Influence of the HLA-Cw6 Allele and IFIH1/MDA5 Gene Variants on the Cardiometabolic Risk Profile of Patients with Psoriatic Disease.

BACKGROUND: Cardiovascular comorbidity is a common companion of psoriasis and psoriatic arthritis (PsA). Recently, a significant link has been found between the HLA-Cw6 allele and a better cardiometabolic profile in these patients. We aimed to check this finding in our setting. METHODS: A cross-sectional observational study (n: 572 psoriasis patients, 30% with PsA) was conducted. Different study variables were collected in detail, as well as classic cardiometabolic risk factors. The distribution of the HLA-Cw6 allele and the IFIH1/MDA5 gene variants previously linked to disease risk were determined in the study cohort and stratified according to the cardiometabolic comorbidity. Linear and logistic regression models were constructed to analyze these associations. RESULTS: The study cohort included 309 men and 263 women, with a mean age of 46.7 years (SD 14.5) and a mean disease duration of 19.4 years (SD 14.8). We confirmed the known association between HLA-Cw6 and type I psoriasis (familial, severe, and early onset). Psoriasis severity (OR: 2.14), female sex (OR: 1.63), and the IFIH1/MDA5 rs1990760 TT genotype (OR: 1.62) were significantly related to PsA, while HLA-Cw6 was protective (OR: 0.65). HLA-Cw6 carriers showed a lower waist perimeter, lower BMI, and lower risk of both hypertension (OR: 0.52, p < 0.001) and diabetes (OR: 0.36, p < 0.001), but these findings were no longer apparent upon adjusting the regression models. No IFIH1/MDA5 gene variant was associated with any cardiometabolic risk factor. CONCLUSIONS: The influence of HLA-Cw6 on the cardiometabolic risk profile of psoriatic patients seems to be explained by other factors (age, sex, duration of the disease or arthritis) and not by this biomarker itself.

Clinical utility of liquid biopsy and integrative genomic profiling in early-stage and oligometastatic cancer patients treated with radiotherapy.

BACKGROUND: Liquid biopsy and Integrative Genomic Profiling (IGP) are yet to be implemented into routine Radiation Oncology. Here we assess the utility of germline, tumour and circulating cell-free DNA-based genomic analyses for the clinical management of early-stage and oligometastatic cancer patients treated by precision radiotherapy. METHODS: We performed germline, tissue- and liquid biopsy NGS panels on 50 early-stage/oligometastatic cancer patients undergoing radiotherapy. We also monitored ctDNA variants in serial liquid biopsies collected during radiotherapy and follow-up and evaluated the clinical utility of such comprehensive approach. RESULTS: The integration of different genomic studies revealed that only 1/3 of the liquid biopsy variants are of tumour origin. Altogether, 55 tumour variants (affecting 3/4 of the patients) were considered potentially actionable (for treatment and prognosis), whereas potential follow-up biomarkers were identified in all cases. Germline cancer-predisposing variants were present in three patients, which would have not been eligible for hereditary cancer testing according to clinical guidelines. The presence of detectable ctDNA variants before radiotherapy was associated with progression-free survival both in oligometastatic patients and in those with early-stage. CONCLUSIONS: IGP provides both valuable and actionable information for personalised decision-making in Radiation Oncology.

Genetic Variants of the NF-κB Pathway: Unraveling the Genetic Architecture of Psoriatic Disease.

Psoriasis is a multifactorial genetic disease for which the genetic factors explain about 70% of disease susceptibility. Up to 30-40% of psoriasis patients develop psoriatic arthritis (PsA). However, PsA can be considered as a "disease within a disease", since in most cases psoriasis is already present when joint complaints begin. This has made studies that attempt to unravel the genetic basis for both components of psoriatic disease enormously difficult. Psoriatic disease is also accompanied by a high burden of comorbid conditions, mainly of the cardiometabolic type. It is currently unclear whether these comorbidities and psoriatic disease have a shared genetic basis or not. The nuclear factor of kappa light chain enhancer of activated B cells (NF-κB) is a transcription factor that regulates a plethora of genes in response to infection, inflammation, and a wide variety of stimuli on several cell types. This mini-review is focused on recent findings that highlight the importance of this pathway both in the susceptibility and in the determinism of some features of psoriatic disease. We also briefly review the importance of genetic variants of this pathway as biomarkers of pharmacological response. All the above may help to better understand the etiopathogenesis of this complex entity.

