versus 2.4%; P = 0.03) and more frequently met IBP criteria from Berlin criteria 7b and 8a (P = 0.04 and 0.02, respectively). The prevalence of SpA was significantly higher in the psoriasis group versus the nonpsoriasis group when using Amor or European Spondyloarthritis Study Group criteria (14.3% versus 1.5%; P < 0.001). Sudden onset of axial pain was significantly higher in the psoriasis group (23.3% versus 13.0%; P = 0.01). Conclusion There is a higher prevalence of lower axial pain, IBP, SpA, and alternating buttock pain associated with a prior diagnosis of psoriasis. These data may influence the way psoriasis patients are approached in primary care and specialty clinics. PMID:25469666
Yamamoto, T; Katayama, I; Nishioka, K
It has been recently hypothesized that superantigens, which stimulate T cells expressing particular T cell receptor Vbeta chain gene segments, play a precipitating or aggravating role in psoriasis. In this study, we investigated the peripheral blood mononuclear cell (PBMC) response of patients with psoriasis vulgaris to staphylococcal superantigens (staphylococcal enterotoxin A (SEA), SEB, and SEC1) and its relationship to clinical and laboratory findings. Cytokine secretion was assessed by ELISA in the supernatants of the cultured PBMCs stimulated with SEB. Results of 3H-TdR uptake showed that the PBMCs' response against SEB in patients with psoriasis vulgaris (34,468 +/- 6,455) (mean DPM SD) was significantly higher than that of normal subjects (22,756 +/- 5,780) (p < 0.005). The stimulation index (SI) of patients with psoriasis vulgaris (n = 37) (63.9 +/- 55) was significantly higher than that of normal subjects (n = 24) (26.0 +/- 23) (p < 0.005) and patients with atopic dermatitis (n = 10) (40.7 +/- 30) (p < 0.05). Similar results were obtained in response to SEA and SEC1. SI weakly correlated with the psoriasis area and severity index (PASI) score (r = 0.62) and the serum interleukin-6 (IL-6) concentration (r = 0.45). IL-2 and tumor necrosis factor (TNF-alpha) were secreted at a significantly increased level by PBMCs from psoriatic patients on incubation with SEB, after a 3 day culture period. A higher level of IL-6 was released by PBMCs stimulated with SEB in psoriatic patients than normal controls, however, the difference was not significant. These results raise the possibility that monocytes, as well as T cells, are markedly activated by staphylococcal superantigen in patients with psoriasis vulgaris, which may play a role in the triggering or aggravating of psoriasis mediated by secreted cytokines.
Henry, Alasdair L.; Kyle, Simon D.; Bhandari, Sahil; Chisholm, Anna; Griffiths, Christopher E. M.; Bundy, Christine
Background Psoriasis is a long-term immune-mediated inflammatory disorder mainly, but not only, affecting skin, and is associated with significant medical and psychological morbidity. Evidence suggests that sleep is disrupted in psoriasis, however high quality empirical evidence is lacking. Given the importance of sleep for health, characterisation of sleep disruption in psoriasis is an important goal. We therefore conducted a systematic review of the sleep-psoriasis literature. Methods Searches were conducted in Pubmed, SCOPUS and Web of Science from inception to May 2016. Studies were compared against inclusion/exclusion criteria and underwent a quality evaluation. Given the heterogeneity of studies, we conducted a narrative synthesis of the findings. Results Searches revealed 32 studies which met our predetermined inclusion/exclusion criteria. Whilst 93.7% of studies reported sleep disruption in this population, ranging from 0.05% to 85.4%, many had important methodological shortcomings. Over half of all quantitative studies (54.8%; 17/31) relied on non-validated measures, contributing to heterogeneity in study findings. In those that employed valid measures, assessing sleep was often not the primary objective. We frequently found the absence of adequate sample size calculations and poor statistical reporting. Conclusion This review showed that in psoriasis, reported sleep rates of sleep disturbance varied substantially. Most studies lacked a hypothesis driven research question and/or failed to use validated measures of sleep. We were unable to draw firm conclusions about the precise prevalence and nature of sleep disturbance within the psoriasis population. We offer suggestions to help advance understanding of sleep disturbance in psoriasis. PMID:27327082
Schrodi, Steven J
Evaluation of: Liu Y, Helms C, Liao W et al. A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci. PLoS Genet. 4, e1000041 (2008). Genome-wide association scans have delivered on their promise of revealing susceptibility polymorphisms underlying common diseases. This comprehensive psoriasis study by Liu and colleagues reports confirmation of previously identified genes (HLA-C, IL12B and IL23R), identifies several novel psoriasis loci and is the first to report psoriatic arthritis association on a genome-wide scale. Along with other recent studies, this work gives further evidence that IL-23-mediated signaling is a key component of both psoriasis and psoriatic arthritis pathogenesis. Importantly, this study provides evidence of a single-nucleotide polymorphism (SNP), 35 kb upstream of HLA-C, which is stronger than Cw 0602 - the variant traditionally attributed to the MHC-linked psoriasis-susceptibility effect. Within this region, the authors also discovered an independent SNP with very strong predisposing effects. SNPs in the COG6 region and the USP8-TNFAIP8l3 region are among the novel psoriasis associations reported. In addition, a region showing linkage on chromosome 1q demonstrated association in the epidermal differentiation complex. Four SNPs over a 439-kb region on chromosome 4q27, where KIAA1109, ADAD1 and two cytokine-encoding genes (IL2 and IL21) reside, exhibit intriguing correlation with psoriatic arthritis, although the signal strength is moderate. These results, while still preliminary, may substantially expand our knowledge of psoriasis and psoriatic arthritis genetics, opening new avenues of chronic inflammatory disease research.
Pang, Xiaowen; Lin, Kai; Liu, Wen; Zhang, Ping; Zhu, Sainan
Psoriasis is a chronic inflammatory skin disease that has been associated with abnormal lipid metabolism. To characterize the lipid profile in Chinese, 86 patients with psoriasis and 84 healthy control subjects were assessed. Compared with healthy controls, the fasting serum values of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) were lower in the patient group. Compared with vulgaris psoriasis, special types of psoriasis had even lower levels of HDL-C and ApoA-I. Considering the severity of psoriasis, the level of ApoA-I and HDL-C were also the only two serum lipid parameters decreased in the mild group compared to those in controls. In the moderate and the severe group, the values of TC, LDL-C, HDL-C and ApoA-I were all decreased compared to healthy control group. Further analysis indicated that the values of HDL-C and ApoA-I were significantly lower in the severe group compared to the moderate group. Correlation analysis indicated that the levels of HDL-C but not ApoA-I was negatively associated with the severity of the disease. Interestingly, when psoriasis was improved by treatment, the serum levels of TG, TC, HDL-C and ApoA-I were increased from the pre-treatment values. We conclude that abnormalities in serum lipid metabolism may play an important role in the pathogenesis of Chinese patients with psoriasis. PMID:26823881
Samarasekera, E J; Sawyer, L; Wonderling, D; Tucker, R; Smith, C H
The majority of people with psoriasis have localized disease, where topical therapy forms the cornerstone of treatment. We set out to summarize evidence on the relative efficacy, safety and tolerability of different topical treatments used in plaque psoriasis. We undertook a systematic review and meta-analyses of randomized trial data of U.K.-licensed topical therapies. The primary outcome was clear or nearly clear status stratified for (i) trunk and limbs; and (ii) scalp. Network meta-analyses allowed ranking of treatment efficacy. In total, 48 studies were available for trunk and limb psoriasis, and 17 for scalp psoriasis (22,028 patients in total); the majority included people with at least moderate severity psoriasis. Strategies containing potent corticosteroids (alone or in combination with a vitamin D analogue) or very potent corticosteroids dominated the treatment hierarchy at both sites (trunk and limbs, scalp); coal tar and retinoids were no better than placebo. No significant differences in achievement of clear or nearly clear status were observed between twice- and once-daily application of the same intervention or between any of the following: combined vitamin D analogue and potent corticosteroid (applied separately or in a single product), very potent corticosteroids, or potent corticosteroids (applied twice daily). Investigator and patient assessment of response differed significantly for some interventions (response rates to very potent corticosteroids: 78% and 39%, respectively). No significant differences were noted for tolerability or steroid atrophy, but data were limited. In conclusion, corticosteroids are highly effective in psoriasis when used continuously for up to 8 weeks and intermittently for up to 52 weeks. Coal tar and retinoids are of limited benefit. There is a lack of long-term efficacy and safety data available on topical interventions used for psoriasis.
Salek, M S; Finlay, A Y; Lewis, J J C; Sumner, M I
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.
Gönül, M; Keseroglu, H; Hacınecipoğlu, F
Methotrexate is extensively used in the treatment of psoriasis. Although safe and effective, its use may inadvertently lead to intoxication. We report a 50-year-old woman being treated with methotrexate for psoriasis who developed methotrexate intoxication after drinking beetroot juice as a herbal remedy. Patients should be warned about the potential adverse effects of herbal therapies during methotrexate treatment.
