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Regulation of expression of the chemokine-scavenging receptor D6 by microRNAs
P8542
P8077
Quality of life and compliance in psoriasis Christos Stamou, MD, University of Athens Medical School, 2nd Department of Dermatology, Attikon General Hospital, Athens Xaidari, Greece; Aikaterini Chliva, MD, PhD, University of Athens Medical School, 2nd Department of Dermatology- Allergiology Department, Attikon General Hospital, Athens Xaidari, Greece; Dimitrios Rigopoulos, MD, PhD, University of Athens Medical School, 2nd Department of Dermatology, Attikon General Hospital, Athens Xaidari, Greece; Georgios Kontochristopoulos, MD, PhD, 2nd Dermatology State Clinic, Andreas Syggros Hospital of Cutaneous & Venereal Diseases, Athens, Greece; Konstantinos Theodoropoulos, MD, University of Athens Medical School, 2nd Department of Dermatology, Attikon General Hospital, Athens Xaidari, Greece; Stamatis Gregoriou, MD, PhD, University of Athens Medical School, 2nd Department of Dermatology, Attikon General Hospital, Athens Xaidari, Greece Introduction: We performed a study to assess the impact of psoriasis quality of life in a large sample of Greek patients with psoriasis in order to identify behavioral patterns toward family and close friends and to evaluate adherence to treatment, an essential factor for disease management. Methods: For the study the participants had to answer an anonymous questionnaire including Dermatology Quality of life Index, questions evaluating sources of information about the disease, degree of satisfaction regarding the information provided by the dermatologist, degree of support by family and friends, issues associated with work environment, primary and secondary nonadherence, and adherence to visit schedule. The questionnaire was completed by 2464 psoriatic patients and statistical analysis was performed. Results: Seventy-three percent of the patients declared they were always buying the agents prescribed by their doctor. Patients having higher impact on QoL declared primary adherence more often (P ¼ .014). Secondary adherence was 37% and also statistically significantly more often among those having a more severe impact on their QoL (P ¼ .006), patients under 18 and patients over 60 years old (P ¼ .001). Women were more likely to adhere to prescribed instructions (P ¼.022; odds ratio, 1.135). Adherence to scheduled visits to the hospital or private practice office was declared by 60% of the patients. Patients with more severe impact on QoL (P ¼.044), patients under 18 and over 60 (P ¼.007), and women (P \.005; odds ratio, 1.224) were more likely to adhere to scheduled appointments to their doctor.
Recently characterized antiinflammatory cytokines in psoriasis Xinaida T. Lima, MD, MPH, Universidade Estadual de Campinas (UNICAMP), Campinas - S~ao Paulo, Brazil; Maria Heloisa Blotta, PhD, Universidade Estadual de Campinas (UNICAMP), Campinas - SP, Brazil; Renata Magalh~aes, MD, PhD, Universidade Estadual de Campinas (UNICAMP), Campinas - S~ao Paulo, Brazil; R^ omulo Oliveira, PhD, Universidade Estadual de Campinas, Campinas - S~ao Paulo, Brazil; Ronei Mamoni, PhD, Universidade Estadual de Campinas (UNICAMP), Campinas - S~ao Paulo, Brazil Background: There have been previous studies evaluating the role of well characterized antiinflammatory cytokines in psoriasis. IL-27 and IL-37 are regulatory cytokines that have been more recently described. A few studies showed controversial findings when attempting to characterize IL-27 in psoriasis and IL-17 stimulation had no effect on psoriasis-derived keratinocytes induction of IL-37. The aim of our study was to evaluate these antiinflammatory cytokines in psoriasis.
Conclusion: The impact of psoriasis on patient quality of life affects adherence to treatment.
