Background: Eczema is an important condition as it affects 20% of children in the UK and is associated with significant morbidity for children and their families. Although some progress in understanding factors associated with the occurrence of eczema has been made, very little is known about factors associated with disease worsening. Most textbooks and review articles quote long lists of exacerbating factors but with very little scientific data to support them. Before I could begin to study this topic, I first had to define a disease flare in eczema, systematically review the literature on flare factors in eczema and review available outcome measures for eczema. Objectives: The objectives of the main study described in this thesis were to assess the role of various environmental factors on the severity of eczema in a cohort of children with eczema. Hypotheses: 1. In hot weather, the combination of heat, sweating and grass pollen precipitates increased severity in children with eczema in the UK. 2. In cold weather, the combination of cold weather, indoor aeroallergen exposure and reduced relative humidity from central heating lead to increased severity in children with eczema in the UK. These first two hypotheses were informed by previous research which proposed "summer" and "winter" types of eczema. 3. Detergents (soap, shampoo) increase the propensity to disease flares triggered by other factors at all temperatures, but more in cold weather due to impaired skin barrier function. 4. UK children with filaggrin mutations are more prone to the effects of climatic factors such as cold and heat than individuals who are wild type for filaggrin. 5. Any combination of greater than or equal to three exposures at any time is associated with worsening of eczema. The exposures assessed included: dust, exposure to pets, shampoo, sweating, swimming, nylon clothing next to the skin and a change in mean temperature of more than 3°C from the previous weekly average. Methods: Pilot study: 30 children with moderate to severe eczema aged 0 to 15 years participated in a panel study over a one month period in June 2003 in Cork, Ireland. This study involved daily completion of a paper diary recording eczema severity and exposures. Feasibility of a panel study design was assessed and associations between exposures and disease severity were analysed. Main study: A prospective cohort study (n=60) of children aged up to 15 years with moderate to severe eczema was studied for between six and nine months with overlapping start dates to allow study of seasonal factors. Exposures studied included: temperature, relative humidity, sun exposure, sweating, clothing, cleansing products/ washing, outdoor pollen level, extent and nature of exposure to household pets, dusty environments and swimming. Children or their parents completed daily novel electronic diaries recording eczema severity and exposures. Portable dataloggers were used to record indoor temperature and relative humidity. External meteorological data was obtained from a local monitoring centre. The primary outcome was a daily "bother" score and the secondary outcomes were daily "scratch" scores and flares of eczema. Autoregressive moving average models (ARMA) were used to model the impact of each exposure on eczema severity for each individual. Standard random effects meta-analysis techniques were used to pool estimated coefficients across participants. Heterogeneity of responses as detected using Chi-squared tests represented inter-individual variation. The body site-specificity of reactions was also examined as was the interaction between filaggrin mutations and disease worsening with exposures. Findings. Pilot study: The pilot study highlighted the issue of drop outs and missing data during the study. 83% (n=25) returned the diaries at the end of the study period, and within these, recording of disease severity was good (97% complete). However, there was variability in recording of exposures (65% to 83% complete). Preliminary findings suggested a temporal association between eczema severity and heat (lag 0, i.e. the day of exposure, p=0.04), damp (lag day 2, p=0.03), sweating and stress (lag day 3, p=0.03 and p=0.02 respectively) and damp (lag day 4, p=0.001). Main study: Primary outcome: "bother scores": Increased disease severity was associated with direct contact with nylon clothing (pooled regression coefficient 0.23, 95% CI 0.03 to 0.43), increasing exposure to dust (pooled regression coefficient 0.53, 0.23 to 0.83), exposure to unfamiliar pets (pooled regression coefficient 0.22, 0.10 to 0.34), sweating (pooled regression coefficient 0.24, 0.09 to 0.39) and shampoo exposure (pooled regression coefficient 0.07, 0.01 to 0.13). The association between shampoo use and worsening of eczema was enhanced in cold weather (pooled regression coefficient 0.30, 0.04 to 0.57). Body site specificity was observed for the reactions to nylon clothing, which was greater on covered sites (trunk p=0.02, limbs p=0.03), reactions to wool clothing on truncal covered sites (p=0.03) but not limbs (p=0.62), while worsening