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Objective: This study aimed to determine the prevalence of the ossification of the ligamenta flava (OLF) among skeletal remains from Poland., Materials and Methods: 124 skeletons aged 25 years and older were analyzed. The presence and size of OLF were observed macroscopically. OLF was recorded at the cranial and caudal attachment sites of each vertebra. The following factors were analyzed: age at death, sex, and presence of other spondyloarthropathies., Results: The crude prevalence of OLF in the analyzed series was 68.55 %. OLF was located most frequently in the lower thoracic spine. A statistically significant relationship was observed between the presence of OLF and age at death. OLF coincided with degenerative spondyloarthropathies of the thoracolumbar spine., Conclusions: The results of this study indicate that OLF was not a rare condition in past populations of European ancestry. Analysis of OLF prevalence in skeletal materials can contribute to reconstruction of the conditions and lifestyles of past people., Significance: This study shed new light on the prevalence of OLF and provides information on the variability of OLF in past European populations. The evaluation of the prevalence of OLF represents an important contribution to the field of paleopathology in understanding disease changes in prehistoric and historic human populations., Limitations: The analyzed material came from unknown populations without demographic data. Sex and age at death were assessed using standard anthropological methods., Suggestions for Further Research: It is important to understand the influence of sociocultural factors and physical activity patterns on the development of OLF., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: In radiographic axial spondyloarthritis (r-axSpA), spinal damage manifests as syndesmophytes and facet joint ankylosis (FJA). We evaluated whether the presence of one lesion increased the risk of the other lesion., Methods: Patients with r-axSpA underwent low-dose CT (ldCT) and MRI of the whole spine at baseline and 2 years. On ldCT, vertebrae were scored for presence and size of syndesmophytes; facet joints were assessed for ankylosis. MR images were assessed for inflammation. Two hypotheses were tested: (i) presence of FJA is associated with new syndesmophyte(s) on the same vertebral unit (VU) 2 years later, and (ii) presence of bridging syndesmophyte(s) is associated with new FJA on the same VU 2 years later. Two generalized estimating equations models were tested per hypothesis using increase of FJA/syndesmophytes (model A) or presence of FJA/syndesmophytes (model B) as outcome, adjusted for inflammation at baseline. Secondary analyses tested the hypotheses with outcomes on adjacent VUs and dose-response effects., Results: Fifty-one patients were included (mean age 49, 84% male, 82% HLA-B27+). Baseline bridging syndesmophytes occurred more often (range: 10-60% per VU) than FJA (range: 8-36%). Odds ratios (ORs) (95% CI) for presence of bridging syndesmophytes on development of FJA were 3.55 (2.03, 6.21) for model A and 3.30 (2.14, 5.09) for model B. ORs for presence of baseline FJA on new syndesmophytes were 1.87 (1.20, 2.92) for model A and 1.69 (0.88, 3.22) for model B. Secondary analyses yielded positive ORs for both hypotheses., Conclusions: Bone formation in vertebrae and in facet joints influence each other's occurrence, with the effect of syndesmophytes being larger than that of FJA., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Aim: To evaluate the effect of subchondral oedema in T2-weighted Dixon magnetic resonance imaging (MRI) sequence evaluation of sacroiliac joint erosion in patients with axial spondyloarthropathy., Materials and Methods: Twenty patients diagnosed with axial spondyloarthritis underwent MRI at a tertiary referral centre from December 2019 to March 2021 were included. In-phase, opposed-phase and fat-only images were scored by two musculoskeletal radiologists independently for the presence of erosions in eight sacroiliac joint quadrants. Sensitivity, specificity and areas under the curve (AUC) of the receiver operating characteristic curve were determined using T1W sequence as reference standard. Intra-observer and interobserver reliability were calculated using Cohen's kappa coefficient., Results: The diagnostic performance of fat-only and in-phase images were similar (AUC 0.857-0.902 and 0.828-0.868) and better than opposed-phase images (AUC 0.613-0.658). The interobserver reliability of fat-only and in-phase images were substantial (k = 0.747 and 0.712), and moderate for opposed-phase images (k = 0.417). Intra-observer reliability was almost perfect for all the images. In the subgroup analysis, the specificity and AUC for oedema-positive group were lower than oedema-negative group in all image sets. Interobserver reliability was substantial for fat-only and in-phase images in both groups, but slight and moderate for the opposed-phase oedema-positive and negative groups, respectively., Conclusion: The presence of subchondral oedema in active sacroiliitis decreased the diagnostic accuracy of sacroiliac joint erosion detection on T2W Dixon MRI images., (Copyright © 2022 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aim: To test the diagnostic efficacy of a multiparametric rheumatology lumbosacral magnetic resonance (MR) imaging protocol in detection and characterization of axial spondylarthritis (SpA) and compare it with serology and clinical findings., Methods: A consecutive series of multiparametric rheumatology lumbosacral MR imaging examinations performed on 3T MR scanner. Three-dimensional inversion recovery turbo spin echo, precontrast and postcontrast fat-suppressed T1-weighted images, as well as diffusion-weighted images were used to detect active erosions and enthesitis using established criteria. Pearson χ2 was used for categorical variables. