To determine the heritability of spine curve using plain radiographs and to identify risk factors for spine curvature including age, body mass index, smoking, bone mineral density (BMD), and lumbar disc degeneration (LDD).

center dot PURPOSE: To determine the prevalence of inflammatory back pain in an anterior uveitis cohort.center dot DESIGN: Retrospective Cohort study.center dot METHODS: Patients with anterior uveitis were recruited from the clinic of an ophthalmologist to complete a survey between March and December 2008. Patients were classified with inflammatory back pain if they had >= 2 positive responses to 4 validated inflammatory back pain questions: presence of morning stiffness > 30 minutes in duration; improvement in back pain with exercise but not with rest; awakening from back pain during the second half of the night only; and presence of alternating buttock pain. Disease activity was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The impact of disease on quality of life was measured using the EuroQOL (EQ-5D) questionnaire. Twenty-five patients underwent further rheumatologic examination.center dot RESULTS: One hundred forty-one of 167 patients (84.4%) completed the survey. Sixty-six of 141 patients (46.8%) were classified to have inflammatory back pain. Mean BASDAI (4.2, SD 2.41) and EQ-5D scores (0.73, SD 0.21) were lower than patients with no inflammatory back pain (0.82, SD 0.16, P =.0048). In the subgroup that underwent rheumatologic assessment, a classification of inflammatory back pain was 92% sensitive and 67% specific for a diagnosis of inflammatory back pain.center dot CONCLUSIONS: The prevalence of inflammatory back pain in a cohort of anterior uveitis patients was found to be 46.8%. Patients with inflammatory back pain had worse quality of life than those without. Ophthalmologists may use these questions on back pain to select patients classified to have inflammatory back pain to refer for early rheumatologic assessment. (Am J Ophthalmol 2012;153:1025-1030. (C) 2012 by Elsevier Inc. All rights reserved.)

Matthew Brown, Peter Donnelly and colleagues report results of a genome-wide association meta-analysis and follow-up study of ankylosing spondylitis. They identify three new risk variants and report a genetic interaction between ERAP1 and HLA-B27, implicating aberrant peptide handling in the pathophysiology of this disease. Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10−8 in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 × 10−6 overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27–positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.

Ankylosing spondylitis (AS) is a common inflammatory arthritic condition.Overt inflammatory bowel disease (IBD) occurs in about 10% of AS patients, and in addition 70% of AS cases may have subclinical terminal ileitis.Spondyloarthritis is also common in IBD patients.We therefore tested Crohn's disease susceptibility genes for association with AS, aiming to identify pleiotropic genetic associations with both diseases.Genotyping was carried out using Sequenom and Applied Biosystems TaqMan and OpenArray technologies on 53 markers selected from 30 Crohn's disease associated genomic regions.We tested genotypes in a population of unrelated individual cases (n = 2,773) and controls (n = 2,215) of white European ancestry for association with AS.Statistical analysis was carried out using a Cochran-Armitage test for trend in PLINK.Strong association was detected at chr1q32 near KIF21B (rs11584383, P = 1.6610 210 , odds ratio (OR) = 0.74, 95% CI:0.68-0.82).Association with disease was also detected for 2 variants within STAT3 (rs6503695, P = 4.6610 24 .OR = 0.86 (95% CI:0.79-0.93);rs744166, P = 2.6610 25 , OR = 0.84 (95% CI:0.77-0.91)).Association was confirmed for IL23R (rs11465804, P = 1.2610 25 , OR = 0.65 (95% CI:0.54-0.79)),and further associations were detected for IL12B (rs10045431, P = 5.2610 25 , OR = 0.83 (95% CI:0.76-0.91)),CDKAL1 (rs6908425, P = 1.1610 24 , OR = 0.82 (95% CI:0.74-0.91)),LRRK2/MUC19 (rs11175593, P = 9.9610 25 , OR = 1.92 (95% CI: 1.38-2.67)),and chr13q14 (rs3764147, P = 5.9610 24 , OR = 1.19 (95% CI: 1.08-1.31)).Excluding cases with clinical IBD did not significantly affect these findings.This study identifies chr1q32 and STAT3 as ankylosing spondylitis susceptibility loci.It also further confirms association for IL23R and detects suggestive association with another 4 loci.STAT3 is a key signaling molecule within the Th17 lymphocyte differentiation pathway and further enhances the case for a major role of this T-lymphocyte subset in ankylosing spondylitis.Finally these findings suggest common aetiopathogenic pathways for AS and Crohn's disease and further highlight the involvement of common risk variants across multiple diseases.

