Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis.

OBJECTIVE: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA. METHODS: We performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case-control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA. RESULTS: We identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDR<0.05). From these, the glycosaminoglycan (GAG) metabolism pathway was confirmed to be disease-specific after comparing the PsA cohort with the cohorts of patients with PsC and RA. Finally, we identified candidate drug targets in the GAG metabolism pathway as well as new PsA indications for approved drugs. CONCLUSION: These findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.

Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate-to-severe plaque psoriasis up to 1 year: Results from the CLEAR study.

BACKGROUND: Secukinumab demonstrated superior efficacy to ustekinumab at week 4 and week 16 of the CLEAR study, with comparable safety, in subjects with moderate-to-severe plaque psoriasis. OBJECTIVE: To compare the efficacy and safety of secukinumab and ustekinumab use over 52 weeks. METHODS: Analysis of 52-week data from CLEAR, a randomized, double-blind, phase 3b study. RESULTS: Among 676 randomized subjects, secukinumab demonstrated superiority to ustekinumab at week 52 in the proportion of subjects with ≥90% improvement in Psoriasis Area and Severity Index (PASI 90) (76% vs 61% [P < .0001]); PASI 100 responses were 46% versus 36% (P = .0103) and Investigator's Global Assessment responses of clear/almost clear skin were 80% versus 65% (P < .0001). Subjects on secukinumab reported greater reductions in psoriasis-related pain, itching, and scaling, and greater improvement across all quality-of-life measures evaluated (Dermatology Life Quality Index [DLQI], EuroQoL 5-Dimension Health Questionnaire, Work Productivity and Activity Impairment Questionnaire-Psoriasis, and Health Assessment Questionnaire-Disability Index). At week 52, 72% of subjects on secukinumab versus 59% on ustekinumab (P = .0008) reported no impact of skin disease on their lives (DLQI 0/1 response). Safety and tolerability was comparable. LIMITATIONS: There was no placebo arm. CONCLUSION: In this head-to-head, double-blind study, secukinumab demonstrated sustained superior efficacy in comparison with ustekinumab in clearing skin through week 52, greater improvement in quality of life, and a favorable and comparable safety profile.

Infections in Moderate to Severe Psoriasis Patients Treated with Biological Drugs Compared to Classic Systemic Drugs: Findings from the BIOBADADERM Registry.

Information regarding the safety of biological drugs prescribed to psoriasis patients on daily and long-term bases is insufficient. We used data from the BIOBADADERM registry (Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases) to generate crude rates of infection during therapy with systemic drugs, including biological drugs (infliximab, etanercept, adalimumab, and ustekinumab) and nonbiological drugs (acitretin, cyclosporine, and methotrexate). We also calculated unadjusted and adjusted risk ratios (RRs) (with propensity score adjustment) of infection, serious infections, and recurrent infections of systemic therapies compared with methotrexate, using Poisson regression. Our study included records of 2,153 patients (7,867.5 person-years). The adjusted RR of overall infection was significantly increased in the groups treated with adalimumab with methotrexate (adjusted RR = 2.13, 95% confidence interval [CI] = 1.2-3.7), infliximab (adjusted RR = 1.71, 95% CI = 1.1-2.65), cyclosporine (adjusted RR = 1.58, 95% CI = 1.17-2.15), ustekinumab with methotrexate (adjusted RR = 1.56, 95% CI = 1.08-2.25), and etanercept (adjusted RR = 1.34, 95% CI: 1.02-1.76) compared with methotrexate alone. Cyclosporine had a significant risk of serious infection (adjusted RR = 3.12, 95% CI = 1.1-8.8), followed by adalimumab combined with methotrexate (adjusted RR = 3.28, 95% CI = 0.8-13.5). Adalimumab in combination with methotrexate had the highest risk of infection recurrence (adjusted RR = 4.33, 95% CI = 2.27-8.24).

