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Background/Purpose The intergenic SNP rs10865331 at 2p15 was identified as a major risk factor for ankylosing spondylitis (AS) susceptibility in genome-wide association studies (GWAS). B3GNT2 gene regulates polylactosamine synthesis is potentially functionally relevant to AS disease development. We investigated whether SNP rs10865331 and two B3GNT2 SNPs (rs11900673 and rs1136151) are associated with AS susceptibility and disease severity in Taiwanese. Methods Distributions of genotypes, alleles, and haplotypes of three SNPs were compared between 1,472 AS patients and 2,117 healthy blood donors and among AS patients stratified by clinical characteristics. Results The intergenic SNP rs10865331 was significantly associated with AS (PFDR = 1.02E-05) in Taiwanese. In AS patients stratified by positivity of HLA-B27 and syndesmophyte formation, all three B3GNT2 locus SNPs (rs11900673, rs1136151, and rs10865331) were significantly associated with syndesmophyte formation among HLA-B27 positive AS patients. Haplotype analyses revealed that the “CTA” (rs11900673C/rs1136151T/rs10865331A) haplotype was significantly associated with AS susceptibility (Padj = 0.0177) and syndesmophyte formation (Padj = 0.016) in HLA-B27 positive patients. In contrast, “TCG” (rs11900673T/rs1136151C/rs10865331G) haplotype showed protection against AS development (Padj = 0.0005 for HLA-B27 positive and Padj = 0.004 for HLA-B27 negative, respectively) and syndesmophyte formation (Padj = 0.0017) in HLA-B27 positive patients. Furthermore, B3GNT2 mRNA expressions were negatively associated with erythrocyte sedimentation rate (ESR, P = 0.0103), C-reactive protein (CRP, P = 0.0353), Bath ankylosing spondylitis functional index (BASFI, P = 0.0171), and syndesmophyte formation (P = 0.0148). Conclusion Our data suggest that B3GNT2 gene may contribute to AS development and affect AS severity by interacting with HLA-B27 in Taiwanese.

Objectives To investigate the occurrence of facet joint ankylosis in the spine of patients with radiographic axial spondyloarthritis (r-axSpA) using low dose computed tomography (ldCT), and to examine the association between facet joint ankylosis and functional impairment. Methods A group of 126 patients with r-axSpA was selected from Incheon Saint Mary's axSpA observational cohort and whole spine ldCT data were examined. Facet joint (right and left, C2–S1) ankylosis was scored from 0–46 (total). The presence of facet joint ankylosis was assessed by two readers, each blinded to the patient data. The inter-reader reliability of facet joint ankylosis scoring was assessed using intraclass correlation coefficients (ICCs). The CT Syndesmophyte Score (CTSS) was assessed. Lumbar spinal mobility was evaluated using the modified Schober test. Functional impairment was measured using the Bath AS functional index (BASFI). Results The ICCs of ankylosed facet joint scores at the cervical, thoracic, lumbar and whole spine were 0.84, 0.88, 0.92 and 0.90, respectively. Facet joint ankylosis was most common in the thoracic spine. Scores for the whole spine correlated positively with the ASDAS, mSASSS and the syndesmophyte score. Multivariate analysis revealed that facet joint ankylosis was significantly associated with decreased lumbar motion. For both readers, the scores for the whole spine were independently associated with BASFI after adjusting for syndesmophyte score and disease activity. Conclusions Facet joint ankylosis in patients with r-axSpA was associated with functional impairment and spinal mobility. Facet joints should be incorporated into a structural damage assessment method.

BACKGROUND CONTEXT Positron emission tomography (PET) is a potential imaging technique for the diagnosis of AS. The visualization of physiological change makes PET potentially suitable for early detection of inflammatory processes, even before anatomical changes occur. Thus, PET might provide specificity via the use of receptor targeting tracers and allows quantification of disease activity in order to accurately monitor therapeutic effects. PURPOSE To examine fluorine-18 sodium fluoride (18F-NaF) PET/computed tomography (PET/CT) findings in patients with inflammatory low back pain and evaluate the utility of this modality in the diagnosis of ankylosing spondylitis (AS) according to the Assessment of SpondyloArthritis International Society (ASAS) criteria. STUDY DESIGN Retrospective cohort study. PATIENTS SAMPLE Sixty-eight patients who underwent 18F-NaF PET/CT imaging between April 2015 and April 2017 for evaluation of inflammatory low back pain. OUTCOME MEASURES We defined AS-positive lesions on PET/CT as symmetric sacroiliac joint uptake that suggests sacroiliitis, syndesmophytes on the spine, and enthesopathy at any site. METHODS All patients were evaluated using the ASAS criteria and assigned to either the AS or the control group. The diagnostic criteria of AS on PET/CT images were defined as 18F-NaF PET/CT images with at least one of AS-positive findings. RESULTS The diagnostic rate of AS was 72.1% among the 68 patients according to the ASAS criteria. The baseline characteristics between the two groups differed significantly in terms of serum C-reactive protein levels and the presence of human leucocyte antigen-B27. Compared to the control group, in the AS group, 39 patients (79.5%) exhibited typical 18F-NaF PET/CT-positive findings, such as enthesopathy (65.3%, p=.003), syndesmophytes (61.2%, p=.006) and symmetric sacroiliitis (67.3%, p=.001). PET-positive findings had significantly higher area under the curve values than did single 18F-NaF PET/CT- positive findings, and they had the best performance for concordant diagnosis according to the ASAS criteria. CONCLUSIONS 18F-NaF PET/CT yielded significantly different findings between the two groups according to the ASAS criteria and is useful for diagnosing AS.

