Bakgrund Psoriasis är en genetisk hudsjukdom som påverkar både den fysiska och psykiska hälsan. Sjukdomen ger röda och fjällande hudutslag, som uppstår på grund av en för snabb tillväxt av hudceller och en låggradig inflammation i kroppen. Det är vanligt att sjukdomen går i skov som kan utlösas av stress eller infektioner. En person med psoriasis kan bli symtomfri med rätt behandling, vilket är varför det är viktigt att sjuksköterskan besitter rätt kompetens för att ha möjlighet att ge stöd och vägledning till personer med psoriasis.  Syfte Syftet var att beskriva personers upplevelser av att leva med psoriasis. Metod Denna litteraturöversikt baserades på 15 vetenskapliga artiklar med både kvantitativ och kvalitativ design. Med hjälp av olika sökordskombinationer inhämtades de vetenskapliga artiklarna från databaserna PubMed och CINAHL. Kvalitetsgranskning av de vetenskapliga artiklarna har gjorts utifrån Sophiahemmet Högskolas bedömningsinstrument. De vetenskapliga artiklarna sorterades vidare in i fyra huvudkategorier med tillhörande subkategorier. Resultat Resultatet visade att personer med psoriasis upplevde en försämrad livskvalitet, ångest, stigmatisering, sömnsvårigheter, smärta och ett försämrat självförtroende. Personer med psoriasis utvecklade ofta olika hanteringsstrategier, som att exempelvis täcka sina hudutslag med kläder, för att undvika situationer som uppfattades som obehagliga. Slutsats Upplevelser om försämrad livskvalitet, stigmatisering och depression var vanligt hos majoriteten av deltagarna i samtliga studier. Sjuksköterskan har ett ansvar om att ge en personcentrerad vård. Litteraturöversikten tyder på att personer med psoriasis är en utsatt grupp på grund av en förhöjd risk för både fysisk och psykisk ohälsa. Sjuksköterskan måste därför besitta tillräcklig kunskap och förståelse för att ha möjlighet att bemöta personer med psoriasis på ett individanpassat sätt där de får rätt verktyg till ökad livskvalitet. / Background Psoriasis is a genetic skin disease that affects both physical and mental health. The disease causes red and scaly skin rashes, which occur due to a too rapid growth of skin cells and a low-grade inflammation of the body. It is common for the disease to go into relapses that can be triggered by stress or infections. A person with psoriasis can become symptom-free with the right treatment, which is why it is important that the nurse possesses the right skills to be able to provide support and guidance to people with psoriasis. Aim  The aim was to describe people's experiences of living with psoriasis. Method  This literature review was based on 15 scientific articles with both quantitative and qualitative design. Using different keyword combinations, the scientific articles were obtained from the PubMed and CINAHL databases. Quality review of the scientific articles has been carried out based on Sophiahemmet University's assessment instrument. The scientific articles were further sorted into four main categories with associated subcategories. Results  The results showed that people with psoriasis experienced a reduced quality of life, anxiety, stigma, difficulty sleeping, pain and a loss of self-confidence. People with psoriasis often developed different coping strategies, such as covering their skin rashes with clothing, to avoid situations that were perceived as unpleasant. Conclusions  Experiences of impaired quality of life, stigma and depression were common in the majority of participants in all studies. The nurse has a responsibility to provide person-centered. The literature review suggests that people with psoriasis are a vulnerable group due to an increased risk of both physical and mental illness. The nurse must therefore have sufficient knowledge and understanding to have the opportunity to respond to people with psoriasis in an individualized way and get the right tools for increased quality of life.

