Background: Sweden has a considerable population originating from countries outside of Europe. Many of them are children and adolescents. The knowledge that nurses and medical doctors have of how to assess and treat skin conditions on melanin-rich skin in children and adolescents is, in many cases, insufficient. Aim: The aim was to explore how nurses and medical doctors experience the assessment, treatment and diagnosing of skin conditions in children and adolescents with melanin-rich skin. Method: A qualitative interview study with a semi structured interview guide. Six nurses and five medical doctors from different hospitals and primary care facilities in Uppsala and Malmö participated. Results: The analysis of the participants’ experiences resulted in three different categories: The Care takers feelings of insecurity, Lack of knowledge/experience and Negative Consequences for the child as patient. The participants believed that their lack of knowledge and experience in assessing and treating skin conditions in children and adolescents with melanin-rich skin is due to the fact that this is not taught in nursing and medical training. As a result patients, children and adolescents, are many times made to suffer. Conclusion: Nurses and medical doctors need more knowledge of and experience in how to assess, treat and diagnose children and adolescents with melanin-rich skin. This can be obtained by including training materials at nursing- and medical schools, texts as well as imagery, on how melanin- rich skin looks in its different variations, how it differs from white skin and how it reacts to various conditions. / Bakgrund: Sverige har en betydande befolkning av människor från utomeuropeiska länder. Många av dessa är barn och ungdomar. Kunskapen som sjuksköterskor och läkare har om hur man bedömer och behandlar åkommor på barn och ungdomar med melaninrik hud är i många fall otillräcklig. Syfte: Syftet med studien var att utforska sjuksköterskors och läkares upplevelser av att undersöka, bedöma och diagnosticera hudåkommor hos barn och ungdomar med melaninrik hud.  Metod: Studien genomfördes med en kvalitativ metod där semistrukturerade intervjufrågor användes för att besvara studiens syfte. Sex sjuksköterskor och fem läkare från olika sjukhus och primärvårdsinrättningar i Uppsala och Malmö deltog. Resultat: Deltagarnas upplevelser delades in i tre olika kategorier: Osäkerhet i bemötandet hos vårdgivaren, Saknad av kunskap/erfarenhet samt Negativa konsekvenser för barnet som patient. En majoritet av deltagarna upplevde att deras brist på kunskap och erfarenhet av hur man på bästa sätt bedömer och behandlar barn och ungdomar med melaninrik hud beror på att detta inte tas upp och lärs ut på ett adekvat sätt under deras respektive utbildningar. Resultatet blir i många fall att barnen och ungdomarna som patienter får lida. Slutsats: Sjuksköterskor och läkare behöver mer kunskap och erfarenhet av att bedöma, behandla och diagnosticera barn och ungdomar med melaninrik hud. Detta kan uppnås genom att utbildningar och program för sjuksköterskor och läkare inkluderar utbildningsmaterial i text och bild om hur melaninrik hud skiljer sig från vit hud, hur den, i sina olika variationer, ser ut sig, ter sig och reagerar på skilda åkommor.

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.

Background: While death from melanoma of the skin has been gradually decreasing over the past few decades, melanoma continues to be the leading causes of death among skin cancers. Less is known about specific causes of mortality among patients with melanoma and how or whether trends in cause of death among patients diagnosed with melanoma have changed in recent years. Objective: To examine temporal trends in the cause-specific mortality among adult patients diagnosed with melanoma in the US between 2000-2013. Methods: US patients ≥ 45 years when diagnosed with melanoma were identified using data from the Surveillance, Epidemiology, and End Results Program, 18 Registries (SEER-18). Joinpoint regression analysis was used to examine the trends in cause-specific mortality among patients who were diagnosed with melanoma and died from either melanoma or other causes of death. Trends were also examined separately by age, sex, and geographic region. Results: A total of 52,675 patients diagnosed with melanoma who died from either melanoma or other cause of death (median age 74 years, 67% male) were included in the analysis. Overall, 31% of deaths were due to melanoma specifically, whereas 69% died from various other causes. A marked decline in melanoma-specific mortality was observed overall and across strata by age, sex, and region in the US beginning around 2013-2014. Among all causes of death, 55% were due to melanoma within 1 year after diagnosis and declined to 25% over the course of 6 years. A marked decline of at least 2.5% in mortality per year from other causes was observed among females, males, those 65 – 74 years or 75 years and older, and those living in northeastern, midwestern, western, and southern regions of US who were diagnosed with melanoma. Conclusions: Changes in cause-specific mortality rate among patients with melanoma were observed overall and across different subgroups. Our findings show that, among those diagnosed with melanoma, the risk of melanoma-specific death is decreasing within the last two decades, and that the deaths among those with melanoma are more likely to be from other causes such as heart disease, lung cancer, and other conditions. Future studies are needed to assess the trends in melanoma mortality as treatments and diagnostic methods continue to advance.