Methods: Patients with active moderate to severe plaque-type psoriasis and healthy volunteers were included. Serum concentrations of IL-27 and IL-37 were measured by ELISA assay. Patients were evaluated for disease severity by a dermatologist and for psoriatic arthritis by a rheumatologist. Results: We evaluated 35 patients with psoriasis and 35 controls. There were no significant differences in age, sex, and BMI between the groups. Mean (SD) age was 56.0 (10.0) and 52.1 (8.1) years old in the psoriasis and control group, respectively. Psoriatic patients had mean PASI of 14.2 and mean BSA of 31.3%. Fifteen patients with psoriasis (42.9%) had arthritis. Although patients with psoriasis had decreased mean concentrations of IL-27 and IL-37 when compared to controls, this difference was not statistically significant (P ¼.22 and 0.18, respectively). On the other hand, we found lower levels of these cytokines in patients with both psoriasis and arthritis when compared to controls (P ¼ .04 and 0.02 for IL-27 and IL-37, respectively). There was a nonsignificant negative correlation between both cytokines and disease severity (PASI and BSA). Interestingly, we detected a remarkably high correlation between IL-27 and IL-37 (P \.001). Conclusions: Serum concentrations of newly described antiinflammatory cytokines IL-27 and IL-37 in patients with psoriatic arthritis and psoriasis were significantly lower than in controls. Although the results were not significant in the analysis of patients with psoriasis, decreased serum levels and a negative correlation of both cytokines with severity may indicate an important role of these interleukins in the disease pathogenesis. Commercial support: None identified.
Commercial support: None identified.
P8262 P8666
Conclusions: The cutaneous manifestations of internal disease can be a sign of an occult disease and a clinical tool to assess the severity of known disease. Recalcitrant psoriasiform eruptions have been described as the only presenting symptom in a variety of conditions. Therefore, it is imperative to be cognizant of associated conditions and possible overlap syndromes.
Regulation of expression of the chemokine-scavenging receptor D6 by microRNAs Kave Shams, MBChB, Institute of Infection, Immunity and Inflammation; College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom; David Burden, MBChB, MD, Department of Dermatology, Western Infirmary, Glasgow, United Kingdom; Gerry Graham, PhD, Institute of Infection, Immunity and Inflammation; College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom; Mark Singh, Institute of Infection, Immunity and Inflammation; College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom Psoriasis is a common debilitating systemic inflammatory skin condition associated with significant morbidity and mortality. Chemokines are the principal regulators of leukocyte migration and are implicated in inflammatory skin diseases, including psoriasis. The atypical chemokine-scavenging receptor D6 lacks the ability to signal, instead scavenging and internalizing inflammatory CC-chemokines and thereby plays a key role in the resolution of inflammation. We have previously explored the association between D6 expression and the distribution of plaques in psoriatic skin, where D6 is predominantly expressed in keratinocytes and lymphatic endothelial cells. D6 expression was significantly elevated in unaffected skin whilst D6 expression in lesional skin was significantly reduced in comparison. Localization of psoriatic plaques may be explained at least in part by a reduced expression of D6, with trauma being one trigger for its reduced expression. To determine the molecular mechanisms that control D6 expression, we have identified three miRNAs that are predicted to bind the 3’-UTR of D6 and that are also differentially expressed in psoriasis; miR-10, miR-146 and miR-203. Here we show that transfection of miR-10 and miR-146 into primary human lymphatic endothelial cells and keratinocytes respectively leads to a significant reduction in D6 expression as assessed through Q-PCR. Protein expression of D6 is significantly reduced (as measured through Western blotting/adjusted densitometry) with miR-10 and miR146 respectively. Immunohistochemistry staining for D6 shows that D6 expression is reduced predominantly in the cytoplasm and is relatively more concentrated in the peri-nuclear region in both cell types upon miR-transfection. We demonstrate for the first time that miR-10 and miR-146 reduce D6 expression at transcript and protein level in lymphatic endothelial cells and keratinocytes respectively. Novel modulators of the chemokine system, such as these miRNAs, constitute an exciting new class of molecules that can be targets for new therapies and/or biomarkers in psoriasis.