Introduction. Plaque psoriasis (psoriasis vulgaris) is a chronic disease and the most common type of psoriasis. It is charactarized by well-defined areas with silvery scaling, erythema, puritus and sometimes pain. Psoriasis affects about 1.5 - 3 % of the world population. Patients with psoriasis often suffer with comorbidies which makes drug therapy essential in relieving symptoms. Mild to moderate disease is treated with topical therapy such as corticosteroids and retinoid creams and with phototherapy. More severe disease is treated with systemic therapy e.g. methotrexate, cyclopsorine and retinoids. Patients who do not respond well to these treatments can be put on antibody therapy, e.g., secukinumab. Secukinumab is a monoclonal antibody that specifically targets the IL-17A. It is used to treat moderate to severe psoriasis. Secukinumab binds to IL-17A and inhibits it to interact with IL-17R. This leads to downregulation of immune response and symptom relieving. Other monoclonal antibodies that are used are risankizumab that binds to the p19 subunit of IL-23 and ustekinumab that binds to the p40 subunit of IL-12 and IL-23. Clinical psoriasis symptoms are evaluated with the Psoriasis Area Severity Index (PASI) from 0 till 72 and with the Inverstigator’s Global Assessment (IGA) from 0 till 5. Method. This thesis is a literature review with an aim to evaluate the efficacy and safety of secukinumab in treating psoriasis vulgaris. The search for articles was done in PubMed with the search words ‘’secukinumab’’ and ‘’plaque psoriasis’’. Included articles were RCT-studies published between 2014 and 2022. Moreover, these studies used the PASI and the IGA scoring system. This thesis excluded studies with children. Overall, this thesis included 6 trials reported in 5 articles. Results. The trials ERASURE, FIXTURE and CAIN demonstrated that 300 mg and 150 mg secukinumab per day were effective in treating moderate to severe psoriasis vulgaris compared to  placebo and etarnecept. The trials CLARITY and CLEAR demonstrated that 300 mg secukinumab was effective in treating moderate to severe psoriasis vulgaris compared to ustekinumab. The trial IMMerge demonstrated that risankizumab was superior in treating psoriasis vulgaris compared to secukinumab. Most of the adverse effects were mild and moderate and the most common reported were nasopharyngitis, upper respiratory tract infection, diarrhea and headache.Conclusion. Secukinumab demonstrates good efficacy and safety in the treatment of moderate to severe psoriasis in patients who have not received a satisfactory result from other drugs therapies.

Psoriasis is a chronic, immune-mediated inflammatory skin disease. Its pathogenesis is associated with dysregulated cooperation among keratinocytes, innate and adaptive immune cells, coupled with environmental triggers, including microbiota. The aim of our study was to describe the microbiota composition in psoriasis and explore the role of bacteria and fungi in the pathogenesis of this disease. We used a mouse model of psoriasis induced by topical application of imiquimod (IISI) in both germ-free (GF) mice and conventional (CV) mice with microbiota manipulated by administration of a mixture of broad-spectrum antibiotics (ATB). ATB treatment markedly changed the intestinal but not the skin bacterial diversity and led to higher resistance to IISI in CV mice. Metronidazole was the most effective antibiotic, alleviating IISI symptoms in CV, but not in GF mice. This confirms that the effect of metronidazole on IISI was microbiota- dependent. Additionally, we characterized the microbiota composition of psoriatic lesions and unaffected skin in psoriatic patients compared to healthy controls, as well as the impact of different sampling approaches on uncovering cutaneous microbiota composition. We observed significant differences in α- and β-diversities when comparing identical samples sequenced on V1V2...