Leibovici, Vera; Ramot, Yuval; Siam, Rula; Siam, Ihab; Hadayer, Noa; Strauss-Liviatan, Nurith; Hochberg, Malka
There are discrepancies in the literature regarding the prevalence of tinea pedis in psoriasis. The aim of this investigation was to conduct a cross-sectional study of the prevalence of tinea pedis in psoriasis compared to atopic dermatitis patients and normal controls. We enrolled 232 psoriatic patients, 190 atopic dermatitis patients and 202 normal controls, between the years 2010 and 2013. The prevalence of tinea pedis was 13.8% in psoriasis patients, not significantly different from that in atopic dermatitis patients 8.4% (P = 0.092)), but significantly higher than in normal controls 7.4% (P = 0.043). Both gender and age affected the prevalence of tinea pedis in psoriasis and normal controls, while only age affected the prevalence of tinea pedis in atopic dermatitis. Regarding gender, there was higher prevalence of tinea pedis in men: 19.1% (P = 0.019) in psoriasis and 12.1% (P = 0.013) in normal controls. Age affected the prevalence of tinea pedis in normal controls (P < 0.001), psoriasis patients (P = 0.001) and atopic dermatitis patients (P = 0.001), with higher prevalence with increasing age. Trichophyton rubrum was the most common species in psoriasis (71.9%), atopic dermatitis (75.0%) and normal controls (73.3%). Our study found a relatively high prevalence of tinea pedis among psoriasis patients.
Fu, Dandan; Song, Xiangfeng; Hu, Hua; Sun, Min; Li, Zhanguo; Tian, Zhongwei
Psoriasis is a common chronic inflammatory and T cell-meditated skin disease. Runt-related transcription factor 3 (RUNX3), one of the runt‑domain family of transcription factors, has been reported to be a susceptibility gene for psoriasis. The present study was designed to delineate the role and underlying mechanism of RUNX3 involved in the differentiation of T helper (Th) 17 and Th22 cells in psoriasis. The results of the present study demonstrated that the expression of RUNX3 increased significantly in CD4‑positive (CD4+) T cells from patients with psoriasis, compared with healthy controls. In addition, increased levels of interleukin (IL)‑6, IL‑20 and IL‑22, and increased frequencies of Th17 and Th22 cells were found in the patients with psoriasis patients, compared with the healthy controls. It was also found that the overexpression of RUNX3 increased the levels of Th17‑ and Th22‑associated cytokines in the CD4+ T cells from the healthy controls. However, the inhibition of RUNX3 reduced the levels of the associated cytokines and decreased the frequency of Th17 and Th22 cells in the CD4+ T cells from the patients with psoriasis. Taken together, the present study suggested that RUNX3 regulated the differentiation of Th17 and Th22 cells in psoriasis, providing a promising therapeutic strategy for the treatment of psoriasis.
Rencz, Fanni; Brodszky, Valentin; Péntek, Márta; Balogh, Orsolya; Remenyik, Eva; Szegedi, Andrea; Holló, Péter; Kárpáti, Sarolta; Jókai, Hajnalka; Herszényi, Krisztina; Herédi, Emese; Szántó, Sándor; Gulácsi, László
Bevezetés: A psoriasis a leggyakoribb krónikus, szisztémás, immunmediált gyulladásos kórkép, amely elsősorban a bőrt és az ízületeket érintheti. Célkitűzés: Arthritis psoriaticával társuló középsúlyos és súlyos psoriasisos betegek életminőségének és betegségköltségeinek vizsgálata. Módszer: Két egyetemi bőrgyógyászati klinikán keresztmetszeti kérdőíves felmérést végeztek. Eredmények: A vizsgált 57 beteg (65% férfi) átlagéletkora 54,3±11,6 év, életminősége az EQ-5D indexszel mérve 0,48±0,4 volt. Az egy betegre jutó éves átlagköltség 2,56 millió Ft, amelyből 71% a biológiai terápiához kapcsolódó költség és 21% az indirekt költség. Az indirekt költség 95%-a, 506 ezer Ft/beteg/év a psoriasis miatti munkából való kiesés miatt jelentkezik. A szisztémás kezelésben nem részesülő (21%), a tradicionális szisztémás (32%) és a biológiai szisztémás terápiában részesülő (47%) betegek egy betegre jutó éves átlagköltsége sorrendben 493 ezer Ft, 513 ezer Ft és 4,84 millió Ft. Következtetések: A biológiai terápia szignifikáns életminőség-javulást eredményez. Mivel az arthritis psoriaticával társuló psoriasis-betegcsoportban a szisztémás kezelések mindkét kórképben hatásosak, ezért a terápiával elérhető egészségnyereség mérése egészség-gazdaságtani szempontból a két kórkép esetén együttesen is célszerű, mert a valós egészséghaszon nagyobb lehet, mintha csak az egyik kórképet vizsgáljuk. Orv. Hetil., 2014, 155(48), 1913–1921.
Finch, P W; Murphy, F; Cardinale, I; Krueger, J G
One of the biological characteristics of psoriasis is excessive flaking of the skin. This is directly related to the marked hyperplasia of epidermal keratinocytes and to incomplete epidermal differentiation. Keratinocyte growth factor (KGF), a potent mitogen for human keratinocytes, is expressed by stromal cells. Alterations in the KGF signaling pathway might account for the epidermal hyperplasia associated with psoriasis. To test this hypothesis, we investigated the expression of KGF and its receptor (KGFR) in psoriasis tissue. KGF and KGFR mRNA levels were found to be frequently elevated in psoriatic skin specimens as compared with normal skin. Increased KGF transcript expression was localized to the dermal layer of the involved skin specimen using in situ hybridization. In contrast, KGFR transcript and protein expression was localized to the basal layer of keratinocytes in normal skin and to the basal and suprabasal layers of the psoriatic epidermis, coincident with the expanded proliferative keratinocyte pool. To identify molecules that might regulate KGFR expression we investigated the effects of various pharmacological agents and cytokines on KGFR synthesis by keratinocytes. Phorbol ester, interleukin-6, interferon-gamma, and ultraviolet B (UVB) treatment all led to substantial down-regulation of KGFR expression. The down-regulation of KGFR synthesis by UVB suggests a possible mechanism for the antiproliferative action of this agent in the treatment of psoriasis. Taken together, these results suggest that increased KGFR-mediated signaling in keratinocytes in the lesional epidermis might account in part for the epidermal hyperplasia in psoriasis.
Glitzner, Elisabeth; Korosec, Ana; Brunner, Patrick M; Drobits, Barbara; Amberg, Nicole; Schonthaler, Helia B; Kopp, Tamara; Wagner, Erwin F; Stingl, Georg; Holcmann, Martin; Sibilia, Maria
Several subtypes of APCs are found in psoriasis patients, but their involvement in disease pathogenesis is poorly understood. Here, we investigated the contribution of Langerhans cells (LCs) and plasmacytoid DCs (pDCs) in psoriasis. In human psoriatic lesions and in a psoriasis mouse model (DKO* mice), LCs are severely reduced, whereas pDCs are increased. Depletion of pDCs in DKO* mice prior to psoriasis induction resulted in a milder phenotype, whereas depletion during active disease had no effect. In contrast, while depletion of Langerin-expressing APCs before disease onset had no effect, depletion from diseased mice aggravated psoriasis symptoms. Disease aggravation was due to the absence of LCs, but not other Langerin-expressing APCs. LCs derived from DKO* mice produced increased IL-10 levels, suggesting an immunosuppressive function. Moreover, IL-23 production was high in psoriatic mice and further increased in the absence of LCs. Conversely, pDC depletion resulted in reduced IL-23 production, and therapeutic inhibition of IL-23R signaling ameliorated disease symptoms. Therefore, LCs have an anti-inflammatory role during active psoriatic disease, while pDCs exert an instigatory function during disease initiation. PMID:25216727
Ishizaki, Masayuki; Muromoto, Ryuta; Akimoto, Toshihiko; Sekine, Yuichi; Kon, Shigeyuki; Diwan, Manish; Maeda, Hiroaki; Togi, Sumihito; Shimoda, Kazuya; Oritani, Kenji; Matsuda, Tadashi
Tyrosine kinase 2 (Tyk2), a member of the Jak kinase family, mediates signals triggered by various cytokines, which are related to the pathogenesis of psoriasis. In this study, we investigated the role of Tyk2 in IL-23-induced psoriasis-like skin inflammation. Tyk2(-/-) mice when injected with IL-23 showed significantly reduced ear skin swelling with epidermal hyperplasia and inflammatory cell infiltration compared with wild-type mice. In addition, Tyk2 deficiency reduced production of pro-inflammatory cytokines and psoriasis-relevant anti-microbial peptides. More noteworthy is that Tyk2 directly regulated IL-22-dependent inflammation and epidermal hyperplasia. Taken together with the inhibition of IL-23-induced inflammation by treatment with neutralizing antibodies against IL-17 or IL-22, Tyk2 participates in both IL-23 and IL-22 signal transduction to mediate psoriasis-like skin inflammation. On the basis of these findings, we demonstrated for the first time that a small-molecule Tyk2 inhibitor significantly inhibited IL-23-induced inflammation and cytokine production in the skin. These observations demonstrate the important role of Tyk2 in experimental skin inflammation and indicate the therapeutic potential of Tyk2 inhibition in human psoriasis.
Ozden, Müge G; Tekin, Nilgün S; Gürer, Mehmet A; Akdemir, Devrim; Doğramacı, Ciğdem; Utaş, Serap; Akman, Ayşe; Evans, Sibel E; Bahadır, Sevgi; Oztürkcan, Serap; Ikizoğlu, Güliz; Sendur, Neslihan; Köse, Osman; Bek, Yüksel; Yaylı, Savaş; Cantürk, Tayyar; Turanl, Ahmet Y
To analyze the effect of possible risk factors, including breastfeeding, on the development of childhood-onset psoriasis, a multicenter case-control study with prospective collection of data was performed. Using a standard questionnaire, personal and specific variables including family history of psoriasis, maternal and environmental tobacco smoke exposure, body mass index (BMI), exclusive and partial breastfeeding for at least 3 and 12 months, cow's milk intake before 1 year, birth delivery method, and stressful life events were collected during 2009 from 537 patients with psoriasis and 511 controls younger than 18. Overall, patients more frequently reported exposure to environmental tobacco smoke at home and stressful life events in the year preceding the diagnosis than controls. The odds ratios (OR) for smoking and stressful life events were 2.90 (95% confidence interval [CI]=2.27-3.78) and 2.94 (95% CI=2.28-3.79), respectively. In addition, children with psoriasis were more likely to have a higher BMI (>26) than controls (OR=2.52; 95% CI=1.42-4.49). High BMI, environmental tobacco smoke exposure at home, and stressful life events may influence the development of pediatric psoriasis.
