M.Tech. / Psoriasis vulgaris (plaque psoriasis) is a chronic recurring inflammatory skin disease that manifests most commonly as well-circumscribed, erythematous papules and plaques of varying sizes, covered with silvery scales (Beers et al., 2010). The condition itself is considered to be difficult to treat and manage by many types of healthcare practitioners, due in part to its unknown aetiology/trigger and partly due to the nature of the disease itself (Medonça and Burden, 2003). The aim of this study was to ascertain the effects of a Homoeopathic complex remedy on psoriasis. A group of twenty seven participants completed the study. Participants were of both sexes, had to be between the ages of 18 and 65 and had to have been previously diagnosed with plaque psoriasis. The study was conducted over four consultations, two weeks apart, over a six week period. The study followed a double-blind, placebo controlled format. Participants were grouped into matching pairs in terms of age and severity of disease and were then randomly assigned into either the treatment or placebo group for the study duration. Participants were evaluated at each consultation using the three primary assessment tools, namely: the psoriasis area and severity index (PASI) used to assess erythema, thickness and scaling of lesions; the psoriasis disability index questionnaire (PDI), a subjective participant-orientated evaluation of the psychological impact of the disease and the 5-D itch scale used to quantitatively rate the subjective experience of pruritus. The secondary tools used at each consultation were for monitoring purposes only and were used to determine: changes in selected lesion area, as well as the effects of the intervention on the total body surface area (TBSA) affected by psoriasis. The TBSA tool was also used to determine whether new lesions developed during the study period. Using non-parametric analyses, the results of the study demonstrated statistically significant improvement in three of the five variables tested. This includes improvement in: lesion appearance (erythema, scaling and thickness) as determined by PASI; improved psychological experience of the disease quantified by PDI and improvement in the degree of pruritus. It was noted that non-parametric analyses also showed improvement in lesion area. However, lesion area measurement was a secondary tool used for monitoring purposes and it was noted that the use of the tool demonstrated short-comings with regards to consistency and reliability. Parametric analyses showed improvement of statistical significance in one of the five variables tested, namely that of pruritus levels as determined by the 5-D itch scale. It was concluded from this study that the homoeopathic complex remedy was found to be effective in the treatment of certain symptoms of psoriasis and as such should be considered as an adjunct therapy in its treatment.

Inflammatory myeloid dendritic cells (DCs) are critical in the pathogenesis and maintenance of psoriasis vulgaris, a chronic inflammatory skin disease of unknown etiology. New ways to define these cells, and their precursors, may allow us to better understand their role in inflammation. Immunohistochemistry was performed on frozen tissue sections of normal and psoriasis biopsies to examine the dermal expression of potential markers of inflammatory DCs, namely CLEC9A, CD103, SlanDC, and TREM-1. The allostimulatory capacity of DC subsets (of SlanDC+ and CD1c+) was compared in a mixed leukocyte assay (MLR). Potential precursors of inflammatory DCs were FACS-sorted for transcriptomic profiling and functional assays. CLEC9A, CD103, and SlanDC did not prove useful in uniquely identifying myeloid dendritic cells in normal skin, and inflammatory dendritic cells in inflammation. TREM-1 was highly upregulated in psoriasis lesional skin as compared to non-lesional, and its activation may be critical in the maintenance of inflammation. Contrary to published findings, CD1c+ DCs possessed a higher allo-stimulatory capacity than SlanDCs, and induced greater IL-17 in T cells. TREM-1 may provide a novel therapeutic target for psoriasis treatment. The six circulating monocyte and dendritic cell populations in human peripheral blood were obtained via FACS sorting, and their genomic profiles will be examined. By comparing the genomic profiles of the six circulating monocyte and dendritic cell populations in human blood, and examining their allo- and autostimulatory capacities in a peptidoglycan (PGN) stimulated in vitro model of inflammation, the source of these inflammatory dendritic cells can be identified, and provide future targets of therapy for this psoriasis.

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.