Bakgrund: Psoriasis är en autoimmun, inflammatorisk och kronisk hudsjukdom där hudbarriären är nedsatt med strukturella och funktionella avvikelser i hornlagret. Målet för behandlingen idag är att minska utbredning och symtom så att drabbade personer i så liten utsträckning som möjligt påverkas i deras vardagliga liv Syfte: Syftet var att beskriva hur vuxna personer som drabbats av psoriasis påverkas av sin sjukdom i sitt vardagliga liv. Metod: Studiens design var en allmän litteraturstudie som utgick från 11 vetenskapliga artiklar. Artiklarna analyserades för att identifiera relevant information som vidare färggrupperades och data kategoriserades. Resultat: Tre kategorier identifierades; fysisk påverkan av psoriasis, psykisk påverkan av psoriasis och social påverkan av psoriasis. Konklusion/implikation: Det vardagliga livet för personer med psoriasis påverkades i stor omfattning då symtom innebar fysiska, psykiska och sociala begränsningar. Det föreligger ett stort behov av personcentrerad vård hos personer med psoriasis. Sjuksköterskor ska värna om patienter och tillämpa god omvårdnad. Att utveckla den personcentrerade vården är av vikt för att hälso- och sjukvården ska kunna möta omvårdnadsbehovet hos personer med psoriasis. / Background: Psoriasis is an autoimmune, inflammatory and chronic skin disease with impaired skin barrier due to structural and functional deviations on the stratum corneum. The goal for treatment is to decrease the spread of the disease and symptoms so that people to a smaller extent get affected in their everyday lives. The Aim: The aim of this study was to describe how people suffering from psoriasis are affected by the disease in their everyday lives. Method: A general literature study design was used. 11 articles were analyzed to identify relevant information which later was color grouped and data was categorized. Results: Three categories were found; physical impact of psoriasis, psychological impact of psoriasis and social impact of psoriasis. Conclusion/Implications: Everyday life for people suffering from psoriasis was affected to a great extent when symtoms meant both physical, psychological and social limitations. There is a great need for person centered care for people with psoriasis. Nurses shall protect patients and apply person centered care. Developing person centered care is of importance for healthcare to be able to meet the needs of people with psoriasis.

Background: Chronic plaque-type psoriasis is a major dermatosis, but a significant question is still unanswered: What defines severity in chronic plaque-type psoriasis? While objective assessments like the Psoriasis Area and Severity Index (PASI) have frequently been used in clinical trials, quality of life (QOL) questionnaires are currently becoming more and more popular. Objective: This article summarizes the most important objective and subjective measurements of severity in psoriasis. For every dermatologist it is critically important to distinguish between severe psoriasis and psoriasis that severely affects QOL. Even if the PASI also has disadvantages, it is the most adequate instrument available to evaluate severity in plaque-type psoriasis. Result: We provide reasons why PASI >12 defines severe, PASI 7–12 moderate and PASI <7 mild chronic plaque-type psoriasis. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Background: Chronic plaque-type psoriasis is a major dermatosis, but a significant question is still unanswered: What defines severity in chronic plaque-type psoriasis? While objective assessments like the Psoriasis Area and Severity Index (PASI) have frequently been used in clinical trials, quality of life (QOL) questionnaires are currently becoming more and more popular. Objective: This article summarizes the most important objective and subjective measurements of severity in psoriasis. For every dermatologist it is critically important to distinguish between severe psoriasis and psoriasis that severely affects QOL. Even if the PASI also has disadvantages, it is the most adequate instrument available to evaluate severity in plaque-type psoriasis. Result: We provide reasons why PASI >12 defines severe, PASI 7–12 moderate and PASI <7 mild chronic plaque-type psoriasis. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