Improving the standard of care for patients with spondyloarthritis-related immune inflammatory conditions: results of a Delphi study and proposal for early detection.

BACKGROUND: Our objective was to provide consensus recommendations on the optimal management of the immune-mediated inflammatory diseases (IMIDs) seen in patients with spondyloarthritis (SpA) using a multidisciplinary approach, and to develop a simple tool to help earlier recognition and referral of coexisting IMIDs in patients who already have one type of IMID. METHODS: A total of 28 experts in the multidisciplinary management of the SpA-associated IMIDs assessed two questionnaires: one with statements focused on the multidisciplinary management of IMIDs, and a second questionnaire focused on questions useful for early recognition and referral. Panelists assessed the statements with a 9-point ordinal scale (1 = strongly disagree, 9 = strongly agree) using a modified Delphi methodology. RESULTS: Consensus was reached on 72 out of the 82 statements (87.8%). Panelists agreed that the multidisciplinary approach to IMIDs is not sufficiently developed. The creation of multidisciplinary IMID units might be necessary. These units might focus primarily on patients with two or more coexisting IMIDs, or on IMIDs that are especially complex from a diagnostic or therapeutic point of view. Specialists who attend to patients with IMIDs should perform a screening for other coexisting IMIDs. A simple tool to help earlier recognition and referral of coexisting IMIDs is proposed. CONCLUSIONS: There is a need to improve care for patients with SpA-associated IMIDs. We provide expert recommendations to guide the adoption of a multidisciplinary approach for these cases, and a simple tool that may be useful for earlier recognition of coexisting IMIDs.

Estado actual de la atención multidisciplinar para pacientes con artritis psoriásica en España: proyecto NEXUS 2.0 / Current status of multidisciplinary care in psoriatic arthritis in Spain: NEXUS 2.0 project

OBJETIVO: 1) Analizar la implementación de los modelos de atención multidisciplinar en pacientes con artritis psoriásica (APs), y 2) definir estándares de calidad de mínimos y de excelencia. MÉTODOS: Se envió una encuesta a profesionales que ya realizan atención multidisciplinar o están en vías preguntando por: 1) tipo de modelo de abordaje multidisciplinar, y 2) grado, prioridad y facilidad de la implementación de los estándares de calidad de estructura, proceso y resultado. En 6 reuniones regionales se presentaron y discutieron los resultados de la encuesta, tanto a nivel nacional como regional, y se definió la prioridad definitiva de los estándares de calidad. En una reunión de grupo nominal, 11 expertos (reumatólogos y dermatólogos) analizaron los resultados de la encuesta y las reuniones regionales. Con ello definieron qué estándares de calidad son actualmente de mínimos y cuáles de excelencia. RESULTADOS: Los modelos de atención multidisciplinar conjunto y paralelo son los más implementados, y los de los estándares de calidad es muy variable: en los de estructura varía del 22 al 74%, en los de proceso del 17 al 54% y en los de resultado del 2 al 28%. De los 25 estándares de calidad originales, 9 se consideran solo de mínimos, 4 de excelencia y 12 tienen definidos unos criterios para ser de mínimos y otros para la excelencia. CONCLUSIONES: La definición de estándares de calidad de mínimos y de excelencia ayudará en la consecución del objetivo de la atención multidisciplinar para pacientes con APs, que es la mejor asistencia sanitaria posible