Incidencia a los 2 años de psoriasis, uveítis y enfermedad inflamatoria intestinal en la cohorte de pacientes con espondiloartritis del estudio AQUILES / Two-year incidence of psoriasis, uveitis and inflammatory bowel disease in patients with spondyloarthritis: a study in the AQUILES cohort

Describir la incidencia a los 2 años de nuevas manifestaciones extraarticulares (uveítis, psoriasis, enfermedad inflamatoria intestinal) en la cohorte de pacientes con espondiloartritis del estudio AQUILES. Pacientes. Durante 2 años se siguieron 513 pacientes con espondiloartritis (62,5% varones, edad media 48 años) diagnosticados de espondilitis anquilosante (EA) (55,6%), artritis psoriásica (25,3%), espondiloartritis indiferenciada (16,2%), artritis enteropática (2,5%) y otros diagnósticos (0,4%). Los nuevos diagnósticos se basaron en los informes de los respectivos especialistas (oftalmólogos, dermatólogos y gastroenterólogos). Resultados. Se establecieron 22 nuevos diagnósticos de las manifestaciones extraarticulares estudiadas (incidencia acumulada: 4,3% [intervalo de confianza del 95% 2,4-6,1]; tasa de incidencia: 17 casos por 10.000 pacientes-año). La uveítis fue el diagnóstico más frecuente (incidencia acumulada del 3,1%), predominantemente en pacientes con EA. En el análisis multivariable, el diagnóstico de EA fue el único predictor de aparición de nueva manifestación extraarticular. Conclusiones. En pacientes con espondiloartritis, la incidencia de uveítis, psoriasis y enfermedad inflamatoria intestinal a los 2 años fue globalmente del 4,3%, principalmente por nuevos diagnósticos de uveítis en pacientes con EA (AU)

Objectives. To describe the 2-year incidence of new extra-articular manifestations (uveitis, psoriasis, inflammatory bowel disease) in a cohort of patients with spondyloarthritis included in the AQUILES study. Patients. Over a period of 2 years, 513 patients with spondyloarthritis (62.5% males, mean age 48 years) diagnosed with ankylosing spondylitis (AS) (55.6%), psoriatic arthritis (25.3%), undifferentiated spondyloarthritis (16.2%), enteropathic arthritis (2.5%), and other diseases (0.4%) were followed. New diagnoses were based on reports of the corresponding specialists (ophthalmologists, dermatologists, gastroenterologists). Results. During the 2-year follow-up, 22 new diagnoses of the extra-articular manifestations were established, with a cumulative incidence of 4.3% (95% confidence interval 2.4-6.1) and an incidence rate of 17 cases per 10,000 patient-year. Uveitis was the most frequent diagnosis (cumulative incidence 3.1%), predominantly in patients with AS. In the multivariate analysis, the diagnosis of AS was the only predictive variable associated to the development of new extra-articular disease. Conclusions. In patients with spondyloarthritis, the 2-year global incidence of uveitis, psoriasis and inflammatory bowel disease (IMID) was 4.3%, particularly due to new diagnoses of uveitis in patients with AS (AU)

Genome-Wide Pathway Analysis Identifies Genetic Pathways Associated with Psoriasis.

Psoriasis is a chronic inflammatory disease with a complex genetic architecture. To date, the psoriasis heritability is only partially explained. However, there is increasing evidence that the missing heritability in psoriasis could be explained by multiple genetic variants of low effect size from common genetic pathways. The objective of this study was to identify new genetic variation associated with psoriasis risk at the pathway level. We genotyped 598,258 single nucleotide polymorphisms in a discovery cohort of 2,281 case-control individuals from Spain. We performed a genome-wide pathway analysis using 1,053 reference biological pathways. A total of 14 genetic pathways (PFDR ≤ 2.55 × 10(-2)) were found to be significantly associated with psoriasis risk. Using an independent validation cohort of 7,353 individuals from the UK, a total of 6 genetic pathways were significantly replicated (PFDR ≤ 3.46 × 10(-2)). We found genetic pathways that had not been previously associated with psoriasis risk such as retinol metabolism (Pcombined = 1.84 × 10(-4)), the transport of inorganic ions and amino acids (Pcombined = 1.57 × 10(-7)), and post-translational protein modification (Pcombined = 1.57 × 10(-7)). In the latter pathway, MGAT5 showed a strong network centrality, and its association with psoriasis risk was further validated in an additional case-control cohort of 3,429 individuals (P < 0.05). These findings provide insights into the biological mechanisms associated with psoriasis susceptibility.

Development of clinical prediction models for good or bad response to classic systemic drugs, anti-TNFs, and ustekinumab in psoriasis, based on the BIOBADADERM cohort.

