Assessing the construct validity of clinical tests to identify sacroiliac joint inflammation in patients with non-radiographic axial spondyloarthritis.

AIM: Magnetic resonance imaging (MRI) can be used to identify sacroiliac joint (SIJ) inflammation and provide an earlier diagnosis of nonradiographic axial spondyloarthritis (nrAxSpA). However, MRI is frequently a resource-limited examination. Our aim was to assess if a set of physical clinical tests can identify SIJ inflammation in patients with nrAxSpA. METHODS: Twenty participants with nrAxSpA underwent two functional tests (active straight leg raise, and stork test on the support side) and four pain provocation tests (Gaenslen's, posterior pelvic pain provocation, Patrick's Faber and palpation of the long dorsal SIJ ligament) for the SIJ, and then proceeded to a contemporaneous reference standard MRI. The Spondyloarthritis Research Consortium of Canada scoring system (SPARCC) was used to score MRI. Specificity, sensitivity, and likelihood ratios (LR) were calculated for individual clinical tests, and for the composite of tests. RESULTS: Pain provocation tests were superior to functional tests, which showed poor accuracy. The Patrick's Faber test was the best performing procedure (sensitivity 71%, specificity 75%, positive LR 2.9, negative LR 0.4). When combining the provocation tests, a positive test in one out of two tests demonstrated the strongest predictive value (sensitivity 86%, specificity 62%, positive LR 2.2, negative LR 0.2). CONCLUSIONS: Sacroiliac joint pain provocation tests correlate modestly with inflammation. The Patrick's Faber test showed the greater LR to identify SIJ inflammation in patients with nrAxSpA. SIJ pain provocation tests may offer a simple and cost-effective way of identifying patients with nrAxSpA who are most likely to have MRI evidence of inflammation.

Association of Crohn's disease-related chromosome 1q32 with ankylosing spondylitis is independent of bowel symptoms and faecal calprotectin.

BACKGROUND: Genome-wide association studies have identified a plethora of risk genes for both Crohn's disease (CD) and ankylosing spondylitis (AS). A subset of genes found to be risk factors for CD have also been found to be risk factors for AS. The objective of our study was to assess whether CD risk genes were associated with non-invasive clinical markers of gut inflammation in patients with AS, indicating a potential subset of patients with clinical as well as genetic overlap. METHODS: A total of 308 Caucasian patients who fulfilled the modified New York Criteria for AS, were assessed for bowel symptoms using the Dudley Inflammatory Bowel Symptom Questionnaire (DISQ). Of these patients, 157 also had faecal calprotectin measured. All AS patients and 568 healthy controls were genotyped for 10 CD risk loci using predesigned single nucleotide polymorphism (SNP) genotyping assays. Chi-square analysis was used to test for association between genotype and DISQ score and faecal calprotectin level. RESULTS: The minor allele of two SNPs, one in chromosome region 1q32 SNP (rs11584383), and one in the gene coding for IL23R (rs11209026) conferred protection against AS. Only the association of 1q32 remained significant after Bonferroni correction for multiple testing. Stratification by DISQ score and faecal calprotectin did not influence the association of 1q32 with AS. CONCLUSION: In patients with AS, the association of the CD 1q32 SNP was independent of non-invasive markers of bowel inflammation. Other CD related SNPs were not found have a significant association with AS.

The oral microbiome of patients with axial spondyloarthritis compared to healthy individuals.

Background. A loss of mucosal tolerance to the resident microbiome has been postulated in the aetiopathogenesis of spondyloarthritis, thus the purpose of these studies was to investigate microbial communities that colonise the oral cavity of patients with axial spondyloarthritis (AxSpA) and to compare these with microbial profiles of a matched healthy population. Methods. Thirty-nine participants, 17 patients with AxSpA and 22 age and gender-matched disease-free controls were recruited to the study. For patients with AxSpA, disease activity was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). All participants underwent a detailed dental examination to assess oral health, including the presence of periodontal disease assessed using probing pocket depth (PPD). Plaque samples were obtained and their bacterial populations were profiled using Ion Torrent sequencing of the V6 region of the 16S rRNA gene. Results.Patients with AxSpA had active disease (BASDAI 4.1 ± 2.1 [mean ± SD]), and a significantly greater prevalence of periodontitis (PPD ≥ 4 mm at ≥4 sites) than controls. Bacterial communities did not differ between the two groups with multiple metrics of α and ß diversity considered. Analysis of operational taxonomic units (OTUs) and higher levels of taxonomic assignment did not provide strong evidence of any single taxa associated with AxSpA in the subgingival plaque. Discussion. Although 16S rRNA gene sequencing did not identify specific bacterial profiles associated with AxSpA, there remains the potential for the microbiota to exert functional and metabolic influences in the oral cavity which could be involved in the pathogenesis of AxSpA.