Introduction and objectives Syndesmophytes appear to falsely raise lumbar bone mineral density values, thereby hindering the diagnosis of osteoporosis by dual-energy X-ray absorptiometry in patients with axial spondyloarthritis. The objective of the study was therefore to analyze the influence of syndesmophytes at the lumbar level on trabecular bone scores and lumbar and femoral neck bone mineral density values and to assess the clinical and analytical factors associated with trabecular bone scores in axial spondyloarthritis. Material and methods From January 2017 to June 2018, a cross-sectional study consecutively included patients with axial spondyloarthritis according to Assessment in Ankylosing Spondylitis criteria. We assessed the trabecular bone scores and bone mineral density values and recorded clinical, demographic, disease-related and laboratory variables. Results The study included 82 patients with axial spondyloarthritis (38 with syndesmophytes and 44 without syndesmophytes). The mean age of the patients with and without syndesmophytes was 55.7 ± 10.27 years and 44.36 ± 11.85 years, respectively (p Conclusion Trabecular bone scores do not appear to be masked by the presence of syndesmophytes.

Background The effects of sacroiliitis and syndesmophyte formation on the cross-correlation between spine and hip joint kinematics in ankylosing spondylitis (AS) are poorly understood. Objective To investigate the cross-correlation between spine and hip joint kinematics differs in healthy individuals and ankylosing spondylitis patients during trunk lateral flexion. Methods Fifty AS patients and thirty-nine healthy adults (controls) were recruited from a medical center. The patients were divided into two subgroups, namely the sacroiliitis (n = 28) and syndesmophyte (n = 22) subgroups. An inertial motion system was used to record kinematic data of spine, pelvic and hip joints during lateral trunk flexion. The maximal cross-correlation coefficient (CCF) and time lag of motion between the spine and hip joint were analyzed. Results The syndesmophyte group had the smallest range of motion in all recorded motion. The sacroiliitis group exhibited higher thoracic flexion, pelvic pitch, and pelvic rotation than the other two groups. In the syndesmophyte group, the CCF between lumbar lateral flexion (LLF) and hip abduction were weakly and LLF and hip rotation were strongly correlated. Considering in time sequence, LLF occurred earlier than hip abduction and hip rotation during trunk lateral flexion; however, both AS subgroups exhibited longer time lags than in the control group. Conclusion The cross-correlation between spine and hip joint kinematics differs in healthy individuals and AS patients during trunk lateral flexion. The motion pattern changes in patients with AS of differing severity may also alter the loads on the spine and hip joints.

We report the case of a 57-year-old man who presented at the emergency department with injuries to his face and head after falling down the stairs. A head computed tomography examination done because he complained of an intense headache revealed air bubbles in the retropharyngeal space. Given this finding, a computed tomography of the neck was done to evaluate the possibility of pharyngeal perforation. Traumatic pharyngeal perforations are uncommon, but those caused by the calcification of the anterior longitudinal ligament, as in our case, are even more uncommon.