OBJECTIVE: 1) To analyze the implementation of multidisciplinary care models in psoriatic arthritis (PsA) patients, 2) To define minimum and excellent standards of care. METHODS: A survey was sent to clinicians who already performed multidisciplinary care or were in the process of undertaking it, asking: 1) Type of multidisciplinary care model implemented; 2) Degree, priority and feasibility of the implementation of quality standards in the structure, process and result for care. In 6 regional meetings the results of the survey were presented and discussed, and the ultimate priority of quality standards for care was defined. At a nominal meeting group, 11 experts (rheumatologists and dermatologists) analyzed the results of the survey and the regional meetings. With this information, they defined which standards of care are currently considered as minimum and which are excellent. RESULTS: The simultaneous and parallel models of multidisciplinary care are those most widely implemented, but the implementation of quality standards is highly variable. In terms of structure it ranges from 22% to 74%, in those related to process from 17% to 54% and in the results from 2% to 28%. Of the 25 original quality standards for care, 9 were considered only minimum, 4 were excellent and 12 defined criteria for minimum level and others for excellence. CONCLUSIONS: The definition of minimum and excellent quality standards for care will help achieve the goal of multidisciplinary care for patients with PAs, which is the best healthcare possible

Current status of multidisciplinary care in psoriatic arthritis in Spain: NEXUS 2.0 project. / Estado actual de la atención multidisciplinar para pacientes con artritis psoriásica en España: proyecto NEXUS 2.0.

OBJECTIVE: 1) To analyze the implementation of multidisciplinary care models in psoriatic arthritis (PsA) patients, 2) To define minimum and excellent standards of care. METHODS: A survey was sent to clinicians who already performed multidisciplinary care or were in the process of undertaking it, asking: 1) Type of multidisciplinary care model implemented; 2) Degree, priority and feasibility of the implementation of quality standards in the structure, process and result for care. In 6 regional meetings the results of the survey were presented and discussed, and the ultimate priority of quality standards for care was defined. At a nominal meeting group, 11 experts (rheumatologists and dermatologists) analyzed the results of the survey and the regional meetings. With this information, they defined which standards of care are currently considered as minimum and which are excellent. RESULTS: The simultaneous and parallel models of multidisciplinary care are those most widely implemented, but the implementation of quality standards is highly variable. In terms of structure it ranges from 22% to 74%, in those related to process from 17% to 54% and in the results from 2% to 28%. Of the 25 original quality standards for care, 9 were considered only minimum, 4 were excellent and 12 defined criteria for minimum level and others for excellence. CONCLUSIONS: The definition of minimum and excellent quality standards for care will help achieve the goal of multidisciplinary care for patients with PAs, which is the best healthcare possible.

Obesity in psoriatic arthritis: Comparative prevalence and associated factors.

Obesity is a common cardiovascular risk factor in psoriatic disease. Although the prevalence of obesity is high, the factors associated with it in patients with psoriatic arthritis (PsA) are poorly understood. We aimed to analyze the frequency and obesity-associated factors in a cohort of PsA.This retrospective cross-sectional study included 290 consecutive patients with PsA according to CASPAR criteria. Three-hundred ten psoriatic patients without arthritis and 600 outpatients without inflammatory conditions were used as comparison populations. The factors associated with obesity were analyzed first using conditional logistic regression. The significant factors in this first model were introduced in a multivariate model using a backward step approach.This series included 159 men (54.8%) and 131 women (45.2%), with an average age of 54 ±â€Š12 years. Obesity was more common both in psoriasis (36.5% vs 22%, OR 2.1 [95%CI: 1.5-2.8), P < .01]) and PsA (27.6% vs 22%, OR 1.4 [95%CI: 1.0-1.9], P < .05) than in the non-inflammatory population. Obesity was more frequent in psoriasis (36.5%) than in PsA (27.6%), OR 1.5 95% CI: 1.1 to 2.1, P < .05. After correcting for age, sex, disease duration, and other confounders, independent associations with obesity (P < .05) were: PsA family history (OR 3.6, 95%CI: 1.1-12.4), evolution as axial disease (OR 4.4, 95%CI: 1.0-15.4), and dyslipidemia (OR 3.5, 95%CI: 1.5-8.6).Obesity is common in psoriatic disease, but much more frequent among patients with cutaneous than joint disease. Patients who present with spondylitis during evolution are more prone to this comorbidity, and therefore, should be closely monitored to correct this eventuality in a timely manner.

Hypertension is associated with increased age at the onset of psoriasis and a higher body mass index in psoriatic disease.