D.Litt. et Phil. / This study explored the impact of psoriasis on the self-concept (a multifaceted, hierarchical construct of self with both cognitive and emotional components) (Hattie & Marsh, 1996), of men and women who live with this cutaneous disease. Psoriasis is a common (frequently occurring), chronic inflammatory dermatological disease that can severely affect the sufferer's quality of life. While the underlying cause is unknown, the immediate cause of psoriasis is the rate of growth and differentiation of the outer layer of the skin. In a process known as hyper-proliferation (renewal of skin every four days as opposed to every 28 days), psoriasis is anatomically disfiguring. Symptoms include: the thickening of psoriatic plaques, the sloughing of silvery scales, severe itching of the affected areas and a thickening and yellowing of the fingernails. The severity of psoriasis varies from small scattered patches to total skin coverage (Young, 2005). Chronic skin diseases, such as psoriasis, can affect one's self-concept at the level of the physical, emotional, social and spiritual dimensions of self (Kew, Nevin & Cruickshank, 2002). According to Gupta and Gupta (1995), sufferers of psoriasis experience external shame (fear of negative evaluations and stigmatisation) as well as internal body shame (negative self-evaluations and self-focussed feelings). According to Stake, Huff and Zand (1995), a disturbance in one dimension of self (e.g. the physical self-concept), invariably effects other self-dimensions (e.g. the private, social self-dimensions). A study by Gupta and Gupta (1995) revealed that psoriasis was a major contributing factor to the onset of psychopathology such as depression, anxiety, unfocussed anger and obsessional behaviours. A study by Choi and Koo (as cited in Young, 2005), found that the impact of psoriasis on the psychological and emotional dimensions of self-concept to be comparable to that experienced by sufferers of more chronic diseases such as cancer, heart disease and clinical depression. General healthcare providers who treat the medical components of psoriasis may be surprised to learn that the emotional and social burdens of psoriasis are often greater than the physical toll of psoriasis on patients. Further, psoriasis is observed to be persistent, unpredictable and stressful over longer periods of time than more serious illnesses (Young, 2005). Although many people with disfiguring skin disorders cope remarkably well psychologically and socially, many do not and may require professional help in describing their bodily being in relation to the world and to come to terms with the positive and negative aspects of self (Van Deurzen-Smith, 1997). Significantly, studies in psychoneuroendocrineimmunology have shown the interconnectedness of emotions and mental attitude to physical health and which underscores the importance of treating the whole person and not just the symptoms (Linsteadt, 2002). Consistently, studies have shown the importance of self-concept to psychological health (Francis, 2002; Hattie & Marsh, 1996; Newell, 2000; Young, 2005) and body satisfaction as being pivotal in one's overall concept of self (Tiggemann & Williamson, 2000). Problematic however is that the literature indicates a dearth of dermatological studies detailing the meaning-making experiences of individuals who have undergone changes to their physical appearance as a result of this and the impact of cutaneous disease on the self-concept (Hill, 2004; Papadopoulos, Bor & Legg, 1999; Thompson & Kent, 2001). Our experiences and how we make sense of what we experience is primarily dependent upon the kinds of bodies we have and also on the ways we interact with the various environments we inhabit. It is through our embodied interactions that we inhabit a world, and it is through our bodies that we are able to understand and act within this world with varying degrees of success (Johnson, 1999). The importance of skin for an individual's psychosocial equilibrium can easily be appreciated. First, the skin represents the outward packaging of our being. Second, the cutaneous surface is what society initially perceives and with dermatological disease being the basis for social stigma. Arguably, having a healthy, unblemished skin can enhance one's self-esteem, self-identity and not infrequently, one's social standing (Koo & Yeung, 2002). Studies investigating the impact of disfiguring cutaneous disease on the self-concept appear to be lacking in the literature. In 2004, at a meeting of the Editorial Board for the Journal of Dermatology Nursing, the need for studies presenting the patient's experience of cutaneous disease was discussed. It was thought that qualitative exploration of the patient's experience of cutaneous disease would provide medical and mental healthcare professionals with valuable insights and important information to help improve dermatology patient care (Hill, 2004). Dermatology and self-concept phenomena tend to be investigated interdependently of each other. Furthermore, the majority of research in this area focuses on quantitative research design. Consequently, much of the depth of information regarding the experiential world of sufferers of cutaneous disease is invariably lost (Hill, 2004; Thompson & Kent, 2001). In light of that stated above, this study explored the meaning-making experience of men and women who suffer from psoriasis and the impact of this on the various dimensions of the self-concept. Due to the sparsity of South African studies investigating qualitatively, the experiences of persons suffering from a common, chronic dermatological condition, this study followed