BACKGROUND: Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is the most severe form of cutaneous adverse drug reaction and is characterized by extensive epidermal destruction of the skin and mucosal surfaces. Controversy remains regarding the immunopathogenesis of the disease. It has long been assumed that CD8 cytotoxic T cells mediate cell death by releasing cytotoxic granules and soluble granulysin that trigger keratinocyte apoptosis. However, this does not explain the massive cell death or inflammation that is observed clinically. We have preliminary evidence from transcriptional profiling of patient skin samples suggesting that the cell death pathways necroptosis and pyroptosis may mediate SJS/TEN. Herein we utilize retrospectively and prospectively collected patient samples to investigate these cell death pathways. OBJECTIVE: The goals of this study are two-fold: (i) to investigate cell death pathways in retrospectively-collected (SJS/TEN) patient skin samples and (ii) to directly test the cell death mediators and pathways mediating SJS/TEN using a novel in vitro model. METHODS: Clinically and histopathologically confirmed SJS/TEN skin specimens and control skin specimens from non-blistering T cell mediated drug reactions and healthy skin were obtained following retrospective analysis from a multi-centered patient database. Gene expression profiling is being performed using the NanoString nCounter® System on these samples as a second patient cohort to confirm and expand on preliminary study findings. In parallel, we have optimized the use of a novel human skin platform for an in vitro model of SJS/TEN. We also collected human serum from a prospective study of SJS/TEN and control patients and have optimized and are actively collecting blister fluid from SJS/TEN and control patients in an ongoing prospective study for use in this model. RESULTS: Through an extensive pathology database and medical record search of potential cases at Brigham and Women's Hospital, we identified a second patient cohort of SJS/TEN, non-blistering delayed-type drug hypersensitivity reactions and healthy controls. We identified and are collecting thorough demographic, clinical and laboratory data on 61 potential candidates for SJS/TEN, 4 for Drug Reaction with Eosinophilia Syndrome (DRESS), and 200 for Morbilliform Drug Eruptions (MDE). This second cohort is in the final step of analysis with review by an expert clinician to confirm cases. In parallel, we have designed an expansive gene panel to confirm cell death mediator and marker transcription in our bank of skin samples. This 815 gene panel uses the pre-designed panel from Nanostring®, spiked with an additional 30 genes specific to apoptosis, pyroptosis, and necroptosis. We reviewed multiple potential in vitro skin models and identified GenoSkin® as the most suitable human skin platform for our in vitro model. We collected serum from 6 SJS/TEN patients and 6 non-blistering drug reaction patients and 3 healthy controls, and are actively collecting blister fluid from SJS/TEN and thermal burn control patients for analysis in this model. CONCLUSIONS: Our preliminary data suggest necroptosis and pyroptosis induced by soluble death mediators tumor necrosis factor (TNF) alpha and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as the main cell death pathways responsible for SJS/TEN. We have successfully identified a large number of potential patient samples of both cases and controls to perform transcriptional profiling using a self-designed gene panel to confirm and expand upon our preliminary data. We have successfully collected prospectively patient serum and are actively collecting patient blister fluid for analysis in an optimized in vitro model using GenoSkin®. SJS/TEN is severely understudied and lacks a standard protocol for care. This stems from uncertainty surrounding disease pathobiology. It is critical that we use innovative approaches to interrogate the mechanism mediating disease to advance the field, and, most importantly, to improve the quality of care for these patients.

Basal cell carcinoma is the most common form of human malignancy, and as such there are varied methods for treating its various forms. Its more advanced and aggressive forms have required both the use of and advent of therapies which offer differing safety profiles, cost, and efficacy. Two therapies which differ substantially in these respects but have overlap in their recommended use are Mohs micrographic surgery and the pharmaceutical drug vismodegib. Few studies have sought to compare the two methods using these criteria, and as vismodegib has only received FDA approval in the past ten years, it is worthwhile to explore the limitations and advantages of each therapy. In exploring previous clinical trials and retrospective studies, the two therapies are put side by side to contrast their results with their shared intended use. The general findings were that Mohs micrographic surgery remains the gold standard for the treatment of locally advanced basal cell carcinoma, and there are few demonstrable instances in which vismodegib could be deemed a more appropriate therapy. The future of vismodegib appears to be in its use as a neoadjuvant therapy for locally advanced basal cell carcinomas for which a decrease in size by vismodegib would allow for better treatment outcomes.

No description available.