BACKGROUND: Identifying patients likely to have very good or bad results from systemic psoriasis therapy could improve efficiency of therapy. OBJECTIVE: To develop prognostic models for good or bad response to classic systemic drugs, anti-TNFs, and ustekinumab in psoriasis. METHODS: Multivariable logistic regression of a prospective multicenter cohort of psoriatic patients in clinical practice (6449 person-years of follow-up). We used as possible predictors demographic characteristics, comorbidities, characteristics of the psoriasis (type, PASI, arthritis), history of past therapy at entry in the cohort, and history of response to previous cycles while in the cohort. We defined good response to a treatment cycle as either cycle end due to disease remission or a cycle longer than 2 years that does not end later due to inefficacy in the follow-up period. Bad response to a treatment cycle was defined as a cycle that is finished due to inefficacy, based on the physician judgment, after more than 3 months of treatment. RESULTS: Patients with fewer previous therapies, lower body mass index, older at start of therapy, and with previous history of good responses to therapy are more likely to have positive results of therapy. However, the predictive characteristics of models are poor. CONCLUSION: Predictive models of clinical response to systemic drugs in psoriasis with the studied variables do not seem to outperform drug selection by a dermatologist.

Two-year incidence of psoriasis, uveitis and inflammatory bowel disease in patients with spondyloarthritis: A study in the AQUILES cohort.

OBJECTIVES: To describe the 2-year incidence of new extra-articular manifestations (uveitis, psoriasis, inflammatory bowel disease) in a cohort of patients with spondyloarthritis included in the AQUILES study. PATIENTS: Over a period of 2 years, 513 patients with spondyloarthritis (62.5% males, mean age 48 years) diagnosed with ankylosing spondylitis (AS) (55.6%), psoriatic arthritis (25.3%), undifferentiated spondyloarthritis (16.2%), enteropathic arthritis (2.5%), and other diseases (0.4%) were followed. New diagnoses were based on reports of the corresponding specialists (ophthalmologists, dermatologists, gastroenterologists). RESULTS: During the 2-year follow-up, 22 new diagnoses of the extra-articular manifestations were established, with a cumulative incidence of 4.3% (95% confidence interval 2.4-6.1) and an incidence rate of 17 cases per 10,000 patient-year. Uveitis was the most frequent diagnosis (cumulative incidence 3.1%), predominantly in patients with AS. In the multivariate analysis, the diagnosis of AS was the only predictive variable associated to the development of new extra-articular disease. CONCLUSIONS: In patients with spondyloarthritis, the 2-year global incidence of uveitis, psoriasis and inflammatory bowel disease (IMID) was 4.3%, particularly due to new diagnoses of uveitis in patients with AS.

Incidencia a los 2 años de nuevas enfermedades inflamatorias mediadas por inmunidad en la cohorte de pacientes con enfermedad inflamatoria intestinal del estudio AQUILES / Two-year incidence of new immune-mediated inflammatory diseases in patients with inflammatory bowel disease: A study in the AQUILES cohort

OBJETIVO: Describir la incidencia a los 2 años de nuevas enfermedades inflamatorias mediadas por inmunidad (espondiloartritis, uveítis, psoriasis) en la cohorte de pacientes con enfermedad inflamatoria intestinal (EII) del estudio AQUILES. MATERIAL Y MÉTODOS: Durante un periodo de 2 años se siguieron 341 pacientes con EII (53% mujeres, edad media 40 años) diagnosticados de enfermedad de Crohn (60,5%), colitis ulcerosa (38,1%) y colitis indeterminada (1,4%). Los nuevos diagnósticos durante el seguimiento de los pacientes se basaron en los informes de los respectivos especialistas (reumatólogos, oftalmólogos y dermatólogos). RESULTADOS: Se establecieron 22 nuevos diagnósticos de enfermedades inflamatorias mediadas por inmunidad en 21 pacientes (incidencia acumulada: 6,5% [intervalo de confianza del 95% -IC 95%-: 3,7-9,2], tasa de incidencia: 26 casos por 10.000 pacientes-año). La mayoría de los diagnósticos fueron nuevos casos de espondiloartritis (n=15). La incidencia acumulada de nuevos diagnósticos de enfermedades inflamatorias mediadas por inmunidad fue similar en pacientes con enfermedad de Crohn (5,8%, IC 95%: 3,4-9,9) y en pacientes con colitis ulcerosa (7,7%, IC 95%: 4,2-13,6). En el análisis multivariable la incidencia de nuevas enfermedades inflamatorias mediadas por inmunidad se asoció a historia familiar de EII (odds ratio=3,6, IC 95%: 1,4-9,4) y a la presencia de manifestaciones extraintestinales de EII (odds ratio=1,8, IC 95%: 0,7-5,2). CONCLUSIONES: En pacientes con EII la incidencia de nuevas enfermedades inflamatorias mediadas por inmunidad a los 2 años de seguimiento fue del 6,5%, siendo más frecuentes en pacientes con manifestaciones extraintestinales de EII e historia familiar de EII