Rafael, Adilia; Torres, Tiago
Psoriasis is a common, chronic and disabling skin disorder affecting approximately 2% of the population, associated with significant negative impact on the patient's quality of life. Approximately 80% of those affected with psoriasis have mild-to-moderate forms and are usually treated with topical therapy, whereas phototherapy and systemic therapies are used for those with severe disease. In the past three decades, the major advances in psoriasis therapy have been in systemic agents for the treatment of moderate-to-severe psoriasis, particularly new immunomodulatory and biological molecules, while topical therapies have remained relatively unchanged over the past decades. Indeed, topical corticosteroids and vitamin D3 analogs are still the gold standard of therapy for mild-to-moderate psoriasis. Thus, there is a need to develop new and more effective topical agents in the short and long term, with a better efficacy and safety profile than corticosteroids and vitamin D3 analogs. Over the past five years, investigation into topical therapy has expanded, with exciting new drugs being developed. Preliminary results of these emerging agents that selectively target disease-defining pathogenic pathways seem to be promising, although long-term and large-scale studies assessing safety and efficacy are still lacking. The aim of this article was to review the clinical and research data of some emerging topical agents, focusing on Janus kinase-signal transducer and activator of transcription and phosphodiesterase type 4 inhibitors, which are currently being investigated.
Kálmán, L János; Gonda, Xénia; Kemény, Lajos; Rihmer, Zoltán; Janka, Zoltán
Stress is considered as a major contributor to the development and exacerbation of psoriasis by a significant proportion of patients and dermatologists. As both stressor and its effects are subject-dependent, thus extremely difficult to measure, our understanding of the exact role of stress in disease development was limited for a long time. In the past decade several new studies were carried out which expanded our knowledge on the pathophysiologic processes linking stress to psoriasis via with their objective measurements and the applied new techniques. The authors review the current literature of both psychological (alexithymia, personality, affect) and biological (cortisol, epinephrine, neurogenic inflammation) factors influencing stress perception and response in psoriasis. Results of recent investigations support previous reports about the interaction between stress and psoriasis with objective evidence. Knowing how effective stress-reducing psychopharmacologic and psychotherapeutic interventions are in the treatment of psoriasis the authors hope that this review contributes to a wider acceptance of the psychosomatic attitude in everyday dermatologic practice.
Abbas, Ossama; Ammoury, Alfred; Abbadi, Mohammad; Malek, Medhat Abdel; Akkash, Laith; Al-Chakharah, Kamal; Al-Hamdi, Khalil; Al-Qarqaz, Firas; Al-Soudani, Abduljabbar; Al-Soudani, Nameer; Dandashle, Anwar; El-Sayed, Fouad; Ghafir, Yasser; Gargour, Nazek; Kabalan, Said; Kibbi, Abdul-Ghani; Oumeish, Isam; Tannous, Zeina; Tomb, Roland
Psoriasis vulgaris is a common chronic, inflammatory, multisystem disorder that affects approximately 1.5% to 3.4% of the population in the Middle East. The disease has an impact on the quality of life in a significant number of affected patients. The majority of patients (approximately 70%) have mild to moderate psoriasis that is manageable with topical agents, which generally show a high efficacy to safety ratio. Topical agents can be used alone when treating patients with limited disease or may be used as adjunctive therapy for patients with more extensive psoriasis undergoing systemic treatment. Treatment should also be customized to meet individual patients' needs. To optimize the topical treatment of psoriasis in the Levant and Iraq area, dermatology experts from Iraq, Jordan, Lebanon, Palestine, and Syria met and initiated a project to develop guidelines and recommendations for the topical management of psoriasis. The guidelines are based on literature evidence and experts' opinions. We present recommendations for the use of topical corticosteroids, vitamin D analogues, calcineurin inhibitors, tazarotene, salicylic acid, anthralin, and coal tar, as well as combination therapy, based on their efficacy and safety profiles.
de la Cruz, Claudia; de Carvalho, André V E; Dorantes, Gladys L; Londoño Garcia, Angela M; Gonzalez, Cesar; Maskin, Matías; Podoswa, Nancy; Redfern, Jan S; Valenzuela, Fernando; van der Walt, Joelle; Romiti, Ricardo
Latin American countries view biosimilar agents as an effective approach to curtail health-care expenditures while maintaining the safety and efficacy profile of their branded innovator comparators. To understand the complexities of the regulatory landscape and key therapeutic issues for use of biosimilars to treat moderate to severe psoriasis in Latin America, the International Psoriasis Council convened dermatology experts from Argentina, Brazil, Chile, Colombia and Mexico in October 2015 to review the definition, approval, marketing and future of biosimilars in each country and develop a consensus statement. The regulatory framework for marketing approval of biosimilars in Latin America is currently a mosaic of disparate, country-specific, regulatory review processes, rules and standards, with considerable heterogeneity in clarity and specificity. Regulations in Argentina, Brazil, Chile and Mexico have undergone multiple refinements whereas Colombia is finalizing draft guidelines. Verification of the similarity in quality, safety and efficacy of biosimilars to the innovator biologic remains a key challenge for policy makers and regulatory authorities. Other key regulatory challenges include: naming of agents and traceability, pharmacovigilance, extrapolation of indications, and interchangeability and substitution. An urgent need exists for more Latin American countries to establish national psoriasis registries and to integrate their common components into a multinational psoriasis network, thereby enhancing their interpretative power and impact. A Latin American psoriasis network similar to PSONET in Europe would assist health-care providers, pharmaceutical companies, regulators and patients to fully comprehend specific products being prescribed and dispensed and to identify potential regional trends or differences in safety or outcomes.
Zhou, Fusheng; Wang, Wenjun; Shen, Changbing; Li, Hui; Zuo, Xianbo; Zheng, Xiaodong; Yue, Min; Zhang, Cuicui; Yu, Liang; Chen, Mengyun; Zhu, Caihong; Yin, Xianyong; Tang, Mingjun; Li, Yongjiang; Chen, Gang; Wang, Zaixing; Liu, Shengxiu; Zhou, Yi; Zhang, Fengyu; Zhang, Weijia; Li, Caihua; Yang, Sen; Sun, Liangdan; Zhang, Xuejun
Psoriasis is a chronic hyperproliferative and inflammatory skin disease caused by the interplay of genetic and environmental factors. DNA methylation has been linked to psoriasis, but the manner in which this process contributes to the disease is not fully understood. In this study, we carried out a three-stage epigenome-wide association study to identify disease-associated differentially methylated sites using a combination of 262 skin and 48 peripheral blood mononuclear cell samples. We not only revealed genome-wide methylation patterns for psoriasis but also identified strong associations between the skin-specific DNA methylation of nine disease-associated differentially methylated sites and psoriasis (Wilcoxon ranked PBonferroni < 0.01; methylation level difference > 0.10). Further analysis revealed that these nine disease-associated differentially methylated sites were not significantly affected by genetic variations, supporting their remarkable contributions to disease status. The expression of CYP2S1, ECE1, EIF2C2, MAN1C1, and DLGAP4 was negatively correlated with DNA methylation. These findings will help us to better understand the molecular mechanism of psoriasis.
Bergboer, Judith G M; Zeeuwen, Patrick L J M; Schalkwijk, Joost
Psoriasis was until recently regarded as a T-cell-driven disease with presumed (auto)immune mechanisms as its primary cause. This view was supported by clinical data and genetic studies that identified risk factors functioning in adaptive and innate immunity, such as HLA-C*06, ERAP1, the IL-23 pathway, and NF-k B signaling. Candidate gene approaches and genome-wide association studies, however, have identified copy number polymorphisms of the b-defensin cluster and deletion of late cornified envelope (LCE) 3B and 3C genes (LCE3C_LCE3B-del) as psoriasis risk factors.As these genes are expressed in epithelial cells and not by the immune system, these findings may cause a change of paradigm for psoriasis, not unlike the reported filaggrin association that has profoundly changed the views on atopic dermatitis. In addition to genetic polymorphisms of the immune system, genetic variations affecting the skin barrier are likely to contribute to psoriasis. Recent studies have shown epistatic interactions involving HLA-C*06, ERAP1, and LCE3C_LCE3B-del, which makes psoriasis a unique model to investigate genetic and biological interactions of associated genes in a complex disease. We present a model for disease initiation and perpetuation, which integrates the available genetic, immunobiological, and clinical data.
Farhangian, Michael E; Feldman, Steven R
The five biologic agents approved for the treatment of psoriasis-etanercept, infliximab, adalimumab, ustekinumab, and secukinumab-have been transformative in the clinical management of severe forms of the disease. However, a significant number of patients fail to respond to these agents or experience a loss of efficacy over time, which may be attributable to the development of antidrug antibodies (ADAs). Increasing evidence, primarily in the context of rheumatoid arthritis or other chronic inflammatory diseases, suggests that concomitant administration of methotrexate may prevent or diminish the development of ADAs, thereby improving response rates. However, methotrexate is infrequently coadministered with biologic agents in patients with psoriasis, and the potential benefits of this strategy in the context of psoriasis are largely unexplored. In this review, we discuss clinical studies regarding the development and consequences of antibodies targeting biologic agents used in the treatment of psoriasis and present key findings describing the potential role of methotrexate as an inhibitor of immunogenicity. We also discuss clinical considerations pertaining to the use of methotrexate as a tool to reduce immunogenicity, and encourage further investigation into potential techniques to optimize this treatment approach in patients with psoriasis.