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were measured for magnetic resonance imaging (MRI) and serology, based on the final diagnosis from rheumatologists. An alpha error below 0.05 was considered statistically significant., Results: The final study sample included 130 consecutive patients (80 women and 50 men; mean ± SD 44 ± 13 and 45 ± 14 years, respectively). Seventy-eight subjects were diagnosed with axial SpA and 52 with non-SpA arthropathy. In the non-SpA group, 27 patients were diagnosed with osteoarthritis, 6 had unremarkable imaging, whereas 19 were considered as clinically undetermined. There was positive correlation between positive MRI results and SpA diagnosis (P < 0.00001). No correlation existed between positive serology alone and SpA diagnosis (P = 0.0634). Although MRI and serology proved equally sensitive in detecting SpA, the specificity and overall accuracy of MRI were significantly higher. Inflammatory activity was detected in 45 (57.7%) cases, in the pelvic enthesis in 29 (37.2%) cases, in the lumbosacral spine in 16 (20.5%) cases, in the hip joints in 15 (19.2%) cases, and in the pubic symphysis in 5 (6.4%). Inactive sacral disease was seen in 7 of 35 enthesitis patients (20.0%), and in 2 SpA cases, there were no sacral lesions., Conclusions: The results suggest that in patients with suspected SpA, MRI should not be limited to the sacroiliac joints, but also include enthesitis sites and other joints of the axial skeleton. The multiparametric rheumatology protocol increases the efficacy of MRI in detecting enthesitis and joint inflammatory disease, thereby offering additional information to the clinician and assisting in the early diagnosis/detecting disease activity., Competing Interests: Disclosures: A.C. serves as a consultant to ICON Medical and Treace Medical Concepts, Inc, and has received a grant from and is a medical advisor for Image biopsy Lab Inc. A.C also receives royalties from Jaypee and Wolters, and serves as a speaker for Siemens. The remaining authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are associated with changes in body composition. Ectopic intramuscular fat (IMAT) may alter muscle function and contribute to cardiometabolic disorders. In a pilot study, we analyzed IMAT in the calf with peripheral quantitative computed tomography (pQCT) and examined correlations between IMAT quantity and body composition parameters. In 20 patients with active RA and 23 with active SpA, IMAT was correlated with visceral fat (VAT; r = 0.5143 and 0.6314, respectively; p < 0.05) and total lean mass (r = 0.5414 and 0.8132, respectively; p < 0.05), but not with whole body fat mass. Total lean mass mediated 16% and 33% of the effects of VAT on IMAT in RA and SpA, respectively. In both RA and SpA, calf muscle area was correlated with total lean mass (r = 0.5940 and r = 0.8597, respectively; p < 0.05) and fat area was correlated with total body fat (r = 0.6767 and 0.5089, respectively; p < 0.05) and subcutaneous fat (r = 0.6526 and 0.5524, respectively; p < 0.05). Fat area was inversely correlated with handgrip and walking tests, and it was associated with disease activity and disability. We showed that ectopic IMAT, measured with pQCT, was correlated with VAT, but not with total body fat, in RA and SpA. This result suggests that metabolically active fat was specifically associated with IMAT.

Objective: To compare immune cell phenotype and function in psoriatic arthritis (PsA) versus psoriasis in order to better understand the pathogenesis of PsA., Methods: In-depth immunophenotyping of different T cell and dendritic cell subsets was performed in patients with PsA, psoriasis, or axial spondyloarthritis and healthy controls. Subsequently, we analyzed cells from peripheral blood, synovial fluid (SF), and skin biopsy specimens using flow cytometry, along with high-throughput transcriptome analyses and functional assays on the specific cell populations that appeared to differentiate PsA from psoriasis., Results: Compared to healthy controls, the peripheral blood of patients with PsA was characterized by an increase in regulatory CD4+ T cells and interleukin-17A (IL-17A) and IL-22 coproducing CD8+ T cells. One population specifically differentiated PsA from psoriasis: i.e., CD8+CCR10+ T cells were enriched in PsA. CD8+CCR10+ T cells expressed high levels of DNAX accessory molecule 1 and were effector memory cells that coexpressed skin-homing receptors CCR4 and cutaneous lymphocyte antigen. CD8+CCR10+ T cells were detected under inflammatory and homeostatic conditions in skin, but were not enriched in SF. Gene profiling further revealed that CD8+CCR10+ T cells expressed GATA3, FOXP3, and core transcriptional signature of tissue-resident memory T cells, including CD103. Specific genes, including RORC, IFNAR1, and ERAP1, were up-regulated in PsA compared to psoriasis. CD8+CCR10+ T cells were endowed with a Tc2/22-like cytokine profile, lacked cytotoxic potential, and displayed overall regulatory function., Conclusion: Tissue-resident memory CD8+ T cells derived from the skin are enhanced in the circulation of patients with PsA compared to patients with psoriasis alone. This may indicate that aberrances in cutaneous tissue homeostasis contribute to arthritis development., (© 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: The Assessment of SpondyloArthritis international Society health index (ASAS-HI) was designed to assess the global health of patients with spondyloarthritis, but its performance in psoriatic arthritis (PsA) is hardly known. We addressed the clinimetric properties of this instrument in patients with PsA., Methods: This was a cross-sectional observational study that included 90 consecutive patients with PsA. The measurement