M.Tech. (Homoeopathy) / Atopic dermatitis (atopic eczema) is a chronic, relapsing, allergic inflammatory skin disease (Hauk, 2008). The prevalence of atopic dermatitis has increased significantly over the past few decades, with highest rates of 45 – 64% occurring amongst preschool children (Butler, 2009), and 40% amongst older children and adults (Manjra, 2005). This increase in prevalence is attributed to environmental factors such as microbial exposure and poor nutrition, which can all lead to atopic dermatitis (Schnopp, 2006). The quality of life of patients suffering from atopic dermatitis and their family members are significantly affected (Manjra, 2005). Atopic dermatitis is characterized by active skin lesions that are red, flaky, dry and itchy and in children commonly occurs in the flexural areas of the body (Fölster-Hols et al., 2007, Schnopp, 2006). Conventional treatment potions for atopic dermatitis are associated with adverse effects in children (Kalicharan et al., 2005). Homoeopathic remedies may offer an alternative option for this condition. This study aimed to assess the effect of a homoeopathic complex consisting of Graphites 6cH, Histaminum 9cH, Psorinum 6cH and Sulphur 6cH, on atopic dermatitis in children. All the participants of the study received the homoeopathic complex. The atopic dermatitis was evaluated using the SCORAD index (Scoring of Atopic Dermatitis) (Appendix F) and the Children’s Dermatology Life Quality Index (CDLQI) (Appendix E). Thirty four participants who met the inclusion and exclusion criteria were recruited to participate in this pre-test – post-test single group study by means of advertisements (Appendix A) placed in and around primary schools in the Gauteng area (with relevant permission given) and in the local newspaper. Participants were also recruited via word of mouth. Once participants were accepted into the study they were allocated into the treatment group which received the homoeopathic complex containing Graphites 6cH, Histaminum 9cH, Psorinum 6cH and Sulphur 6cH. The study was completed over a four week period. The percentage of the area affected, the intensity of the symptoms, the pruritus and the loss of sleep as well as the quality of life of the participants suffering from atopic dermatitis were aspects of the condition evaluated on a weekly basis. The results for the CDLQI showed improvements in the participant’s perception of itching/ pain of the affected area, as well as their quality of sleep. These improvements were shown to have occurred gradually over the study period. There were however no statistically significant changes noted in the mental and emotional quality of life of the participants.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18509号 / 医博第3929号 / 新制||医||1005(附属図書館) / 31395 / 京都大学大学院医学研究科医学専攻 / (主査)教授 三森 経世, 教授 鈴木 茂彦, 教授 長田 重一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Indiana University-Purdue University Indianapolis (IUPUI) / Atopic dermatitis (AD) is a pruritic, chronic inflammatory skin disease with a lifetime prevalence of 10-20% in children and 1-3% in adults, worldwide. In the past three decades, prevalence of the disease has increased by two to three-fold in industrialized countries, with higher incidences in urban regions compared to rural regions. Mice with an activating mutation in STAT6, known as STAT6VT, constitutively express STAT6 in T-cells. Our preliminary data suggests significant differences between the STAT6VT transgenic mice from WT littermate controls treated with SLS. These findings correlate with evidence that there are abnormalities in the barrier function between these mice

A 13-year-old girl presented in mild distress with moderate to severe erythema and cracking to the dorsal aspects of both hands. She reported associated pruritus and pain.

Dermatological conditions affect between 15 to 25% of canines. Canine Atopic Dermatitis (CAD) is one of the most prevalent of these conditions and is a chronic inflammatory disorder with a wide array of causes and triggers and no known cure. Symptoms of this condition can be persistent and often lead to significant discomfort, leading many owners to seek preventative care in an attempt to avoid expensive veterinary care and discomfort in their dogs. Sebaceous Adenitis (SA) is another skin condition, which while less common, is also a disorder of the inflammatory pathways and affects keratin production in the coats of dogs. It has more persistent symptoms and requires rigorous grooming care to prevent its onset, and as a result is the cause for euthanasia in many of the breeds which it affects. Similar to CAD, owners of dogs with SA seek preventative care to avoid flares of the conditions that are often coupled with secondary infections that perpetuate the skin’s poor condition. Due to the overwhelming variety and misleading advertising that currently exists in the dog food market, one key element to preventative treatment that is confusing to many owners is manipulation of the diet. Research has demonstrated that certain dietary components may be important. These include increased protein composition, supplementation of vitamins A, D, and E, essential fatty acid supplements, and the use of probiotics and prebiotics. Increasing the proportion of dietary protein to total energy intake allows for greater consumption of amino acids, which can be utilized to renew epidermal cells, including hair follicles. It is speculated that Vitamin A supplementation may slow down the rate of hyperkeratinization seen in SA as it attenuates epithelial cell turnover. Supplementation with vitamin E has been found to improve pruritus in CAD and acts as an anti-inflammatory in areas which are affected by a loss of sebum, as seen in SA. It may also act to improve antibody responses in hypersensitivity reactions, which are exaggerated immunologic responses to allergens, seen in CAD. It is known that an increase in dietary vitamin D enhances immunomodulatory roles that lead to its ability to reduce lesions in both CAD and SA. Essential fatty acids (FA), of which two are omega-3 and omega-6 FA, are useful supplements for dogs with CAD, as they may affect mediators of inflammation specific to inflammatory skin disorders. Additionally, supplementation with essential FA may replenish a factor lacking in an impaired skin barrier. The breakdown in the epithelial barrier leads to increased cutaneous permeability and decreased membrane fluidity. It is important to balance the more pro-inflammatory effects of omega-6 FA with the anti-inflammatory effects of omega-3 FA. Two balanced sources of these essential fatty acids that often appear in the literature are evening primrose and borage oils, which supply gamma linoleic acid (GLA), a less inflammatory omega-6 FA. Probiotics/prebiotics aid in repairing possible issues observed in the gut-skin axis seen in AD though the strains which provide benefits are not consistent in the literature. In summary, there are promising developments on the treatment of CAD and SA through diet, although extensive research is needed to validate these studies and clarify the results prior to usage by the general public.