Duarte, Gleison Vieira; de Oliveira, Maria de Fátima S. P.; Follador, Ivonise; Silva, Thadeu Santo; de Carvalho Filho, Edgar Marcelino
BACKGROUND Psoriasis is an immune-mediated disease that manifests predominantly in the skin, although systemic involvement may also occur. Although associated comorbidities have long been recognized and despite several studies indicating psoriasis as an independent risk factor for cardiovascular events, little has been done in general medical practice regardind screening. In the United States, less than 50% of clinicians are aware of these recommendations. OBJECTIVE To identify the prevalence of these comorbidities in 296 patients followed up at a university dermatology clinic. METHODS Systematically investigated comorbidity frequencies were compared with general practitioners' registry frequencies. Clinical features correlated with comorbidities were also investigated. RESULTS High prevalences of systematically investigated comorbidities such as hypertension (30%) and dyslipidemia (26.5%) were documented. Conversely, data from general practitioners' records showed that 33% of dyslipidemia cases were undiagnosed and indicated possible underdiagnosis of some comorbidities. Furthermore, an association was found between: the number of comorbidities and psoriasis duration, age and high body mass index an association was found between the number of comorbidities and psoriasis duration, age, high body mass index, waist circumference or waist-to-hip ratio. (p<0.05). CONCLUSION Disease duration, age and high body mass index, waist circumference or waist-to-hip ratio are possible criteria for choosing which patients should be screened for comorbidities. Underdiagnosis of comorbidities by general practitioners highlights the need for a multidisciplinary approach in psoriasis management. PMID:28099594
Weng, Shu-Wen; Chen, Bor-Chyuan; Wang, Yu-Chiao; Liu, Chun-Kai; Chang, Ching-Mao
Traditional Chinese medicine (TCM) has long been used for patients with psoriasis. This study aimed to investigate TCM usage in patients with psoriasis. We analyzed a cohort of one million individuals representing the 23 million enrollees randomly selected from the National Health Insurance Research Database in Taiwan. We identified 28,510 patients newly diagnosed with psoriasis between 2000 and 2010. Among them, 20,084 (70.4%) patients were TCM users. Patients who were female, younger, white-collar workers and lived in urbanized area tended to be TCM users. The median interval between the initial diagnosis of psoriasis to the first TCM consultation was 12 months. More than half (N = 11,609; 57.8%) of the TCM users received only Chinese herbal medicine. Win-qing-yin and Bai-xian-pi were the most commonly prescribed Chinese herbal formula and single herb, respectively. The core prescription pattern comprised Mu-dan-pi, Wen-qing-yin, Zi-cao, Bai-xian-pi, and Di-fu-zi. Patients preferred TCM than Western medicine consultations when they had metabolic syndrome, hepatitis, rheumatoid arthritis, alopecia areata, Crohn's disease, cancer, depression, fatty liver, chronic airway obstruction, sleep disorder, and allergic rhinitis. In conclusion, TCM use is popular among patients with psoriasis in Taiwan. Future clinical trials to investigate its efficacy are warranted. PMID:27822287
Takeda, Yukimasa; Bui, Thi; Neil, Jessica; Rickard, David; Millerman, Elizabeth; Therrien, Jean-Philippe; Nicodeme, Edwige; Brusq, Jean-Marie; Birault, Veronique; Viviani, Fabrice; Hofland, Hans; Jetten, Anton M.; Cote-Sierra, Javier
Background Psoriasis is a chronic inflammatory skin disorder involving marked immunological changes. IL-17-targeting biologics have been successful in reducing the disease burden of psoriasis patients with moderate-to-severe disease. Unfortunately, the stratum corneum prevents penetration of large molecule weight proteins, including monoclonal antibodies. Thus, for the majority of psoriasis patients ineligible for systemic treatments, a small molecule targeting RORγt, the master regulator of IL-17 family cytokines, may represent an alternative topical medicine with biologic-like efficacy. Methods and Findings The preclinical studies described in this manuscript bridge the gap from bench to bedside to provide the scientific foundation for a compound entering clinical trials for patients with mild to moderate psoriasis. In addition to several ex vivo reporter assays, primary T cell cultures, and the imiquimod mouse model, we demonstrate efficacy in a newly developed human ex vivo skin assay, where Th17-skewed cytokine expression is induced from skin-resident immune cells. Importantly, the skin barrier remains intact allowing for the demonstration of topical drug delivery. With the development of this novel assay, we demonstrate potent compound activity in the target tissue: human skin. Finally, target engagement by this small molecule was confirmed in ex vivo lesional psoriatic skin. Conclusions Our work describes a progressive series of assays to demonstrate the potential clinical value of a novel RORγ inverse agonist small molecule with high potency and selectivity, which will enter clinical trials in late 2015 for psoriasis patients. PMID:26870941
Onsun, Nahide; Arda Ulusal, Hande; Su, Ozlem; Beycan, Ismet; Biyik Ozkaya, Dilek; Senocak, Mustafa
The aims of this study were to determine the prevalence of H. pylori seropositivity in patients with psoriasis, to evaluate the relationship between PASI (Psoriasis Area and Severity Index) scores and H. pylori infection, and to assess the impact of H. pylori infection on the response to treatment. A total of 300 patients with psoriasis and 150 non-psoriatic healthy controls were enrolled in the study. Patient PASI scores were recorded and H. pylori stool antigen tests performed in both patients and controls. Fifty patients with H. pylori infections were randomly assigned to one of two groups, one of which received acitretin with H. pylori treatment and the other acitretin alone. Statistical analyses were performed using chi-square and logistic regression tests. PASI scores were significantly higher in patients with H. pylori infections. Treatment aimed at eradicating H. pylori infection enhanced the effectiveness of acitretin therapy and shortened response times. Our results suggest that H. pylori infection plays a role in the severity of psoriasis, and that eradicating such infections enhances the effectiveness of psoriasis treatment.
Félix Garza, Zandra C.; Liebmann, Joerg; Born, Matthias; Hilbers, Peter A. J.; van Riel, Natal A. W.
Clinical investigations prove that blue light irradiation reduces the severity of psoriasis vulgaris. Nevertheless, the mechanisms involved in the management of this condition remain poorly defined. Despite the encouraging results of the clinical studies, no clear guidelines are specified in the literature for the irradiation scheme regime of blue light-based therapy for psoriasis. We investigated the underlying mechanism of blue light irradiation of psoriatic skin, and tested the hypothesis that regulation of proliferation is a key process. We implemented a mechanistic model of cellular epidermal dynamics to analyze whether a temporary decrease of keratinocytes hyper-proliferation can explain the outcome of phototherapy with blue light. Our results suggest that the main effect of blue light on keratinocytes impacts the proliferative cells. They show that the decrease in the keratinocytes proliferative capacity is sufficient to induce a transient decrease in the severity of psoriasis. To study the impact of the therapeutic regime on the efficacy of psoriasis treatment, we performed simulations for different combinations of the treatment parameters, i.e., length of treatment, fluence (also referred to as dose), and intensity. These simulations indicate that high efficacy is achieved by regimes with long duration and high fluence levels, regardless of the chosen intensity. Our modeling approach constitutes a framework for testing diverse hypotheses on the underlying mechanism of blue light-based phototherapy, and for designing effective strategies for the treatment of psoriasis. PMID:28184200
Totté, J E E; van der Feltz, W T; Bode, L G M; van Belkum, A; van Zuuren, E J; Pasmans, S G M A
Staphylococcus aureus might amplify symptoms in chronic inflammatory skin diseases. This study evaluates skin and mucosal colonization with S. aureus in patients with psoriasis, acne and rosacea. A systematic literature search was conducted. Both odds ratios (OR) for colonization in patients versus controls and the prevalence of colonization in patients are reported. Fifteen articles about psoriasis and 13 about acne (12 having a control group) were included. No study in rosacea met our inclusion criteria. For psoriasis, one study out of three controlled studies showed increased skin colonization (OR 18.86; 95 % confidence interval [CI] 2.20-161.99). Three out of the five studies that reported on nasal colonization showed significant ORs varying from 1.73 (95 % CI 1.16-2.58) to 14.64 (95 % CI 2.82-75.95). For acne one of the three studies that evaluated skin colonization reported a significant OR of 4.16 (95 % CI 1.74-9.94). A relation between nasal colonization and acne was not found. Limitations in study design and low sample sizes should be taken into consideration when interpreting the results. Colonisation with S. aureus seems to be increased in patients with psoriasis. This bacterial species, known for its potential to induce long-lasting inflammation, might be involved in psoriasis pathogenesis. Information on acne is limited. Prospective controlled studies should further investigate the role of S. aureus in chronic inflammatory skin diseases.
Ruszczak, Z; Ciborska, L; Kaszuba, A
The lymphocyte transformation test (LTT) was given to 20 healthy subjects and 43 patients with generalized psoriasis vulgaris: it was given right after stimulation with PHA (spontaneous) and after stimulation with allogenic and autogenic protein factor (NPF). NPF was isolated from secondary lysosome granules of peripheral blood neutrophils. The results were analyzed using computer statistic tests. No distinct differences were noticed between the spontaneous transformation test in psoriatic patients compared to the controls. After stimulation with PHA, the percentage of blast cells was significantly lower in patients with psoriasis. When allogenic and autogenic NPF was used for stimulation, the LTT values were significantly higher in the psoriasis group than in the control subjects. This fact points out the increase in sensitivity of lymphocytes to NPF in active psoriasis and the possibility of abnormal neutrophil-lymphocyte interactions in vivo. This phenomenon may be intensified when under the influence of bacterial or viral agents, or medicaments; the degranulation of secondary lysosome granules of neutrophils occurs, causing the release of NPF. These investigations support our opinion that psoriasis is a systemic disease and that NPF plays a considerable role in the psoriatic reaction.
