Metabolomics analysis revealed significantly higher synovial Phe/Tyr ratio in reactive arthritis and undifferentiated spondyloarthropathy.

OBJECTIVE: To compare the synovial phenylalanine/tyrosine (Phe/Tyr) ratio between ReA/uSpA and RA and OA by NMR spectroscopy. METHODS: Paired SF and serum of 30 patients with ReA/uSpA were collected and analysed using a 1D 1H Carr Purcell Meiboom Gill NMR spectra recorded on 800 MHz NMR spectrometer equipped with a TCI Cryoprobe (at 300 K). Phe and Tyr were quantified. SF from 25 patients with RA fulfilling ACR classification criteria and 21 patients with OA were taken as inflammatory and non-inflammatory controls. RESULTS: The synovial Phe/Tyr ratio was significantly higher in ReA/uSpA compared with RA and OA. Synovial Phe/Tyr ratios were comparable in RA and OA patients. Compared with serum, the Phe/Tyr was significantly higher in the SF in ReA/uSpA. The Phe/Tyr ratio was also found to be positively correlated between serum and SF samples, with a regression coefficient (r2) of 0.287. CONCLUSIONS: This NMR-based metabolomics study demonstrates that the synovial Phe/Tyr ratio is specifically elevated in ReA/uSpA.

Radiographic sacroiliitis develops predictably over time in a cohort of familial spondyloarthritis followed longitudinally.

Objectives: Radiographic sacroiliitis is an important outcome in SpA and is considered a hallmark to ascertain the diagnosis of AS. The aim of the current study was to investigate factors associated with the presence of radiographic sacroiliitis at baseline and the predictors of progression to AS in a family cohort of SpA. Methods: A total of 953 patients fulfilling the Assessment of SpondyloArthritis international Society criteria for SpA and having at least one first- or second-degree SpA-affected relative were included. Pelvic X-rays were examined blindly and independently by two qualified examiners using the modified New York criteria. Of the 446 cases without definite sacroiliitis at inclusion, 145 patients were followed up with new pelvic X-rays for 3-15 years. Regression analysis was used to assess factors associated with definite radiographic sacroiliitis. Results: Factors independently associated with radiographic sacroiliitis at inclusion were male sex, younger age at disease onset, longer disease duration, inflammatory back pain, uveitis and lack of enthesitis. During the follow-up, 27.3% of the patients with axial SpA developed definite sacroiliitis, whereas there was no progression in patients with peripheral SpA. After 15 years of follow-up, a Kaplan-Meier estimate of the proportion of patients with definite radiographic sacroiliitis reached 68.5%. Factors associated with progression to definite sacroiliitis were a low-grade radiographic sacroiliitis at inclusion, occurrence of buttock pain and the absence of peripheral arthritis during the follow-up period. Conclusions: These data confirm that progression to radiographic disease occurs most often over time in axial SpA patients.

Educational needs in patients with spondyloarthritis in Sweden - a mixed-methods study.

BACKGROUND: There is a demand for a flexible and individually tailored patient education to meet patients' specific needs and priorities, but this area has seldom been studied in patients with spondyloarthritis (SpA), a family of inflammatory rheumatic diseases. The aim of the present study was to identify needs and priorities in patient education in patients with SpA. A second aim was to investigate patients' experiences and preferences of receiving patient education. METHODS: Data collection included a questionnaire survey with the Educational Needs Assessment Tool (ENAT) and interviews, using a mixed-methods design. Patients were identified through a specialist clinic register. Descriptive data are presented as mean with standard deviation, or frequencies. Chi-square test and independent-samples t-test were used for group comparisons. A manifest qualitative conventional content analysis was conducted to explore patients' experiences and needs in patient education, based on two focus groups (n = 6) and five individual interviews. RESULTS: Almost half (43%) of the 183 SpA patients had educational needs, particularly regarding aspects of self-help, feelings, and the disease process. More educational needs were reported by women and in patients with higher disease activity, while duration of disease did not affect the needs. The qualitative analysis highlighted the importance of obtaining a guiding, reliable, and easily available patient education for management of SpA. Individual contacts with healthcare professionals were of importance, but newer media were also requested. CONCLUSION: There are considerable educational needs in patients with SpA, and education concerning self-help, feelings, and the diseases process were raised as important issues. Healthcare professionals need to consider the importance of presenting varied formats of education based on the experiences and preferences of patients with SpA.

The clinical utility of faecal calprotectin in patients with differentiated and undifferentiated spondyloarthritis: Relevance and clinical implications.