an existential phenomenological approach in describing the impact of psoriasis on the self-concept as told from the perspective of the men and women who live with this. Existential phenomenology seeks to explicate the essence, structure and form of both human experiences and behaviour as revealed through essentially descriptive techniques that includes disciplined reflection (Sokolowski, 2000). Given the apparent lack of awareness and knowledge of psychological processes, meaning-making and coping strategies utilised by psoriasis sufferers in their experience of this, this methodology was thought most appropriate (Hill, 2004; Newell, 2000; Papadopoulos, et al., 1999; Thompson & Kent, 2001). In terms of the areas of participation, three male and four female sufferers of psoriasis participated in the study. For all participants, psoriasis was in the active phase and covered most parts of their body. Data was collected using a questionnaire set consisting of semi-structured questions and the research question, which was open-ended. The method of data analysis was based on an integration of the works by various phenomenologists and involved six phases, namely: bracketing, intuitive grasp, eidetic reduction, textural and structural descriptions, composite textural and structural descriptions, and the final synthesis. The participants confirmed that the statements generated were accurately reflected. The results evidenced several prominent themes shared by the group, namely: (a) that the severity of the physical manifestations and the painful symptoms of psoriasis can result in negative self-concept evaluations; (b) a lack of empathy and a failure to provide knowledge on psoriasis and a priori caution of the side-effects of psoriatic medications by the medical doctors consulted was experienced by the participants as disempowering and adversely affected their emotional well-being; (c) the doctor/patient relationship was observed as pivotal in influencing the participants general concept of self; (d) the participants acceded that medical aids need to place psoriasis on the list of chronic medical conditions; (e) social stigma adversely affects self-concept evaluations; (f) public education on psoriasis is required; (g) drawing on various methods of coping was deemed crucial to the enhancement of the self-concept in the participants journey towards psychological health; (h) positive meaning-making from the psoriatic/self-concept experience enhanced quality of life issues; and finally, (i) trait self-esteem and healthy self-concept development may be important determinant factors in the psychological recovery of patients suffering from psoriasis. More specifically, in terms of self-evaluation, the participants experienced psoriasis as an assault on the physical self that was painful, embarrassing and humiliating. In redefining psoriasis in this way, the participants redefined their body image (mental construct of the body), and with the pervasiveness of negative self-evaluations an offshoot of continuous negative cognitive and emotional schemas of the body. Regarding the doctor/patient relationship, the results of the study show a need for medical doctors to expand their focus of treating the symptoms of psoriasis to incorporate a more holistic treatment approach that places emphasis on psychological, social and nutritional processes. The willingness of medical professionals to network with psychologists and other healthcare professionals and also being prepared to integrate the concept of holism into their treatment programmes was thought one method of attaining a holistic approach to the treatment and management of dermatology patients. Significantly, the doctor/patient relationship was also experienced as being an important factor in the patients drive to want to heal (healing is not here equated with cure but rather being able to approach living with psoriasis more positively). The participants in this study experienced doctors to be largely unsympathetic and not well versed in the physiology of psoriasis. Additionally, the degree of psychological trauma experienced by the participants in their suffering with psoriasis seemed to go unnoticed by the treating doctors. To this end, helplessness and feelings of disempowerment were heightened. In terms of treatment implications, the participants claimed that their treating doctors failed to inform them of the severity of the side-effects, the dangers of various treatments, and the possible inefficacy of many treatments utilised. The participants experience of this resulted in the following: a) diminished trust in the doctor/patient relationship and the medical profession generally; b) heightened body shame and repulsion of self (as opposed to feeling repulsed by the psoriasis alone); c) intense anger and with some participants describing emotional anarchy; and finally, d) in feeling left out of the treatment decision-making process, participants felt as though they had lost