Jakobsen, Maria; Stenderup, Karin; Rosada, Cecilia; Moldt, Brian; Kamp, Søren; Dam, Tomas N; Jensen, Thomas G; Mikkelsen, Jacob Giehm
Tumor necrosis factor-alpha (TNF-alpha) is upregulated in psoriatic skin and represents a prominent target in psoriasis treatment. The level of TNF-alpha-encoding mRNA, however, is not increased in psoriatic skin, and it remains unclear whether intervention strategies based on RNA interference (RNAi) are therapeutically relevant. To test this hypothesis the present study describes first the in vitro functional screening of a panel of short hairpin RNAs (shRNAs) targeting human TNF-alpha mRNA and, next, the transfer of the most potent TNF-alpha shRNA variant, as assessed in vitro, to human skin in the psoriasis xenograft transplantation model by the use of lentiviral vectors. TNF-alpha shRNA treatment leads to amelioration of the psoriasis phentotype in the model, as documented by reduced epidermal thickness, normalization of the skin morphology, and reduced levels of TNF-alpha mRNA as detected in skin biopsies 3 weeks after a single vector injection of lentiviral vectors encoding TNF-alpha shRNA. Our data show efficient lentiviral gene delivery to psoriatic skin and therapeutic applicability of anti-TNF-alpha shRNAs in human skin. These findings validate TNF-alpha mRNA as a target molecule for a potential persistent RNA-based treatment of psoriasis and establish the use of small RNA effectors as a novel platform for target validation in psoriasis and other skin disorders.
Villadsen, Louise S; Schuurman, Janine; Beurskens, Frank; Dam, Tomas N; Dagnaes-Hansen, Frederik; Skov, Lone; Rygaard, Jorgen; Voorhorst-Ogink, Marleen M; Gerritsen, Arnout F; van Dijk, Marc A; Parren, Paul W H I; Baadsgaard, Ole; van de Winkel, Jan G J
Psoriasis is a chronic inflammatory disease of the skin characterized by epidermal hyperplasia, dermal angiogenesis, infiltration of activated T cells, and increased cytokine levels. One of these cytokines, IL-15, triggers inflammatory cell recruitment, angiogenesis, and production of other inflammatory cytokines, including IFN-gamma, TNF-alpha, and IL-17, which are all upregulated in psoriatic lesions. To investigate the role of IL-15 in psoriasis, we generated mAb's using human immunoglobulin-transgenic mice. One of the IL-15-specific antibodies we generated, 146B7, did not compete with IL-15 for binding to its receptor but potently interfered with the assembly of the IL-15 receptor alpha, beta, gamma complex. This antibody effectively blocked IL-15-induced T cell proliferation and monocyte TNF-alpha release in vitro. In a human psoriasis xenograft model, antibody 146B7 reduced the severity of psoriasis, as measured by epidermal thickness, grade of parakeratosis, and numbers of inflammatory cells and cycling keratinocytes. These results obtained with this IL-15-specific mAb support an important role for IL-15 in the pathogenesis of psoriasis.
Danielsen, Kjersti; Wilsgaard, Tom; Olsen, Anne Olaug; Furberg, Anne-Sofie
Overweight is a proposed risk factor for psoriasis. How-ever, evidence from prospective studies is limited. The aim of this study was to investigate the association be-tween overweight, weight gain and risk of psoriasis, and potential synergism with smoking, within a population-based cohort including 8,752 individuals followed from 1994 up to 2008. There was a 32% increased odds of psoriasis from a body mass index (BMI) of 27 kg/m2, in multi-variable logistic regression analysis, further increasing to 43% at BMI 28 kg/m2, and to 71% at BMI ≥ 30 kg/m2 in non-smokers. There was a dose-response association between weight gain from age 25 years, with up to 90% higher odds of psoriasis from middle age, independent of weight category. There was no indication of a synergism between overweight and smoking, and no interaction with sex. Overweight and weight gain represent modifiable risk factors that may be targets for primary prevention of psoriasis.
Zhu, Jing; Bao, Xiaoqing; Zhang, Mei-Jue
Objective: To research epidermal cellular vegetal cycle and the difference of DNA content between pre and post Intravascular Low Level Laser Irradiation treatment of psoriasis. Method: 15 patients suffered from psoriasis were treated by intravascular low level laser irradiation (output power: 4-5mw, 1 hour per day, a course of treatment is 10 days). We checked the different DNA content of epidermal cell between pre and post treatment of psoriasis and 8 natural human. Then the percentage of each phase among the whole cellular cycle was calculated and the statistical analysis was made. Results: The mean value of G1/S phase is obviously down while G2+M phase increased obviously. T test P<0.05.The related statistical analysis showed significant difference between pre and post treatments. Conclusions: The Intravascular Low Level Laser Irradiation (ILLLI) in treatment of psoriasis is effective according to the research of epidermal cellular vegetal cycle and the difference DNA content of Intravascular Low Level Laser Irradiation between pre and post treatment of psoriasis
Sundarrajan, Sudharsana; Arumugam, Mohanapriya
Psoriasis is a chronic inflammatory disease of the skin with an unknown aetiology. The disease manifests itself as red and silvery scaly plaques distributed over the scalp, lower back and extensor aspects of the limbs. After receiving scant consideration for quite a few years, psoriasis has now become a prominent focus for new drug development. A group of closely connected and differentially co-expressed genes may act in a network and may serve as molecular signatures for an underlying phenotype. A weighted gene coexpression network analysis (WGCNA), a system biology approach has been utilized for identification of new molecular targets for psoriasis. Gene coexpression relationships were investigated in 58 psoriatic lesional samples resulting in five gene modules, clustered based on the gene coexpression patterns. The coexpression pattern was validated using three psoriatic datasets. 10 highly connected and informative genes from each module was selected and termed as psoriasis specific hub signatures. A random forest based binary classifier built using the expression profiles of signature genes robustly distinguished psoriatic samples from the normal samples in the validation set with an accuracy of 0.95 to 1. These signature genes may serve as potential candidates for biomarker discovery leading to new therapeutic targets. WGCNA, the network based approach has provided an alternative path to mine out key controllers and drivers of psoriasis. The study principle from the current work can be extended to other pathological conditions.
Malakouti, Mona; Jacob, Sharon E; Anderson, Nancy J
Psoriasis is a chronic inflammatory skin disease that has a negative impact on psychosocial well-being and cardiometabolic health. Treatment options for moderate-to-severe psoriasis have expanded with the development of interleukin-17 (IL-17) inhibitors, the first of which is now available – secukinumab. Secukinumab is a fully human monoclonal immunoglobulin G1 κ antibody that selectively inhibits the ligand IL-17A. In head-to-head studies, it is more effective than etanercept and ustekinumab, particularly in achieving Psoriasis Area and Severity Index (PASI) 90/100 and achieving PASI 50/75 as early as week 4. No head-to-head trials are available for comparison of adalimumab to secukinumab. Significant improvement in health care-related quality of life was also observed using the dermatology quality index in clinical studies. Safety data for secukinumab is comparable to available biologics. Specific safety concerns for the use of secukinumab include its use in patients with inflammatory bowel disease, reversible transient neutropenia, in those with a latex allergy, and the occurrence of mild to moderate oral or genital candidiasis. Secukinumab is an effective and safe treatment option that achieves high clearance rates up to PASI 90 and 100 as monotherapy in cases of moderate-to-severe psoriasis. It may be particularly helpful in patients with psoriasis who have formed antidrug antibodies or failed other biologic agents and in patients with psoriatic arthritis or ankylosing spondylitis. PMID:27785085
Dilek, Aziz Ramazan; Taşkın, Yakup; Erkinüresin, Taşkın; Yalçın, Ömer; Saral, Yunus
Introduction Histological changes of psoriasis include invasion of neutrophils into the epidermis and formation of Munro abscesses in the epidermis. Neutrophils are the predominant white blood cells in circulation when stimulated; they discharge the abundant myeloperoxidase (MPO) enzyme that uses hydrogen peroxide to oxidize chloride for killing ingested bacteria. Aim To investigate the contribution of neutrophils to the pathogenesis of psoriasis at the blood and tissue levels through inducible nitric oxide synthase (iNOS) and MPO. Material and methods A total of 50 adult patients with a chronic plaque form of psoriasis and 25 healthy controls were enrolled to this study. Serum MPO and iNOS levels were measured using ELISA method. Two biopsy specimens were taken in each patient from the center of the lesion and uninvolved skin. Immunohistochemistry was performed for MPO and iNOS on both normal and psoriasis vulgaris biopsies. Results While a significant difference between serum myeloperoxidase levels were detected, a similar statistical difference between participants in the serum iNOS levels was not found. In immunohistochemistry, intensely stained leukocytes with MPO and intensely staining with iNOS in psoriatic skin was observed. Conclusions Neutrophils in psoriasis lesions are actively producing MPO and this indirectly triggers the synthesis of iNOS. Targeting of MPO or synthesis of MPO in the lesion area may contribute to development of a new treatment option. PMID:28035220
Mantovani, Alessandro; Gisondi, Paolo; Lonardo, Amedeo; Targher, Giovanni
Over the past 10 years, it has become increasingly evident that nonalcoholic fatty liver disease (NAFLD) is a multisystem disease that affects multiple extra-hepatic organ systems and interacts with the regulation of several metabolic and immunological pathways. In this review we discuss the rapidly expanding body of clinical and epidemiological evidence supporting a strong association between NAFLD and chronic plaque psoriasis. We also briefly discuss the possible biological mechanisms underlying this association, and discuss treatment options for psoriasis that may influence NAFLD development and progression. Recent observational studies have shown that the prevalence of NAFLD (as diagnosed either by imaging or by histology) is remarkably higher in psoriatic patients (occurring in up to 50% of these patients) than in matched control subjects. Notably, psoriasis is associated with NAFLD even after adjusting for metabolic syndrome traits and other potential confounding factors. Some studies have also suggested that psoriatic patients are more likely to have the more advanced forms of NAFLD than non-psoriatic controls, and that psoriatic patients with NAFLD have more severe psoriasis than those without NAFLD. In conclusion, the published evidence argues for more careful evaluation and surveillance of NAFLD among patients with psoriasis.