properties of ASAS-HI were analysed against the Disease Activity index for PSoriatic Arthritis (DAPSA) and the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire. A multivariate analysis was performed to weigh the ASAS-HI items associated with DAPSA active disease and PsAID high impact., Results: Mean ASAS-HI was 5.8 (4.3). Convergent validity was high both against DAPSA (ρ 0.78, P < 0.0001) and PsAID (ρ 0.80, P < 0.0001). ASAS-HI showed a high discriminant capacity for both DAPSA remission [optimal criterion ≤ 2, area under the receiver operating characteristic curve (AUC) 0.92 (95% CI: 0.85, 0.97), P < 0.0001], and low activity [optimal criterion ≤6, AUC 0.87 (95% CI: 0.79, 0.94), P < 0.0001]. The ASAS-HI items significantly associated with DAPSA active disease were: 'I find it hard to stand for long' (β 4.48, P < 0.0001), 'I find it hard to concentrate' (β 2.94, P = 0.042) and 'I sleep badly at night' (β 1.86, P = 0.044). As for PsAID, the only item significantly associated with a high impact was 'I sleep badly at night' (β -3.29, P = 0.015)., Conclusion: We demonstrated construct validity of ASAS-HI, a spondyloarthritis instrument, for the assessment of global health in patients with PsA., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Activation of the coagulation system has been related to disease activity in some inflammatory diseases. Here, we aimed to investigate the relationship between coagulation function and the disease activity of axial spondyloarthritis (axSpA)., Methods: This study retrospectively recruited 144 axSpA patients and 55 healthy controls. The patients were divided into an active group (Bath Ankylosing Spondylitis Disease Activity Index, BASDAI ≥ 4) and a remission group (BASDAI < 4). The coagulation, inflammatory and clinical parameters were detected. The correlations between these parameters were analyzed with Spearman's correlation analysis. Receiver operating characteristic (ROC) curve analysis was performed to compare the values of these variables in discriminating disease activity. Furthermore, binary logistic regression analysis was used to assess the risk factors for axSpA disease activity., Results: Fibrinogen (FIB) was increased in the axSpA group compared to healthy controls (P < 0.001). Additionally, FIB and D-dimer were higher in the active group than in the remission group (P < 0.05, respectively). FIB and D-dimer were positively correlated with ESR, CRP, BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) (P < 0.05, respectively). The area under the curve (AUC) of FIB was higher than that of ESR, CRP and D-dimer. The optimal cut-off value of FIB was 3.23 g/L, with a specificity of 62.0% and sensitivity of 75.0%. FIB (OR = 4.335, 95% CI: 1.262-14.888, P = 0.020) and BASFI score (OR = 1.878, 95% CI: 1.441-2.448, P < 0.001) were independent risk factors affecting disease activity., Conclusion: Activated coagulation is closely related to the disease activity of axSpA. FIB and D-dimer might be novel indicators for monitoring the disease activity of axSpA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: To identify the incidence of spinal-only changes (including both acute inflammatory and chronic structural changes) in patients with suspected spondyloarthropathy (SpA) to determine whether MRI of the sacroiliac joints would be sufficient in the initial radiological work-up and whether the number of spinal magnetic resonance imaging (MRI) examinations performed could be reduced., Materials and Methods: This was a retrospective study of patients with suspected SpA referred from the rheumatology department of a university teaching hospital undergoing MRI both of the whole spine and of the sacroiliac joints over a 3-year period. Imaging was assessed for the presence of acute inflammatory and chronic structural changes., Results: Three hundred and sixty-five patients with suspected SpA undergoing both whole spine and sacroiliac joint MRI were identified. The majority (79.2%) had no spinal or sacroiliac joint inflammation. Spinal-only changes (acute inflammatory and/or chronic structural) were detected in only 0.8% (3/365) of cases. The majority of positive spinal cases had inflammatory changes involving the thoracic spine (21/24). The majority of positive sacroiliac joint cases were bilateral (51/73)., Conclusion: The extremely low incidence of spinal-only inflammatory or structural change indicates that sacroiliac joint MRI may be sufficient for initial radiological work-up of SpA with spinal MRI reserved for instances where there is spinal symptomatology and uncertainty in the clinical diagnosis following interdisciplinary discussion or where a baseline is required., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

Purpose: To confirm the interest of 3-dimensional ultrashort echo-time (3D-UTE) sequences to assess morphologic aspects in normal and pathological Achilles entheses in a rat model of spondyloarthropathy (SpA) with histological correlations, in comparison with conventional RARE T2 Fat-Sat sequences, and, furthermore, to evaluate the feasibility of a 3D multiecho UTE sequence performed before and after the intravenous injection of ultrasmall superparamagnetic iron oxide (USPIO) particles to assess macrophagic involvement in the Achilles enthesis in the same rat model of SpA., Materials and Methods: Fourteen rats underwent in vivo MRI of the ankle at 4.7 T, including a 3D RARE T2 Fat-Sat sequence and a 3D ultrashort echo-time (UTE) sequence for morphologic assessment at baseline and day 3 after induction of an SpA model, leading to Achilles enthesopathy in the left paw (right paw serving as a control). A 3D multiecho UTE sequence was also performed at day 3 before and then 24 (4 rats) and 48 (2 rats) hours after intravenous injection of USPIO. Visual analysis and signal intensity measurements of all images