Introduktion: Psoriasis är en kronisk inflammatorisk systemsjukdom som drabbar främst hud och leder.  På grund av mycket snabbt tillväxt av hudceller ger psoriasis utslag på huden.  En av de vanligaste typerna av psoriasis är plack-psoriasis som kännetecknas av större än 0,5 cm i diameter runda fjällande hudutslag som kliar. Mekanismen som ligger bakom plack-psoriasis medieras med hjälp av T-celler och dendritiska celler som är en viktig del av immunsystemet. Stimulering av dessa immunceller leder till frisättning av följande proinflammatoriska cytokiner såsom IL-17, IFN-γ, TNF samt IL-22. Dessa cytokiner utövar sin effekt på keratinocyter genom att öka psoriatisk inflammation. Flera biologiska läkemedel utvecklas nu för behandling av plack-psoriasis. I detta arbete har fokus lagts på två av dem, sekukinumab som är en IL-17A hämmare och ustekinumab, som är en IL-12 och IL-23 hämmare. Syfte: Syftet med arbetet är att undersöka effektivitet av sekukinumab vid behandling av plack-psoriasis. Vidare undersöks även hur behandling av plack-psoriasis med sekukinumab skiljer sig från behandling med ustekinumab gällande minskning av plack-psoriasis. Metod: Detta arbete är en litteraturstudie som inkluderar fem vetenskapliga artiklar som baserades på randomiserade kontrollerade studier som sponsrades av läkemedelsföretag.  Resultat: Resultatet av de fem studier visar att behandling med hjälp av sekukinumab 300 mg och 150 mg var mer effektiv än behandling med ustekinumab 45/90 mg, enligt PASI 75, PASI 90 och PASI 100. Diskussion: Alla fem studierna var dubbel-blinda randomiserade kontrollerade studier vilket leder till säkra och tillförlitliga resultat. Däremot var samtliga studier sponsrade av läkemedelsföretag vilket kan leda till att positiv effekt beskrivs i större utsträckning för att kunna sälja sin produkt.  Slutsats: Sekukinumab 300 mg och 150 mg är signifikant mer effektiv än placebo och signifikant mer effektiv än ustekinumab 45/90 mg vid behandling av medelsvår och svår plack-psoriasis. / Introduction: Psoriasis is a chronic inflammatory systemic disease that mainly affects the skin and joints. Due to the very rapid growth of skin cells, psoriasis causes rashes on the skin. One of the most common types of psoriasis is plaque psoriasis which is characterized by larger than 0.5 cm in diameter round scaly skin rash that itches. The mechanism behind plaque psoriasis is mediated by T cells and dendritic cells, which are an important part of the immune system. Stimulation of these immune cells leads to the release of the following proinflammatory cytokines such as IL-17, IFN-γ, TNF and IL-22. These cytokines exert their effect on keratinocytes by increasing psoriatic inflammation.  Several biological drugs are now being developed for the treatment of plaque psoriasis. In this study, the focus has been on two of them, secukinumab which is an IL-17A inhibitor and ustekinumab, which is an IL-12 and IL-23 inhibitor. Purpose: The purpose of this study is to investigate the efficacy of secukinumab in the treatment of plaque psoriasis. Furthermore, it is also investigated if the treatment of plaque psoriasis with secukinumab differs from treatment with ustekinumab regarding reduction of plaque psoriasis. Method: This work is a literature study that includes five scientific articles based on randomized controlled trials sponsored by pharmaceutical companies.  Results: The results of the five studies show that treatment with secukinumab 300 mg and 150 mg was more effective than treatment with ustekinumab 45/90 mg, according to PASI 75, PASI 90 and PASI 100. Discussion: All five studies were double-blind randomized controlled trials leading to safe and reliable results. On the other hand, all studies were sponsored by pharmaceutical companies, which may lead to a positive effect being described to a greater extent in order to be able to sell their product. Conclusion: Secukinumab 300 mg and 150 mg are significantly more effective than placebo and significantly more effective than ustekinumab 45/90 mg in the treatment of moderate to severe plaque psoriasis.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12957号 / 論医博第2099号 / 新制||医||1011(附属図書館) / 32356 / 京都大学大学院医学研究科医学専攻 / (主査)教授 生田 宏一, 教授 岩井 一宏, 教授 椛島 健治 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Psoriasis är en av de vanligast förekommande hudsjukdomarna och mer än två procent har denna kroniska sjukdom i Sverige. Som allmänsjuksköterska är sannolikheten stor att vi kommer att stöta på patienter med sjukdomen. Syftet med denna studie var att öka kunskapen och fördjupa förståelsen för personer med denna sjukdom ur aspekterna livskvalitet, copingstrategier samt ta reda på om sjuksköterskan med några omvårdnadsåtgärder kan underlätta för patienter med psoriasis. Denna litteraturstudie visade tydligt att psoriasis påverkar livskvalitén. För att få fram den kunskapen använde man olika mätinstrument. Det framkom att det fysiska, psykiska och sociala livet påverkades samt ekonomin. När det gällde copingstrategier fann man att oavsett om man var frisk eller sjuk använde man samma strategier. Ingen forskning har bedrivits angående omvårdnadsåtgärder rörande psoriasis för allmänsjuksköterskan. Mer forskning behövs kring allmänsjuksköterskans vårdande roll. Denna studie har trots detta ett framtida värde då den ger värdefull information som vi kan använda oss av i omvårdnadsarbetet. / Psoriasis is one of the most common skin-diseases and more than two percent suffers from this chronic disease in Sweden. As a general nurse it is very likely that we will meet patients with this disease. We want to create a greater understanding and knowledge about how a nurse can support and make it easier for these patients. The aim of this study was to increase the knowledge and deepens the understanding of patients with psoriasis regarding aspects of quality of life, copingstrategies and nursinginterventions. This literature review clearly showed that psoriasis influenced quality of life. To get these results the researchers used different kinds of instruments. It showed that physical, psychological and social life where affected and also their financial state. When it came to copingstrategies the findings showed that no matter if you were healthy or sick you used the same kind of strategies. No research has been done about nursing interventions for the general nurse. We therefore need more research about the general nurses care-giving roll. This study has though a future value as it gives us information about what we can do for patients with psoriasis in our nursing care.