Weng, Shu-Wen; Chen, Bor-Chyuan; Wang, Yu-Chiao; Liu, Chun-Kai; Sun, Mao-Feng; Chang, Ching-Mao; Lin, Jaung-Geng; Yen, Hung-Rong
Traditional Chinese medicine (TCM) has long been used for patients with psoriasis. This study aimed to investigate TCM usage in patients with psoriasis. We analyzed a cohort of one million individuals representing the 23 million enrollees randomly selected from the National Health Insurance Research Database in Taiwan. We identified 28,510 patients newly diagnosed with psoriasis between 2000 and 2010. Among them, 20,084 (70.4%) patients were TCM users. Patients who were female, younger, white-collar workers and lived in urbanized area tended to be TCM users. The median interval between the initial diagnosis of psoriasis to the first TCM consultation was 12 months. More than half (N = 11,609; 57.8%) of the TCM users received only Chinese herbal medicine. Win-qing-yin and Bai-xian-pi were the most commonly prescribed Chinese herbal formula and single herb, respectively. The core prescription pattern comprised Mu-dan-pi, Wen-qing-yin, Zi-cao, Bai-xian-pi, and Di-fu-zi. Patients preferred TCM than Western medicine consultations when they had metabolic syndrome, hepatitis, rheumatoid arthritis, alopecia areata, Crohn's disease, cancer, depression, fatty liver, chronic airway obstruction, sleep disorder, and allergic rhinitis. In conclusion, TCM use is popular among patients with psoriasis in Taiwan. Future clinical trials to investigate its efficacy are warranted.
Mantovani, Alessandro; Gisondi, Paolo; Lonardo, Amedeo; Targher, Giovanni
Over the past 10 years, it has become increasingly evident that nonalcoholic fatty liver disease (NAFLD) is a multisystem disease that affects multiple extra-hepatic organ systems and interacts with the regulation of several metabolic and immunological pathways. In this review we discuss the rapidly expanding body of clinical and epidemiological evidence supporting a strong association between NAFLD and chronic plaque psoriasis. We also briefly discuss the possible biological mechanisms underlying this association, and discuss treatment options for psoriasis that may influence NAFLD development and progression. Recent observational studies have shown that the prevalence of NAFLD (as diagnosed either by imaging or by histology) is remarkably higher in psoriatic patients (occurring in up to 50% of these patients) than in matched control subjects. Notably, psoriasis is associated with NAFLD even after adjusting for metabolic syndrome traits and other potential confounding factors. Some studies have also suggested that psoriatic patients are more likely to have the more advanced forms of NAFLD than non-psoriatic controls, and that psoriatic patients with NAFLD have more severe psoriasis than those without NAFLD. In conclusion, the published evidence argues for more careful evaluation and surveillance of NAFLD among patients with psoriasis. PMID:26861300
Johnston, A.; Arnadottir, S.; Gudjonsson, J. E.; Aphale, A.; Sigmarsdottir, A. A.; Gunnarsson, S. I.; Steinsson, J. T.; Elder, J. T.; Valdimarsson, H.
Summary Background Obesity is a significant risk factor for psoriasis and body mass index (BMI) correlates with disease severity. Objectives To investigate the relationship between obesity and psoriasis, focusing on the role of adipokines such as leptin and resistin. Patients/Methods Psoriasis patients (n=30) were recruited and their BMI, waist circumference and disease severity (PASI) were recorded. Fasting serum samples were obtained on enrollment and after a course of UVB treatment. Age, sex and BMI-matched healthy controls were also recruited. Results On enrollment, serum leptin and soluble leptin receptor levels were not raised compared with the controls. However, resistin, IL-1β, IL-6, CCL2, CXCL8 and CXCL9 were all significantly elevated in the patient group and serum resistin correlated with disease severity (r=0.372, p=0.043). Improvement after UVB treatment was accompanied by decreased serum CXCL8. In vitro, both leptin and resistin could induce CXCL8 and TNF-α production by blood monocytes, and leptin could additionally induce IL-1β and IL-1ra production. Leptin also dose dependently increased secretion of the growth factor amphiregulin by ex vivo-cultured lesional psoriasis skin. Conclusions These data support the view that leptin and resistin may be involved in the pathogenesis of psoriasis in overweight individuals, possibly by augmenting the cytokine expression by the inflammatory infiltrate. PMID:18547319
Safety profiles and efficacy of infliximab therapy in Japanese patients with plaque psoriasis with or without psoriatic arthritis, pustular psoriasis or psoriatic erythroderma: Results from the prospective post-marketing surveillance.
Torii, Hideshi; Terui, Tadashi; Matsukawa, Miyuki; Takesaki, Kazumi; Ohtsuki, Mamitaro; Nakagawa, Hidemi
A large-scale prospective post-marketing surveillance was conducted to evaluate the safety and efficacy of infliximab in Japanese patients with plaque psoriasis, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma. This study was conducted in all psoriasis patients treated with infliximab after its Japanese regulatory approval. Infliximab was administrated at 5 mg/kg at weeks 0, 2 and 6, and every 8 weeks thereafter. Patients were serially enrolled and observed for 6 months to evaluate the safety and efficacy. The safety and efficacy were evaluated in 764 and 746 patients, respectively. Incidences of any and serious adverse drug reactions were 22.51% and 6.94%, respectively, and those of any and serious infusion reactions were 6.15% and 1.31%, respectively, which were comparable with the results in the post-marketing surveillance with 5000 rheumatoid arthritis patients in Japan. Major adverse drug reactions during the follow-up period were infections (5.10%) including pneumonia, cellulitis and herpes zoster, however, no tuberculosis was observed. The safety profiles were equivalent, regardless of the psoriasis types. No new safety problems were identified. The response rates on global improvement and median improvement rate of Psoriasis Area and Severity Index in all patients were 88.0% and 85.0%, respectively. Of note, the efficacy was equivalent for each psoriasis type as well as for each body region. Infliximab was also effective in pustular psoriasis symptoms, joint symptoms and nail psoriasis, as well as improvement of quality of life. Infliximab was confirmed to be highly effective and well tolerated in treating refractory psoriasis, including pustular psoriasis and psoriatic erythroderma.
Canavan, Theresa N; Elmets, Craig A; Cantrell, Wendy L; Evans, John M; Elewski, Boni E
Our ability to successfully treat patients with moderate to severe psoriasis has improved significantly over the last several years with the development of more targeted therapies. IL-17A, a member of the IL-17 family of interleukins, is involved in regulating the innate and adaptive immune systems and has been identified as a key cytokine involved in the pathogenesis of psoriasis and psoriatic arthritis. In this review, we summarize our understanding of IL-17 and its role in psoriasis and psoriatic arthritis, as well as key findings from clinical trials using anti-IL-17 medications for the treatment of the aforementioned diseases. Secukinumab, ixekizumab, and brodalumab are three anti-IL-17 medications used for treating psoriasis, of which only secukinumab is FDA approved; ixekizumab and brodalumab remain under clinical development. Results from clinical trials show that these three medications are highly effective in treating psoriasis and appear to be as safe as other biologic treatments that are FDA approved.
Armstrong, April W; Callis Duffin, Kristina; Garg, Amit; Gelfand, Joel M; Gottlieb, Alice B; Krueger, Gerald G; Qureshi, Abrar A; Rosen, Cheryl F
At the 2011 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) in Naples, Italy, the GRAPPA dermatology members led discussions on priority research areas in psoriasis and psoriatic arthritis (PsA). These discussions centered on 3 primary areas: evaluation of PsA screening tools, updates on psoriasis comorbidities, and new developments in genetics and comparative effectiveness research. Introductory presentations were followed by engaging panel discussions and audience interaction. The members agreed that screening tools are highly valuable in early detection of PsA among dermatology patients and that efforts are necessary to develop tools suitable for adoption in clinical practice. Members also agreed that a collaborative investigation to evaluate the effect of psoriasis treatments on cardiovascular comorbidities would be highly informative. Finally, the members supported continued efforts to explore the genetic basis of psoriasis and more studies focused on comparative effectiveness of existing treatments.
Armstrong, April W; Voyles, Stephanie V; Armstrong, Ehrin J; Fuller, Erin N; Rutledge, John C
Psoriasis and atherosclerosis are diseases in which effector T lymphocytes such as Helper T cells type 1 (Th1) and 17 (Th17) play integral roles in disease pathogenesis and progression. Regulatory T cells (Treg) also exert clinically important anti-inflammatory effects that are pathologically altered in psoriasis and atherosclerosis. We review the immunological pathways involving Th1, Th17 and Treg cells that are common to psoriasis and atherosclerosis. These shared pathways provide the basis for mechanisms that may explain the epidemiologic observation that patients with psoriasis have an increased risk of heart disease. Improved understanding of these pathways will guide future experiments and may lead to the development of therapeutics that prevent or treat cardiovascular complications in patients with psoriasis.