of hand eczema was associated with exposure to pets (p<0.001). The only interaction with filaggrin mutations was observed for the 2282del4 mutation and worsening of eczema in summer. Significant heterogeneity of responses between individuals was observed for exposure to grass pollen and outdoor temperature. In regard to the final hypothesis, a combination of any three of seven likely variables was associated with worsening of eczema (pooled regression coefficient 0.41, 0.20 to 0.63). Secondary outcome: "scratch" scores: Increased disease severity was seen associated with swimming (pooled regression coefficient 0.14,0.00 to 0.28), exposure to wool clothing (pooled regression coefficient 0.28, 0.11 to 0.45), sweating (pooled regression coefficient 0.15, 0.04 to 0.26), shampoo (pooled regression coefficient 0.07, 0.01 to 0.13), dust (pooled regression coefficient 0.36, 0.12 to 0.59) and high grass pollen levels (pooled regression coefficient 0.10, 0.01 to 0.73). Secondary outcome: flares of eczema: Only swimming was clearly associated with worsening of eczema using this outcome measure (pooled regression coefficient 0.42, 0.05 to 0.80). Conclusions: The following factors were shown to be associated with disease worsening in children with eczema in this UK study: clothing (wool and nylon), sweating, shampoo, swimming, dust, contact with unfamiliar pets and high grass pollen levels. Relative to the study hypotheses, the association between shampoo exposure and eczema worsening was shown to be increased in cold weather. There was also evidence showing an association between various combinations of exposures and disease worsening. There was insufficient evidence to support the other hypotheses tested in this study but this may be explained by low prevalence of these exposures. The implications of the findings of this study for clinical practice are that for the first time, it has been shown that shampoo exposure may be associated with eczema worsening and that this is more pronounced in cold weather. This study also suggests that worsening of eczema may be more complicated in that multiple exposures acting in concert may be associated with worsening of disease. Future research with increased participant numbers is required to specifically study possible gene-environment interactions with filaggrin mutations and their relevance in relation to disease flares and to look at shampoo formulations in relation to worsening of eczema.

Vitiligo is the most common skin disorder resulting in depigmentation, but high-quality research is lacking. A Cochrane review of interventions for vitiligo published in 2010 highlighted methodological limitations with existing trials; which have generally been too small and heterogeneous to inform clinical recommendations. The objective of this thesis was to improve the evidence base for the treatment of vitiligo. This PhD was funded by the National Institute for Health Research, as part of the research programme called “Setting Priorities and Reducing Uncertainties for people with Skin Diseases”. It includes the following: 1) identifying the most important research priorities for patients and clinicians, thereby informing the research agenda; 2) conducting a systematic review of outcome measures used in vitiligo trials and a survey of the most desirable outcomes for patients and clinicians; and 3) conducting a pilot double blind, randomised controlled trial (RCT) on home hand-held phototherapy in preparation of the first national multi-centre RCT for the treatment of vitiligo. For the prioritisation exercise, a total of 660 treatment uncertainties were submitted by 460 patients and clinicians. The identified priority areas included interventions such as combination of topical agents and phototherapy. The systematic review on outcome measures identified 25 different domains that had been used in previous trials. Although percentage repigmentation was measured in 96%; 48 different scales had been used. In contrast, patients and clinicians favoured the use of “cosmetically acceptable” repigmentation. Finally, a 4-month pilot trial recruited 29 participants and tested the logistics of running a future RCT. This work resulted in a commissioned call and funding of a national RCT on vitiligo (topical corticosteroids in combination with home hand-held phototherapy); the initiation of an international consensus exercise on core outcome measures for use in vitiligo trials; and informed the design and conduct of a future national RCT.