Many surgical procedures in the head and neck regions produce visible scarring. The most common of these surgeries are tracheotomies and thyroidectomies. The recent COVID-19 pandemic has caused an increase in tracheotomy scars, particularly in those who survived severe infection with the disease and required long-term ventilation. Individuals with neck scars are at an increased risk of health consequences such as reduced quality of life, depression, and negative body image. Research on attitudes toward and reactions to individuals with such scarring is limited. The purpose of this study is to examine how people rate images of scarred individuals on personality and attractiveness attributions. In addition, dermatography, or medical tattooing, is an emerging cosmetic intervention used to mask scarring, and has demonstrated positive outcomes in cases of breast cancer. This study further aims to examine how people rate images of individuals with scars covered with medical tattoos. Personality attributions were measured using the Five Factor Scale and various dimensions of attractiveness were measured using the Interpersonal Attraction Scale. Acceptability of medical tattooing as a cosmetic intervention for head and neck scars was also examined using the Decision Satisfaction Scale. Participants consisted of 456 young adults and were presented with two series of images, each consisting of a young adult, the young adult with a neck scar, and the young adult with a tattoo covering the scar. Participants were asked to rate each image directly after viewing. We hypothesized that those without scars and those with medical tattoos would be rated more positively on personality and attraction scales than would those with scars. Multivariate analysis confirms scarring and medical tattoos influence personality attributions. Non-scarred individuals were rated more positively in perceived Agreeableness and Conscientiousness traits when compared to scarred individuals. However, when compared to non-scarred individuals, scarred individuals were rated more positively on the Openness to Experience trait. This demonstrates the variability of impressions that a neck scar can elicit. Reactions to scars covered with tattoos were mixed. Medical tattoo recipients were rated more positively on Extraversion and Openness to Experience traits compared to scarred individuals. They were also rated lower on Conscientiousness compared to scarred individuals. Acceptability of medical tattooing was higher in participants who reported lower levels of religiosity and higher levels of social media use. This study highlights the varying effects that head and neck scars can have on appearance and the use of medical tattooing in clinical practice.

Atopic dermatitis (AD) is a common skin disease that is characterized by chronic, relapsing skin inflammation and eczematous, itchy lesions. In AD, systemic and local eosinophilia and basophilia is thought to contribute to disease progression in both acute and chronic lesions. It has been previously shown that in chronic allergic inflammatory diseases, tissue eosinophilia and basophilia may in part result from eosinophil/basophil (Eo/B) progenitors trafficking from the bone marrow and maturing in tissue in response to type 2 cytokines including IL-5 and IL-3. We therefore proposed that a similar mechanism could be contributing to the pathogenesis of AD. First, we compared lesional and non-lesional AD tissue, and found approximately 10-fold higher levels of Eo/B progenitors in the lesional tissue (p<0.05). As previous research has shown an increase in Eo/B progenitors in the airways of allergic asthmatics post inhaled allergen challenge, we next examined whether Eo/B progenitors increased locally in the acute phase of AD using the intradermal allergen challenge model. Compared to intradermal diluent challenge there was an increase in Eo/B progenitors (5.5-fold), eosinophils (18-fold) and basophils (2.5-fold) 24 hours post intradermal allergen challenge (all p<0.05). These increases were consistent with findings in allergic airways. Lastly, we examined the relationship between disease severity and Eo/B progenitors in inflamed lesional (chronic) and allergen-challenged (acute) tissue. We found that Eo/B progenitors in lesional tissue positively correlated with disease severity (EASI R=0.71, p<0.05 and SCORAD R=0.65, p<0.05), while in allergen-challenged tissue a trend was seen for a positive correlation between Eo/B progenitors and disease severity (EASI R=0.48, p=0.07 and SCORAD R=0.46, p=0.09). These results highlight the potential involvement of Eo/B progenitors in the disease pathogenesis of AD. / Thesis / Master of Science (MSc) / Atopic dermatitis is a common skin disease that is characterized by chronic, relapsing skin inflammation and eczematous, itchy lesions. In other allergic diseases, a cell called the “eosinophil/basophil progenitor” contributes to the accumulation of inflammatory cells in the diseased organ. We proposed that eosinophil/basophil progenitors found in the skin may be contributing to the development of local allergic inflammation. In patients with moderate-to-severe atopic dermatitis we compared acute responses to intradermal allergen and chronic skin lesions to diluent-challenged and un-affected skin, respectively. Allergen-challenged skin had more eosinophil/basophil progenitors, mature eosinophils and basophils 24 hours’ post-challenge compared to unchallenged skin (p<0.05). Chronic skin lesions had more eosinophil/basophil progenitors than un-affected skin (p<0.05). The number of eosinophil/basophil progenitors positively correlated to disease severity as determined by EASI and SCORAD. Our results suggest that accumulation of eosinophil/basophil progenitors in skin of atopic dermatitis patients could support allergic inflammation and contribute to disease severity.