were performed at different locations of the Achilles enthesis and preinsertional area. Visual analysis and T2∗ measurements were performed before and after USPIO injection, on the 3D multiecho UTE sequence in the same locations. Normal and pathological values were compared by Wilcoxon signed-rank tests. MR findings were compared against histological data., Results: 3D-UTE sequences enabled morphologic identification of the anterior fibrocartilage and posterior collagenic areas of the Achilles enthesis. Visual analysis and signal intensity measurements distinguished SpA-affected entheses from healthy ones at day 3 ( P =0.02). After administration of USPIO, no differences in signals were detected. Similarly, both visual analysis and signal T2∗ measurements in the enthesis were unable to distinguish the SpA-affected tendons from healthy ones ( P =0.914). Neither the normal anatomy of the enthesis nor its pathological pattern could be distinguished using the standard RARE sequence. Histology confirmed the absence of USPIO in Achilles entheses, despite marked signs of inflammation., Conclusion: Unlike conventional RARE T2 Fat-Sat sequences, 3D-UTE sequences enable morphologic assessment of normal enthesis anatomy and early detection of abnormalities in pathological conditions. However, 3D multiecho UTE sequences combined with USPIO injections with T2∗ measurements were unable to detect macrophagic involvement in these pathological conditions.

Objectives: To study the presence of high signal intensity of the intervertebral disc, syndesmophytes, vertebral corner bridging and transdiscal ankylosis on spinal T1-weighted MR images in spondyloarthritis (SpA)., Methods: A retrospective case-control study of whole spine MRI examinations, obtained in 100 patients with axial SpA and in 100 control patients, was performed. All disco-vertebral units (DVUs) were analyzed on T1-weighted MR images for normal or high signal intensity of the intervertebral disc, presence of syndesmophytes, vertebral corner bridging or transdiscal ankylosis and correlated with final diagnosis. Sensitivity, specificity, and positive and negative likelihood ratios were calculated., Results: In this study group, intradiscal high signal intensity, vertebral corner bridging and transdiscal ankylosis on T1-weighted MR images of the spine were all highly specific (specificity: 100%) for diagnosis of axial SpA. However, these signs all had low sensitivity (vertebral corner bridging: 15.0%; intradiscal high signal intensity on T1-weighted MR images: 12.0%; transdiscal ankylosis: 8.0%). Syndesmophytes on spinal MRI were observed in 25 patients but had a more limited diagnostic value (sensitivity: 16.0%, specificity: 91.0%)., Conclusions: When present in a patient with inflammatory back pain, intradiscal high signal intensity on T1-weighted MR images could be a specific and reliable sign of the presence of axial SpA. Vertebral corner bridging and transdiscal ankylosis also show potential as specific and reliable signs of axial SpA. In contrast, syndesmophytes on MRI do not show potential as a specific or reliable sign of axial SpA., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Genetic investigations on ancient human remains affected by rheumatological pathologies are a research field of particular interest for identifying the pathogenesis of diseases, especially those having an autoimmune background such as spondyloarthopaties (SpA). Reliable studies concerning this topic require collaboration between multiple disciplines, usually starting from paleopathologic observations up to molecular genetic screening. Here, we focused our investigation in a medieval necropolis in the Basque Country (13th-15th century, N = 163), which presents a high frequency of joint pathologies through two approaches: on the one hand, the analysis of joint manifestations for the differential diagnosis of the SpA and, on the other hand, the determination of the alleles of the HLA-B gene. The morphological analysis allowed determining that 30% of the individuals had rheumatic bone manifestations, with SpA being the most frequent (45%). The genetic analysis of individuals with and without pathologies, based on the study of the HLA-B gene, allowed finding 17 alleles for this gene, with HLA-B40, HLA-B27 and HLA-B35 being the most frequent. Although these alleles have been traditionally described as genetic markers associated to the development of SpA, in this study they were also found in individuals with other rheumatic diseases (osteoarthritis and rheumatoid arthritis) and even in individuals without pathologies. These data confirm the complexity of the relationship of the HLA-B gene variants with SpA, since it is not possible to establish a diagnosis of SpA with these variants alone. However, we suggest that allele HLA-B40, in combination with some specific rheumatic bone manifestations, facilitates the diagnosis of SpA., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Inflammatory arthritis is documented for the first time in snakes. Ossification of the intervertebral capsule and zygapophyseal joints resulting in segmental vertebral fusion was observed in the aquatic Cretaceous snake Lunaophis aquaticus. Such pathologic alterations are pathognomonic for the spondyloarthropathy form of inflammatory arthritis. A survey of 2144 snakes in recent collections, performed to identify Holocene prevalence, revealed only two occurrences in extant snakes. The findings in Bitis gabonica and Elaphe taeniura were indistinguishable from those noted in Lunaophis aquaticus and identical to those previously recognized in modern varanids. The pathology likely represents a form of reactive arthritis related to enteropathic infection. While the disease probably did not affect general locomotion, its vertebral column position may have compromised mating.