OBJECTIVE:To replicate and refine the reported association of ankylosing spondylitis (AS) with two non-synonymous single nucleotide polymorphisms (nsSNPs) on chromosome 16q22.1. METHODS:Firstly, 730 independent UK patients with AS were genotyped for rs9939768 and rs6979 and allele frequencies were compared with 2879 previously typed historic disease controls. Secondly, the two data sets were combined in meta-analyses. Finally, 5 tagging SNPs, located between rs9939768 and rs6979, were analysed in 1604 cases and 1020 controls. RESULTS:The association of rs6979 with AS was replicated, p=0.03, OR=1.14 (95% CI 1.01 to 1.28), and a trend for association with rs9939768 detected, p=0.06, OR=1.25 (95% CI 0.99 to 1.57). Meta-analyses revealed association of both SNPs with AS, p=0.0008, OR=1.31 (95% CI 1.12 to 1.54) and p=0.0009, OR=1.15 (95% CI 1.06 to 1.23) for rs9939768 and rs6979, respectively. New associations with rs9033 and rs868213 (p=0.00002, OR=1.23 (95% CI 1.12 to 1.36) and p=0.00002 OR=1.45 (95% CI 1.22 to 1.72), respectively, were identified. CONCLUSIONS:The region on chromosome 16 that has been replicated in the present work is interesting as the highly plausible candidate gene, tumour necrosis factor receptor type 1 (TNFR1)-associated death domain (TRADD), is located between rs9033 and rs868213. It will require additional work to identify the primary genetic association(s) with AS.

Objective. The Visual Assessment of the Spine Bruckel Instrument (VASBI) is a new status tool developed by the Spondylitis Association of America and the University of Toronto to reflect spinal appearance in patients with ankylosing spondylitis (AS). Our objective was to validate the VASBI according to the Outcome Measures in Rheumatoid Arthritis Clinical Trials filter (truth, discrimination, and feasibility). Methods. Three hundred patients with AS were asked to rate their degree of perceived spinal deformity using the VASBI. To evaluate construct validity, VASBI scores were compared with functional outcome, spinal mobility, and radiographic spinal damage. Test-retest reliability was evaluated using kappa statistic (κ). Results. Patient VASBI demonstrated strong correlation with spinal mobility (r = 0.543) and moderate correlation with functional impairment (r = 0.490) and structural damage (r = 0.309). Reliability for VASBI was very good (κ = 0.973, p < 0.001). Conclusion. The VASBI is a novel tool with practical applications in a busy clinical setting as it simplifies assessment of AS spinal deformity. Our study demonstrates that the VASBI has good feasibility, construct validity, and reliability.

OBJECTIVES:It has been shown previously that IL-23R variants are associated with AS. We conducted an extended analysis in the UK population and a meta-analysis with the previously published studies, in order to refine these IL-23R associations with AS.METHODS:The UK case-control study included 730 new cases and 1331 healthy controls. In the extended study, the 730 cases were combined with 1088 published cases. Allelic associations were analysed using contingency tables. In the meta-analysis, 3482 cases and 3150 controls from four different published studies and the new UK cases were combined. DerSimonian-Laird test was used to calculate random effects pooled odds ratios (ORs).RESULTS:In the UK case-control study with new cases, four of the eight SNPs showed significant associations, whereas in the extended UK study, seven of the eight IL-23R SNPs showed significant associations (P < 0.05) with AS, maximal with rs11209032 (P < 10(-5), OR 1.3), when cases with IBD and/or psoriasis were excluded. The meta-analysis showed significant associations with all eight SNPs; the strongest associations were again seen not only with rs11209032 (P = 4.06 x 10(-9), OR approximately 1.2) but also with rs11209026 (P < 10(-10), OR approximately 0.6).CONCLUSIONS:IL-23R polymorphisms are clearly associated with AS, but the primary causal association(s) is(are) still not established. These polymorphisms could contribute either increased or decreased susceptibility to AS; functional studies will be required for their full evaluation. Additionally, observed stronger associations with SNPs rs11209026 and rs11465804 upon exclusion of IBD and/or psoriasis cases may represent an independent association with AS.

Objective. Rheumatologists base many clinical decisions regarding the management of inflammatory joint diseases on joint counts performed at clinic. We investigated the reliability and accuracy of physically examining the metacarpophalangeal (MCP) joints to detect inflammatory synovitis using magnetic resonance imaging (MRI) as the gold standard. Methods. MCP joints 2 to 5 in both hands of 5 patients with rheumatoid arthritis (RA) and 5 with psoriatic arthritis (PsA) were assessed by 5 independent examiners for joint-line swelling (visually and by palpation); joint-line tenderness by palpation (tender joint count, TJC) and stress pain; and by MRI (1.5 Tesla superconducting magnet). Interrater reliability was assessed using kappa statistics, and agreement between examination and corresponding MRI assessment was assessed by Fisher’s exact tests (p < 0.05 considered statistically significant). Results. Interrater agreement was highest for visual assessment of swelling (κ = 0.55–0.63), slight-fair for assessment of swelling by palpation (κ = 0.19–0.41), and moderate (κ = 0.41–0.58) for assessment of joint tenderness. In patients with RA, TJC, stress pain, and visual swelling assessment were strongly associated with MRI evaluation of synovitis. Visual swelling assessment demonstrated high specificity (> 0.8) and positive predictive value (= 0.8). For PsA, significant associations exist between TJC and MRI synovitis scores (p < 0.01) and stress pain and MRI edema scores (p < 0.04). Assessment of swelling by palpation was not significantly associated with synovitis or edema as determined by MRI in RA or PsA (p = 0.54–1.0). Conclusion. In inflammatory arthritis, disease activity in MCP joints can be reliably assessed at the bedside by examining for joint-line tenderness (TJC) and visual inspection for swelling. Clinical assessment may have to be complemented by other methods for evaluating disease activity in the joint, such as MRI, particularly in patients with PsA.