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Human T lymphotropic virus type -1 (HTLV-1) infections are important causes of mortality and morbidity in endemic areas worldwide. There is neither a vaccine specific for the virus nor satisfactory treatment for the associated malignancy or inflammatory syndromes. HTLV-1 associated infective dermatitis (IDH) is a chronic dermatitis that has been observed in a variable proportion of HTLV-1 infected children. IDH may serve as an early clinical marker for HTLV-1 and an indicator of increased risk for developing other HTLV-1 associated conditions such as adult T cell leukaemia/lymphoma (ATLL) and HTLV-1-associated myelopathy or transient spastic paraparesis (HAM/TSP). However the mechanisms underlying IDH and the relationships with HAM/TSP and ATLL are poorly understood. We undertook skin biopsies from 14 cases with IDH, and controls which included five asymptomatic carriers (ACs) and 18 healthy uninfected individuals from South Africa. We conducted clinical assessments, proviral load, allergen-specific IgE, peripheral blood and cutaneous T cell and virological analyses. We obtained relevant clinical history and examined all cases and controls based on a pre-formed questionnaire. Despite the partial clinical similarities with atopic dermatitis, the individuals with IDH did not have an increased incidence of atopic disease including asthma or rhinitis. Furthermore house dust mite-specific IgE levels were not elevated in the cases compared to the controls, suggesting that atopy is not a predisposing factor for the development of IDH in HTLV-1 infected individuals. Circulating proviral load was significantly higher in those with IDH compared to asymptomatic carriers and skin biopsy revealed acanthosis, and lymphocytic epidermotropism associated with a superficial perivascular and periadnexal lymphocytic infiltration of CD8+, and CD4+ T cells. Furthermore IDH associated with an infiltrate of epidermal and dermal FoxP3+ T cells and lesional down-regulation of filaggrin expression compared to non-lesional skin. We did not observe an elevation of pro-inflammatory cytokines in the sera of individuals with IDH compared to the controls. We investigated integration patterns in the skin and blood of 10 cases with IDH, and two asymptomatic carrier (AC) individuals from South Africa. We first showed that the virus is present in the skin at high levels (total mean levels of 47.09 proviral copies per 1000 cells) as comparable to that which has been observed in blood (total mean levels 137 proviral copies per 1000 cells). Using a high throughput Illumina sequencing system in collaboration with Professor Bangham, we mapped and quantified the relationship between oligoclonal proliferation of HTLV-1 infected T cells in the skin and blood of IDH patients. It was found that in IDH, a selective outgrowth of certain clones is favoured, supporting the possibility of skin-specific factors exerting positive selection on proliferation. In IDH, there was not a preferential integration of the provirus in transcriptionally active regions of the gene sites, as had been observed in other HTLV-1 associated conditions. These observations imply that the selection forces that favour oligoclonal proliferation of HTLV-1+ T cells differ fundamentally between simple HTLV-1 infection and other events associated with the dermatitis. In conclusion, these data show that HTLV-1 is not associated with an atopic diathesis. Given the lack of elevated pro-inflammatory cytokines and presence of a cutaneous infiltrate of FoxP3+ T cells, the findings suggest that high levels of HTLV-1 replication promotes a regulatory environment leading to filaggrin down-regulation, cutaneous susceptibility to infection, and secondary inflammatory skin disease. Viral integration patterns would support the presence of skin-specific positive selection, perhaps eventually leading to expansion of particular clones with the potential to develop towards ATLL. It remains to be explained whether the high viral load in IDH changes over time, more specifically in the steps leading to ATLL.