Ossification of the ligamentum flavum of the spine (OLF) is rarely reported in individuals of European ancestry. It has, however, been observed in archaeological skeletons from Europe. The aim of this study was to revisit OLF rates, utilising a mid-nineteenth-century skeletal sample from Ireland. The hypothesis was that the OLF prevalence rate was similar to studies on non-Europeans. Spines from 345 individuals were analysed, and the extent of OLF recorded on the cranial and caudal attachment sites of each vertebra using the following classification system: Grade 0 (no change); Grade 1 (<2 mm); Grade 2 (2-4 mm); Grade 3 (≥4 mm). OLF was observed at prevalence rates of 83.6%. There was no disparity in prevalence based on sex, except for individuals aged 36-45 years at death in which the male rate was higher. Advancing age was a determining factor in the OLF occurrence with an onset in young adulthood (18-25 years), and most severe grades occurring over the age of 25 years. OLF coincides with spinal osteoarthritis, spondylosis deformans and Schmorl's nodes in both sexes, and with intervertebral osteochondrosis in females. The results of this study indicate that OLF is likely to be an understudied rather than rare condition in European populations.

Introduction: The prevalence of Sjögren's syndrome (SS) in patients with the diagnosis of SpA has been reported to be higher than normal population. Yet, the vice-versa is unclear. In this study, we aimed to investigate the prevalence of IBP, radiologic sacroiliitis and SpA in patients with primary SS., Methods: 85 patients followed at the rheumatology clinics of the Marmara and Kocaeli Universities with the diagnosis of primary SS between November 2011 and August 2012 were included in this study. The control group consisted of 100 age-and gender-matched patients. Inflammatory back pain and axial SpA were diagnosed according to the assessment of spondylo arthritis International Society (ASAS) criteria., Results: 83 patients were (97%) female and 2 (3%) were male. Mean age of the patients was 49.1 (±11) years. Mean disease duration was 7.3 (±4) years. The patient and control groups were comparable in terms of age and gender (p > 0.05). Inflammatory back pain was observed in 21 (24.7%) of 85 primary SS patients and in 4 (4%) of 100 control subjects (p < 0.001), radiographic sacroiliitis was demonstrated in 9 (10.5%) of primary SS patients and 2 (2%) of the control subjects (p = 0.025). Remaining SpA findings were not encountered in either group., Conclusion: inflammatory back pain and radiologic sacroiliitis is increased in patients with primary SS. Whether IBP, SI joint inflammation and radiologic sacroiliitis is due to the co-existence of SpA and primary SS or IBP is an underdiagnosed clinical feature of SS deserves further studies of large patient numbers.

Objective: Inflammatory bowel disease (IBD) is generally reported to be associated with spondylarthropathies (SpA) in 5%-15% of cases. Systematic colonoscopic assessment by protocol demonstrated mucosal inflammation characteristic of Crohn disease (CD) in up to one-third of patients with SpA. Video capsule endoscopy (CE) is a superior diagnostic tool to detect small bowel mucosal disease. Our study compared the accuracy of CE to standard colonoscopy for detection of inflammatory bowel lesions in patients with SpA, and to describe predictors of small bowel inflammation (SBI) in this cohort., Methods: Prospective cross-sectional study of adult patients followed for SpA. Patients were evaluated by CE and standard colonoscopy with biopsies. SBI was quantified using the Lewis Score. Additional screening tests included fecal calprotectin (FCP), C-reactive protein (CRP), and a diagnostic panel of serologic, inflammatory and genetic tests (SGI)., Results: There were 64 patients recruited (53% female, mean age 42 ± 13 yrs). Chronic gastrointestinal (GI) symptoms were present in 57%. CE revealed significant SBI in 27/64 (42.2%), compared to 7/64 (10.9%) by standard colonoscopy (p = 0.035). Elevated FCP was associated with small bowel CD (OR 4.5, 95% CI 1.01-19.9; p = 0.042). No correlation was observed with presence of GI symptoms, CRP, or SGI results. Finding CD led to a change in management in 65.2% of cases., Conclusion: CE uncovered SBI consistent with CD in 42.2% of patients with SpA, with a significant incremental yield over colonoscopy of 31%. FCP levels were significantly correlated with CE results, while GI symptoms and SGI results were poor predictors of SBI.