Introduction Grenz ray therapy ( has long been used as treatment for inflammatory skindiaseases R ecent h ealth technology assessment reports have concluded that because ofinsufficient evidence of its efficacy they do not promote further use of GRT for benigndisorders. Aim T o investigate the effect, estimate remission times and summarize the outcome of the GRTseries administered over a six year period for the treatment of inflammatory diseases at theUniversity Hospital Örebro Methods A total of 204 treatment serie s were included by review of patient files spanningfrom 201 5 to 2020. Symptom scores of one to fifteen were recorded at start and end oftreatment. Data on recurrence was collected over a follow up period of 12 months after theend of treatment. Results Al l diagnoses had reduced symptom severity score s post treatment, with psoriasis ofthe scalp showing a 71.4% reduction and genital lichen showing a symptom score reductionof 25.0% Non reponse was lowest for hand dermatitis, and highest for lichen and eczema ofthe body. In patients with an initial effect post t reatment, a majority did not experience arecurrence within 12 months. Conclusion Positive effects were of GRT was indicated especially for scalp psoriasis andhand dermatitis, a ltough effect size is undetermined. The least effect was indicated for genitallichen. Hand dermatitis had the lowest recurrence rate in the follow up period. Furtherresearch of the subject is needed to determine the utility o f the method

Psoriasis is a chronic inflammatory disease of the skin and joints associated with several comorbidities such as arthritis, diabetes mellitus and metabolic syndrome, including obesity, hypertension and dyslipidaemia, Crohn’s disease, uveitis and psychiatric and psychological diseases. Psoriasis has been described as an independent risk factor for cardiovascular diseases and thus patients with psoriasis should be monitored for the development of cardiovascular disease or metabolic syndrome. However, there is mounting evidence that psoriasis also affects the development of osteoporosis, an important metabolic disease with enormous clinical and socioeconomic impact. At present, there are still controversial opinions about the role of psoriasis in osteoporosis. A more in depth analysis of this phenomenon is of great importance for affected patients since, until now, bone metabolism is not routinely examined in psoriatic patients, which might have important long-term consequences for patients and the health system. In the present review, we summarize current knowledge on the impact of psoriatic inflammation on bone metabolism and osteoporosis.