Smith, Rh Ll; Hébert, H L; Massey, J; Bowes, J; Marzo-Ortega, H; Ho, P; McHugh, N J; Worthington, J; Barton, A; Griffiths, C E M; Warren, R B
Family studies have provided overwhelming evidence for an underlying genetic component to psoriasis. Toll-like receptors (TLRs) are key transmembrane proteins in both the innate and adaptive immune responses which are known to be integral processes in psoriasis. Recent functional studies support this notion having suggested a role for TLR4 in the pathogenesis of psoriasis. Furthermore a missense polymorphism in the TLR4 gene has been associated with a number of autoimmune conditions, including Crohn diseases, making TLR4 a viable candidate gene for investigation. The aim of this study was to investigate polymorphisms across the TLR4 region with a high-density single nucleotide polymorphism (SNP) panel in a large cohort of patients with chronic plaque type psoriasis. Twenty SNPs were successfully genotyped using Sequenom iPLEX Gold platform in 2826 UK chronic plaque type psoriasis patients including subgroup data on presence of confirmed psoriatic arthritis (n = 1839) and early-onset psoriasis (n = 1466) was available. Allele frequencies for psoriasis patients were compared against imputed Wellcome Trust Case Control Consortium controls (n = 4861). Significant association was observed between a missense variant rs4986790 of TLR4 (Asp229Gly) and plaque type psoriasis (p = 2 × 10(-4)) which was also notable in those with psoriatic arthritis (p = 2 × 10(-4)) and early-onset psoriasis (p = 8 × 10(-4)). We present data suggestive of an association between a functional variant and an intronic variant of TLR4 and chronic plaque type psoriasis and psoriatic arthritis. However, validation of this association in independent cohorts will be necessary.
Brauchli, Yolanda B; Jick, Susan S; Miret, Montserrat; Meier, Christoph R
Psoriasis has been associated with lymphohematopoietic and solid cancers; however, reports have been inconsistent. Cancer incidence was compared between psoriasis and psoriasis-free patients, and the roles of psoriasis duration and treatment were explored in this observational study using the UK General Practice Research Database. Among 67,761 patients, 1,703 patients had incident cancer; of whom 54% had a history of psoriasis. Incidence rate ratios for lymphohematopoietic and pancreatic cancers were 1.81 (95% confidence interval (CI) 1.35-2.42) and 2.20 (95% CI 1.18-4.09), respectively. In a nested case-control analysis, adjusted odds ratios (ORs) for cancer overall were 1.50 (95% CI 1.30-1.74) for psoriasis of >or=4 years duration and 1.53 (95% CI 0.97-2.43) for patients receiving systemic treatment (marker of disease severity). Lymphohematopoietic malignancy risk was highest in patients with systemic treatment. The OR for patients without systemic treatment was 1.59 (95% CI 1.01-2.50) for psoriasis of <2 years and 2.12 (95% CI 1.45-3.10) for that of >or=2 years duration. Risks of bladder/kidney and colorectal cancers were increased with longer-duration psoriasis. Psoriasis patients may have an increased overall risk of incident cancer (mainly lymphohematopoietic and pancreatic). Longer-term psoriasis and more severe disease may increase the risk of some cancers. These observations need further confirmation, particularly because of the potential of findings by chance in observational studies with subgroup analyses.
Sundarrajan, Sudharsana; Lulu, Sajitha; Arumugam, Mohanapriya
Psoriasis is a chronic disease of the skin characterized by hyper proliferation and inflammation of the epidermis and dermal components of the skin. T-cell-dependent inflammatory process in skin governs the pathogenesis of psoriasis. An in-silico search strategy was utilized to identify psoriatic therapeutic drug targets. The gene expression profiling of psoriatic skin identified a total of 427 differentially expressed genes (DEGs). Gene ontology investigation of DEGs identified genes involved in calcium binding, apoptosis, keratinisation, lipid transportation and homeostasis apart from immune mediated processes. The protein interaction networks identified proteins involved in various signaling mechanisms with high degree of interconnections. The gene modules derived from the main network were enriched with rich kinome. These sub-networks were dominated by the presence of non-receptor kinase family members which are major signal transmitters in immune response. The computational approach has aided in the identification of non-receptor kinases as potential targets for psoriasis drug development.
de Vasconcellos, Jaqueline Barbeito; Pereira, Daniele do Nascimento; Vargas, Thiago Jeunon de Sousa; Levy, Roger Abramino; Pinheiro, Geraldo da Rocha Castelar; Cursi, Ígor Brum
The use of tumor necrosis factor antagonists (anti-TNF) has become a usual practice to treat various inflammatory diseases. Although indicated for the treatment of psoriasis, anti-TNF may paradoxically trigger a psoriasiform condition. We present a case of a female patient who, during the use of infliximab for rheumatoid arthritis, developed psoriasis. In an attempt to switch anti-TNF class, we observed a cumulative worsening of the lesions requiring suspension of the immunobiological agent and the introduction of other drugs for clinical control. The therapeutic challenge of this paradoxical form of psoriasis is the focus of our discussion. The use of another anti-TNF in these patients is a matter of debate among experts. PMID:28300922
Ito, Hoshiko; Imamura, Sadao
The Koebner phenomenon (KP) was first introduced by Heinrich Koebner in the 1870s to describe the appearance of psoriatic lesions following trauma in psoriasis patients. KP has since been defined in numerous diseases, including necrobiosis lipoidica diabeticorum (NLD). Since most Koebnerized dermatological lesions can localise to a site of previous trauma, Weiss et al. (Eur Acad Dermatol Venereol 2002;16:241–248) classified them into four categories (I–IV) according to the Boyd-Nelder classification (Int J Dermatol 1990;29:401–410) system. In this system, necrobiosis lipoidica is classified as category III, which includes diseases that occasionally localise at the site of trauma. We report a case of NLD that developed after scald in a psoriasis patient. NLD after trauma has often been reported, but this is the first case of NLD that coincidentally occurred at a scald site in a psoriasis patient. PMID:26889139
Sakharuk, N A
Among the factors, contributing to the development of candidiasis in the oral cavity, eczema and psoriasis have great value. The most common type of agent which causes oral candidiasis is fungi C. albicans, but the role of non-albicans species is also sufficient. In order to identify candidiasis, candidiasis carriage and species identification of the causative agent, using clinical and laboratory methods have been examined 222 persons with psoriasis, 110 - with eczema and 93 persons became the control group. Among patients with skin diseases (psoriasis, eczema) incidence of oral candidiasis was significantly higher compared with the control group (p<0.05). No significant differences in the frequency of detection of the representatives of the type, other than C. albicans, have been found. The most frequent causative agents of candidiasis in all investigated groups after C. albicans were C. krusei and C. parapsilosis.
Hecker, D; Worsley, J; Yueh, G; Lebwohl, M
Tazarotene is the first receptor-selective retinoid indicated for the topical treatment of plaque psoriasis. It is being used clinically in combination with other topical antipsoriatic treatments, although its stability in the presence of these products has not been examined extensively. This study examines the compatibility of tazarotene 0.05% gel with 17 other topical products used in the treatment of psoriasis, assessed over a 2-week period. Tazarotene showed minimal degradation (<10%) at 0, 8, 24, and 48 hours after compounding with each of the 17 products. In addition, after 1 and 2 weeks, degradation of tazarotene remained less than 10% for 15 of the 17 products tested. Tazarotene appeared to have minimal impact on the stability of the other products. These results suggest that tazarotene gel can be successfully coprescribed with a range of commonly used topical psoriasis treatments without adversely affecting the chemical stability of either agent.
Maul, Julia-Tatjana; Carraro, Sabina; Stierlin, Johanna; Geiges, Michael L.; Navarini, Alexander A.
The making of wax moulages was an exclusive and sought-after art that was primarily used for teaching, but also to document clinical and laboratory research during the first half of the 20th century. Applying the technique of moulage-making to document a case of psoriasis improvement for posterity, a moulage of the trunk of a patient with psoriasis vulgaris was taken prior to treatment with biologics – adalimumab, a TNF-α antagonist – and again 3 month after adalimumab was first given. Our modern moulage shows in the most realistic way the science-driven improvement of psoriasis achievable nowadays with biologics. However, the real clinical picture of the disease is shrouded by showing only one detail of the patient – by accident the one with the best clinical improvement. All available techniques to document skin disease have advantages and limitations and nothing beats seeing live patients. PMID:26557072
Clobetasol propionate is a super-high potent class 1 topical corticosteroid available in several formulations, including a spray formulation that is approved for use up to 4 weeks in patients aged 18 years and older with moderate to severe plaque psoriasis. The efficacy and safety of clobetasol propionate spray 0.05% has been extensively evaluated in clinical trials in more than 2200 patients with moderate to severe plaque psoriasis. This article reviews the efficacy, safety, and tolerability of clobetasol propionate spray 0.05%. Clobetasol propionate spray 0.05% is a topical product with a documented efficacy and safety profile with good acceptability in patients with moderate to severe plaque psoriasis.
Reuter, Juliane; Wölfle, Ute; Weckesser, Steffi; Schempp, Christoph
Plant extracts and isolated compounds are increasingly used in cosmetics and food supplements to improve skin conditions. We first introduce the positive plant monographs with dermatological relevance of the former German Commission E. Subsequently clinical studies with botanicals for atopic dermatitis, psoriasis, acne, condylomata acuminata and herpes simplex are discussed. The best studies have been conducted with atopic dermatitis and psoriasis patients. Mahonia aquifolium, Hypericum perforatum, Glycyrrhiza glabra and certain traditional Chinese therapies have been shown to be effective in the treatment of atopic dermatitis. Mahonia aquifolium, Indigo naturalis and Capsicum frutescens are effective treatments for psoriasis. Green tea extract and tea tree oil have been investigated in the treatment of acne. Podophyllin and green tea extract are effective treatments for condylomata acuminata. Balm mint and a combination of sage and rhubarb have been shown to be effective in the treatment of herpes simplex in proof of concept studies.