BACKGROUND AND AIMS: High blood pressure (HBP) is a common comorbidity in psoriatic disease. Some studies indicate a higher prevalence of HBP among arthritis patients, in relation to psoriasis alone, within the psoriatic spectrum. Our objective was to study the prevalence of HBP in both types of patients as well as to analyse the factors associated with it. METHODS: A cross-sectional observational study of 600 patients with psoriatic disease attended in a multidisciplinary clinic of a reference centre. We first analysed the frequency of this comorbidity and then the factors associated with it using conditional logistic regression. The significant factors in this first model were introduced in a multivariate model using a backward step approach. RESULTS: A total of 144 patients were hypertensive (24%). Of patients with arthritis, 86/290 (29.7%) had HBP, compared with 58/310 (18.7%) with psoriasis (OR 1.7 95%, CI 1.25-2.50, p = 0.003). Hypertension was independently associated with higher age at onset of psoriasis (OR 1.04, 95%CI 1.03-1.06, p < 0.001) and a higher body mass index (OR 1.13, 95%CI, 1.06-1.22, p < 0.001). CONCLUSIONS: HBP is more prevalent in patients with arthritis within the spectrum of psoriatic disease. Patients with a higher body mass index and those with later-onset psoriasis are more prone to this comorbidity. KEY POINTS: • The factors of psoriatic disease associated with HBP are little known. • HBP is more prevalent in patients with arthritis within the spectrum of psoriatic disease. • In patients with psoriatic disease, for each point of increase in the body mass index, the risk of HBP increases by 13%. • For each year of onset of psoriasis above 40 years, the risk of HBP increases by 4%.

Polyarticular evolution and late-onset psoriasis may be associated with cardiovascular disease in psoriatic arthritis.

BACKGROUND AND AIMS: Patients with psoriatic arthritis (PsA) have high prevalence of cardiovascular risk factors (CVRF), and they also show higher rates of cardiovascular disease (CVD). We aimed to corroborate these findings and identify factors associated with these events in our clinical setting. METHODS: This cross-sectional study included 340 consecutive patients seen in a tertiary care hospital. The prevalence of CVRF was compared to that of 600 outpatients without inflammatory conditions. To analyze CVD-associated factors, odds ratio (OR) values were calculated by conditional logistic regression analysis. Significant variables in the univariate analysis were then introduced in a multivariate analysis with a backward stepwise approach. RESULTS: Patients with psoriatic arthritis had higher frequencies of hypertension (36% vs 23%, OR 2.4, 95%CI: 1.6-2.7, P < 0.0001), diabetes (13.8% vs 5%, OR 2.8, 95%CI: 1.7-4.3, P < 0.0001), obesity (35% vs 22%, OR 2.1, 95%CI: 1.5-2.8, P < 0.0001) and tobacco use (26% vs 21%, OR 1.4, 95%CI: 1.0-1.8, P < 0.05). More PsA patients had CVD compared to non-inflammatory patients (9.4% vs 5.8%, OR 1.68, 95%CI: 1.02-2.76, P < 0.05). Independent CVD-associated factors were: an age of onset of psoriasis >40 years (OR 3.4, 95%CI: 1.1-10.0, P < 0.05), a high number of swollen joints during evolution (OR 2.9, 95%CI: 1.1-8.0, P < 0.05), hypertension (OR 5.3, 95%CI: 1.6-17.6, P < 0.01) and dyslipidemia (OR 2.6, 95%CI: 1.0-7.2, P < 0.05). CONCLUSIONS: Cardiovascular risk should be carefully evaluated in patients with PsA whose disease presents a high inflammatory burden and in those with late-onset psoriasis.

Minimal Disease Activity and Patient-Acceptable Symptom State in Psoriatic Arthritis: A Real-World Evidence Study With Ustekinumab.