Commercial support: None identified.
Commercial support: None identified.
Recalcitrant psoriasiform eruptions: A harbinger of serious internal disease? Todd Mollet, MD, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States; Laura Buford, MS, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States; Travis Blalock, MD, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Background: Recalcitrant psoriasiform eruptions have previously been described in association with malignancy, various nutritional deficiencies, pregnancy, and cytotoxic drug use. To our knowledge, recalcitrant psoriasiform eruptions have not been described in the context of antisynthetase (AS) syndrome. AS syndrome is characterized by the presence of antiaminoacyl-tRNA synthetase (anti-ARS) antibodies, myositis, interstitial lung disease, Raynaud phenomenon, and mechanic’s hands; however, not all clinical features are necessary for diagnosis. Several different anti-ARS antibodies have been described, and distinct clinical phenotypes are defined for each autoantibody. Observation: We report a case of a 56-year-old white female with a 2-year history of recalcitrant psoriasiform eruptions. Histologic examination revealed features of psoriasiform spongiotic dermatitis and sebopsoriasis. Her medical history includes diabetes mellitus, hypertension, chronic anemia, and interstitial lung disease. Over the course of illness, the patient was diagnosed with AS syndrome characterized by anti-PL7 subtype of anti-ARS antibodies. The patient failed multiple medications including topical steroids, prednisone, methotrexate, soriatane, Humira, and cyclosporine, before being started on azathioprine and Stelara. An extensive investigation of her psoriasiform lesions in the context of AS syndrome led us to consider the type Wong variant dermatomyositis. The possibility of this rare diagnosis was supported by the presence pityriasis rubra pilariselike eruptions and elevated serum aldolase; however, the biopsy was more consistent with psoriasis. The patient eventually progressed to erythroderma, which improved after treating methicillin-sensitive Staphylococcus aureus (MSSA) superinfection.
AB182
J AM ACAD DERMATOL
MAY 2014
P8077
Quality of life and compliance in psoriasis Christos Stamou, MD, University of Athens Medical School, 2nd Department of Dermatology, Attikon General Hospital, Athens Xaidari, Greece; Aikaterini Chliva, MD, PhD, University of Athens Medical School, 2nd Department of Dermatology- Allergiology Department, Attikon General Hospital, Athens Xaidari, Greece; Dimitrios Rigopoulos, MD, PhD, University of Athens Medical School, 2nd Department of Dermatology, Attikon General Hospital, Athens Xaidari, Greece; Georgios Kontochristopoulos, MD, PhD, 2nd Dermatology State Clinic, Andreas Syggros Hospital of Cutaneous & Venereal Diseases, Athens, Greece; Konstantinos Theodoropoulos, MD, University of Athens Medical School, 2nd Department of Dermatology, Attikon General Hospital, Athens Xaidari, Greece; Stamatis Gregoriou, MD, PhD, University of Athens Medical School, 2nd Department of Dermatology, Attikon General Hospital, Athens Xaidari, Greece Introduction: We performed a study to assess the impact of psoriasis quality of life in a large sample of Greek patients with psoriasis in order to identify behavioral patterns toward family and close friends and to evaluate adherence to treatment, an essential factor for disease management. Methods: For the study the participants had to answer an anonymous questionnaire including Dermatology Quality of life Index, questions evaluating sources of information about the disease, degree of satisfaction regarding the information provided by the dermatologist, degree of support by family and friends, issues associated with work environment, primary and secondary nonadherence, and adherence to visit schedule. The questionnaire was completed by 2464 psoriatic patients and statistical analysis was performed. Results: Seventy-three percent of the patients declared they were always buying the agents prescribed by their doctor. Patients having higher impact on QoL declared primary adherence more often (P ¼ .014). Secondary adherence was 37% and also statistically significantly more often among those having a more severe impact on their QoL (P ¼ .006), patients under 18 and patients over 60 years old (P ¼ .001). Women were more likely to adhere to prescribed instructions (P ¼.022; odds ratio, 1.135). Adherence to scheduled visits to the hospital or private practice office was declared by 60% of the patients. Patients with more severe impact on QoL (P ¼.044), patients under 18 and over 60 (P ¼.007), and women (P \.005; odds ratio, 1.224) were more likely to adhere to scheduled appointments to their doctor.