This report describes two adjacent, longitudinally-fused anterior cervical vertebrae from a basal archosauromorph. The specimen was collected from the Denwa Formation, Satpura Gondwana Basin, India. The differential diagnosis of the fusion includes genetic or environmentally-mediated congenital malformations, nonspecific spondyloarthopathy, and various infectious agents. These observations represent the first published recognition of archosauromorph vertebral pathology from specimens that were discovered in India. The observations affirm that basal archosauromorphs suffered from disorders that have been observed in later dinosaurs and modern-day vertebrates. Considering the process of orderly differential diagnosis is an important aspect of understanding lesions of ancient bones., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Spondyloarthropathies, the second most frequently occurring form of chronic inflammatory arthritis, affects young adults in particular. However, a proper model with which to study the biology of this disease and to develop therapeutics is lacking. One of the most accepted animal models for this disease uses HLA-B27/Hu-β2m transgenic rats; however, only 30%-50% of male HLA-B27/Hu-β2m rats develop spontaneous, clinically apparent spondylitis and have a variable time until disease onset. Here, we report a high-incidence, low-variation spontaneous mouse model that delineates how the combination of inflammatory cytokine interleukin-27 (IL-27) signaling deficiency and mitogenic signaling (mutant p53R172H) in vivo, leads to bone loss in the vertebral bodies and ossification of the cartilage in the intervertebral discs. In this human disease-like mouse model, bone loss and pathogenic bone development are seen as early as 4 months of age in the absence of inflammatory aggregates in the enthesis or intervertebral disc.

The present study is focused on a group of arthropathies that may have very similar bone manifestations (rheumatoid arthritis, ankylosing spondylitis, reactive arthritis, psoriatic arthritis, osteoarthritis and diffuse idiopathic skeletal hyperostosis), which makes it more difficult to diagnose them in human remains from archaeological contexts. A stepwise recording form was designed in order to improve the identification and differential diagnosis of these pathological conditions in bone remains, particularly in joint manifestations of the spine, pelvis, hands, feet and other limb joints. This recording form was applied in the analysis of two medieval individuals from the Basque Country (Spain) who presented very severe arthropathic manifestations. The use of this recording form allowed the researchers the diagnosis of ankylosing spondylitis in one of them and diffuse idiopathic skeletal hyperostosis in the other., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Considerable progress has been made recently in understanding the complex pathogenesis and treatment of spondyloarthropathies (SpA). Currently, along with traditional disease modifying anti-rheumatic drugs (DMARDs), TNF-α, IL-12/23 and IL-17 are available for treatment of such diseases as ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Although they adequately control inflammatory symptoms, they do not affect the abnormal bone formation processes associated with SpA. However, the traditional therapeutic approach does not cover the regenerative treatment of damaged tissues. In this regards, stem cells may offer a promising, safe and effective therapeutic option. The aim of this paper is to present the role of mesenchymal stromal cells (MSC) in pathogenesis of SpA and to highlight the opportunities for using stem cells in regenerative processes and in the treatment of inflammatory changes in articular structures., Competing Interests: The authors declare no conflict of interest.

The IL-17/1L-23 axis is important in the pathogenesis of spondyloarthropathy. Innate cells produce IL-17 in addition to Th17 cells. We studied the frequencies of natural killer (NK) (total, CD56 bright , CD56 dim , perforin+ and granzyme+), NK-T, γδ-T, and IFN-γ+, IL-17+ NK and γδ-T cells in peripheral blood (PB) and synovial fluid (SF) of ReA/uSpA patients. PB from 45 patients and paired SF from 39 patients were studied, together with PB from 18 healthy controls (HC). The frequency of γδ-T cells was decreased (p<0.05) while IL-17 producing NK and γδ-T cells were increased (p<0.05) in PB of patients as compared to HC. In SF, CD56 bright NK cells were increased (p<0.001) but had reduced expression of perforin and granzyme (p<0.0001) as compared to PB. Frequency of IL-17+, IFN-γ+ NK and γδ-T cells was higher in SF as compared to PB (p<0.05). We suggest that innate cells by producing pro-inflammatory cytokines may contribute to pathogenesis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The spondyloarthritides (SpA) are a group of rheumatic diseases characterized by ossification and inflammation of entheseal tissue, the region where tendon attaches to bone. Interleukin-23 (IL-23) is involved in the pathogenesis of SpA by acting on IL-23 receptor (IL-23R) expressed on enthesis-resident lymphocytes. Upon IL-23 binding, CD3+CD4-CD8- tissue-resident lymphocytes secrete IL-17A and IL-22, leading to inflammation, bone loss, and ossification. Knowledge about enthesis-resident lymphocytes remains fragmentary, and the contribution of entheseal γ/δ T cells in particular is not clear. This study was undertaken to investigate the presence of γ/δ T cells in the enthesis., Methods: We used 2-photon microscopy and flow cytometry to analyze entheseal lymphocytes from C57BL/6, Tcrd-H2BeGFP, Rorc-GFP, and IL-23R-eGFP mice. To analyze entheseal γ/δ T cells in IL-23-induced inflammation, Tcrd-H2BeGFP mice were crossed with mice of the susceptible B10.RIII background. Hydrodynamic injection of IL-23 minicircle DNA was performed for overexpression of IL-23 and induction of inflammation. Light-sheet fluorescence microscopy was used to visualize arthritic inflammation., Results: Activated Vγ6+CD27- γ/δ T cells were abundant in uninflamed entheseal tissue and constituted the large majority of retinoic acid receptor-related orphan nuclear receptor γt (RORγt)+IL-23R+ enthesis-resident lymphocytes. Fetal thymus-dependent γ/δ T cells were the main source of IL-17A at the enthesis. Under inflammatory conditions, γ/δ T cells increased in number at the Achilles tendon enthesis, aortic root, and adjacent to the ciliary body., Conclusion: Entheseal γ/δ T cells are derived from fetal thymus and are maintained as self-renewing tissue-resident cells. As main IL-17A producers within tissues exposed to mechanical stress including enthesis, γ/δ T cells are key players in the pathogenesis of IL-23-induced local inflammation., (© 2016, American College of Rheumatology.)

