5231
5284
The expression of DJ-1 and PTEN in keloid Moon Kyun Cho, MD, Department of Dermatology, Soonchunhyang University College of Medicine; Jin Ho Bae, MD, Department of Dermatology, Soonchunhyang University College of Medicine; Sung Woo Cho, MD, Molecular Cancer Research, Soonchunhyang University College of Medicine; Sukh Que Park, MD, Molecular Cancer Research, Soonchunhyang University College of Medicine
The impact of severity of atopic dermatitis on patient-reported outcomes of adults with moderate-to-severe atopic dermatitis Jeffrey Vietri, PhD, Kantar Health; Fredrik Nyberg, MPH, AstraZeneca Global Medical Affairs; Nebibe Varol, PhD, AstraZeneca Background: Atopic dermatitis (AD) can cause considerable impact to patients’ quality of life at higher levels of severity, but few data from population-based studies are available to quantify the relationship between severity of AD and outcomes from the patients’ perspective. Objective: To assess the relationship between severity of AD and patient-reported outcomes among adults with moderate-to-severe AD. Method: Respondents who reported having dermatitis, atopic dermatitis, or eczema in survey-panel-based general health questionnaires in France, Germany, and the United Kingdom (UK) were invited to complete a new internet survey to confirm their dermatitis was AD. Respondents were asked to complete the patient-oriented score of atopic dermatitis (PO-SCORAD) to measure severity of AD, measures of health-related quality of life (general: EuroQol 5 dimensions questionnaire [EQ-5D-5L]; dermatology-specific: Dermatology Life Quality Index [DLQI]), disease activity (Patient-Oriented Eczema Measure [POEM]), and impairment to work and daily activities (Work Productivity and Activity Impairment questionnaire, Specific Health Problem [WPAI-SHP]). Respondents were classified into moderate or severe AD using established cut-offs for the PO-SCORAD (25-50 and [ 50 points, respectively), and groups were compared using t tests. Correlations between PO-SCORAD and the outcome measures were also estimated.
Background: Keloids are benign skin tumors that present excessive collagen bundle formed by increased proliferation in keloid fibroblasts. Phosphatase and tensin homologue (PTEN) acts as a tumor suppressor and it is known to be implicated in cutaneous fibrotic diseases including scleroderma and hypertrophic scar. DJ-1, a multifunctional protein is important for oncogenic activity and also functions as a negative regulator of PTEN function. For these reasons, we hypothesized that PTEN and DJ-1 may mediate keloid formation by alternating the apoptosis and cell proliferation of keloid fibroblasts. Objective: This study aims to investigate the expression of PTEN and DJ-1 in keloid tissues. Methods: To examine PTEN and DJ-1 expression, the specimens of 8 keloid tissues and normal skin tissues were analyzed through western blotting and/or immunohistochemical staining. Using the fibroblasts transfected with DJ-1-specific small interfering RNA (siRNA), We evaluated the expression of DJ-1 related protein including PTEN, AKT, pAKT and collagen I & III by western blot analysis. We also investigated the relationship between DJ-1 expression and cell proliferation in fibroblasts. Results: In Western blot analysis and immunohistochemical staining, decreased expression of PTEN is observed in keloid tissues compared to normal skin tissues. Meanwhile, increased expression of DJ-1 is observed in keloid tissues compared to normal tissues in western blot analysis and immunohistochemical staining. Besides, the degree of expression showed a statistically significant difference, respectively (P \ .05). An increase in the rate of apoptosis was found in normal human fibroblasts after transfection with DJ-1-specific siRNA. Knockdown of DJ-1 by siRNA led to increased expression of PTEN. Interestingly, cells silencing by DJ-1 siRNA showed decreased expression of collagen I and III as well as phosphorylation of AKT. Conclusion: These results indicate that PTEN expression is downregulated while DJ1, a negative regulator of PTEN, is upregulated in keloid tissues compared to normal skin tissues. Therefore, we suggest that PTEN and its negative regulator DJ-1 are involved in keloid formation and that loss of PTEN and increased DJ-1 ay play part in keloid formation through AKT pathway. Commercial support: None identified.