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 is not an illness just of these days. 3-7% of world population suffers from this illness. This diploma work focuses on quality of life of ill people. We guess that it influences such a client in a holistic way. This illness interferes into personal, professional and social life. So psoriasis is not just an illness but also an everyday problem or handicap for those who get ill.Two questionnaires were made for this research, where first of those is focused on quality of life by a standard questionnaire and the second one was created on the base of analysis of D. Johnson model. Those questionnaires were given out to ill in South and Central Counties of Bohemia. The respondents were to chose, after their completing, which one is more sensitive to problems implying from this illness. The results are graphically shown and then paid attention in chapter Discussion.Finally I would like to say, those hypotheses were acknowledged. Psoriasis influences life in a holistic way, a nurse can have a significant influence on well-being of a client with this illness in area of her nursing interventions and D. Johnson model is an effective tool for providing those ill with psoriasis with care.

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In der vorliegenden Arbeit wurde die Expression von Angiotensinogen, Renin, Angiotensin-Converting-Enzym (ACE) und von den Agiotensin-Rezeptoren AT1 und AT2 in humaner Haut untersucht, um zu sehen, ob humane Haut ein lokales Gewebe Renin-Angiotensin-System (RAS) besitzt und fähig ist, Angiotensin II (Ang II) zu synthetisieren sowie welche physiologische Rolle Ang II in humaner Haut haben könnte. Außerdem wurde das Expressionsmuster von Angiotensinogen, Renin und ACE in gesunder humaner Haut mit dem in Psoriasis, Basaliom und Spinaliom (SCC) verglichen, um einen Einblick in pathophysiologische Funktionen des RAS zu gewinnen. Mit Hilfe von RT-PCR konnten alle Komponenten des RAS in vitro auf mRNA Ebene in kultivierten primären Keratinozyten, Melanozyten, dermalen Fibroblasten und dermalen mikrovaskulären Endothelzellen (MVEC´s) nachgewiesen werden, mit einer Ausnahme: Melanozyten scheinen keine AT2-Rezeptoren zu exprimieren. Immunhistochemische Untersuchungen zeigten die Expression aller Komponenten auf Proteinebene in Epidermis und dermalen Gefäßwänden in Gewebeschnitten humaner Haut. Zusätzlich erfolgte der Nachweis von Ang II in kultivierten Keratinozyten mittels enzymatischen immunometrischen Assays. Während Angiotensinogen, Renin und ACE bei immunhistochemischen Untersuchungen an Gewebeschnitten gesunder menschlicher Haut in allen Epidermalschichten gleichmäßig verteilt waren, zeigte sich bei der Psoriasis eine deutliche Betonung der unteren Epidermalschichten. Immunhistochemische Untersuchungen von Basaliomen erbrachten eine verminderte Expression von Angiotensinogen und Renin innerhalb der Tumornester. ACE wurde in den Tumorzellen noch weniger exprimiert. In immunhistochemischen Untersuchungen von Spinaliomen färbten sich die Tumorzellen deutlich homogen an. Die Experimente haben gezeigt, dass alle Komponenten des RAS in enger Lokalisation in menschlicher Haut vorkommen und dass folglich ein lokales Gewebe RAS in humaner Haut existiert sowie dass humane Haut fähig ist, Ang II ohne Zufuhr weiterer Komponenten und ohne regulatorische Einflüsse aus der Zirkulation zu synthetisieren. Eine mögliche physiologische Rolle von Ang II könnte die Regulation von Keratinozyten-Proliferation und –Differenzierung über seine Rezeptoren sein. Bezüglich der pathophysiologischen Rolle haben die Untersuchungen eine Fehlregulation des kutanen RAS in Epidermis psoriatisch veränderter Haut gezeigt, welches ein Hinweis auf eine pathogenetische Rolle des RAS bei der gestörten Keratinozyten-Proliferation und –Differenzierung sein könnte. Das Expressionsmuster in den untersuchten Tumoren war uneinheitlich, weshalb eine Interpretation der Rolle des RAS in kutanen Tumoren ohne weitere Untersuchungen kaum möglich erscheint. 1 / The present study was designed to elucidate whether a local tissue renin-angiotensin system (RAS) is expressed in human skin, whether cutaneous cells are able to autonomously synthesise angiotensin II (Ang II), and to get a first insight into a putative physiological role of Ang II in this location. For this purpose, the expression of angiotensinogen, renin, angiotensin-converting enzyme (ACE) and of the angiotensin receptors AT1 and AT2 was examined in human skin samples and in diverse cutaneous cells in primary culture on mRNA- and protein-level. Furthermore, the study compared the expression pattern of angiotensinogen, renin and ACE in healthy human skin with that in psoriasis, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) to look for possible differences between healthy and diseased skin. Using mRNA derived from cultured primary keratinocytes, melanocytes, dermal fibroblasts and dermal microvascular endothelial cells (MVECs), all components of the RAS could be demonstrated by RT-PCR except for AT2 receptors in melanocytes. Immunohistochemical stainings of cryostat sections of human skin revealed the expression of all components at protein level within the epidermis and in dermal vessel walls. In addition, the presence of Ang II in cultured keratinocytes and their supernatants could be proven by enzyme immunometric assay giving strong evidence for the ability of keratinocytes to autonomously synthesise Ang II. Regarding the comparison of RAS expression in healthy versus diseased skin, expression of angiotensinogen, renin and ACE was altered in all dermatoses examined. While in normal skin, RAS components were distributed equally and homogenously throughout all layers of the epidermis, in psoriatic skin their expression was more intense in the basal epidermal layers and less intense in the upper layers. In BCC sections, expression of angiotensinogen and renin was down-regulated, and tumour cells stained negatively for ACE. In SCC cryostat sections, tumour cells stained positively for all RAS components with an intensity comparable to normal skin. Taken together, the experiments revealed that a local tissue RAS exists in human skin, and that human skin is able to autonomously synthesise Ang II without any supply of components from the circulation. The physiological role of Ang II in normal skin may comprise the regulation of keratinocyte proliferation and differentiation. Concerning a putative pathophysiological role of Ang II in skin, this study provides evidence for a deregulation of the RAS in psoriatic skin and in BCC pointing to an involvement of the RAS in the pathomechanisms of these dermatoses. 1