Objective: The Assessment of SpondyloArthritis international Society (ASAS) has previously published criteria for spondyloarthritis (SpA). In the Spines of Southern Denmark cohort, which included patients with persistent low back pain and an unknown proportion of patients with SpA, our objectives were 1) to estimate the prevalence of magnetic resonance imaging (MRI) findings and clinical features included in the ASAS criteria for SpA and 2) to explore the associations between MRI findings and clinical features., Methods: We included patients ages 18-40 years with persistent low back pain who had been referred to the Spine Centre of Southern Denmark. We collected information on clinical features (including HLA-B27 and high-sensitivity C-reactive protein) and MRI findings in the spine and sacroiliac (SI) joints., Results: Of 1,020 included patients, 537 (53%) had at least 1 of the clinical features included in the ASAS criteria for SpA. Three clinical features were common-inflammatory back pain according to the ASAS criteria, a good response to nonsteroidal antiinflammatory drugs (NSAIDs), and family history of SpA. The prevalence of these features ranged from 15% to 17%. Sacroiliitis on MRI according to the ASAS definition was present in 217 patients (21%). Of those 217 patients, 91 (42%) had the minimum amount of bone marrow edema required according to the ASAS definition (a low bone marrow edema score). The presence of HLA-B27, peripheral arthritis, a good response to NSAIDs, and preceding infection were independently positively associated with MRI findings in the SI joints (odds ratios [ORs] of 1.9-9.0). The remaining 8 clinical features were not positively associated with MRI findings. Importantly, only age was independently associated with low bone marrow edema score at the SI joints (OR of 1.1 per year)., Conclusion: In this population, 53% had at least 1 clinical feature included in the ASAS criteria for SpA, and 21% had sacroiliitis according to the ASAS definition; furthermore, the associations between the clinical and imaging domains were inconsistent. The results indicate a need for further investigation of the importance of these findings in SpA, including investigation of the minimum requirements for defining sacroiliitis on MRI., (© 2016, American College of Rheumatology.)

Increased knowledge about pathological processes active in inflammatory joint diseases is needed to initiate personalized medicine based on targeted treatments in the future. The molecular and cellular pathways that are active during joint inflammation may differ between the various inflammatory joint diseases, between different patient subgroups within one disease, or even between different stages of the disease in a single patient. In this review, we evaluate synovial inflammation in terms of descriptive histopathology through to more functional studies on human synovial tissue inflammation in RA and SpA, in phenotypic subgroups of RA and SpA patients, and during the disease course of both diseases., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using pharmacokinetic modeling (PKM) provides quantitative measures that mirror microvessel integrity and can be used as an objective marker of the level of synovial inflammation. The aim of this study was to investigate the PKM parameters K(trans) , kep , and ve in a prospective cohort of disease-modifying antirheumatic drug (DMARD)-naive patients with early arthritis, and to validate the results by assessing their correlation with the number of synovial endothelial cells (ECs)., Methods: Forty-seven patients with early arthritis (arthritis duration <1 year, DMARD naive; comprising 14 patients with rheumatoid arthritis, 22 with unclassified arthritis, 6 with spondyloarthritis [SpA], and 5 with other arthritides) were included. At baseline, DCE-MRI was performed on an inflamed knee joint of each patient. These images were used to calculate the K(trans) (volume transfer constant between the plasma and extracellular extravascular space [EES]), the kep (transfer constant between the EES and plasma), and the ve (fractional volume of the EES). Second, markers of disease activity were collected. Finally, vascularity was evaluated by immunohistochemical analysis of synovial tissue samples obtained from the inflamed knee joints, using antibodies to detect von Willebrand factor (vWF), a marker of ECs., Results: The 3 PKM parameters differed significantly between diagnostic groups at baseline, with the highest K(trans) value being observed in patients with SpA (median 0.050/minute, interquartile range [IQR] 0.041- 0.069). Furthermore, the K(trans) , kep , and ve values correlated significantly with markers of disease activity. Finally, the PKM parameters K(trans) and kep , but not ve , correlated significantly with synovial expression of vWF (r = 0.647, P = 0.004 for K(trans) ; r = 0.614, P = 0.007 for kep ; r = 0.398, P = 0.102 for ve )., Conclusion: These results suggest that the K(trans) , kep , and ve can be used to detect synovial inflammation in patients with early arthritis, and these PKM parameters may be helpful in differential diagnosis. This approach may also be useful in translational research analyzing tissue microcirculation and angiogenesis., (© 2016, American College of Rheumatology.)