Psoriasis is an immune mediated inflammatory disease which affects 2-3% of the world’s population. Over the last decade, psoriasis has been acknowledged as an independent risk factor for atherosclerosis. The precise mechanism or mechanisms of the heightened risk is widely speculated. Endothelial cells and macrophages are central players in the immunopathological development of both diseases. Interleukin-36 cytokines (IL-36) have been heavily implicated in psoriasis immunopathology. Significant upregulation of epidermal IL-36 is a recognised characteristic of psoriatic skin inflammation. IL-36 induces inflammatory responses in dendritic cells, fibroblasts and epithelial cells. While vascular alterations are a hallmark of psoriatic lesions and dermal endothelial cells are well known to play a critical role in dermal inflammation, the effects of IL-36 on endothelial cells have not been defined. We report that endothelial cells including dermal microvascular cells express a functionally active IL-36 receptor. Adhesion molecules VCAM-1 and ICAM-1 are upregulated following IL-36γ stimulation, and this is reversed in the presence of the endogenous IL-36 receptor antagonist. IL-36γ-stimulated endothelial cells secrete the proinflammatory chemokines IL-8, CCL2 and CCL20. Chemotaxis assays showed increased migration of T-cells following IL-36γ stimulation of endothelial cells. Both resident and infiltrating inflammatory myeloid cells contribute to the immunopathology of psoriasis by promoting the IL-23/IL-17 axis. We show that IL-36γ induces the production of psoriasis-associated cytokines from macrophages (IL-23, TNFα) and that this response is enhanced in macrophages from psoriasis patients. This effect is specific for IL-36γ and could not be mimicked by other IL-1 family cytokines such as IL-1α. Furthermore, IL-36γ stimulated macrophages potently activated endothelial cells as illustrated by ICAM-1(CD54) upregulation, and led to increased adherence of monocytes, effects that were markedly more pronounced for psoriatic macrophages. Interestingly, regardless of stimulus, monocytes isolated from psoriasis patients showed increased adherence to both the stimulated and unstimulated endothelium when compared to monocytes from healthy individuals. Collectively, these findings add to the growing evidence for IL-36γ having roles in psoriatic responses, by enhancing endothelium directed leukocyte infiltration into the skin and strengthening the IL-23/IL-17 pathway. Our findings also point to a cellular response which could potentially support cardiovascular comorbidities in psoriasis. / University of Bradford and the Centre for Skin Sciences

Psoriasis is a chronic inflammatory disease of the skin and joints. More recent data emphasize an association with dysregulated glucose and fatty acid metabolism, obesity, elevated blood pressure and cardiac disease, summarized as metabolic syndrome. TNF-a and IL-17, central players in the pathogenesis of psoriasis, are known to impair bone formation. Therefore, the relation between psoriasis and bone metabolism parameters was investigated. Two serum markers of either bone formation—N-terminal propeptide of type I procollagen (P1NP) or bone resorption—C-terminal telopeptide of type I collagen (CTX-I)—were analyzed in a cohort of patients with psoriasis vulgaris. In patients with psoriasis, P1NP serum levels were reduced compared to gender-, age-, and body mass index-matched healthy controls. CTX-I levels were indistinguishable between patients with psoriasis and controls. Consistently, induction of psoriasis-like skin inflammation in mice decreases bone volume and activity of osteoblasts. Moreover, efficient anti-psoriatic treatment improved psoriasis severity, but did not reverse decreased P1NP level suggesting that independent of efficient skin treatment psoriasis did affect bone metabolism and might favor the development of osteoporosis. Taken together, evidence is provided that bone metabolism might be affected by psoriatic inflammation, which may have consequences for future patient counseling and disease monitoring.