Recently characterized antiinflammatory cytokines in psoriasis Xinaida T. Lima, MD, MPH, Universidade Estadual de Campinas (UNICAMP), Campinas - S~ao Paulo, Brazil; Maria Heloisa Blotta, PhD, Universidade Estadual de Campinas (UNICAMP), Campinas - SP, Brazil; Renata Magalh~aes, MD, PhD, Universidade Estadual de Campinas (UNICAMP), Campinas - S~ao Paulo, Brazil; R^ omulo Oliveira, PhD, Universidade Estadual de Campinas, Campinas - S~ao Paulo, Brazil; Ronei Mamoni, PhD, Universidade Estadual de Campinas (UNICAMP), Campinas - S~ao Paulo, Brazil Background: There have been previous studies evaluating the role of well characterized antiinflammatory cytokines in psoriasis. IL-27 and IL-37 are regulatory cytokines that have been more recently described. A few studies showed controversial findings when attempting to characterize IL-27 in psoriasis and IL-17 stimulation had no effect on psoriasis-derived keratinocytes induction of IL-37. The aim of our study was to evaluate these antiinflammatory cytokines in psoriasis.
Conclusion: The impact of psoriasis on patient quality of life affects adherence to treatment.
Methods: Patients with active moderate to severe plaque-type psoriasis and healthy volunteers were included. Serum concentrations of IL-27 and IL-37 were measured by ELISA assay. Patients were evaluated for disease severity by a dermatologist and for psoriatic arthritis by a rheumatologist. Results: We evaluated 35 patients with psoriasis and 35 controls. There were no significant differences in age, sex, and BMI between the groups. Mean (SD) age was 56.0 (10.0) and 52.1 (8.1) years old in the psoriasis and control group, respectively. Psoriatic patients had mean PASI of 14.2 and mean BSA of 31.3%. Fifteen patients with psoriasis (42.9%) had arthritis. Although patients with psoriasis had decreased mean concentrations of IL-27 and IL-37 when compared to controls, this difference was not statistically significant (P ¼.22 and 0.18, respectively). On the other hand, we found lower levels of these cytokines in patients with both psoriasis and arthritis when compared to controls (P ¼ .04 and 0.02 for IL-27 and IL-37, respectively). There was a nonsignificant negative correlation between both cytokines and disease severity (PASI and BSA). Interestingly, we detected a remarkably high correlation between IL-27 and IL-37 (P \.001). Conclusions: Serum concentrations of newly described antiinflammatory cytokines IL-27 and IL-37 in patients with psoriatic arthritis and psoriasis were significantly lower than in controls. Although the results were not significant in the analysis of patients with psoriasis, decreased serum levels and a negative correlation of both cytokines with severity may indicate an important role of these interleukins in the disease pathogenesis. Commercial support: None identified.
Commercial support: None identified.
P8262 P8666
Conclusions: The cutaneous manifestations of internal disease can be a sign of an occult disease and a clinical tool to assess the severity of known disease. Recalcitrant psoriasiform eruptions have been described as the only presenting symptom in a variety of conditions. Therefore, it is imperative to be cognizant of associated conditions and possible overlap syndromes.