A strong association between ERAP1 and ankylosing spondylitis (AS) was recently identified by the Wellcome Trust Case Control Consortium and the Australo-Anglo-American Spondylitis Consortium (WTCCC-TASC) study. ERAP1 is highly polymorphic with strong linkage disequilibrium evident across the gene. We therefore conducted a series of experiments to try to identify the primary genetic association(s) with ERAP1. We replicated the original associations in an independent set of 730 patients and 1021 controls, resequenced ERAP1 to define the full extent of coding polymorphisms and tested all variants in additional association studies. The genetic association with ERAP1 was independently confirmed; the strongest association was with rs30187 in the replication set (P = 3.4 x 10(-3)). When the data were combined with the original WTCCC-TASC study the strongest association was with rs27044 (P = 1.1 x 10(-9)). We identified 33 sequence polymorphisms in ERAP1, including three novel and eight known non-synonymous polymorphisms. We report several new associations between AS and polymorphisms distributed across ERAP1 from the extended case-control study, the most significant of which was with rs27434 (P = 4.7 x 10(-7)). Regression analysis failed to identify a primary association clearly; we therefore used data from HapMap to impute genotypes for an additional 205 non-coding SNPs located within and adjacent to ERAP1. A number of highly significant associations (P < 5 x 10(-9)) were identified in regulatory sequences which are good candidates for causing susceptibility to AS, possibly by regulating ERAP1 expression.

Objectives. Many AS patients report periods of perceived higher disease activity (flares). This pilot study aims to document disease activity patterns reported by AS patients and examine associations with disease-specific health status measures.Methods. Consecutive AS patients (n = 114) were asked whether they experience flares, and if they experience symptoms of AS between flares. They were shown the Flare Illustration of disease patterns over time and asked to select the pattern that best described their disease (i) since symptom onset and (ii) in the past year. Associations between reported disease pattern and disease activity (Bath AS Disease Activity Index, BASDAI); functional impairment (Bath AS Functional Index, BASFI); AS Quality of Life (ASQoL); Back Pain (Nocturnal and Overall) and demographic features were assessed in a subsample (n = 83) (statistical significance defined at P <= 0.05).Results. Since disease onset 108/113 patients (96%) reported flares, and 82/99 (83%) reported symptoms of AS between flares. Flares typically lasted days or weeks. When patients were asked to characterize their disease pattern using the Flare Illustration, patterns with constant symptoms predominated (> 70% of patients) and patterns with constant symptoms since onset (vs intermittent symptoms) were associated with worse health status (ASQoL: P = 0.007; BASDAI: P = 0.029; BASFI: P = 0.013, overall back pain: P = 0.025).Conclusions. Almost all AS patients report flares in disease activity: 70-80% report constant symptoms with single/repeated flares, while 20-30% report flares with no intermittent symptoms. The former is associated with a significantly poorer health status. These findings will be validated in a prospective study.

OBJECTIVE:To determine whether the assessments of peripheral joints and enthesitis were reproducible for both AS and PsA with axial disease, and whether dactylitis assessment is reproducible in patients with PsA.METHODS:A group of 20 rheumatologists from 11 countries with expertise in spondyloarthritis (SpA) met for a combined physical examination exercise to assess 10 patients with PsA with axial involvement (9 men, 1 woman, mean age 52 yrs, disease duration 17 yrs) and 9 patients with AS (7 men, 2 women, mean age 38 yrs, disease duration 16 yrs). A modified Latin-square design that enabled assessment of patient, assessor, and order effect was used. Measures included were number of tender and swollen joints, presence of enthesitis using 6 different indices, and dactylitis score. Data were analyzed using intraclass correlation (ICC) adjusted for order of measurements.RESULTS:The majority of the variance was contributed by the patients. There was no order effect. The assessment of tender joints (ICC 0.69) was more reliable than the assessment of swollen joints (ICC 0.54). Moreover, there was better agreement in patients with PsA (ICC 0.78) than in patients with AS (ICC 0.62). There was excellent agreement on the number of active enthesitis sites (ICC 0.86). All the enthesitis indices provided substantial to excellent agreement among observers. Agreement for the dactylitis score was substantial (ICC 0.70).CONCLUSION:The assessment of peripheral joints is more reliable in patients with PsA. Enthesitis instruments can be used reliably in patients with AS and patients with PsA with spinal involvement. The Leeds dactylitis instrument functions well in PsA.