BACKGROUND/AIMS: Ustekinumab (UST) is a fully human immunoglobulin G1 monoclonal antibody approved for treating moderate to severe psoriasis and, more recently, psoriatic arthritis (PsA) as well. However, information regarding its clinical usefulness in a real-world setting is scarce. We aimed to evaluate the effectiveness and safety of UST in a real-world clinical setting. METHODS: This single-center observational study included PsA outpatients (n = 50) treated with UST from March 2015 to March 2017. Only patients who used at least 3 doses of UST were analyzed. The percentage of patients who achieved a minimal disease activity (MDA) response was collected. The impact of the disease was also evaluated according to the recently developed Psoriatic Arthritis Impact of Disease (PsAID) questionnaire. A binary logistic regression multivariate model was performed to look for variables predicting MDA. RESULTS: Twenty-seven patients (54%) reached an MDA state. Mean PsAID in MDA group was 3.5 ± 2.9 versus 6.8 ± 5.1 in non-MDA patients (p < 0.001). Among the patients who achieved MDA, 19 (70.4%) had a patient-acceptable symptom state according to the PsAID, whereas only 5 (21.7%) of the 23 patients who did not reach an MDA achieved a patient-acceptable symptom state (p < 0.001). Higher basal Psoriasis Area and Severity Index decreased the odds of achieving MDA (odds ratio [OR], 0.80; 95% CI, 0.65-0.99; p = 0.038), whereas a longer use of UST (OR, 1.52; 95% CI, 1.13-2.06; p = 0.015) and a previous failure to 1 anti-tumor necrosis factor α (OR, 18; 95% CI, 2.52-128.63; p = 0.004) increased this odds. We found no major safety problems. CONCLUSIONS: Ustekinumab was effective and safe in this PsA population. Minimal disease activity and PsAID may be useful tools in the evaluation of PsA therapeutic interventions in routine clinical practice.

Standards of care and quality indicators for multidisciplinary care models for psoriatic arthritis in Spain.

To define and give priority to standards of care and quality indicators of multidisciplinary care for patients with psoriatic arthritis (PsA). A systematic literature review on PsA standards of care and quality indicators was performed. An expert panel of rheumatologists and dermatologists who provide multidisciplinary care was established. In a consensus meeting group, the experts discussed and developed the standards of care and quality indicators and graded their priority, agreement and also the feasibility (only for quality indicators) following qualitative methodology and a Delphi process. Afterwards, these results were discussed with 2 focus groups, 1 with patients, another with health managers. A descriptive analysis is presented. We obtained 25 standards of care (9 of structure, 9 of process, 7 of results) and 24 quality indicators (2 of structure, 5 of process, 17 of results). Standards of care include relevant aspects in the multidisciplinary care of PsA patients like an appropriate physical infrastructure and technical equipment, the access to nursing care, labs and imaging techniques, other health professionals and treatments, or the development of care plans. Regarding quality indicators, the definition of multidisciplinary care model objectives and referral criteria, the establishment of responsibilities and coordination among professionals and the active evaluation of patients and data collection were given a high priority. Patients considered all of them as important. This set of standards of care and quality indicators for the multidisciplinary care of patients with PsA should help improve quality of care in these patients.

Prevalence and type II diabetes-associated factors in psoriatic arthritis.

Diabetes is a common cardiovascular risk factor in psoriatic arthritis (PsA). Although the prevalence of diabetes is high, the factors associated with it in PsA are poorly understood. We aimed to analyse the prevalence of type II diabetes and diabetes-associated factors in a hospital-based population with PsA. This cross-sectional study included 340 consecutive patients attended in a tertiary care hospital. The prevalence of diabetes was compared to that of 600 outpatients without inflammatory conditions. To analyse diabetes-associated factors, odds ratio (OR) values were calculated by conditional logistic regression analysis. Significant variables in the univariate analysis were then introduced in a multivariate analysis with a backward stepwise approach. Diabetes was more prevalent among PsA patients (13.8 vs. 5%, OR 2.8, 95% CI: 1.7-4.3, p < 0.0001). Diabetes-associated factors in the univariate analysis (p < 0.05) were the following: an age of onset of psoriasis > 40 years, an age of onset of arthritis > 40 years, a low educational level, family history of psoriasis, pustular psoriasis, high number of swollen joints during follow-up, hypertension, dyslipidemia, obesity, and cardiovascular events. After controlling for several confounders, diabetes was significantly associated with late-onset psoriasis (OR 8.2, 95% CI: 1.9-12.4, p = 0.002) and hypertension (OR 7.5, 95% CI: 1.5-13.3, p = 0.008). Diabetes risk should be carefully evaluated in patients with PsA whose psoriasis begins after 40 years.