OBJECTIVE: To describe the 2-year incidence of new immune-mediated inflammatory diseases (spondylarthritis, uveitis, psoriasis) in the cohort of patients with inflammatory bowel disease (IBD) included in the AQUILES study. MATERIALS AND METHODS: Over a 2-year period, 341 patients with IBD (53% women, mean age 40 years) diagnosed with Crohn's disease (60.5%), ulcerative colitis (38.1%) and indeterminate colitis (1.4%) were followed up. New diagnoses made during follow-up were based on reports of the corresponding specialists (rheumatologists, ophthalmologists, and dermatologists). RESULTS: A total of 22 new diagnoses of immune-mediated inflammatory diseases were established in 21 patients (cumulative incidence of 6.5%, 95% confidence interval [CI] 3.7-9.2, incidence rate of 26 cases per 10,000 patient-years). Most diagnoses were new cases of spondylarthritis (n=15). The cumulative incidence of new diagnoses of immune-mediated inflammatory diseases was similar in patients with Crohn's disease (5.8%, 95% CI 3.4-9.9) and in patients with ulcerative colitis (7.7%, 95% CI 4.2-13.6). On multivariate analysis, the incidence of new immune-mediated inflammatory diseases was significantly associated with a family history of IBD (odds ratio=3.6, 95% CI 1.4-9.4) and the presence of extraintestinal manifestations of IBD (odds ratio=1.8, 95% CI .7-5.2). CONCLUSIONS: In patients with IBD, the incidence of new immune-mediated inflammatory diseases at 2 years of follow-up was 6.5%. These diseases were more frequent in patients with extraintestinal manifestations of IBD and a family history of IBD

Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial.

BACKGROUND: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has shown superior efficacy to etanercept with similar safety in moderate to severe plaque psoriasis (FIXTURE study). OBJECTIVE: We sought to directly compare efficacy and safety of secukinumab versus ustekinumab. METHODS: In this 52-week, double-blind study (NCT02074982), 676 subjects were randomized 1:1 to subcutaneous injection of secukinumab 300 mg or ustekinumab per label. Primary end point was 90% or more improvement from baseline Psoriasis Area and Severity Index (PASI) score (PASI 90) at week 16. RESULTS: Secukinumab (79.0%) was superior to ustekinumab (57.6%) as assessed by PASI 90 response at week 16 (P < .0001). The 100% improvement from baseline PASI score at week 16 was also significantly greater with secukinumab (44.3%) than ustekinumab (28.4%) (P < .0001). The 75% or more improvement from baseline PASI score at week 4 was superior for secukinumab (50.0%) versus ustekinumab (20.6%) (P < .0001). Percentage of subjects with the Dermatology Life Quality Index score 0/1 (week 16) was significantly higher with secukinumab (71.9%) than ustekinumab (57.4%) (P < .0001). The safety profile of secukinumab was comparable with ustekinumab and consistent with pivotal phase III secukinumab studies. LIMITATIONS: The study was not placebo-controlled and of short-term duration. CONCLUSIONS: Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe psoriasis and improving health-related quality of life with a comparable safety profile over 16 weeks.

[Two-year incidence of new immune-mediated inflammatory diseases in patients with inflammatory bowel disease: A study in the AQUILES cohort]. / Incidencia a los 2 años de nuevas enfermedades inflamatorias mediadas por inmunidad en la cohorte de pacientes con enfermedad inflamatoria intestinal del estudio AQUILES.