Results: The final sample included 548 respondents with moderate-to-severe AD (France: N ¼ 221; Germany: N ¼ 209; UK: N ¼ 118). Respondents were mostly female (69%), had a mean age of 45 years, had been diagnosed a mean of 19 years, and 67% were employed. Relative to moderate AD (N ¼ 413), those with severe AD (N ¼ 135) had lower EQ-5D index scores (0.61 vs 0.79), higher DLQI scores (14.4 vs 6.3), POEM scores (14.3 vs 8.0), and more impairment to work (48% vs 24%), and daily activities (52% vs 26%), all P \.01. Follow-up analyses subdividing the severe AD group suggested that outcomes were worse as PO-SCORAD scores increased among these patients. Among respondents with moderate-to-severe AD, the relationship between severity of AD and outcomes was also seen in correlations between PO-SCORAD scores and EQ-5D index scores (rs ¼ -.39), DLQI scores (rs ¼ 0.62), impairment to work (rs ¼ 0.46) and activity impairment (rs ¼ 0.52), all P \.01. Conclusions: Greater severity of AD is associated with poorer patient reported outcomes across domains, with more-severe patients having higher unmet needs. Commercial support: The study was sponsored 100% by AstraZeneca.
5559 The impact of quantifiable parameters on treatment adherence for children with chronic inflammatory skin disease Reena Varade, MD, Saint Louis University; Elaine Siegfried, MD, Saint Louis University; Eric Armbrecht, PhD, Saint Louis University; Erin Williams, MD, Saint Louis University Background: Chronic inflammatory skin disease (atopic dermatitis, psoriasis, and overlap) is a common cause of morbidity in children, with the highest impact on burden-of-disease by disability adjusted life years (DALYs). Although effective standard-of-care medical therapy is defined, poor adherence to treatment is the major factor contributing to suboptimal disease control. Despite its importance, factors contributing to adherence have not been well-defined. Parameters that have been explored include complexity of treatment regimens, lack of knowledge, infrequent follow up, medication phobia and financial burden Self-reports by patients and caregivers often overestimate treatment adherence, so quantifiable measures may be more objective. Objective: The purpose of our study is to examine the impact of quantifiable factors on medical adherence in children with chronic inflammatory skin disease. A secondary endpoint is to evaluate the importance of adherence based on severity of disease and to determine the validity of a simplified, 3 part Physician Global Adherence (PGA). Methods: Prospective data collection via an Epic-based system, for all children attending the pediatric dermatology clinic at Cardinal Glennon Children’s hospital. Individual quantifiable factors such as medication quantity, bathing frequency, use of bleach baths, emollient, exposure to complex topicals, methotrexate use and number of siblings was studied and compared to the PGA. Results: 260 subjects were included in the analysis of the study. In regards to topical use, there was no pattern noted with adherence amongst Elidel, Protopic and mometasone. There was insufficient data in regards to bleach bath and emollient use. Adherence versus average number of siblings revealed no significant association. 61 patients were analyzed when looking at adherence score compared to response to treatment. Revealed that of patients with mild disease, 15 had excellent adherence and of those 15 around 50% had an excellent response however of patients rated with moderate disease e 15 had excellent adherence as well but only 26% had an excellent response.
4578 The impact of specialist orientation in dermatology for medical family and community residency Tatiana Gomes, MD, Residencia de Medicina de Famılia e Comunidade Introduction: With the advance of Family Medicine Strategy in the city of Rio de Janeiro, were implemented in 2012, the residency program (RMFCRJ) that has as objective, prepare the resident to solve problems, with high quality and resolution within the Primary Health care. To this goal, it was requested matrix support of professionals in other specialties. Skin lesions have significant impact on the quality of individuals life, generating psychosocial problems that can compromise the work activities and contribute to social isolation. Among the patients who consult general practitioners, 15-30% have some dermatologic complaints, and of these 4-6% are referred to specialists, resulting in a high demand for specialty. Objective: Evaluate the impact of specialist orientation in dermatology at RMFCRJ teams of CF. Dalmir de Abreu Salgado through referrals to tertiary services in dermatology (before and after the implementation of this activity), and also to emphasize the importance of this as a general practitioner qualification process for a more efficient approach.
Conclusion: PGA did not reflect correlation with adherence based on individual components. Adherence was also not impacted by the average number of siblings. Lastly, adherence is most important for the treatment of mild disease because severe disease is much more difficult to treat and often does not improve even with excellent adherence.
Methodology: Number and profile analysis of the dermatology referrals requested by SISREG platform, equivalent to the year 2012 (without matrix in dermatology), July to December/2013 and January-December/2014 (with matrix). Results and conclusions: It was revealed a striking decrease in the number of referrals to dermatology and more specific and precise in justified diagnosis. We have the matrix in dermatology as a tool that increases the resident instrumental to solve frequent demands in their clinical practice, reducing unnecessary demand for specialized care.
Commercial support: None identified.
Commercial support: None identified.
AB254
J AM ACAD DERMATOL
JUNE 2017