control over their own body. In terms of medical aid support, the participants pointed out that psoriasis is not on the government approved list of chronic conditions and as such, given their experiences, acceded that this is something that needed to be challenged. Regarding social stigma, the participants’ experience of this appeared to result in re-enforcing a sense of their feeling socially shunned and physically alienated from their familiar body. Furthermore, it would appear that social stigma might play a participatory role in increasing the severity of the psoriatic condition due to the stress evoked in the experience of feeling socially stigmatised and also the heightening of psychological difficulties experienced as participants moved from pride to shame. All participants felt public education and awareness of the onset, cause and course of psoriasis was required. Methods of coping utilised by the participants included: the seeking out of empathetic medical practitioners, psychotherapy, hypnotherapy, assertiveness skills training, implementing spirituality in their lives, and drawing upon the support of family and friends. Finally, in the midst of much adversity, the participants found an inner strength from which to reclaim their sense of self and which they attribute to having had a positive demeanour prior to suffering from psoriasis. In the deconstruction (fracturing) of self, the participants seemed to have felt compelled into a process of change that could be characterised as a reconstruction of self - an evolving of the old and new dimensions of self that would evolve further into a stronger and more resilient sense of self that characterises the participants today. The participants to this study embarked upon a journey of self-empowerment and which was a defining factor in their making meaning from their suffering. Not alluded to in the literature is that, for the participants, psoriasis became a tool that they utilised to reclaim their lives and to re-build the self anew. The results of this study reveal many important areas for future research with persons suffering from psoriasis and dermatological conditions generally, such as: i) the focussing on levels of trait self-esteem in effecting how positive change in one's self-concept may or may not occur; ii) the exploration of disfiguring skin conditions as an impetus for self-concept enhancement and creating meaning in one’s life; iii) exploring the efficacy of combining psychotherapy with medical treatments in the management of dermatology patients; iv) exploring the role of the doctor/patient relationship in the patient’s drive towards psychological health and treatment compliance; and finally, v) exploring the impact of dermatological disease on the family of the sufferer, especially given the significance of the familial system in the sufferers coping. Importantly, the results of this study suggest that having a healthy self-concept prior to the development of illness or disease is pivotal in accounting for why some people recover remarkably well psychologically and others do not. The findings of this study are valuable and will have important implications for all within the healing profession in helping to effect positive change in their future endeavours with persons who suffer from dermatological disease.

Carrapatos são parasitas hematófagos que secretam, em sua saliva, componentes imunomoduladores capazes de promover sua alimentação e suprimir as respostas imunológicas do hospedeiro. Dentre as classes de imunomoduladores presentes na saliva, encontram-se as evasinas, proteínas com capacidade de ligarem-se a quimiocinas, inibindo sua atividade relacionada ao recrutamento de células imunes. Neste trabalho, nós descrevemos a produção recombinante e caracterização estrutural e funcional de uma nova evasina putativa, a proteína Bm-nr-264079, identificada no sialotranscriptoma do carrapato bovino R. microplus. Observamos que a proteína Bm-nr-264079 apresenta similaridade estrutural com outras evasinas de carrapatos Rhipicephalus sanguineus já caracterizadas. A proteína foi produzida na forma recombinante com sucesso a partir da expressão em Escherichia coli Rosetta e purificação em condição desnaturante por cromatografia de afinidade a metais. Esta proteína apresentou atividade inibitória sobre o desenvolvimento de psoríase em modelo animal, limitando o desenvolvimento de lesão local nos animais tratados após a indução da doença por aplicação de imiquimode. A proteína Bm-nr- 264079 não apresentou efeito inibidor do crescimento de Staphylococcus aureus e Streptococcus uberis, bactérias que comumente colonizam a pele de bovinos suscetíveis à infestação por R. microplus. Os resultados aqui apresentados demonstram que a proteína Bm-nr-264079, em sua forma recombinante, apresenta atividade inibidora da inflamação, com potencial atividade de evasina. Novos estudos são necessários para uma caracterização mais específica das possíveis atividades farmacológicas