OBJECTIVES: There is cumulative evidence in the literature supporting a potential role of faecal calprotectin (FCP) as a biomarker for gut inflammation in spondyloarthritis (SpA). However its relevance in undifferentiated SpA (USpA) is still uncertain. The aim of the current study is to assess the diagnostic significance of FCP levels in patients with differentiated and undifferentiated SpA. MATERIAL AND METHODS: A total of 52 differentiated SpA, 33 USpA and 50 controls could be included. For all patients, clinical evaluation, routine laboratory investigations, FCP levels, and occult blood in stool were performed. When indicated imaging and/or endoscopies were performed. RESULTS: The differentiated SpA patients were 12 (23.1%) with ankylosing spondylitis, 21 (40.4%) with psoriatic arthritis, 13 (25%) with ulcerative colitis, 5 (9.6%) with Crohn's disease (CD) and one (1.9%) with reactive arthritis. The mean FCP level in 85 patients correlated with CRP and ESR. Within the SpA group ulcerative colitis and Crohn's disease patients had increased FCP levels compared to other SpA subgroups and USpA patients (p<0.001). The mean FCP levelwas significantly higher in the SpA patients compared to USpA and controls (p<0.001). CONCLUSIONS: Elevated FCP levels may identify patients who are most likely to have SpA already in the unclassified phase of the disease. Further studies in different series of patients are needed to evaluate the potential diagnostic and prognostic roles of FCP in both differentiated and undifferentiated phases of the disease.

A pilot study of the association of tumor necrosis factor alpha polymorphisms with psoriatic arthritis in the Romanian population.

Tumor necrosis factor alpha (TNF-alpha) is an important pro-inflammatory cytokine implicated in the pathogenesis of psoriatic arthritis. We have performed a case-control association study of three TNF-alpha gene polymorphisms in a group of Romanian psoriatic arthritis patients versus ethnically matched controls. A second group of patients with undifferentiated spondyloarthritis was used in order to look for similarities in the genetic background of the two rheumatic disorders. The -857C/T polymorphism was associated with susceptibility to psoriatic arthritis in our population at the individual level (p = 0.03, OR 1.65, 95% CI 1.05-2.57) and in combined haplotypes with the -238G/A and -308G/A SNPs. Regarding the investigated polymorphisms and derived haplotypes, no potential association was found with the susceptibility to undifferentiated spondyloarthritis in Romanian patients.

Ankylosing spondylitis and undifferentiated spondyloarthritis: The relationship between living with these diseases and psychological well-being.

BACKGROUND AND PURPOSE: This study explored the psychological impact of living with chronic pain as a result of ankylosing spondylitis or undifferentiated spondyloarthritis. The aim was to investigate individual's current pain experience and their current psychological state. METHODS: A total of 161 individuals who had a clinical diagnosis of ankylosing spondylitis or undifferentiated spondyloarthritis participated in an online survey. This survey measured daily/weekly pain, quality of life and psychological wellbeing. RESULTS: Results indicated that participants reported feeling high levels of pain consistently that impaired their daily functioning more than 50% of the time. Furthermore, on average participants reported experiencing extremely severe levels of psychological distress, that significantly correlated with their experience with pain. CONCLUSIONS: This research is significant as it highlights a need to address the psychological well-being of individuals who are diagnosed with chronic rheumatic disease in conjunction with the support they receive for their physical well-being. Furthermore, health professionals need to be mindful of the degree of debilitation associated with these diseases.

The Clinical Utility of Faecal Calprotectin in Patients with Differentiated and Undifferentiated Spondyloarthritis: Relevance and Clinical Implications.

OBJECTIVES: There is cumulative evidence in the literature supporting a potential role of faecal calprotectin (FCP) as a biomarker for gut inflammation in spondyloarthritis (SpA). However its relevance in undifferentiated SpA (USpA) is still uncertain. The aim of the current study is to assess the diagnostic significance of FCP levels in patients with differentiated and undifferentiated SpA. MATERIAL AND METHODS: A total of 52 differentiated SpA, 33 USpA and 50 controls could be included. For all patients, clinical evaluation, routine laboratory investigations, FCP levels, and occult blood in stool were performed. When indicated imaging and/or endoscopies were performed. RESULTS: The differentiated SpA patients were 12 (23.1%) with ankylosing spondylitis, 21 (40.4%) with psoriatic arthritis, 13 (25%) with ulcerative colitis, 5 (9.6%) with Crohn's disease (CD) and one (1.9%) with reactive arthritis. The mean FCP level in 85 patients correlated with CRP and ESR. Within the SpA group ulcerative colitis and Crohn's disease patients had increased FCP levels compared to other SpA subgroups and USpA patients (p<0.001). The mean FCP levelwas significantly higher in the SpA patients compared to USpA and controls (p<0.001). CONCLUSIONS: Elevated FCP levels may identify patients who are most likely to have SpA already in the unclassified phase of the disease. Further studies in different series of patients are needed to evaluate the potential diagnostic and prognostic roles of FCP in both differentiated and undifferentiated phases of the disease.