Construct validity of clinical spinal mobility tests in ankylosing spondylitis: a systematic review and meta-analysis.

The study aimed to determine, using systematic review and meta-analysis, the level of evidence supporting the construct validity of spinal mobility tests for assessing patients with ankylosing spondylitis. Following the guidelines proposed in the Preferred Reporting Items for Systematic reviews and Meta-Analyses, three sets of keywords were used for data searching: (i) ankylosing spondylitis, spondyloarthritis, spondyloarthropathy, spondylarthritis; (ii) accuracy, association, construct, correlation, Outcome Measures in Rheumatoid Arthritis Clinical Trials, OMERACT, truth, validity; (iii) mobility, Bath Ankylosing Spondylitis Metrology Index-BASMI, radiography, spinal measures, cervical rotation, Schober (a further 19 keywords were used). Initially, 2558 records were identified, and from these, 21 studies were retained. Fourteen of these studies were considered high level of evidence. Compound indexes of spinal mobility showed mostly substantial to excellent levels of agreement with global structural damage. Individual mobility tests for the cervico-thoracic spine showed only moderate agreements with cervical structural damage, and considering structural damage at the lumbar spine, the original Schober was the only test that presented consistently substantial levels of agreement. Three studies assessed the construct validity of mobility measures for inflammation and low to fair levels of agreement were observed. Two meta-analyses were conducted, with assessment of agreement between BASMI and two radiological indexes of global structural damage. The spinal mobility indexes and the original Schober test show acceptable construct validity for inferring the extent of structural damage when assessing patients with ankylosing spondylitis. Spinal mobility measures do not reflect levels of inflammation at either the sacroiliac joints and/or the spine.

Role of Physical Evaluation in the Early Identification of Axial Spondyloarthritis: A Research Proposal.

The aim of this study was to present a rationale to explore the use of clinical tests for the sacroiliac joints to detect early axial spondyloarthritis (SpA) and to suggest a protocol to validate these clinical tests. Based on the European Guidelines for Diagnosis and Treatments of Pelvic Girdle Pain, we propose a set of six clinical tests to identify the likely presence of inflammation in the sacroiliac joints associated with early axial SpA. As magnetic resonance imaging (MRI) is the current gold standard used to identify inflammation in the sacroiliac joints, the results of the proposed set of clinical tests are compared with those from the MRI examinations. We hypothesize that specific clinical tests, which combine pain provocation and functional tests, for assessing the sacroiliac joints will help to identify early active inflammation at the sacroiliac joints in axial SpA. If such tests prove to be sensitive and specific, they could add further value to the diagnostic classification criteria for axial SpA.

Criterion-concurrent validity of spinal mobility tests in ankylosing spondylitis: a systematic review of the literature.

OBJECTIVE: To examine the level of evidence for criterion-concurrent validity of spinal mobility assessments in patients with ankylosing spondylitis (AS). METHODS: Guidelines proposed in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses were used to undertake a search strategy involving 3 sets of keywords: accura*, truth, valid*; ankylosing spondylitis, spondyloarthritis, spondyloarthropathy, spondylarthritis; mobility, spinal measure*, (a further 16 keywords with similar meaning were used). Seven databases were searched from their inception to February 2014: AMED, Embase, ProQuest, PubMed, Science Direct, Scopus, and Web of Science. The Quality Assessment of Diagnostic Accuracy Studies (with modifications) was used to assess the quality of articles reviewed. An article was considered high quality when it received "yes" in at least 9 of the 13 items. RESULTS: From the 741 records initially identified, 10 articles were retained for our systematic review. Only 1 article was classified as high quality, and this article suggests that 3 variants of the Schober test (original, modified, and modified-modified) poorly reflect lumbar range of motion where radiographs were used as the reference standard. CONCLUSION: The level of evidence considering criterion-concurrent validity of clinical tests used to assess spinal mobility in patients with AS is low. Clinicians should be aware that current practice when measuring spinal mobility in AS may not accurately reflect true spinal mobility.

Fatigue in patients with spondyloarthritis associates with disease activity, quality of life and inflammatory bowel symptoms.