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Medicine in the discipline of Dermatology Johannesburg, 2017 / Introduction: Vitiligo is a skin pigmentation disorder and has an estimated global prevalence of around one to two percent. Vitiligo can significantly affect patients’ Quality of life (QoL). It is cosmetically and psychologically devastating, and can affect anyone irrespective of race, skin type or ethnicity. There is a paucity of research evaluating the QoL amongst vitiligo patients in Africa and Sub-Saharan Africa in particular. The objectives of this study were to demonstrate how vitiligo has altered the QoL of vitiligo patients treated at the skin outpatients’ clinics in Johannesburg, South Africa. Methods: Our research was a prospective cross-sectional study of all individuals who were diagnosed with vitiligo at the three dermatology outpatients’ clinics in three academic public hospitals, and the phototherapy daycare centre in Johannesburg. All patients fulfilling the inclusion criteria were requested to take part in the study. Data was obtained from enrolled individuals using a data collection sheet and the Dermatology Life Quality index questionnaire. This information was analysed using statistical software (STATA version 12). Results: A total of ninety-five (n=95) respondents were included as per inclusion criteria in our study. Our cohort comprised of sixty-two females (n=62, 65.26%), thirty-three males (n=33, 34. 74%). DLQI scores were in the ranges of 0 to 28 and the mean was 10.06±6.52, which indicates a moderate Quality of life (QoL) impairment in our cohort. Conclusion: Our study has shown that vitiligo moderately affects the QOL life of adult South African vitiligo patients. Therefore, treatment measures should be directed towards medical and psychological aspects of our patients for better treatment outcomes and improved QoL. This would be an argument for establishment of psychodermatology clinics at our referral hospitals. / MT2017

This thesis contributes to the understanding of the psychosocial factors associated with skin conditions and the lived experience of visible difference. Chapter one is a systematic literature review that identifies the psychosocial factors associated with the onset and living with alopecia for children and young people. A systematic review of the literature indicated relational factors and frequency of negative life events were associated with the onset of alopecia for young people. Although the findings into the psychosocial factors associated with living with alopecia are mixed, anxiety was the most frequently reported factor for children and young people. The quality of the papers included in the review are mixed, with varying population samples, measures and methodological limitations. Clinical and research implications are discussed. Chapter two is a qualitative research study that explored the lived experience of six women with rosacea using interpretative phenomenological analysis (IPA). Participants’ experiences of rosacea were characterised by an internal struggle to feel in control of their skin condition whilst externally, learning to navigate complex social interactions. Clinical and research implications are discussed. Chapter three is a reflective account of the researcher’s experiences during the research process. The researcher’s reflections have been structured around the Acceptance and Commitment Therapy (ACT) Hexaflex model. Particular attention has been paid to the experiences that reflect the researcher’s values, cognitive defusion, acceptance, contact with the present moment, self as context and committed action.

Erosive lichen planus affecting the vulvovaginal region (ELPV) is a rare chronic inflammatory condition causing painful raw areas that can lead to scarring, at the vaginal entrance. Symptoms considerably impact upon daily function and quality of life. There is risk of cancerous change in affected skin of 1-3%. A Cochrane Systematic Review, published in 2012, found no randomised controlled trials (RCT) on which to base treatment for ELPV. Retrospective case series suggest that super-potent topical corticosteroids are frequently used as first-line therapy, although one third of patients fail to respond adequately and require escalation of therapy. There is clinical uncertainty regarding which second-line therapies should be used. The following steps were taken to inform the design of an RCT to determine optimal second-line therapy for EVLP resistant to topical steroids: • A multi-centre retrospective review and audit of case notes to assess current clinical management in the UK. • A qualitative investigation with UK clinicians to establish their views and principles of management of ELPV. • An international multi-disciplinary electronic-delphi consensus exercise to agree a set of diagnostic criteria for ELPV. • A systematic review to assess existing outcome measure tools that have been used in randomised controlled trials of vulval skin disorders. • Assessment of patients views through a survey of a national patient group and subsequent focus groups with patients. The resulting multi-centre, four-armed, open-label, pragmatic randomised controlled trial will compare hydroxychloroquine, methotrexate and mycophenolate mofetil against a standard care group of clobetasol propionate 0.05% plus a short course of oral prednisolone. This will be the first RCT to test systemic agents for patients with ELPV and will add to the existing evidence base. The methodologies employed to develop the RCT protocol, and the trial design itself, may act as a template for clinical research into the therapeutic management of other rare inflammatory conditions.