OBJECTIVE: To describe the 2-year incidence of new immune-mediated inflammatory diseases (spondylarthritis, uveitis, psoriasis) in the cohort of patients with inflammatory bowel disease (IBD) included in the AQUILES study. MATERIALS AND METHODS: Over a 2-year period, 341 patients with IBD (53% women, mean age 40 years) diagnosed with Crohn's disease (60.5%), ulcerative colitis (38.1%) and indeterminate colitis (1.4%) were followed up. New diagnoses made during follow-up were based on reports of the corresponding specialists (rheumatologists, ophthalmologists, and dermatologists). RESULTS: A total of 22 new diagnoses of immune-mediated inflammatory diseases were established in 21 patients (cumulative incidence of 6.5%, 95% confidence interval [CI] 3.7-9.2, incidence rate of 26 cases per 10,000 patient-years). Most diagnoses were new cases of spondylarthritis (n=15). The cumulative incidence of new diagnoses of immune-mediated inflammatory diseases was similar in patients with Crohn's disease (5.8%, 95% CI 3.4-9.9) and in patients with ulcerative colitis (7.7%, 95% CI 4.2-13.6). On multivariate analysis, the incidence of new immune-mediated inflammatory diseases was significantly associated with a family history of IBD (odds ratio=3.6, 95% CI 1.4-9.4) and the presence of extraintestinal manifestations of IBD (odds ratio=1.8, 95% CI .7-5.2). CONCLUSIONS: In patients with IBD, the incidence of new immune-mediated inflammatory diseases at 2 years of follow-up was 6.5%. These diseases were more frequent in patients with extraintestinal manifestations of IBD and a family history of IBD.

A deletion at ADAMTS9-MAGI1 locus is associated with psoriatic arthritis risk.

OBJECTIVE: Copy number variants (CNVs) have been associated with the risk to develop multiple autoimmune diseases. Our objective was to identify CNVs associated with the risk to develop psoriatic arthritis (PsA) using a genome-wide analysis approach. METHODS: A total of 835 patients with PsA and 1498 healthy controls were genotyped for CNVs using the Illumina HumanHap610 BeadChip genotyping platform. Genomic CNVs were characterised using CNstream analysis software and analysed for association using the χ(2) test. The most significant genomic CNV associations with PsA risk were independently tested in a validation sample of 1133 patients with PsA and 1831 healthy controls. In order to test for the specificity of the variants with PsA aetiology, we also analysed the association to a cohort of 822 patients with purely cutaneous psoriasis (PsC). RESULTS: A total of 165 common CNVs were identified in the genome-wide analysis. We found a highly significant association of an intergenic deletion between ADAMTS9 and MAGI1 genes on chromosome 3p14.1 (p=0.00014). Using the independent patient and control cohort, we validated the association between ADAMTS9-MAGI1 deletion and PsA risk (p=0.032). Using next-generation sequencing, we characterised the 26 kb associated deletion. Finally, analysing the PsC cohort we found a lower frequency of the deletion compared with the PsA cohort (p=0.0088) and a similar frequency to that of healthy controls (p>0.3). CONCLUSIONS: The present genome-wide scan for CNVs associated with PsA risk has identified a new deletion associated with disease risk and which is also differential from PsC risk.

Use of off-label doses is frequent in biologic therapy for moderate to severe psoriasis: A cross-sectional study in clinical practice.

INTRODUCTION: Biologic medications increase dramatically the burden of a chronic and high prevalent disease like psoriasis. The objective of the study was to quantify the use of dose reduction or dose escalation strategies, not reflected in the drug summary of product characteristics, in clinical practice. METHODS: An observational, cross-sectional study of a subset of patients from the Spanish Registry for Systemic Treatments in Psoriasis (BIOBADADERM) treated for over six consecutive months with the same biologic agent. RESULTS: The study included 637 patients. At the cut-off date, the initial dose had been reduced in 223 patients (35%; 95% CI: 31.3-38.9%) and escalated in 46 (7.2%; 95% CI: 5.3-9.5%). When compared with the patients treated with standard doses, the patients on reduced doses had a lower PASI score at the cut-off date (a mean 2.6 versus 1; -1.6 points) and exhibited greater improvement in PASI since the start of biologic therapy (mean reduction over baseline 75% versus 87%). By contrast, the patients receiving an escalated dose had higher PASI scores (2.6 versus 8.0) and showed less improvement in PASI (75% versus 46.8%). CONCLUSION: Off-label doses of biologic agents for psoriasis are frequent in clinical practice. This information is especially relevant for pharmacoeconomic models.