The study aimed to assess the severity of fatigue in patients with axial spondyloarthritis (AxSpA), to assess the performance of two different fatigue measures in AxSpA, and to examine disease variables which may influence the severity of fatigue. Fatigue was examined among 67 patients with AxSpA using two measures: the fatigue Visual Analogue Scale (VAS) from the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Multidimensional Assessment of Fatigue (MAF) score. These measures were tested for convergent validity using linear regression analysis. Correlations between fatigue measured using both questionnaires, and key disease variables was examined using the following assessments: BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire, spondyloarthritis modification of the Dudley Inflammatory Bowel Symptom Questionnaire (DISQ) and pain VAS. Human leucocyte antigen (HLA) B27 and CRP were performed and followed by physical examination, Bath AS Metrology Index (BASMI) and Ankylosing Spondylitis Disease Activity Score (ASDAS). Correlations were assessed using multivariate regression analysis. Mean (±SD) fatigue measured by MAF (range 0-50) was 24.7 (±11.5) and 5.14 (±2.47) on the BASDAI VAS fatigue item (range 0-10). The MAF scores and BASDAI VAS fatigue were strongly correlated (r = 0.71, P < 0.001), but 50 % of variance remained unexplained, so both were retained as separate variables in bivariate and multivariate analyses. In multivariate regression models, a significant relationship for both fatigue measures was consistently noted with DISQ bowel symptom scores. MAF fatigue scores were most strongly associated with poorer ASQoL in multivariate models and mediated the effects of BASFI functioning, ASDAS disease activity and HLA-B27 status that were apparent in multivariate models. Patients with AxSpA experience substantial fatigue, which is associated with poorer quality of life. Fatigue VAS and MAF scores were strongly correlated. Factors most strongly associated with fatigue were disease activity and inflammatory bowel symptoms.

Prevalence of HLA-B27 in the New Zealand population: effect of age and ethnicity.

INTRODUCTION: HLA-B27 genotyping is commonly used to support a diagnosis of ankylosing spondylitis (AS). A recent study has suggested that HLA-B27 may adversely affect longevity. The objectives of this study were to determine, for the first time, the prevalence of HLA-B27 in the New Zealand population, and to test whether HLA-B27 prevalence declines with age. METHODS: 117 Caucasian controls, 111 New Zealand Maori controls, and 176 AS patients were directly genotyped for HLA-B27 using PCR-SSP. These participants and a further 1103 Caucasian controls were genotyped for the HLA-B27 tagging single nucleotide polymorphisms (SNPs) rs4349859 and rs116488202. All AS patients testing positive for HLA-B27 of New Zealand Maori ancestry underwent high resolution typing to determine sub-allele status. RESULTS: HLA-B27 prevalence was 9.2% in New Zealand Caucasian controls and 6.5% in Maori controls. No decline in HLA-B27 prevalence with age was detected in Caucasian controls (p = 0.92). Concordance between HLA-B27 and SNP genotypes was 98.7-99.3% in Caucasians and 76.9-86% in Maori. Of the 14 AS patients of Maori ancestry, 1 was negative for HLA-B27, 10 were positive for HLAB*2705, and 3 positive for HLAB*2704. All cases of genotype discordance were explained by the presence of HLAB*2704. CONCLUSIONS: HLA-B27 prevalence in New Zealand Caucasians is consistent with that of Northern European populations and did not decline with increasing age. In Maori with AS who were HLA-B27 positive, 76.9% were positive for HLA-B*2705, suggesting that genetic susceptibility to AS in Maori is primarily due to admixture with Caucasians.

The immune response to autologous bacteroides in ankylosing spondylitis is characterized by reduced interleukin 10 production.

OBJECTIVE: Ileocolitis is a recognized feature of ankylosing spondylitis (AS) and is likely to play a role in the pathogenesis of AS, in conjunction with the normal intestinal microbiota. In order to investigate the host immune response in AS, we measured cytokines in tissue culture following exposure of peripheral blood mononuclear cells (PBMC) to autologous colonic bacteria. METHODS: Twenty-one patients with AS and 21 matched controls were recruited. Subjects in the AS group were assessed clinically. Bacteroides species belonging to the B. fragilis group were selectively cultured from stool samples and paired with blood samples from each participant. Ten cultures of autologous Bacteroides were randomly selected from cultures grown from the fecal specimens of each of the 21 patients with AS and 21 controls. These were then tested for reactivity with PBMC and the cytokines produced by proliferating lymphocytes [interleukin 10 (IL-10), IL-17, interferon-gamma, tumor necrosis factor-alpha] were measured in cell culture supernatants. Differences between groups were analyzed using censored normal regression analysis. RESULTS: The patients with AS had severe active AS with Bath AS Disease Activity Index 5.5 (+/-1.6) and C-reactive protein (mg/l) 13.8 (+/-12.2) (mean+/-standard deviation). IL-10 concentrations in ex vivo assay supernatants were lower in the AS group compared with controls (p=0.047). There were no statistically significant differences between the groups for other cytokines. CONCLUSION: In AS, reduced IL-10 production in response to stimulation with autologous Bacteroides cultures may represent a mechanism by which intestinal inflammation develops and persists, a situation analogous to inflammatory bowel disease.