Petrozzi, J W; Barton, J O; Kligman, A; de los Reyes, O
Analysis of standard fluorescent sunlamps (Westinghouse) indicates that in addition to UVB (290 to 320 nm), a considerable amount of UVA (320 to 400 nm) is also present in their emissions. Since the benefits of topical psoralen administration and UVA have already been demonstrated, and prior experience by ourselves and others with UVB has indicated that some psoriasis benefited from UVB alone, localized areas and plaques of 20 patients were treated with topical administration of psoralens and fluorescent sunlamp bulbs to determine if such a light source with this emission spectrum would be advantageous. Results indicated a total resolution in 17 of 20 patients after an average of 18 treatments. Adverse blistering phototoxic reactions and excessive hyperpigmentation were not encountered. The UVB erythema response of normal skin served as the guide to light dosage in the same manner as administration of the Goeckerman regimen. Therefore, the use of psoralens was very effective when combined with fluorescent sunlamp irradiation; however, the potential risks of photocarcinogenicity makes this treatment experimental and should be reserved for recalcitrant cases.
Matthews, D; Fry, L; Powles, A; Weber, J; McCarthy, M; Fisher, E; Davies, K; Williamson, R
Psoriasis is an inflammatory skin disease that affects 2% of the population. It is characterised by red, scaly skin patches which are usually found on the scalp, elbows and knees, and may be associated with severe arthropathy. The lesions are caused by abnormal keratinocyte proliferation, and infiltration of inflammatory cells into the dermis and epidermis. The usual age of onset of psoriasis is between 15 and 30 years, although it can present at any age. Psoriasis is recognised to have a large genetic component. Twin studies show the concordance in monozygotic twins to be between 65-70%, compared to between 15-20% in dizygotic twins. Family studies estimate the risk to first degree relatives at between 8-23%. However, there are also several environmental factors, including streptococcal infection and stress, that affect the onset and presentation of the disease. The mode of inheritance of psoriasis is unclear. We conducted a genome-wide scan to search for psoriasis susceptibility loci in a single large multiplex family. Parametric linkage analysis indicated that a susceptibility locus for familial psoriasis was located on chromosome 4q. Investigation of this locus in five further multiplex families using both parametric and non-parametric methods gave significant localisation to chromosome 4q. The maximum total pairwise lod score obtained was 3.03 with the microsatellite marker D4S1535 at theta = 0.08. Non-parametric multipoint analysis with GENEHUNTER- demonstrated significant excess allele sharing, with a P value of 0.0026, at the same locus.
Schukur, Lina; Geering, Barbara; Charpin-El Hamri, Ghislaine; Fussenegger, Martin
Psoriasis is a chronic inflammatory skin disease characterized by a relapsing-remitting disease course and correlated with increased expression of proinflammatory cytokines, such as tumor necrosis factor (TNF) and interleukin 22 (IL22). Psoriasis is hard to treat because of the unpredictable and asymptomatic flare-up, which limits handling of skin lesions to symptomatic treatment. Synthetic biology-based gene circuits are uniquely suited for the treatment of diseases with complex dynamics, such as psoriasis, because they can autonomously couple the detection of disease biomarkers with the production of therapeutic proteins. We designed a mammalian cell synthetic cytokine converter that quantifies psoriasis-associated TNF and IL22 levels using serially linked receptor-based synthetic signaling cascades, processes the levels of these proinflammatory cytokines with AND-gate logic, and triggers the corresponding expression of therapeutic levels of the anti-inflammatory/psoriatic cytokines IL4 and IL10, which have been shown to be immunomodulatory in patients. Implants of microencapsulated cytokine converter transgenic designer cells were insensitive to simulated bacterial and viral infections as well as psoriatic-unrelated inflammation. The designer cells specifically prevented the onset of psoriatic flares, stopped acute psoriasis, improved psoriatic skin lesions and restored normal skin-tissue morphology in mice. The antipsoriatic designer cells were equally responsive to blood samples from psoriasis patients, suggesting that the synthetic cytokine converter captures the clinically relevant cytokine range. Implanted designer cells that dynamically interface with the patient's metabolism by detecting specific disease metabolites or biomarkers, processing their blood levels with synthetic circuits in real time, and coordinating immediate production and systemic delivery of protein therapeutics may advance personalized gene- and cell-based therapies.
Lu, Chuanjian; Deng, Jingwen; Li, Li; Wang, Dongmei; Li, Guozheng
Traditional Chinese medicine (TCM) is one of the oldest forms of medical system. With syndrome as the core of diagnosis and therapy in TCM, it has the advantage of collecting macroscopic information of patients for diagnosis. To understand the in vivo mechanism of TCM, a metabolomics approach was used to investigate the global biological characterization of the urine of psoriasis patients with Blood Stasis Syndrome and the therapeutic metabolomics mechanism of the Optimized Yinxieling formula. A total of 41 cases of psoriasis patients with Blood Stasis Syndrome and 19 healthy volunteers were enrolled in this study. Fasting urine samples from patients with consecutive Optimized Yinxieling intake after 0, 4, 8 and 12 weeks and from healthy volunteers were analyzed by Orthogonal Projection on Latent Structures Discriminant Analysis (OPLS-DA), which was utilized for High Performance Liquid Chromatography (HPLC) analysis and temporal metabolic changes identification. For psoriasis group, the scores of PASI of patients decreased after 12 weeks of Optimized Yinxieling treating. The metabolic variations visualized not only in the healthy group and psoriasis group, but also in the psoriasis group before and after Optimized Yinxieling treatment, demonstrated that the metabolic characteristics of the two groups were significantly different. The optimized complex structure of the target proteins from Protein Data Bank was analyzed by software package Discovery Studio. With docking score of original inhibitor and the receptor as the threshold values, two compounds from Chinese medicinal chemical database were predicted to have good interactions with the target proteins. The Metabolomics technique combining molecular docking analysis enhanced our current understanding of the metabolic response to Blood Stasis Syndrome of Psoriasis and the action mechanism of Optimized Yinxieling. This article is part of a Special Issue entitled: Computational Proteomics, Systems Biology
Chambers, Cindy J.; Parsi, Kory K.; Schupp, Clayton; Armstrong, April W.
Background Previous research suggests that technology-enabled healthcare delivery may improve access to dermatologic specialty care. Outcomes research utilizing validated outcomes measures is necessary for evaluation of novel healthcare delivery models. Objective To compare the clinical equivalence of a novel patient-centered online healthcare delivery model with standard in-office care for follow-up management of psoriasis patients. Methods Sixty-four participants with psoriasis were randomized to receive follow-up care either in-office or online over a 24-week period. Patients randomized to the online group underwent standardized training on capturing high-quality digital images of their psoriatic skin and transmitting these images and clinical history to a dermatologist securely. The dermatologist then performed asynchronous, online evaluation and provided recommendations directly to patients. We used clinically validated disease severity and quality of life measures to assess effectiveness between the models. Results Both online and in-office groups showed improvement in psoriasis disease severity as measured by mean improvement in Psoriasis Area and Severity Index (PASI) (online group: μ = −3.4,, in-office: μ = −3.4,). Patient-centered online care resulted in similar improvement in psoriasis severity compared to in-person follow-up care (mean difference in PASI change 0.1, 95% CI: −2.2 to 2.3, a priori equivalence margin of 2.5). Investigator’s Global Assessment (IGA) and Dermatology Life Quality Index (DLQI) scores also improved during the study period; no significant differences existed between the two groups. Limitations The follow-up period was limited to 24 weeks. Conclusion A patient-centered online model may be an effective alternative to in-office care for follow-up management of psoriasis. PMID:21890236
Tervaniemi, Mari H.; Siitonen, H. Annika; Söderhäll, Cilla; Minhas, Gurinder; Vuola, Jyrki; Tiala, Inkeri; Sormunen, Raija; Samuelsson, Lena; Suomela, Sari; Kere, Juha; Elomaa, Outi
CCHCR1 (Coiled-Coil α-Helical Rod protein 1), within the major psoriasis susceptibility locus PSORS1, is a plausible candidate gene with the psoriasis associated risk allele CCHCR1*WWCC. Although its expression pattern in psoriatic skin differs from healthy skin and its overexpression influences cell proliferation in transgenic mice, its role as a psoriasis effector gene has remained unsettled. The 5′-region of the gene contains a SNP (rs3130453) that controls a 5′-extended open reading frame and thus the translation of alternative isoforms. We have now compared the function of two CCHCR1 isoforms: the novel longer isoform 1 and the previously studied isoform 3. In samples of Finnish and Swedish families, the allele generating only isoform 3 shows association with psoriasis (P<10−7). Both isoforms localize at the centrosome, a cell organelle playing a role in cell division. In stably transfected cells the isoform 3 affects cell proliferation and with the CCHCR1*WWCC allele, also apoptosis. Furthermore, cells overexpressing CCHCR1 show isoform- and haplotype-specific influences in the cell size and shape and alterations in the organization and expression of the cytoskeletal proteins actin, vimentin, and cytokeratins. The isoform 1 with the non-risk allele induces the expression of keratin 17, a hallmark for psoriasis; the silencing of CCHCR1 reduces its expression in HEK293 cells. CCHCR1 also regulates EGF-induced STAT3 activation in an isoform-specific manner: the tyrosine phosphorylation of STAT3 is disturbed in isoform 3-transfected cells. The centrosomal localization of CCHCR1 provides a connection to the abnormal cell proliferation and offers a link to possible cellular pathways altered in psoriasis. PMID:23189171