Identification and management of comorbidity in psoriatic arthritis: evidence- and expert-based recommendations from a multidisciplinary panel from Spain.

The objective is to establish recommendations, based on evidence and expert opinion, for the identification and management of comorbidities in patients with psoriatic arthritis (PsA). The following techniques were applied: discussion group, systematic review, and Delphi survey for agreement. A panel of professionals from four specialties defined the users, the sections of the document, possible recommendations, and what systematic reviews should be performed. A second discussion was held with the results of the systematic reviews. Recommendations were formulated in the second meeting and voted online from 1 (total disagreement) to 10 (total agreement). Agreement was considered if at least 70% voted ≥7. The level of evidence and grade of recommendation were assigned using the Oxford Centre for Evidence-Based Medicine guidance. The full document was critically appraised by the experts, and the project was supervised at all times by a methodologist. In a final step, the document was reviewed and commented by a patient and a health management specialist. Fourteen recommendations were produced, together with a checklist to facilitate the implementation. The items with the largest support from evidence were those related to cardiovascular disease and risk factors. The panel recommends paying special attention to obesity, smoking, and alcohol consumption, as they are all modifiable factors with an impact on treatment response or complications of PsA. Psychological and organizational aspects were also deemed important. We herein suggest practical recommendations for the management of comorbidities in PsA based on evidence and expert opinion.

Modelos de atención multidisciplinar en pacientes con artritis psoriásica en España / Multidisciplinary care models for patients with psoriatic arthritis

Objetivo. Describir la estructura y procesos de distintos modelos de atención multidisciplinar de pacientes con artritis psoriásica (APs) en España, así como las barreras y facilitadores en su implantación. Métodos. Se realizó un estudio cualitativo mediante entrevistas estructuradas a 24 profesionales (12 reumatólogos y 12 dermatólogos que realizan atención multidisciplinar en pacientes con APs). Se recogieron datos relacionados con el centro, servicio, población atendida y sobre el modelo de atención multidisciplinar (tipo, recursos materiales y humanos, requerimientos de los profesionales, objetivos, criterios de entrada y salida, agendas, protocolos de actuación, responsabilidades, toma de decisiones, actividad investigadora y docente, sesiones clínicas conjuntas, creación/inicio, planificación, ventajas/desventajas del modelo y barreras/facilitadores en la implantación del modelo. Se describen sus características. Resultados. Analizamos 12 modelos de atención multidisciplinar en APs, implantados desde hace al menos 1-2 años, que globalmente pueden resumirse en 3 subtipos diferentes: presencial conjunto, presencial paralelo y circuito preferencial. La implantación de uno u otro modelo es consecuencia de la adaptación a las circunstancias del centro y profesionales. Una correcta planificación de la implantación es fundamental. La implicación y buena sintonía entre profesionales así como un acceso y criterios de derivación bien definidos son facilitadores muy importantes en la implantación de un modelo. La gestión de las agendas y la recogida de datos para medir resultados de salud de estos modelos son las principales barreras. Conclusiones. Existen distintos modelos de atención multidisciplinar implantados que tienen como objetivo intentar mejorar la atención del paciente con APs, la eficiencia del sistema y la colaboración entre especialistas (AU)