desta proteína / Ticks are hematophagous parasites that secrete, in their saliva, immunomodulatory components capable of promoting their feeding and suppressing the immune responses of the host. Among the classes of immunomodulators present in saliva, we have the evasins, proteins capable of binding to chemokines, inhibiting the recruitment of immune cells. In this work, we describe the recombinant production and structural and functional characterization of a novel putative evasin, the protein Bm-nr-264079, identified in the sialotranscriptome of the R. microplus cattle tick. We have found that the protein Bm-nr-264079 shows structural similarity to other already characterized Rhipicephalus sanguineus tick evasins. The protein was successfully produced with expression in Escherichia coli Rosetta and purification in denaturing condition by metal affinity chromatography. This protein showed inhibitory activity on the development of psoriasis in the animal model, limiting the development of local lesion in the treated animals after the induction of the disease by the application of imiquimod. The protein Bm-nr-264079 showed no inhibitory effect on the growth of Staphylococcus aureus and Streptococcus uberis, bacteria that commonly colonize the skin of cattle susceptible to R. microplus infestations. The results presented herein demonstrate that Bm-nr-264079, in its recombinant form, exhibits antiinflammatory activity with potential evasin activity. Further studies are needed to characterize more specifically the pharmacological activities of this protein

Epigenetic regulation is now known to play an important role in determining stem cell fate during normal tissue development and disease pathogenesis. In this study, we report loss of 5-hydroxymethylcytosine (5-hmC) mediated by ten-eleven translocation (TET) methylcytosine dioxygenases in keratinocyte stem cells (KSCs) and in their progenitor transit-amplifying (TA) cells of psoriatic lesions. We establish the DNA hydroxymethylation profile in both human psoriasis as well as in the imiquimod (IMQ)-induced mouse psoriasis model. Genome-wide mapping of 5-hmC in IMQ-treated mice epithelium revealed a loci-specific reduction of 5-hmC in genes associated with maintaining stem cell homeostasis including those involved in the RAR and Wnt/β-catenin signaling pathways. Restoration of TET expression in human KSC cultures via vitamin C treatment increased 5-hmC levels and induced more normal KSC differentiation. We found that by modulating 5-hmC levels in vitro, we could alter downstream expression of genes important in regulating stem cell homeostasis like nestin as well as IL-17R known to promote the psoriatic phenotype. Our findings demonstrate that loss of 5-hmC is a critical epigenomic phenomenon in KSCs and TA cells during psoriasis pathogenesis. / 2019-12-17T00:00:00Z

Background: Psoriatic arthritis (PsA) is a chronic heterogenous inflammatory arthritis with five phenotypes. The two least studied phenotypes are investigated in this thesis, including: psoriatic spondyloarthropathy (PsSpA) and psoriatic arthritis mutilans (PAM). The aims of this thesis were to determine the prevalence, clinical characteristics and radiographic characteristics of PsSpA and PAM in a cohort of PsA patients, and serum-soluble bone- turnover biomarkers of these phenotypes. Aims: Comparisons were made with PsA patients without axial disease (pPsA), and ankylosing spondylitis (AS) patients. Methods: A prospective single-centre cross-sectional study was conducted of PsA and AS patients. Serum on psoriasis-only patients (PsC) and healthy controls (HC) were also obtained. Multivariate clinical, radiographic, genetic and serum biomarker comparisons were made between these five groups of subjects. Results: The study enrolled 201 PsA and 201 AS patients, who were then reclassified as 118 PsSpA, 127 pPsA and 157 AS cases, alongside 200 PsC and 50 HC subjects. Several clinical biomarkers, imaging biomarkers, serum-soluble biomarkers and genetic biomarkers were identified that differentiate PsSpA from pPsA and AS. PsSpA affected a significant proportion of PsA patients, and was not a milder version of AS. PsSpA involvement was as disabling and clinically impactful as AS. PAM was found to be associated with PsSpA, and clinical biomarkers of PAM occurrence and radiographic progression were identified. Conclusions: In conclusion, this thesis indicates that PsSpA is on a spectrum of musculoskeletal disease, in between pPsA and AS; with PsSpA comprising a continuum itself, and with a phenotype expression related to disease duration. These findings may prompt the inception of an international-consensus classification system for PsSpA, for which there is a great clinical need. Given that PsSpA has its own discrete clinical and biomarker signature, its clinical management and research should be tailored from that of pPsA and AS. Ultimately this may further the effort for stratified and personalised medicine.