Prevalence and distribution of peripheral musculoskeletal manifestations in spondyloarthritis including psoriatic arthritis: results of the worldwide, cross-sectional ASAS-PerSpA study.

OBJECTIVES: To characterise peripheral musculoskeletal involvement in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), across the world. METHODS: Cross-sectional study with 24 participating countries. Patients with a diagnosis of axial SpA (axSpA), peripheral SpA (pSpA) or PsA according to their rheumatologist were included. The investigators were asked which diagnosis out of a list of six (axSpA, PsA, pSpA, inflammatory bowel disease-associated SpA, reactive arthritis or juvenile SpA (Juv-SpA)) fitted the patient best. Peripheral manifestations (ie, peripheral joint disease, enthesitis, dactylitis and root joint disease), their localisation and treatments were evaluated. RESULTS: A total of 4465 patients were included (61% men, mean age 44.5 years) from four geographic areas: Latin America (n=538), Europe plus North America (n=1677), Asia (n=975) and the Middle East plus North Africa (n=1275). Of those, 78% had ever suffered from at least one peripheral musculoskeletal manifestation; 57% had peripheral joint disease, 44% had enthesitis and 15% had dactylitis. Latin American had far more often peripheral joint disease (80%) than patients from other areas. Patients with PsA had predominantly upper limb and small joint involvement (52%).Hip and shoulder involvement was found in 34% of patients. The prevalence of enthesitis ranged between 41% in patients with axSpA and 65% in patients with Juv-SpA. Dactylitis was most frequent among patients with PsA (37%). CONCLUSION: These results suggest that all peripheral features can be found in all subtypes of SpA, and that differences are quantitative rather than qualitative. In a high proportion of patients, axial and peripheral manifestations coincided. These findings reconfirm SpA clinical subtypes are descendants of the same underlying disease, called SpA.

Axial and peripheral spondyloarthritis: does psoriasis influence the clinical expression and disease burden? Data from REGISPONSER registry.

OBJECTIVE: To evaluate whether the presence of psoriasis influences the clinical expression, disease activity and disease burden in both axial and peripheral phenotypes of spondyloarthritis (SpA). METHODS: Patients from the Spanish REGISPONSER registry classified as having SpA according to the ESSG criteria were included. Patients were classified as psoriatic or non-psoriatic depending on the presence of cutaneous or nail psoriasis; thereafter, they were classified as having either axial [presence of radiographic sacroiliitis OR inflammatory back pain (IBP)] or peripheral phenotype (absence of radiographic sacroiliitis AND absence of IBP AND presence of peripheral involvement). Pair-wise univariate and multivariate analyses among the four groups (psoriatic/non-psoriatic axial phenotypes and psoriatic/non-psoriatic peripheral phenotypes) were performed with adjustment for treatment intake. RESULTS: A total of 2296 patients were included in the analysis. Among patients with axial phenotype, psoriasis was independently associated (P < 0.05) with HLA-B27+ [odds ratio (OR) 0.27], uveitis (OR 0.46), synovitis (ever) (OR 2.59), dactylitis (OR 2.78) and the use of conventional synthetic DMARDs (csDMARDs) (OR 1.47) in comparison with non-psoriatic patients. Among patients with peripheral phenotype and adjusting for csDMARD intake, psoriasis was independently associated with higher age at disease onset (OR 1.05), HLA-B27+ (OR 0.14) and heel enthesitis (OR 0.22). Higher scores for patient-reported outcomes and greater use of treatment at the time of the study visit were observed in psoriatic patients with either axial or peripheral phenotype. CONCLUSION: These findings suggest that, among all patients with SpA, psoriasis is associated with differences in clinical expression of SpA, a greater disease burden and increased use of drugs.

Cardiovascular risk factors in patients with spondyloarthritis from Northern European and Mediterranean countries: An ancillary study of the ASAS-COMOSPA project.

OBJECTIVES: The objectives of this study were: (1) to compare the prevalence of cardiovascular disease and cardiovascular risk factors among different phenotypes of spondyloarthritis (SpA); (2) to assess the differences in cardiovascular disease and cardiovascular risk factors between two geographical areas, i.e. Northern Europe vs. Mediterranean region; (3) to identify potential predictive factors for high Framingham Risk Score regarding disease features in SpA and geographical area. METHODS: Ancillary analysis of the international, multicentric, observational, cross-sectional ASAS-COMOSPA study. Cardiovascular disease and cardiovascular risk factors were compared depending on SpA phenotype and geographical regions. Potential factors associated with higher cardiovascular risk (i.e. Framingham Risk Score) were determined by a multiple logistic regression. RESULTS: The most frequent cardiovascular risk factor and cardiovascular disease were smoking (31.2%) and ischemic heart disease (3.2%), respectively. Regarding SpA phenotype, axial SpA patients showed significantly lower prevalence (P<0.05) of hypertension (19.2% vs. 33.8% vs. 26.6% for axial, peripheral and mixed phenotypes, respectively), type 2 diabetes mellitus (4.3% vs. 8.5% vs. 7.4%), dyslipidemia (13.9% vs. 28.4% vs. 15.2%) and ischemic heart disease (2.4% vs. 7.0% vs. 3.2%). Regarding geographical area, a higher frequency of hypertension (34.7% vs. 19.4%,), dyslipidemia (19.3% vs. 14.4%), obesity (29.3% vs. 20.7%) and ischemic heart disease (6.2% vs. 1.8%) was observed for Northern Europe vs. Mediterranean Region, respectively. CONCLUSIONS: Our results suggest that SpA phenotype and geographical area are associated with the prevalence of cardiovascular risk factors and the cardiovascular risk itself, observed in patients in the ASAS-COMOSPA cohort.