Background: Financial constraints challenge evidence of the effectiveness of dermatological inpatient management. Objective: To evaluate the effectiveness of hospitalization in atopic dermatitis and psoriasis regarding initial and sustained benefits. Methods: Prospective study on adults with psoriasis vulgaris (n = 22) and atopic dermatitis (n = 14). At admission, discharge, and 3 months after discharge, validated outcomes of objective and subjective disease severity were assessed by trained investigators. Results: Hospitalization resulted in substantial benefit in quality of life and clinical disease severity. Looking at mean scores, the observed benefit appeared stable until 3-month follow-up. The analysis of individual patient data revealed significant changes in disease severity between discharge and 3-month follow-up with some patients relapsing, others further improving. Reasons for hospitalization and treatment performed were not related to sustained benefit. Conclusions: In psoriasis vulgaris and atopic dermatitis, hospitalization effectively improved quality of life and clinical disease severity. Further research should focus on prognostic factors for sustained improvement. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Background: Financial constraints challenge evidence of the effectiveness of dermatological inpatient management. Objective: To evaluate the effectiveness of hospitalization in atopic dermatitis and psoriasis regarding initial and sustained benefits. Methods: Prospective study on adults with psoriasis vulgaris (n = 22) and atopic dermatitis (n = 14). At admission, discharge, and 3 months after discharge, validated outcomes of objective and subjective disease severity were assessed by trained investigators. Results: Hospitalization resulted in substantial benefit in quality of life and clinical disease severity. Looking at mean scores, the observed benefit appeared stable until 3-month follow-up. The analysis of individual patient data revealed significant changes in disease severity between discharge and 3-month follow-up with some patients relapsing, others further improving. Reasons for hospitalization and treatment performed were not related to sustained benefit. Conclusions: In psoriasis vulgaris and atopic dermatitis, hospitalization effectively improved quality of life and clinical disease severity. Further research should focus on prognostic factors for sustained improvement. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.