Objective: To investigate whether the impact of long-term treatment (> 3 years) with TNF inhibitors (TNFi) on radiographic progression in AS is associated with the level of acute phase reactants during therapy. Methods: One hundred and one consecutive AS patients under TNFi [65 men; age: 41.6 ± 11 years (mean ± SD), with symptom duration: 17 ± 10 years] were included in this retrospective study. Lateral X-rays of cervical and lumbar spine, obtained before TNFi initiation, were compared to those obtained after a period of 7 ± 2.5 (range: 3–15) years. The levels of CRP and ESR were evaluated every 6 months. The modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) assessed the radiographic damage. New syndesmophyte formation or ΔmSASSS-score/year ≥ 1 unit/year was defined as radiographic progression. Results: Forty-seven patients (46.5%) showed radiographic progression. ΔmSASS-score/year was positively correlated with both, baseline CRP (r = 0.35, P < 0.001) and ESR (r = 0.3, P < 0.01), as well as with time-averaged CRP (r = 0.3, P < 0.01). Furthermore, ΔmSASS-score/year was significantly higher (P < 0.0001) in patients with syndesmophytes at baseline [0.9 (0.4–1.8), median (IQR)] compared to those without [0 (0–0.4)]. In the multivariate logistic regression analysis, independent risk factors for spinal radiographic progression during TNFi treatment were the presence of syndesmophytes at baseline (OR: 14.7, 95%CI:4.9–44) and the time-averaged CRP > 5 mg/L (OR:7.6, 95%CI: 2.5–23). No gender differences were observed. Conclusion: In AS patients with long standing disease, radiographic progression during TNFi treatment is significantly associated with higher levels of time-averaged CRP.

Patients with spondyloarthritis (SpA) have an elevated incidence of osteoporosis and are at increased risk of pathological vertebral fracture. Evaluation of bone density by dual energy X-ray absorptiometry (DXA) has its limits in fracture prediction, already known in this population. One hypothesis is that the presence of lumbar syndesmophyte could overestimate the spine bone mineral density (BMD). Trabecular bone score (TBS) is a new texture measurement correlated with bone microarchitecture. Previous studies have shown that TBS is mildly impacted by osteoarthritis and thus could be a predictor of fracture better than spine BMD. We aimed to evaluate a male population of SpA with BMD and TBS measurement and see the impact of lumbar syndesmophytes.Two cohorts of SpA male patients (Lausanne, Sofia) with SpA disease, clinical and bone parameters (femoral neck and total spine BMD+spine TBS) were merged. We compared BMD and TBS results regarding to the presence/absence of syndesmophytes.Our study concerned 51 men [29 with lumbar syndesmophytes (L1 to L4,≥1), 22 without], fulfilling the European Spondyloarthropathy Study Group (ESSG) and the Assessment of SpondyloArthritis international Society (ASAS) criteria. Mean age was 52.18 years old (no difference between the 2 groups) and mean body mass index (BMI) 27.47kg/mOur results showed that SpA men with and without syndesmophytes have lower results compared to the normal population regarding hip BMD, spine TBS and spine BMD except for men with syndesmophytes who have a normal BMD spine T-score. These results suggest that TBS is not influenced by the syndesmophytes in opposite to spine BMD and could be measured in this population in addition to the neck BMD to assess the bone fragility.

Objective Uveitis is a frequent extra rheumatological manifestation in axial Spondyloarthritis (SpA). The aim of study was to evaluate the prevalence and incidence of uveitis over the first five years of a prospective nationwide cohort of patients with high suspicion of early axial SpA, and to evaluate its associated factors. Methods DESIR is a prospective observational cohort of patients with recent onset inflammatory back pain (more than 3 months, less than 3 years), suggestive of axial SpA, All available factors in the database were compared between patients with and without uveitis at 5 years, by uni and then multivariate analysis. Baseline factors associated with new cases of uveitis occurrence over the 5 years were also analyzed. Significance: P less than 0.05. Results After 5 years, 91 patients (out of 480 with complete follow-up) had at least one uveitis episode, giving an estimated prevalence of 18.9% [95% CI: 15.4–22.4]. In multivariate analysis, uveitis was significantly associated with dactylitis, and elevated ESR. New incident uveitis occurred in 31 cases over 5 years, giving an estimated incidence rate of 1.29 [0.84–1.74]/100 patient-years. Incidence of new uveitis was associated in multivariate analysis with baseline factors: diagnosis of SpA, sacro iliac MRI inflammatory SPARCC score, dactylitis, syndesmophyte score. No significant association was found with HLA-B27, DMARDs, BASDAI, ASDAS, BASFI. Conclusion Five-years data of the DESIR cohort allowed an estimation of incidence rate of uveitis of 1.3/100p-y; over five years, uveitis was associated with dactylitis, biologic and sacro iliac MRI inflammation.