Prevalence of chronic widespread pain in a population-based cohort of patients with spondyloarthritis - a cross-sectional study.

BACKGROUND: Chronic pain, regional or widespread, is a frequent and multidimensional symptom in arthritis. There is still limited information on chronic pain in spondyloarthritis, which is important to recognize for adequate diagnosis and treatment. Our objective was to study differences in prevalence of chronic widespread pain in two spondyloarthritis subgroups: ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (USpA). METHODS: A population-based postal survey involving questions on the duration, distribution, and intensity of pain was answered by 940 patients with AS (ICD-10 M45.9) or USpA (ICD-10 M46.1-0, M46.8-9). The patients were categorized as having chronic widespread pain, chronic regional pain, or no chronic pain, and prevalence estimates for the pain groups were calculated, including age- and sex-adjusted prevalence. RESULTS: The prevalence of chronic widespread pain was 45.3% in AS vs. 49.3% in USpA, and that of chronic regional pain was 17.7% vs. 21.9% (p = 0.033). More women than men reported having chronic widespread pain (54.1% vs. 41.2%, p ≤ 0.001), while the sex distribution for chronic regional pain was equal. Reports of pain intensity were equal in AS and USpA, with no significant difference in pain intensity between women and men who had chronic regional pain or chronic widespread pain. In the multiple logistic regression analysis, chronic widespread pain was associated to female sex, being an ever-smoker, and having a higher body mass index, controlled for SpA subgroup and disease duration. CONCLUSIONS: The prevalence of chronic widespread pain in patients with AS and USpA is high, and with a female predominance, but with no difference in pain intensity between women and men. Chronic pain can complicate the clinical evaluation in patients with SpA, and highlights the need for a thorough clinical examination, including evaluation of inflammation and an accurate pain analysis, to individualize non-pharmacological and pharmacological treatment decisions.

Relationship of HS CRP and Sacroiliac Joint Inflammation in Undifferentiated Spondyloarthritis.

OBJECTIVE: Elevation of serum high sensitivity C-reactive protein (hs-CRP) level has been demonstrated as a risk factor for varying diseases, as well as a biomarker for predicting recovery after operation of lumber disc herniation. Our objective was to investigate the relationship between serum hs-CRP and sacroiliac (SI) joint inflammation in patients with undifferentiated spondyloarthritis (uSpA). METHODS: In this retrospective study, we enrolled patients with uSpA who underwent hs-CRP testing between January 2007 and September 2013. Serum hs-CRP was analyzed at our central laboratory. All enrolled patients underwent skeletal scintigraphic scan with quantitative sacroiliac measurement. RESULTS: A total of 29 patients were enrolled with mean age 32.27 years and female:male ratio of 6:23. Pearson's correlation coefficient showed a significant difference between hs-CRP in serum and SI/S ratio in uSpA, particularly the middle part of the sacroiliac joint, either right side or left side. The significantly high concentration of serum hs-CRP might indicate a systemic inflammatory response to flare-up of the SI joint and might be an indicator of SI inflammation in uSpA.

Clinical characteristics of peripheral spondyloarthritis without psoriasis, inflammatory enteropathy or preceding infection, from a single rheumatology clinic in northern India.

The objective of this study was to characterise the peripheral arthritis of spondyloarthritis (pSpA) excluding psoriatic-, inflammatory enteropathy-related, post-infectious reactive-SpA and arthritis associated with axial SpA/ankylosing spondylitis (axSpA/AS). Patients presenting with the clinical features of the broad spectrum of SpA were screened for the presence of peripheral arthritis using the Assessment of SpondyloArthritis International Society (ASAS) criteria. The other conditions that could cause pSpA, e.g. psoriasis, inflammatory enteropathy, reactive arthritis and axSpA/AS, were excluded. Their assessment included clinical, laboratory and imaging features. Of a total of 405 patients seen within the spectrum of SpA, 25 (6.2%) patients were identified as pSpA with none of the conditions that could be attributed to their disease. The male to female ratio was 2.6:1; the pattern of involvement was predominantly lower extremity asymmetrical large joint oligoarthritis in persons below the age of 40 years (60% were <30 years of age). Some had soft tissue and/or extra-articular manifestations characteristic of SpA (36%) and family history (20%) of SpA spectrum of diseases. When compared to peripheral arthritis reported in axial axSpA/AS, root/central joint involvement was minimal in pSpA. Otherwise, the pattern of arthritis appeared similar. Exclusive peripheral arthritis without the presence of the other disease-defining conditions is uncommon, seen only in 6.2% of the SpA spectrum diseases. The pattern of joint involvement was similar to that observed with axSpA/AS except that the root/central joints were not seen.