Manifestaciones extraarticulares en pacientes con espondiloartritis. Características basales de la cohorte de pacientes con espondiloartritis del estudio AQUILES / Extra-articular disease in patients with spondyloarthritis. Baseline characteristics of the spondyloarthritis cohort of the AQUILES study

Objetivos. Evaluar la prevalencia de enfermedad extraarticular (uveítis, psoriasis y enfermedad inflamatoria intestinal [EII]) en una cohorte de pacientes con espondiloartritis (EsA). Pacientes y métodos. AQUILES es un estudio observacional, prospectivo y multicéntrico, en 3 cohortes de pacientes con una de las siguientes enfermedades inflamatorias mediadas por inmunidad (EIMI): EsA, psoriasis y EII. En la cohorte presente se incluyó a pacientes ≥ 18 años con EsA atendidos en consultas hospitalarias de Reumatología. El objetivo principal fue evaluar la coexistencia de estas enfermedades y de uveítis, valorada sobre la base de la historia clínica del paciente hasta el momento de entrar en el estudio. Resultados. Se incluyó a 601 pacientes con EsA (varones: 63,1%, mujeres: 36,9%). Los diagnósticos fueron: espondilitis anquilosante (55,1%); artritis psoriásica (25,2%); espondiloartritis indiferenciada (16,1%); artritis enteropática (2,5%), y otros (1,3%). En el 43,6% (IC del 95%, 39,7-47,6) coexistió al menos una de las 3 enfermedades mencionadas, predominando psoriasis (prevalencia: 27,8%, IC del 95%, 24,4-31,5), uveítis (13,6%, IC del 95%m 11,1-16,6) y EII (5,1%, IC del 95%, 3,7-7,2). En pacientes con espondilitis anquilosante, la prevalencia fue del 25,3% (EII: 3,9%, psoriasis: 5,4%, uveítis: 19,0%) y en pacientes con artritis psoriásica fue del 94,7%, debido a la presencia de psoriasis (94,0%). La coexistencia de estas manifestaciones se asoció a mayor edad, sexo femenino y presencia de otras manifestaciones extraarticulares de las EsA distintas de las estudiadas. Conclusiones. La enfermedad extraarticular en pacientes con EsA es frecuente y en este estudio se asoció a la edad, el sexo femenino y la presencia de otras manifestaciones extraarticulares de EsA (AU)

Objectives. To describe the prevalence of extra-articular disease (uveitis, psoriasis and inflammatory bowel disease [IBD]), in a cohort of patients with spondyloarthritis (SpA). Patients and methods. AQUILES is an observational, prospective and multicentric study of three cohorts of patients with one of the following immune-mediated inflammatory diseases (IMID): SpA, psoriasis, or IBD. In the present cohort, patients ≥18 years of age with SpA were enrolled from Rheumatology clinics. The main objective was to assess the coexistence of these diseases and of uveitis, based on the patients’ clinical history up to the study entry. Results. A total of 601 patients with SpA (men: 63.1%; women: 36.9%) were enrolled. The specific diagnoses were: ankylosing spondylitis (55.1%), psoriatic arthritis (25.1%), undifferentiated spondyloarthritis (16.1%), enteropathic arthritis (2.5%), and others (1.3%). In 43.6% (95% CI: 39.7-47.6) of the patients, at least one of the three abovementioned diseases was encountered, predominantly psoriasis (prevalence 27.8%, 95% CI: 24.4-31.5), uveitis (13.6%, CI 95%: 11.1-16.6) and IBD (5.1%, 95% CI: 3.7-7.2). In patients with ankylosing spondylitis the proportion of other disease was 25.3% (IBD: 3.9%, psoriasis: 5.4%, uveitis: 19.0%) whilst it was 94.7% in psoriatic arthritis, due to the presence of psoriasis (94.0%). The coexistence of these diseases was associated with age, female gender and the presence of other extra-articular manifestations associated with SpA. Conclusions. Extra-articular disease in patients with SpA is common and, in this study, it was associated to age, female gender and the presence of other SpA-related extra-articular manifestations (AU)

Extra-articular disease in patients with spondyloarthritis. Baseline characteristics of the spondyloarthritis cohort of the AQUILES study.