Objetive. To describe (structure, processes) of the multidisciplinary care models in psoriatic arthritis (PsA) in Spain, as well as barriers and facilitators of their implementation. Methods. A qualitative study was performed following structured interviews with 24 professionals (12 rheumatologists, 12 dermatologists who provide multidisciplinary care for patients with PsA). We collected data related to the hospital, department, population and multidisciplinary care model (type, physical and human resources, professional requirements, objectives, referral criteria, agendas, protocols, responsibilities, decision- making, research and education, clinical sessions, development and planning of the model, advantages and disadvantages of the model, barriers and facilitators in the implementation of the model. The models characteristics are described. Results. We analyzed 12 multidisciplinary care models in PsA, with at least 1-2 years of experience, and 3 subtypes of models, face-to-face, parallel, and preferential circuit. All are adapted to the hospital and professionals characteristics. A proper implementation planning is essential. The involvement and empathy between professionals and an access and well-defined referral criteria are important facilitators in the implementation of a model. The management of agendas and data collection to measure the multidisciplinary care models health outcomes are the main barriers. Conclusions. There are different multidisciplinary care models in PsA that can improve patient outcomes, system efficiency and collaboration between specialists (AU)

Multidisciplinary Care Models for Patients With Psoriatic Arthritis. / Modelos de atención multidisciplinar en pacientes con artritis psoriásica en España.

OBJETIVE: To describe (structure, processes) of the multidisciplinary care models in psoriatic arthritis (PsA) in Spain, as well as barriers and facilitators of their implementation. METHODS: A qualitative study was performed following structured interviews with 24 professionals (12 rheumatologists, 12 dermatologists who provide multidisciplinary care for patients with PsA). We collected data related to the hospital, department, population and multidisciplinary care model (type, physical and human resources, professional requirements, objectives, referral criteria, agendas, protocols, responsibilities, decision- making, research and education, clinical sessions, development and planning of the model, advantages and disadvantages of the model, barriers and facilitators in the implementation of the model. The models characteristics are described. RESULTS: We analyzed 12 multidisciplinary care models in PsA, with at least 1-2 years of experience, and 3 subtypes of models, face-to-face, parallel, and preferential circuit. All are adapted to the hospital and professionals characteristics. A proper implementation planning is essential. The involvement and empathy between professionals and an access and well-defined referral criteria are important facilitators in the implementation of a model. The management of agendas and data collection to measure the multidisciplinary care models health outcomes are the main barriers. CONCLUSIONS: There are different multidisciplinary care models in PsA that can improve patient outcomes, system efficiency and collaboration between specialists.

A polyarticular onset and diabetes could be the main predictors of cardiovascular events in psoriatic arthritis.

OBJECTIVES: We aimed to determine which disease features could be associated to the risk of cardiovascular (CV) events in a PsA cohort from a tertiary care institution. METHODS: We conducted an age- and sex-matched case-control study in which the cases were all PsA patients who developed cardiovascular (CV) events during the study period (2010-14). The control group was free of CV events during the same period. Univariate analysis was performed to examine unadjusted associations of potential risk factors. Significant variables in the univariate analysis were then introduced in a multivariate analysis with a backward stepwise approach. RESULTS: Of the 206 patients enrolled, 17 (8.3%) patients developed a total of 25 CV events (10 stroke, 9 acute coronary events and 6 ischaemic peripheral vascular events). In univariate analysis these patients showed more pustular psoriasis (OR 5.5, p=0.02), polyarticular onset (OR 3.2, p=0.03), polyarthritis during follow-up (OR 2.9, p=0.04), arthritis onset after 40 yr (OR 3.7, p=0.02), high lipid levels (OR 2.8, p=0.04), hypertension (OR 6.4, p=0.0008), diabetes (OR 12.1, p<0.0001) and lower educational level (OR 3.2, p=0.05). After controlling for age and other confounders, a polyarticular onset of PsA (OR 3.7, p=0.043) and diabetes (OR 8.1, p=0.001) remained as independently related to the risk of CV events. CONCLUSIONS: Traditional CV risk factors as well as factors related to the inflammatory nature of the disease were the main predictors of CV complications in this PsA population.

Identification of two rare and novel large deletions in ITGB4 gene causing epidermolysis bullosa with pyloric atresia.