No description available.

No description available.

Chronic itch has a significant impact on quality of life for millions of patients worldwide, on a level comparable to that of chronic pain. Yet, although there are a host of effective drugs available for pain, there are no therapies that specifically target chronic itch. Current experimental approaches to investigate the pathogenesis of chronic pruritus and to test novel therapeutic agents are largely limited to rodent models. However, rodent models display significant dermatological, neurophysiological, and immunological differences from humans with chronic itch. The disadvantages of the current rodent paradigms call for the design of a valid primate model of chronic itch. For four years, we have monitored scratching behavior in a primate colony (n=35) of Cynomolgus macaques (Macaca fascicularis) suffering from idiopathic chronic itch. By comparing molecular and genetic analyses of the primates’ skin to their quantified scratching behavior, we attempted to characterize the underlying mechanisms of chronic itch in this model. Furthermore, the expression of itch-related proteins was examined in both the primate model and in humans with pruritic diseases. The first aim of the study was to characterize the underlying molecular and genetic basis of chronic itch in the primate model. We were able to distinguish specific peripheral targets related to pruritus by correlating the genetic and protein expression results to the primates’ scratching severity. In Aim 1a, RNA-sequencing was performed on skin biopsies from the primates to identify differentially expressed genes in pruritic, lichenified versus non-pruritic, non-lichenified skin. These results were then correlated to the quantified primate scratching behavior. This led to the identification of over 400 genes that were differentially expressed in the skin based on scratching intensity. Many of these differentially expressed transcripts were associated with sensory nerve fibers, keratinocytes, mast cells, or lymphocytes. Selected genes that were overexpressed and correlated to itch intensity were then targeted for immunohistochemical and proteomic analysis in Aim 1b. Immunohistochemical examination of the primate skin biopsies revealed that histamine levels were not elevated in primates that exhibited increased scratching behavior. However, mast cells containing tryptase were significantly increased in the skin of primates with severe scratching as compared to primates with mild scratching. The increased levels of gastrin-releasing peptide and substance P in lichenified skin were also found to be correlated to the primates’ scratching behavior. Of note, transient receptor potential channels V1, V3, and A1 were increased in the epidermis of primate skin, but the numbers of TRPV1+ and TRPA1+ nerve fibers were not significantly different between lichenified and non-lichenified skin. Transcriptome analysis of the opioid receptors and their ligands showed that primates with severe scratching behavior had a significant imbalance between the µ- and κ-opioid receptors and ligands. The µ-opioids had upregulated gene expression, while the κ-opioids were downregulated. In Aim 2, to further characterize this primate model of chronic itch, we compared immunohistochemical results from the primate studies to human findings. Lesional and non-lesional skin biopsies from patients with atopic dermatitis, psoriasis, and cutaneous T-cell lymphoma underwent immunohistochemical analysis in order to reveal the similarities and differences between the primate model and different types of chronic itch in humans. As in the primate model, substance P was found to be increased in the skin of lesional atopic and psoriasis skin. Additionally, similar to primate skin, human atopic and psoriatic skin had high levels of tryptase and its receptor in the epidermis. While IL-31 was only slightly elevated in primates, patients with cutaneous T-cell lymphoma or atopic dermatitis showed a significant correlation between itch severity and IL-31 levels. In conclusion, our primate model displayed expression patterns of many endogenous pruritogens and receptors that were similar to those of humans with atopic dermatitis or psoriasis. While the primate model did not completely mimic these specific pruritic diseases, the overlap of pruritic components suggests a commonality of signaling pathways across several different chronic itch states. The similarity of this primate model to human disease offers the combined advantages of experimental modeling and long-term behavioral follow-up. / Biomedical Sciences