Since the 1800's, technological advances have extended the foundation on which telemedicine could build. With its evolution, telemedicine has proven to be a means of offering effective health care interventions, from a multitude of disciplines. Teledermatology, a specialty application of telemedicine, offers great potential in improving the standard of dermatologic care by bridging the gap between the expert opinion of dermatologists and those without access to basic dermatologic care, particularly in developing nations, where skin disease continues to be a major public health problem. In Honduras, the setting for this study, and other developing nations, technology to support telemedicine is available. Dermatologic disease is among the most common disease presentations in the developing world, which left untreated due to a lack of access to adequate medical care, can progress causing increased morbidity or even death. A potential but untested solution is teledermatology. Teledermatology offers great potential in improving the standard of dermatologic care by bridging the gap between the expert opinion of dermatologists and those without access to basic dermatologic care. The purpose of this study was to evaluate the prevalence and types of dermatologic conditions and the feasibility of a store-and-forward teledermatology system in an underserved area of Honduras, so as to potentially provide more timely diagnosis and treatment, implementation of preventative measures, and offer long term solutions.so as The justification and significance of this study was the potential of store-and-forward teledermatology to improve the standard of dermatologic care by improving access of populations in underserved areas to dermatology specialists through affordable technology. The methodology of this study was primarily case study descriptive. This study was conducted at a public primary care clinic (JMA Clinic) and satellite sites in underserved areas of Francisco Morazán, Honduras. During a four week period in Spring 2011, patients with dermatologic conditions were examined and photos taken of condition. The patient information was sent to 3 U.S. board certified dermatologists, who provided diagnosis and treatment within 24 hours, which allowed the clinic physician sufficient time to review recommendations before patient follow-up. Patients would receive follow-up within 48 hours of initial visit. Diagnostic agreement, image quality, and user satisfaction were evaluated. IRB forms were submitted and clearance given. The data was analyzed with SPSS using descriptive statistics. The primary findings were the types of dermatologic conditions, interobserver agreement, image quality, and patient and physician satisfaction. The findings of this study substantiate the need for dermatologic care, as approximately 1 out of every 5 patients of the JMA Clinic presented with a dermatologic condition. The majority of these patients were children or women in their late 20s and early 30s; many of whom had their condition for more than a year and most had not received prior therapy. The types of dermatologic conditions observed were typical of that seen at a dermatology clinic in the U.S., yet inclusive of tropical and regional differences. Dermatitis, infectious and pigmentary conditions were the most common presentations. The interobserver diagnostic agreement achieved was 78%, and improved when considering differential diagnoses. Image quality received high ratings. Patients and physicians recorded a high level of overall satisfaction. Physicians indicated improved knowledge of teledermatology. Because of the unique environment and circumstances, the results are limited to the setting in which the study occurs. This project was a pilot study limited to 4 weeks of data collection and will be limited in significance by its duration and small sample size with respect to the conclusions that can be drawn about the prevalence and types of dermatologic conditions. This study illustrates that teledermatology is a viable means of providing dermatologic care to those in an underserved area of Honduras, where a lack of or limited access to general healthcare or specialty dermatologic care exists. The data offers insights to draw conclusions and recommendations on the potential for similar models to be implemented in underserved areas throughout Honduras and other similar regions. / Ph. D.

No / To date there is ample evidence that patients with vitiligo accumulate millimolar concentrations of hydrogen peroxide (H2O2) in their epidermis as well as in their blood lymphocytes/monocytes. Several enzymes are affected by this H2O2 including catalase, glutathione peroxidase, and 4¿-carbinolamine dehydratase. The latter enzyme disrupts the recycling of the essential cofactor (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (6BH4) for the aromatic amino acid hydroxylases as well as the nitric oxide synthases. In this report we have elucidated the influence of H2O2 on dihydropteridine reductase (DHPR), the last enzyme in the 6BH4-recycling process. Here we show for the first time that concentrations of less than 30 ¿M H2O2 increase DHPR activities, whereas levels greater than 30 ¿M H2O2 deactivate the enzyme based on the oxidation of Met146 and Met151 in the sequence, consequently leading to disruption of the NADH-dependent enzyme active site. This oxidation was confirmed by Fourier transform-Raman spectroscopy yielding the expected SO band at 1025 cm characteristic of methionine sulfoxide. Hence these results unmasked a novel regulatory mechanism for DHPR enzyme activity. Moreover, we also demonstrated that DHPR activities in whole blood of patients with vitiligo are significantly decreased in untreated patients, whereas activities are normalized after removal of epidermal H2O2 with a topical pseudocatalase (PC-KUS). Taken together, these new data add more evidence to a systemic involvement of H2O2 in the pathomechanism of vitiligo.