Epidermolysis bullosa with pyloric atresia (EB-PA) is a rare autosomal recessive hereditary disease with a variable prognosis from lethal to very mild. EB-PA is classified into Simplex form (EBS-PA: OMIM #612138) and Junctional form (JEB-PA: OMIM #226730), and it is caused by mutations in ITGA6, ITGB4 and PLEC genes. We report the analysis of six patients with EB-PA, including two dizygotic twins. Skin immunofluorescence epitope mapping was performed followed by PCR and direct sequencing of the ITGB4 gene. Two of the patients presented with non-lethal EB-PA associated with missense ITGB4 gene mutations. For the other four, early postnatal demise was associated with complete lack of ß4 integrin due to a variety of ITGB4 novel mutations (2 large deletions, 1 splice-site mutation and 3 missense mutations). One of the deletions spanned 278 bp, being one of the largest reported to date for this gene. Remarkably, we also found for the first time a founder effect for one novel mutation in the ITGB4 gene. We have identified 6 novel mutations in the ITGB4 gene to be added to the mutation database. Our results reveal genotype-phenotype correlations that contribute to the molecular understanding of this heterogeneous disease, a pivotal issue for prognosis and for the development of novel evidence-based therapeutic options for EB management.

Age at disease onset may help to further characterize the disease phenotype in psoriatic arthritis.

OBJECTIVE: To evaluate whether the age of disease presentation helps to better characterize the disease phenotype in PsA. METHODS: Retrospective cohort study that included 205 consecutive patients fulfilling the CASPAR criteria for PsA. Study outcomes were assessed using univariate and multivariate analyses according to the age of onset of both skin and joint disease (cut off at 40years). RESULTS: Early onset psoriasis (EOP) showed more extensive skin involvement (OR 2.3, P=0.011), axial pattern as disease onset (OR 4.6, P=0.009) and mixed pattern during evolution (OR 2.4, P=0.019), family history of both psoriasis (OR 3.1, P=0.003) and PsA (OR 4.0, P=0.021), higher prevalence of HLA-C*06 (OR 2.03, P=0.03) and HLA-B*27 (OR 2.7, P=0.02). Early onset arthritis (EOA) had more family history of PsA (OR 2.9, P=0.007), and HLA-B*27 positivity (OR 5.9, P<0.0001). Patients with late onset arthritis (LOA) were more likely to have DM (OR 4.0, P=0.009), hypertension (OR 2.5, P=0.004), dyslipidemia (OR 2.3, P=0.011), and obesity (OR 1.7, P=0.012). Late onset psoriasis (LOP) tended to have more obesity (OR 1.9, P=0.035), DM (OR 9.4, P<0.0001), hypertension (OR 4.1, P<0.0001), and ischemic heart disease during follow-up (OR 5.9, P=0.021). In multivariate analysis, LOP predicted DM development (OR 12.1, P=0.006). LOA was shown to be an independent risk factor for hypertension (OR 5.2, P=0.039). CONCLUSION: Age at disease onset exerts a strong influence on several domains of disease phenotype in PsA. Therefore, this descriptor should be considered a good stratification option for epidemiological and genetic studies in PsA.

The Region Centromeric to HLA-C Is a Key Region for Understanding the Phenotypic Variability of Psoriatic Arthritis.

With the aim of clarifying the role of several polymorphisms around the HLA-C locus in the clinical expression of PsA, the distribution of several polymorphic markers and genes located around the HLA-C locus was analyzed in a well-established cohort of 110 patients with PsA, 50 patients with psoriasis alone, and 110 healthy controls. The frequency of these genes was also analyzed by PsA articular models, based on three main subgroups: oligoarthritis, polyarthritis, and spondylitis. Distal interphalangeal joint (DIP) involvement was associated with the presence of MICB-CA20 (OR 6.0, 95% CI: 1.58-22.69, P = 0.005). HLA-DRB∗07 was associated with oligoarticular forms of PsA (OR 4.1, 95% CI: 1.8-9.3, P = 0.0007). The spondylitic forms overexpressed the antigen HLA-B∗27 (OR 5.7, 95% CI: 2.4-13.6, P = 0.0001). MICA-A5.1 showed association with polyarthritis (OR 3.7, 95% CI: 1.5-8.8, P = 0.006). Genes telomeric to HLA-C were overexpressed in psoriasis but not in PsA subphenotypes. This study shows that the region centromeric to HLA-C is a key region that expresses not only disease risk genes but also genes that help explain the phenotypic variability of PsA.