Assessment of Fatigue in Spondyloarthritis and Its Association with Disease Activity.

OBJECTIVE: To evaluate fatigue in patients with spondyloarthritis (SpA) and to define its association with disease-related factors and patients' features. METHODS: A cross-sectional multicenter study which includes 2251 patients with SpA selected from the national Spondyloarthropathies Registry (the Spanish Society of Rheumatology; REGISPONSER) Spanish cohort. The primary outcome was the assessment of fatigue performed with the first item of the Bath Ankylosing Spondyloarthritis Disease Activity Index followed by the study of its relation with different factors organized into 4 groups: sociodemographics, emotional, disease-related, and disease activity. Univariate logistic regressions, multivariate logistic regression, and multiple linear regressions were performed to relate fatigue with the studied covariates. RESULTS: Mean fatigue score in all patients with SpA was 4.3 ± 2.9, with statistically significant differences between different SpA types. In univariate logistic regressions, significant differences were seen for many variables included in the 4 groups. Multivariate logistic regression showed that high fatigue score was related with sex (female), emotional component, the Ankylosing Spondylitis Quality of Life score, stiffness, and high levels of 2 visual analog scale items (vertebral pain in the last week and patient's global assessment of disease activity). The multivariate linear regression showed that fatigue was mainly explained by disease-related factors and disease activity (54.1%), but sex and emotional status may also be involved in 13.5% of the variance. CONCLUSION: Fatigue is associated with disease-related factors and mostly with SpA activity. However, the emotional component and sex may contribute to the onset of fatigue.

Candidate's single-nucleotide polymorphism predictors of treatment nonresponse to the first anti-TNF inhibitor in ankylosing spondylitis.

The objective of this study is to identify single-nucleotide polymorphisms (SNPs) predictors of treatment nonresponse to the first anti-TNF-alpha agent in ankylosing spondylitis (AS). Patients were classified as "nonresponders" if they failed to achieve improvement ≥50 % of the initial BASDAI. We selected candidate SNPs previously reported, associated with susceptibility or pathogenesis of AS and with other spondylarthropaties (SpAs). The predictors of nonresponse were modeled with multiple logistic regression. The predictive power of the genetic model of nonresponse to treatment was tested with AUC-ROC. One hundred and twenty-one (121) AS patients fulfilled the inclusion criteria. Of the candidate SNPs tested for association with treatment effectiveness, five independent predictors were identified: rs917997, rs755622, rs1800896, rs3740691, and rs1061622. The genetic model of nonresponse to treatment had a predictive power of 0.77 (95 % CI 0.68-0.86). Our study identified several polymorphisms which could be the useful genetic biomarkers in predicting nonresponse to anti-TNF-alpha therapy.

Both baseline clinical factors and genetic polymorphisms influence the development of severe functional status in ankylosing spondylitis.

Functional severity in ankylosing spondylitis (AS) patients is variable and difficult to predict early. The aim of our study was to assess whether a combination of baseline clinical factors and genetic markers may predict the development of severe functional status in AS. We performed a cross-sectional association study on AS patients included in the Spanish National Registry of Spondyloarthropathies--REGISPONSER. Bath Ankylosing Spondylitis Functional Index (BASFI) was standardized by adjusting for disease duration since the first symptoms (BASFI/t). We considered as severe functional status the values of BASFI/t in the top of the 60th (p60), 65th (p65), 70th (p70), and 75th (p75) percentile. We selected 384 single nucleotide polymorphisms (SNPs) distributed in 190 genes to be analyzed. The study cohort included 456 patients with mean age 50.8(± 10.5) years and with mean disease duration since first symptoms 24.7 (± 10.1) years. Older age at disease onset and neck pain at baseline showed statistical significant association with severe BASFI/t. Polymorphisms associated in the allele frequencies test with severe BASFI/t in all classifications were: rs2542151 (p60 [P = .04], p65 [P = .04], p70 [P = .001] and p75 [P = .001]) and rs2254441 (p60 [P = .004], p65 [P = .02], p70 [P = .01] and p75 [P<.001]).. Genotype association, after adjustment for covariates, found an association in three of the four patients' classifications for rs2542151 and in two of the classifications for rs2254441.Forward logistic regression did not identify any model with a good predictive power for severe functional development.In our study we identified clinical factors and 24 polymorphisms associated with development of severe functional status in AS patients. Validation of these results in other cohorts is required.

