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This thesis discusses some aspects of the use of ultraviolet rays to treat skin disease. The early history of dermatological phototherapy in Scotland is summarised as an introduction to the more recent developments described in a chapter on the Scottish phototherapy and photochemotherapy audit of 1996/1997 (funded by the Clinical Resource and Audit Group, the Scottish Office). This audit revealed some aspects of the phototherapy service that could be improved, and identified areas of particular importance for future research. Firstly, what type of UVB phototherapy lamp is most effective: the narrow-band (311-313nm) TL-01 lamp, or the broad-band UVB lamp? A meta-analysis conducted as part of this thesis gave a clear answer. TL-01 UVB is much more effective than broad-band UVB. The second included study was a randomised, controlled study that has contributed to deciding the optimal treatment frequency for TL-01 UVB phototherapy of psoriasis. Although 5x weekly treatment cleared psoriasis slightly more quickly than 3x weekly treatment, the difference in speed of clearance was too small to warrant the significantly greater frequency of acute erythema during treatment, and the greater number of exposures and dose required. The final question, answered by a randomised, controlled trial, in conjunction with a systematic review of the previous literature, was: for chronic plaque psoriasis, is TL-01 UVB or psoralen-UVA photochemotherapy to be preferred? The study conducted for this thesis showed TL-01 UVB to be more effective. Heterogeneity in findings of the studies addressing this question highlighted the importance of the particular treatment regimens selected for comparison, but the overall conclusion was that TL-01 UVB is the first choice of these two therapies.

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Ultraviolet (UV) B therapy can induce complete clearance of psoriasis and often leads to prolonged remission following a treatment period. UVB phototherapy is a commonly used, highly effective treatment modality, but despite this its mechanism of action remains poorly understood. This thesis investigates the importance of keratinocyte apoptosis in UVB-induced clearance of psoriasis using a novel approach, and employs a mathematical model to explore the effects of this on epidermal homeostasis. The in vivo effects of two wavelengths of UVB were compared, one of which is clinically effective in clearing psoriasis (311nm), and one which is ineffective (290nm) even at high doses. This allowed investigation of which effects of UVB are relevant to plaque clearance; eliminating „bystander‟ effects such as erythema. The study showed significant keratinocyte apoptosis in lesional psoriatic epidermis following 311nm UVB compared to 290nm UVB; peaking 16-24h post irradiation. To determine clinical significance, a computational model of psoriatic epidermis was created utilising histological and kinetic parameters. The model predicted that apoptosis should occur in both stem and TA cells to account for plaque remodelling. This was confirmed and quantified experimentally, with real-time assays determining the rate of keratinocyte apoptosis. These data were fed back into the model and demonstrated that the observed level of keratinocyte apoptosis was sufficient to account for complete remodelling of psoriatic plaques in response to therapeutic UVB. The data was supported by gene array studies, which showed differential regulation of apoptotic genes at early time-points following 311nm rather than 290nm UVB. Finally, the wavelength dependence of UVB-induced apoptosis was examined, and only wavelengths which can clear psoriasis (i.e. greater than 300nm & less than 320nm UVB) induced significant epidermal apoptosis. In summary, this thesis demonstrates that keratinocyte apoptosis is a key mechanism of psoriatic clearance in response to UVB.

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 Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Currently few studies have investigated the accuracy of using transcutaneous bilirubinometry after phototherapy especially in the outpatient setting. The purpose of this study was to evaluate the accuracy of transcutaneous bilirubin measurements (TCB) after phototherapy for neonates with jaundice. At the Maricopa Integrated Health System, neonates who undergo phototherapy for hyperbilirubinemia come in for outpatient follow‐up at the Comprehensive Health Center following their discharge. For those neonates, current protocol calls for serum bilirubin (TSB) to be measured to properly monitor bilirubin levels, however transcutaneous measurements were made and recorded as well. In this study, we compared the values of total serum bilirubin and transcutaneous bilirubin in jaundiced neonates who underwent phototherapy. From October 2013‐April 2015, a total 67 healthy infants were seen in the Pediatric Clinic who had received phototherapy in our hospital, only 36 (54%) of those met minimum data criteria to be included in the study. The absolute difference between mean serum bilirubin and transcutaneous bilirubinometry in healthy outpatient newborns who received inpatient phototherapy was 0.4 and is clinically insignificant. The average time from hospital discharge to return to clinic was 47 hours. We conclude that for the outpatient physician, transcutaneous bilirubinometry can be used following phototherapy, which facilitates faster, more convenient, and painless follow‐up visits.

碩士 / 國立臺灣大學 / 臨床醫學研究所 / 103 / Background: Phototherapy might increase bone mineral density. However, it is unknown whether phototherapy can reduce the risk of fractures in patients with vitiligo. Objectives: To investigate the effect of phototherapy on fracture risk in vitiligo patients aged 40 or older. Methods: This population-based cohort study used the 2000–2010 Taiwan National Health Insurance Research Database (NHIRD) to identify 3,863 patients newly diagnosed with vitiligo between 2003 and 2009 at age ≥40 years. Study subjects were classified into three cohorts: 1) frequent phototherapy; 2) infrequent phototherapy; and 3) no phototherapy. Patients were followed until the first hip or vertebral fracture or 31 December 2010. Data were analysed using Cox regression models and also stratified by age and gender. Results: Frequent phototherapy decreased the fracture risk in patients aged 40–64 years (adjusted hazard ratio=0.18, p=0.009); however, stratification by gender confirmed the fracture prevention effect of frequent phototherapy in female patients only (adjusted hazard ratio=0.19, p=0.014). Limitations: Some potential confounding variables for fractures were not available in the Taiwan NHIRD. Conclusions: This study provides the first evidence that frequent phototherapy can reduce the risk of fractures among middle-aged women with vitiligo.