OBJECTIVES: To describe the prevalence of extra-articular disease (uveitis, psoriasis and inflammatory bowel disease [IBD]), in a cohort of patients with spondyloarthritis (SpA). PATIENTS AND METHODS: AQUILES is an observational, prospective and multicentric study of three cohorts of patients with one of the following immune-mediated inflammatory diseases (IMID): SpA, psoriasis, or IBD. In the present cohort, patients ≥18 years of age with SpA were enrolled from Rheumatology clinics. The main objective was to assess the coexistence of these diseases and of uveitis, based on the patients' clinical history up to the study entry. RESULTS: A total of 601 patients with SpA (men: 63.1%; women: 36.9%) were enrolled. The specific diagnoses were: ankylosing spondylitis (55.1%), psoriatic arthritis (25.1%), undifferentiated spondyloarthritis (16.1%), enteropathic arthritis (2.5%), and others (1.3%). In 43.6% (95% CI: 39.7-47.6) of the patients, at least one of the three abovementioned diseases was encountered, predominantly psoriasis (prevalence 27.8%, 95% CI: 24.4-31.5), uveitis (13.6%, CI 95%: 11.1-16.6) and IBD (5.1%, 95% CI: 3.7-7.2). In patients with ankylosing spondylitis the proportion of other disease was 25.3% (IBD: 3.9%, psoriasis: 5.4%, uveitis: 19.0%) whilst it was 94.7% in psoriatic arthritis, due to the presence of psoriasis (94.0%). The coexistence of these diseases was associated with age, female gender and the presence of other extra-articular manifestations associated with SpA. CONCLUSIONS: Extra-articular disease in patients with SpA is common and, in this study, it was associated to age, female gender and the presence of other SpA-related extra-articular manifestations.

DRESS syndrome secondary to ibuprofen as a cause of hyperacute liver failure.

Acute liver failure has a high mortality and its most frequent cause in Spain is viral infection. In this article, we present a case of fulminant liver failure. The failure is secondary to an idiosyncratic reaction to ibuprofen, an entity included in the DRESS syndrome. This syndrome plays a key role in the differential diagnosis of acute liver failure, since its unfortunate course often requires liver transplantation as the only useful therapeutic weapon. This case illustrates the need for an efficient coordination between hospitals as a key factor for improving the prognosis.

Enfermedades inflamatorias mediadas por inmunidad en pacientes con enfermedad inflamatoria intestinal. Datos basales del estudio Aquiles / Immune-mediated inflammatory diseases in patients with inflammatory bowel disease. Baseline data from the Aquiles study

OBJETIVO: Determinar la prevalencia de enfermedades inflamatorias mediadas por inmunidad (EIMI) en una cohorte de pacientes con enfermedad inflamatoria intestinal (EII) reclutada en consultas hospitalarias de aparato digestivo para el estudio Aquiles, un estudio prospectivo de 2 años de seguimiento. Material y métodos Se incluyeron pacientes de ≥ 18 años con diagnóstico previo o nuevo de EII (enfermedad de Crohn [EC], colitis ulcerosa [CU] o colitis indeterminada). Los diagnósticos se recogieron de forma transversal de la historia clínica en el momento de incorporar a cada paciente al estudio. Resultados Se incluyeron 526 pacientes (edad media 40,2 años; 47,3% hombres, 52,7% mujeres), 300 con EC (57,0%), 218 con CU (41,4%) y 8 colitis indeterminada. Presentaron otra EIMI 71 pacientes (prevalencia: 13,5%, IC 95%: 10,8-16,7): 47 fueron espondiloartritis (prevalencia: 8,9%); 18 psoriasis (3,4%); 5 pioderma gangrenoso (1,0%) y 11 uveítis (2,1%). La prevalencia de EIMI fue mayor en pacientes con EC respecto a pacientes con CU (17,0% [IC 95%: 13,2-21,7] frente a 9,2% [IC 95%: 6,0-13,8], p = 0,011). En el análisis multivariante, las variables asociadas a la presencia de EIMI fueron el diagnóstico de EC (OR = 1,8 [IC 95%: 1,1-3,2]) y un tiempo de evolución de la EII ≥ 4 años (OR = 2,1 [IC 95%: 1,1-4,1] en aquellos con 4-8 años, y OR = 2,1 [IC 95%: 1,2-3,9] en los de ≥ 8 años frente a < 4 años). CONCLUSIONES: En la cohorte de pacientes con EII del estudio Aquiles, el 13,5% presentó otra EIMI, con una prevalencia mayor en pacientes con EC y > 4 años de evolución de la enfermedad