Objectives To better understand the effect of TNF-α inhibitors (TNFi) on new bone formation in ankylosing spondylitis (AS) patients. Methods We systematically searched the articles in EMBASE and PubMed. Results Fifteen articles were enrolled. In all the 9 TNFi-treated cohorts, the vertebral corners with inflammatory lesions at baseline were at higher risk to develop new syndesmophytes than those without inflammatory lesions, although a few syndesmophytes also developed at the vertebral corners without inflammatory lesions at baseline. The advanced inflammatory lesions including fat deposition on baseline MRI showed a higher risk for syndesmophyte formation than the acute inflammatory lesions. Because the number of analyzed vertebral corners were too small, it might not be true that new syndesmophytes developed more frequently at the corners with inflammatory lesions completely resolved than those with persistent inflammation after TNFi treatment. Four studies with 2-year follow-up revealed null effect of TNFi on radiographic progression compared with historical controls with lower disease activity, and 3 studies with ≥ 4-year follow-up proved inhibitory effect of TNFi on new bone formation in AS patients. Patients with a delay of > 10 years in starting TNFi therapy were more likely to experience radiographic progression as compared to those who started earlier. Conclusions In TNFi treated AS patients, baseline inflammation is linked with syndesmophyte development. An earlier initiation of TNFi therapy may slow the radiographic progression in AS, and TNFi may lose its benefit of retarding new bone formation at advanced stage of AS especially after the focal fat infiltration or syndesmophyte formation.

New bone formation of the entheses with possible progression to ankylosis is among the hallmarks of axial spondyloarthritis. Radiographic scores are available for evaluating axial new bone formation. The complex systems that underlie new bone formation involve Wnt bone-formation signaling and the natural Wnt inhibitors DKK-1 and sclerostin, as well as growth factors such as the bone morphogenetic proteins (BMPs); these systems are modulated by proinflammatory cytokines, most notably TNF. Factors that predict progressive new bone formation include the presence of syndesmophytes, various biological markers (CRP, MMP-3, sclerostin, DKK-1, and BMP), smoking, and prior vertebral corner abnormalities (inflammation and, above all, resolved inflammation). Nonsteroidal antiinflammatory agents seem able to slow the pace of radiographic progression, an effect not documented to date with TNF antagonists in patients with axial spondyloarthritis.

Objectives: To analyze the clinical features of uveitis in psoriatic arthritis (PsA) and to investigate the factors predicting its appearance. Patients and Methods: Retrospective cohort study (1991-2000) of 71 patients diagnosed with PsA according to the criteria of Moll and Wright. All patients were studied according to a standard protocol. The group was divided into 3 articular categories: axial, oligoarticular, and polyarticular. Human leukocyte antigen (HLA)-Cw typing was performed by the polymerase chain reaction–sequence specific oligonucleotide probes (PCR-SSOP) method in 65 patients and in 177 healthy donors. HLA-DR typing was done by serologic methods in the 71 patients and in 82 healthy donors from the same racial and geographic origin. The HLA-B27 allele also was tested among the study population. All subjects with possible inflammatory ocular disease received a complete ophthalmologic examination at the Ophthalmology Department of our hospital. Only patients with uveitis were analyzed. Univariate and multivariate analyses were applied. Results: Thirteen patients had uveitis (18% of this series), 4 (31%) had an insidious onset, and the remaining had acute-onset uveitis. Five cases (39%) had bilateral-simultaneous uveitis. Ten (77%) presented with anterior uveitis only, 2 with anterior and posterior pole involvement, and only 1 case with isolated posterior pole involvement. Four patients needed oral corticosteroids; 2 of them also used immunosuppresive drugs. None of our patients developed sequelae or complications. In univariate analysis, uveitis was associated with inflammatory back pain ( P =.02), sacroiliac pain ( P =.001), syndesmophytes ( P =.001), bilateral sacroileitis ( P =.0001), HLA-DR13 ( P =.002), and HLA-B27 ( P =.026). In multivariate analysis, the predictive factors for uveitis were bilateral sacroileitis (OR 17, 95% CI: 3.7-76, P =.0002), HLA-DR13 (OR 24, 95% CI: 3.78-150, P =.0056), and syndesmophytes (OR 9.7, 95% CI: 0.97-97, P =.05). Conclusions: Insidious onset, bilaterality, posterior pole involvement, and chronicity are common in PsA patients with uveitis. In this study, extensive axial involvement (bilateral sacroileitis and syndesmophytes), and the HLA-DR13 antigen were the best predictors for the appearance of uveitis. Semin Arthritis Rheum 31:264-270. Copyright 2002, Elsevier Science (USA). All rights reserved.

This article examines some fundamental features of the histopathology of ankylosing spondylitis (AS) such as inflammation in the entheses and syndesmophyte formation. This may be linked to the generation of transforming growth factor in inflammation, which can stimulate bone formation, and to the molecular composition of entheses where molecules are present, such as the proteoglycan aggrecan, that are normally found in cartilage. Immunity to these molecules is observed in patients with AS and in experimental immunity to aggrecan, or the G1 domain only, which can cause spondylitis. Involvement of other tissues (the eye and arterial vessels) may be due to crossreactive immunity.