Regulation of expression of the chemokine-scavenging receptor D6 by microRNAs Kave Shams, MBChB, Institute of Infection, Immunity and Inflammation; College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom; David Burden, MBChB, MD, Department of Dermatology, Western Infirmary, Glasgow, United Kingdom; Gerry Graham, PhD, Institute of Infection, Immunity and Inflammation; College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom; Mark Singh, Institute of Infection, Immunity and Inflammation; College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom Psoriasis is a common debilitating systemic inflammatory skin condition associated with significant morbidity and mortality. Chemokines are the principal regulators of leukocyte migration and are implicated in inflammatory skin diseases, including psoriasis. The atypical chemokine-scavenging receptor D6 lacks the ability to signal, instead scavenging and internalizing inflammatory CC-chemokines and thereby plays a key role in the resolution of inflammation. We have previously explored the association between D6 expression and the distribution of plaques in psoriatic skin, where D6 is predominantly expressed in keratinocytes and lymphatic endothelial cells. D6 expression was significantly elevated in unaffected skin whilst D6 expression in lesional skin was significantly reduced in comparison. Localization of psoriatic plaques may be explained at least in part by a reduced expression of D6, with trauma being one trigger for its reduced expression. To determine the molecular mechanisms that control D6 expression, we have identified three miRNAs that are predicted to bind the 3’-UTR of D6 and that are also differentially expressed in psoriasis; miR-10, miR-146 and miR-203. Here we show that transfection of miR-10 and miR-146 into primary human lymphatic endothelial cells and keratinocytes respectively leads to a significant reduction in D6 expression as assessed through Q-PCR. Protein expression of D6 is significantly reduced (as measured through Western blotting/adjusted densitometry) with miR-10 and miR146 respectively. Immunohistochemistry staining for D6 shows that D6 expression is reduced predominantly in the cytoplasm and is relatively more concentrated in the peri-nuclear region in both cell types upon miR-transfection. We demonstrate for the first time that miR-10 and miR-146 reduce D6 expression at transcript and protein level in lymphatic endothelial cells and keratinocytes respectively. Novel modulators of the chemokine system, such as these miRNAs, constitute an exciting new class of molecules that can be targets for new therapies and/or biomarkers in psoriasis.
Commercial support: None identified.
Commercial support: None identified.
Recalcitrant psoriasiform eruptions: A harbinger of serious internal disease? Todd Mollet, MD, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States; Laura Buford, MS, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States; Travis Blalock, MD, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Background: Recalcitrant psoriasiform eruptions have previously been described in association with malignancy, various nutritional deficiencies, pregnancy, and cytotoxic drug use. To our knowledge, recalcitrant psoriasiform eruptions have not been described in the context of antisynthetase (AS) syndrome. AS syndrome is characterized by the presence of antiaminoacyl-tRNA synthetase (anti-ARS) antibodies, myositis, interstitial lung disease, Raynaud phenomenon, and mechanic’s hands; however, not all clinical features are necessary for diagnosis. Several different anti-ARS antibodies have been described, and distinct clinical phenotypes are defined for each autoantibody. Observation: We report a case of a 56-year-old white female with a 2-year history of recalcitrant psoriasiform eruptions. Histologic examination revealed features of psoriasiform spongiotic dermatitis and sebopsoriasis. Her medical history includes diabetes mellitus, hypertension, chronic anemia, and interstitial lung disease. Over the course of illness, the patient was diagnosed with AS syndrome characterized by anti-PL7 subtype of anti-ARS antibodies. The patient failed multiple medications including topical steroids, prednisone, methotrexate, soriatane, Humira, and cyclosporine, before being started on azathioprine and Stelara. An extensive investigation of her psoriasiform lesions in the context of AS syndrome led us to consider the type Wong variant dermatomyositis. The possibility of this rare diagnosis was supported by the presence pityriasis rubra pilariselike eruptions and elevated serum aldolase; however, the biopsy was more consistent with psoriasis. The patient eventually progressed to erythroderma, which improved after treating methicillin-sensitive Staphylococcus aureus (MSSA) superinfection.
AB182
J AM ACAD DERMATOL
MAY 2014