OBJECTIVE: To determine the prevalence of immune-mediated inflammatory diseases (IMID) in a cohort of patients with inflammatory bowel disease(IBD) enrolled in hospital gastroenterology outpatients units for the AQUILES study, a prospective 2-year follow-up study. MATERIAL AND METHODS: We included patients ≥18 years old with a prior or new diagnosis of IBD (Crohn disease [CD], ulcerative colitis [UC] or indeterminate colitis). Diagnoses were collected in a cross-sectional manner from the clinical records at enrollment of a new patient in the study. RESULTS: We included 526 patients (mean age 40.2 years; 47.3% men, 52.7% women), 300 with CD (57.0%), 218 with UC (41.4%) and 8 with indeterminate colitis. Other types of IMID were present in 71 patients (prevalence: 13.5%, 95% CI: 10.8-16.7): 47 were spondyloarthropathies (prevalence: 8.9%); 18 psoriasis (3.4%); 5 pyoderma gangrenosum (1.0%), and 11 uveitis (2.1%). The prevalence of IMID was higher in patients with CD than in those with UC (17.0% [95% CI: 13.2-21.7] vs 9.2% [95% CI: 6.0-13.8], p=0.011). In the multivariate analysis, the variables associated with the presence of IMID were diagnosis of CD (OR=1.8 [95% CI: 1.1-3.2]) and duration of IBD ≥4 years (OR=2.1 [95% CI: 1.1-4.1] in those with disease duration 4-8 years, and OR=2.1 [95% CI: 1.2-3.9] in those with ≥8 years vs. <4 years).CONCLUSIONS: In the cohort of patients with IBD in the AQUILES study, 13.5% had another IMID, with a higher prevalence in patients with CD and>4 years since disease onset (AU)

Cardiovascular risk factors and cardiovascular diseases in patients with moderate to severe psoriasis under systemic treatment. PSO-RISK, descriptive study.

BACKGROUND: The prevalence of cardiovascular risk factors (CVRF) in psoriasis has not been studied in large Spanish samples. OBJECTIVE: To assess the prevalence of major CVRFs in psoriasis patients requiring systemic treatments. MATERIAL AND METHODS: Cross-sectional study in psoriasis patients from 33 hospital dermatology offices throughout Spain. Blood pressure (BP) was measured and a fasting lab test was performed. Each CVRF was diagnosed according to the recommendations of international societies. RESULTS: In 368 patients (mean age 48 years old, 36% women), 80.2% had at least one CVRF. The prevalence of each CVRF was similar in men and women and slightly higher in patients with psoriatic arthritis and in patients with a history of more severe disease. The percentage of patients treated with drugs to control CVRF was low (∼ 50% of those with each CVRF). A total of 20.7% had experienced some cardiovascular disease (CVD) episode. CONCLUSION: The prevalence of CVRF was high, higher than in the general Spanish population, and 20% had already suffered CVD. However, the percentage with drug treatments for CVRF was low.

Síndrome DRESS secundario a ibuprofeno como causa de fallo hepático hiperagudo / DRESS syndrome secondary to ibuprofen as a cause of hyperacute liver failure

El fallo hepático agudo presenta alta mortalidad, siendo su primera etiología en España la viral. Presentamos un caso de fallo fulminante secundario a una reacción idiosincrásica a ibuprofeno, englobado en el síndrome de DRESS (Drug Rash with Eosinophilia and Systemic Symptoms). Dicho síndrome constituye un diagnóstico clave en el diagnóstico diferencial del fracaso hepático agudo, ya que su curso infausto obliga en muchas ocasiones a la realización de trasplante hepático como única terapéutica útil. Este caso es un buen ejemplo de la necesidad de la rapidez y la eficiencia en la coordinación a nivel intrahospitalario y entre centros sanitarios como factor clave en la mejoría del pronóstico (AU)

Acute liver failure has a high mortality and its most frequent cause in Spain is viral infection. In this article, we present a case of fulminant liver failure. The failure is secondary to an idiosyncratic reaction to ibuprofen, an entity included in the DRESS syndrome. This syndrome plays a key role in the differential diagnosis of acute liver failure, since its unfortunate course often requires liver transplantation as the only useful therapeutic weapon. This case illustrates the need for an efficient coordination between hospitals as a key factor for improving the prognosis (AU)

Paraneoplastic autoimmune multiorgan syndrome (paraneoplastic pemphigus) with unusual manifestations and without detectable autoantibodies.

We describe a patient with paraneoplastic autoimmune multiorgan syndrome (PAMS) secondary to a lymphoblastic T- cell lymphoma who presented with a lichenoid dermatitis and vitiligo, later developing bronchiolitis obliterans and autoimmune hepatitis. Notably, he had no detectable autoantibodies. The development of vitiligo and autoimmune hepatic involvement probably indicate a role for cytotoxic T- cell lymphocytes in the pathogenesis of this syndrome.