Lam Man Ching. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 101-114). / Abstracts in English and Chinese; appendices also in Chinese. / Chapter Chapter 1 --- Introduction and Literature Review / Chapter 1.1 --- General introduction of atopic dermatitis --- p.1 / Chapter 1.1.1 --- Definition and its nature --- p.1 / Chapter 1.1.2 --- Epidemiology and prevalence of atopic dermatitis --- p.1 / Chapter 1.1.3 --- Factors and triggers related to high risk of atopic dermatitis --- p.3 / Chapter 1.2 --- Pathogenesis of atopic dermatitis --- p.5 / Chapter 1.2.1 --- Nature of complexity of pathogenesis --- p.5 / Chapter 1.2.2 --- Role of T-helper cell in atopic dermatitis and its paradigm model --- p.5 / Chapter 1.2.3 --- Nature of immunoglobulin-E and its role in atopic dermatitis --- p.6 / Chapter 1.2.4 --- Chemokines in pathogenesis of atopic dermatitis: CTACK and TARC --- p.7 / Chapter 1.2.5 --- Role of antimicrobial peptides and innate immunity --- p.8 / Chapter 1.3 --- Measurements of atopic dermatitis severity and related quality of life impairment --- p.9 / Chapter 1.3.1 --- Scoring of atopic dermatitis severity and the SCO Ring Atopic Dermatitis Index --- p.9 / Chapter 1.3.2 --- Quality of life measurement --- p.9 / Chapter 1.3.3 --- The Children's Dermatology Life Quality Index (CDLQI) --- p.10 / Chapter 1.4 --- Pruritus in atopic dermatitis and its underlying mechanisms --- p.11 / Chapter 1.4.1 --- Introduction to pruritus --- p.11 / Chapter 1.4.2 --- Difference between pruritus and pain --- p.11 / Chapter 1.4.3 --- Pathogenesis and neuronal pathways of pruritus --- p.12 / Chapter 1.4.4 --- Neurogenic itch --- p.13 / Chapter 1.4.5 --- Role of histamines in pruritus of AD --- p.14 / Chapter 1.4.6 --- Substance-P --- p.14 / Chapter 1.4.7 --- Brain-derived neurotrophic factor and other recent mediators in pruritus --- p.15 / Chapter 1.5 --- "Scratching, nocturnal scratching and sleeping behavior in atopic dermatitis subjects and related research progress" --- p.16 / Chapter 1.5.1 --- Overview --- p.16 / Chapter 1.5.2 --- "Interrelationship between pruritus, scratching and sleep disturbance" --- p.17 / Chapter 1.5.3 --- Current methodologies in nocturnal scratching and sleep quality measurement --- p.18 / Chapter Chapter 2 --- Objectives --- p.25 / Chapter Chapter 3 --- Methodologies and Materials / Chapter 3.1 --- Validation of a new methodology /device --- p.27 / Chapter 3.1.1. --- Device selection --- p.27 / Chapter 3.1.2 --- Study design --- p.27 / Chapter 3.1.3 --- Validation of the Digitrac with laboratory markers --- p.29 / Chapter 3.1.4 --- Factor and statistical analysis --- p.31 / Chapter 3.2 --- Application of Digitrac in traditional Chinese herbal medication (TCHM / TCM) clinical trial --- p.32 / Chapter 3.2.1 --- Current AD treatment using corticosteroids and their drawbacks --- p.32 / Chapter 3.2.2 --- Recent trend on TCM treatment --- p.32 / Chapter 3.2.3 --- Study plan --- p.33 / Chapter 3.2.4 --- "Validation with laboratory markers, Staphylococcus aureus infection and statistical analysis" --- p.35 / Chapter 3.3 --- Application of Digitrac in a trial of 0.1% tacrolimus ointment in treatment of atopic dermatitis --- p.37 / Chapter 3.3.1 --- Topical immunomodulators as a treatment approach of AD --- p.37 / Chapter 3.3.2 --- Mechanism of tacrolimus in suppressing AD and pruritus --- p.37 / Chapter 3.3.3 --- Study plan --- p.39 / Chapter 3.4 --- Further application of Digitrac in pruritus of other medical fields --- p.41 / Chapter Chapter 4 --- Results and Discussions / Chapter 4.1 --- Digitrac validation --- p.52 / Chapter 4.1.1 --- General demographic background data --- p.52 / Chapter 4.1.2 --- Wrist activities --- p.53 / Chapter 4.1.3 --- Laboratory markers and factor analysis --- p.54 / Chapter 4.1.4 --- Interpretation of results --- p.55 / Chapter 4.1.5 --- Drawbacks of the validation --- p.58 / Chapter 4.1.6 --- Summary --- p.59 / Chapter 4.2 --- Digitrac in traditional Chinese herbal medication clinical trial --- p.68 / Chapter 4.2.1 --- General information --- p.68 / Chapter 4.2.2 --- "SCORAD, wrist activities and CDLQI" --- p.69 / Chapter 4.2.3 --- Laboratory findings --- p.70 / Chapter 4.2.4 --- Interpretation of results --- p.71 / Chapter 4.2.5 --- Safety of TCM use --- p.73 / Chapter 4.2.6 --- Summary --- p.74 / Chapter 4.3 --- Tacrolimus clinical trial --- p.81 / Chapter 4.4 --- Application of Digitrac in other areas of study --- p.90 / Chapter 4.4.1 --- Pemphigoid gestationis case study --- p.90 / Chapter 4.4.2 --- T-cell lymphoma case study --- p.92 / Chapter Chapter 5 --- Further Discussions and Conclusion --- p.98 / References --- p.101 / Appendices --- p.116

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