<p>Positive patch test reactions to gold are commonly seen in dermatology clinics, but it is veryunusual for the patients to actually have any clinical symptoms. It is also common with irritantreactions that are not linked to adaptive immunity. Therefore, a deeper understanding of themechanisms underlying allergic contact dermatitis (ACD) reaction, and the search for acomplementing diagnostic tool, is important.</p><p>In paper I we included three subject groups; one with morphologically positive patch testreactions to gold sodium thiosulphate (GSTS, the gold salt used in patch testing), one withnegative patch tests, and one with irritant reactions to gold. Blood samples were collected andexamined regarding the proliferation rate and which cytokines were secreted after culturingwith GSTS. We saw that the cultured lymphocytes from the allergic donors proliferated at asignificantly higher rate than the two other subject groups, and that the cells secreted cytokinesof both Th1 (Interferon (IFN) -g and Interleukin (IL) -2) and Th2 (IL-13 and IL-10) types. Theallergic donors secreted significantly higher levels of IFN-g, IL-2 and IL-13 than the two othersubject groups. Both the negative and irritant subject groups showed suppressed levels of thecytokines as compared with the unstimulated cultures, demonstrating the immunosuppressingeffects of gold.</p><p>We also examined whether any of the analyzed markers, alone or combined, could be usedas an aid for diagnosing ACD to gold. We found that the IFN-g assay yielded the highestsensitivity (81.8 %) and specificity (82.1 %), and also identified 87.5 % of the irritant group asnon-allergic.</p><p>In paper II we decided to investigate what cell types and subsets that reacted to the goldstimulation. We analyzed proliferation rate and expression of CD45RA, CD45R0, cutaneouslymphocyte-associated antigen (CLA) and the chemokine receptors CXCR3, CCR4 andCCR10. Similar to what has previously been published about nickel (Ni) allergy, the cells fromthe gold-allergic subjects that reacted to the GSTS stimulation expressedCD3+CD4+CD45R0+CLA+. However, contrary to findings in studies on Ni-reactive cells, wesaw no differences between allergic and non-allergic subjects regarding any of the chemokine receptors studied.</p><p>In conclusion, we found that analysis of IFN-g might be a useful complement to patchtesting, possibly of interest in avoiding the need for repeated tests to rule out irritant reactions.We also saw that the cells that proliferated in response to gold were memory T-cells expressingCD4 and CLA, the marker for skin-homing. However, these cells did not express elevatedlevels of any of the chemokine receptors analyzed, showing that there are both similarities anddifferences between the mechanisms for Ni allergy and gold allergy.</p>

Positive patch test reactions to gold are commonly seen in dermatology clinics, but it is veryunusual for the patients to actually have any clinical symptoms. It is also common with irritantreactions that are not linked to adaptive immunity. Therefore, a deeper understanding of themechanisms underlying allergic contact dermatitis (ACD) reaction, and the search for acomplementing diagnostic tool, is important. In paper I we included three subject groups; one with morphologically positive patch testreactions to gold sodium thiosulphate (GSTS, the gold salt used in patch testing), one withnegative patch tests, and one with irritant reactions to gold. Blood samples were collected andexamined regarding the proliferation rate and which cytokines were secreted after culturingwith GSTS. We saw that the cultured lymphocytes from the allergic donors proliferated at asignificantly higher rate than the two other subject groups, and that the cells secreted cytokinesof both Th1 (Interferon (IFN) -g and Interleukin (IL) -2) and Th2 (IL-13 and IL-10) types. Theallergic donors secreted significantly higher levels of IFN-g, IL-2 and IL-13 than the two othersubject groups. Both the negative and irritant subject groups showed suppressed levels of thecytokines as compared with the unstimulated cultures, demonstrating the immunosuppressingeffects of gold. We also examined whether any of the analyzed markers, alone or combined, could be usedas an aid for diagnosing ACD to gold. We found that the IFN-g assay yielded the highestsensitivity (81.8 %) and specificity (82.1 %), and also identified 87.5 % of the irritant group asnon-allergic. In paper II we decided to investigate what cell types and subsets that reacted to the goldstimulation. We analyzed proliferation rate and expression of CD45RA, CD45R0, cutaneouslymphocyte-associated antigen (CLA) and the chemokine receptors CXCR3, CCR4 andCCR10. Similar to what has previously been published about nickel (Ni) allergy, the cells fromthe gold-allergic subjects that reacted to the GSTS stimulation expressedCD3+CD4+CD45R0+CLA+. However, contrary to findings in studies on Ni-reactive cells, wesaw no differences between allergic and non-allergic subjects regarding any of the chemokine receptors studied. In conclusion, we found that analysis of IFN-g might be a useful complement to patchtesting, possibly of interest in avoiding the need for repeated tests to rule out irritant reactions.We also saw that the cells that proliferated in response to gold were memory T-cells expressingCD4 and CLA, the marker for skin-homing. However, these cells did not express elevatedlevels of any of the chemokine receptors analyzed, showing that there are both similarities anddifferences between the mechanisms for Ni allergy and gold allergy.