Are ankylosing spondylitis, psoriatic arthritis and undifferentiated spondyloarthritis associated with an increased risk of cardiovascular events? A prospective nationwide population-based cohort study.

BACKGROUND: To investigate the risk of first-time acute coronary syndrome (ACS), stroke and venous thromboembolism (VTE) in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA) and undifferentiated spondyloarthritis (uSpA), compared to each other and to the general population (GP). METHODS: This is a prospective nationwide cohort study. Cohorts with AS (n = 6448), PsA (n = 16,063) and uSpA (n = 5190) patients and a GP (n = 266,435) cohort, were identified 2001-2009 in the Swedish National Patient and Population registers. The follow-up began 1 January 2006, or 6 months after the first registered spondyloarthritis (SpA) diagnosis thereafter, and ended at ACS/stroke/VTE event, death, emigration or 31 December 2012. Crude and age- and sex-standardized incidence rates (SIRs) and hazard ratios (HRs) were calculated for incident ACS, stroke or VTE, respectively. RESULTS: Standardized to the GP cohort, SIRs for ACS were 4.3, 5.4 and 4.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort, respectively, compared to 3.2 in the GP cohort. SIRs for stroke were 5.4, 5.9 and 5.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort compared to 4.7 in the GP cohort. Corresponding SIRs for VTE were 3.6, 3.2 and 3.5 events per 1000 person-years at risk compared to 2.2 in the GP cohort. Age-and sex-adjusted HRs (95% CI) for ACS events were significantly increased in AS (1.54 (1.31-1.82)), PsA (1.76 (1.59-1.95)) and uSpA (1.36 (1.05-1.76)) compared to GP. Age-adjusted HRs for ACS was significantly decreased in female AS patients (0.59 (0.37-0.97)) compared to female PsA patients. Age-and sex-adjusted HRs for stroke events were significantly increased in AS (1.25 (1.06-1.48)) and PsA (1.34 (1.22-1.48)), and nonsignificantly increased in uSpA (1.16 (0.91-1.47)) compared to GP. For VTE the age-and sex-adjusted HRs for AS, PsA and uSpA were equally and significantly increased with about 50% compared to GP. CONCLUSIONS: Patients with AS, PsA and uSpA are at increased risk for ACS and stroke events, which emphasizes the importance of identification of and intervention against cardiovascular risk factors in SpA patients. Increased alertness for VTE is warranted in patients with SpA.

Entesis, entesopatía y espondiloartritis / Entheses, enthesopathy and spondyloarthritis

Las espondiloartritis (SpA) comprenden un grupo heterogéneo de enfermedades inflamatorias articulares que comparten varias características clínicas y de laboratorio, una fuerte tendencia a la asociación familiar dada por una susceptibilidad genética relacionada con la presencia del antígeno de histocompatibilidad HLA-B27, compromiso de las entesis, afectación predominante del esqueleto axial, artritis asimétrica de grandes articulaciones en los miembros inferiores y relación con la infección como factor desencadenante de las mismas. Las SpA incluyen varios subtipos: la artropatía psoriásica (PsA), las espondiloartritis no definidas (uSpA), la artritis asociada a enfermedades inflamatorias intestinales (EII), la artritis reactiva (ReA) y la espondilitis anquilosante (EA). La característica histopatológica fundamental de las SpA es la entesitis, la cual está dada por la inflamación patológica de las entesis comprometidas, que son los sitios de inserción de los tendones, ligamentos, fascias y cápsulas articulares al hueso; así como también el sitio de unión del cartílago al hueso subcondral.

Spondyloarthritis are a heterogeneous group of inflammatory joint diseases, which share clinic and laboratory characteristics, a strong relation to hereditary factors (mainly antigen HLA-B27), enthesesitis (most commonly affecting axial skeleton), large joints asymmetric arthritis mostly in lower limbs, and its relationship with infections as a triggering factor. Spondyloarthitis include various subtypes: Psoriatic Arthropathy (PsA), Undifferentiated Spondiloarthritis (uSpA), Arthritis related to inflammatory bowel disease (IBD), Ankylosing Spondylitis (AS) and Reactive Arthritis (ReA). Fundamental histopathologic characteristic of the Spondyloarthritis is enthesitis on the sites of attachment of tendons, ligaments, joint capsules and fascias to the bone, but also over the cartilage at the subchondral bone.