Ultrasound findings in AL musculoskeletal amyloidosis.

Systemic AL amyloidosis is one of the differential diagnosis of chronic musculoskeletal disease, especially when swollen and painful joints is associated with claw hands. Ultrasound evaluation is a good diagnosis tool, showing a characteristic joint and tendon involvement and assisting in guided biopsy procedure. We report a 55 year old caucasian woman, diagnosed for two years with RA without improvement under different DMARDs, admitted for fixed flexion contractures of both hands ("claw hands"), worsening pain and swelling of small joints of hands and feet, elbows and shoulders. Pad shoulder sign and bilateral anterior wrist and elbow pads, macroglossia, thickened skin of fingers and ecchymotic rashes on forearm and around eyes were observed. Ultrasound examinations showed subdeltoid and bicipitoradial bursitis, presence of inhomogeneous hypoechoic material around bicipital tendons and tenosinovitis of the extensor tendons of the hand, and synovial thickening of elbow and shoulder joints. Complete analysis of the bone marrow biopsy and biopsy specimens from subacromial bursa were positive for AL amyloidosis.

Relative value of the lumbar spine and hip bone mineral density and bone turnover markers in men with ankylosing spondylitis.

The purpose of this study is to evaluate bone mineral density (BMD) and bone turnover markers in men with ankylosing spondylitis (AS) and to determine their relationship with clinical features and disease activity. Serum carboxi terminal cross-linked telopeptide of type I collagen (CTX), osteocalcin (OC) levels, and BMD of lumbar spine and proximal femur were evaluated in 44 males with AS, 18-60 years of age, and compared with those of 39 age-matched healthy men. Men with AS had a significantly lower BMD at the femoral neck and total hip as compared to age-matched controls (all p < 0.01). Osteopaenia or osteoporosis was found in 59.5% AS patients at the lumbar spine and in 47.7% at the femoral neck. Mean serum levels of OC and CTX were similar in AS patients and controls. There were no significant differences in BMD and bone turnover markers when comparing subgroups stratified according to disease duration or presence of peripheral arthritis. No correlations were found between disease activity markers and BMD or OC and CTX. In a cohort of relatively young males with AS, we found a high incidence of osteopaenia and osteoporosis. Disease activity and duration did not show any significant influence on BMD or serum levels of OC and CTX.

Usefulness of a centralized system of data collection for the development of an international multicentre registry of spondyloarthritis.

OBJECTIVE: To present the usefulness of a centralized system of data collection for the development of an international multicentre registry of SpA. METHOD: The originality of this registry consists in the creation of a virtual network of researchers in a computerized Internet database. From its conception, the registry was meant to be a dynamic acquiring system. RESULTS: REGISPONSER has two developing phases (Conception and Universalization) and gathers several evolving secondary projects (REGISPONSER-EARLY, REGISPONSER-AS, ESPERANZA and RESPONDIA). Each sub-project answered the necessity of having more specific and complete data of the patients even from the onset of the disease so, in the end, obtaining a well-defined picture of SpAs spectrum in the Spanish population. CONCLUSION: REGISPONSER is the first dynamic SpA database composed of cohorts with a significant number of patients distributed by specific diagnosis, which provides basic specific information of the sub-cohorts useful for patients' evaluation in rheumatology ambulatory consulting.

Infliximab reduces myeloperoxidase concentration in chronic inflammatory joint diseases.

UNLABELLED: The present study evaluated the effect of infliximab on the myeloperoxidase (MPO) concentration in chronic inflammatory joint disease. Eighteen patients were divided into active and inactive groups. Erythrocyte sedimentation rate, C-reactive protein, white blood cell counts, MPO concentration, and biomarkers of oxidative stress were measured before and after the infusion of infliximab. Patients with active disease showed increases in concentrations of MPO and biomarkers of oxidation, but decreases in antioxidant parameters. After infliximab treatment, both inflammatory parameters and MPO concentrations were normalized. IN CONCLUSION: (1) the MPO concentration is related to inflammatory activity and could play an important role in the maintenance and outbreak of oxidative stress present in these diseases, and (2) infliximab inhibits MPO concentration.

Panorama de la clasificación y la susceptibilidad genética de las espondiloartritis / Overview of the classification and immunogenetics of spondyloarthritis

Las espondiloartritis constituyen uno de los grupos más importantes de enfermedades reumáticas. En este capítulo se abordan los aspectos relacionados con la clasificación y el diagnóstico y los aspectos relacionados con la susceptibilidad genética, con el propósito de tomarlos en cuenta durante la lectura de los capítulos que siguen (AU)

The spondyloarthritidies constitute one of the most important groups of rheumatic diseases. In this chapter, we approached aspects related with classification and diagnosis as well as genetic susceptibility. Both topics are important in reading the chapters that follow this one (AU)