Radiation dermatitis is a common side effect of external beam radiation therapy. The purpose of this study was to evaluate the effectiveness of applying an aloe vera based skin gel to the target area skin in preventing the development of radiation dermatitis to postlumpectomy/ mastectomy patients receiving external beam radiation therapy in an ambulatory radiation-oncology clinic in the southeastern region of the United States. In this descriptive correlational study, a convenience sample of willing participants (n=18) was followed from initial treatment through the one-month follow-up examination to assess the intensity of their skin reaction. Five research questions were examined pertaining to the relationship between prognostic indicators and the development of radiation dermatitis when RadiacareR gel was used before and throughout external beam radiation therapy post-mastectomy or post-lumpectomy. The prognostic indicators used in this study were: Breast size > C-cup, prior chemotherapeutic exposure, length of incision, age of client, and weight changes since diagnosis. Analysis of Variance (ANOVA) and Pearson's Correlation Coefficients were used in the data analysis with a confidence of p=0.05. This study indicated that breast size and weight changes were the most prognostic of the factors studied. The small sample size and lack of randomization or control group limit the generalizability of these findings to clinical practice; however, it does support the need for continued research in this area. Recommendations for future studies include comparing Body Mass Index (BMI) to incidence and determining a relationship between gel use and treatment breaks and if there is a difference in the length of time until the skin is restored to baseline upon completion of therapy.

Inaug.-Diss.--Universität Erlangen-Nürnberg, Erlangen. / At head of title: Aus dem Seminar für Geschichte der Medizín der Universität Erlangen-Nürnberg. Vita.

Background Incontinence-associated dermatitis (IAD) is a common and preventable condition in older adults with incontinence. People suffering from IAD are usually disdained by individuals, professionals, policy makers, caregivers, and communities. To date, a standard guideline on IAD management is still lacking in Hong Kong. Thus, it is important to develop an evidence-based incontinence-associated guideline for older adults with incontinence in Hong Kong. Objectives This thesis aims to identify the best available evidence for skin care management for people suffering from IAD and to develop an evidence-based practice guideline to reduce the incidence of IAD. Methods Review of literature related to the management of IAD was performed on electronic database according to the inclusion and exclusion criteria. The inclusion criteria included randomized controlled trials and quasi-experiments. In addition, the studies should be in English and should contain the full text. The target participants should be patients aged 60 or above who are suffering from urinary, fecal, or double incontinence and are using diapers. Participants should include cognitively impaired patients, as well as those experiencing skin redness or injury at the perineal or thigh area resulting from incontinence. All non-medical regimens, skin care products, and absorbent diapers or pads designed for managing incontinence related to skin breakdown in older adults with incontinence were also included. The quality of the literatures was assessed according to the checklist provided by the Scottish Intercollegiate Guidelines Network (SIGN) (2011), and the data obtained from the reviewed papers were extracted and summarized in eight tables of evidence. Then, an IAD skin care management guideline was developed based on these pieces of evidence. The transferability, the feasibility, and the cost-benefit ratio of implementing the proposed IAD skin care management guideline were assessed. In addition, the communication plan, the evaluation plan, and the pilot study of the proposed guideline were included in this thesis. Results The proposed IAD skin care management guideline is a structured skin care management program for older adults with incontinence. With the help of the proposed guideline, registered nurses could provide a standard IAD skin care program based on best available evidence. Moreover, reviewed studies show that the IAD severity score, which is used to evaluate the prevalence of IAD, can be reduced by 47 % by implementing the proposed guideline. In addition, a systematic communication plan with stakeholders, an evaluation plan, and a pilot study were designed to examine the feasibility and the transferability of the proposed guideline. Patient outcome is the main outcome measure, and this measure is directly related to the IAD severity score. In this study, the IAD severity score was reduced, indicating that the proposed IAD skin care management program is effective, feasible, and cost-effective in the local setting. Conclusion The proposed skin care management guideline for caring for older adults with IAD was developed based on best available evidence. The prevalence of IAD is expected to be reduced after the implementation of this guideline. / published_or_final_version / Nursing Studies / Master / Master of Nursing