Objective: To investigate changes in magnetic resonance imaging (MRI)-assessed inflammation and structural lesions in the sacroiliac (SI) joints during treatment with adalimumab versus placebo., Methods: In a 48-week double-blind, placebo-controlled trial, 52 patients with spondyloarthritis were randomized to receive subcutaneous injections of either adalimumab 40 mg (n = 25) or placebo (n = 27) every other week for 12 weeks. Patients in the adalimumab group continued to receive and patients in the placebo group were switched to adalimumab 40 mg every other week for an additional 12 weeks. MRI of the SI joints was performed at weeks 0, 12, 24, and 48, and the images were assessed independently in a blinded manner using the modified Berlin and the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores for inflammation and structural lesions of the SI joints., Results: At baseline, 56% of the adalimumab group and ∼72% of the placebo group had an MRI-assessed inflammation score of ≥1. Among the patients with inflammation at baseline, the mean percent reductions in MRI scores for inflammation from week 0 to 12 were greater in the adalimumab group compared with the placebo group (Berlin method, -62% versus -5%; SPARCC method, -58% versus -12% [both P < 0.04]). Furthermore, the mean SPARCC erosion score decreased (-0.6) and the SPARCC backfill score increased (+0.8) in the adalimumab group from week 0 to week 12. From week 12 to week 24, larger absolute reductions in the Berlin/SPARCC inflammation scores and the SPARCC erosion score and larger increases in the Berlin/SPARCC fatty lesion scores were seen in the placebo group compared with the adalimumab group. In univariate regression analyses (analysis of covariance) and multivariate stepwise regression analyses, treatment with adalimumab was independently associated with regression of the SPARCC erosion score from week 0 to 12 but not with changes in the other types of MRI lesions., Conclusion: Significant changes in the Berlin and SPARCC MRI-assessed inflammation scores and in the SPARCC MRI-assessed erosion scores occurred within 12 weeks after initiation of adalimumab. Tumor necrosis factor inhibitor treatment was associated with resolution of erosions and the development of backfill., (© 2016, American College of Rheumatology.)

Objective: Investigating changes in patient classification (ASAS (Assessment of SpondyloArthritis international Society) axSpA criteria) based on evaluation of images of the sacro-iliac joints (MRI-SI and X-SI) by local and central readers., Methods: The DESIR cohort included patients with inflammatory back pain (IBP; ≥3 months, but <3 years), suggestive of axSpA. Local radiologists/rheumatologists (local-reading) and two central readers (central-reading) evaluated baseline images. Agreement regarding positive MRI (pos-MRI) between central readers and between local-reading and central-reading was calculated (κs). Number of patients classified differently (ASAS criteria) by using local-reading instead of central-reading was calculated., Results: Inter-reader agreement between the two central readers and between local-reading and central-reading was substantial (κ=0.73 and κ=0.70, respectively). In 89/663 MRI-SIs (13.4%) local-reading and central-reading disagreed; 38/223 patients (17.0%) with pos-MRI (local-reading) were negative by central-reading; 51/440 patients (11.6%) with neg-MRI (local-reading) were positive by central-reading.In 163/582 patients eligible for applying ASAS criteria (28.0%), local-reading and central-reading disagreed on positive imaging (MRI-SI and/or X-SI; κ=0.68). In 46/582 patients (7.9%) a different evaluation resulted in a different classification; 18/582 patients (3.1%) classified no-SpA (central-reading) were axSpA by local-reading; 28/582 patients (4.8%) classified axSpA (central-reading) were no-SpA by local-reading. Among axSpA patients (central-reading), 16/419 patients (3.8%) fulfilling imaging-arm by central-reading fulfilled clinical-arm by local-reading; 29/419 patients (6.9%) fulfilling clinical-arm by central-reading fulfilled also imaging-arm by local-reading., Conclusions: In patients with recent onset IBP, trained readers and local rheumatologists/radiologists agree well on recognising a pos-MRI. While disagreeing in 28% of the patients on positive imaging (MRI-SI and/or X-SI), classification of only 7.9% of the patients changed based on a different evaluation of images, showing the ASAS axSpA criteria's robustness., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To determine candidate lesion-based criteria for a positive sacroiliac joint (SIJ) MRI based on bone marrow oedema (BMO) and/or erosion in non-radiographic axial spondyloarthritis (nr-axSpA); to compare the performance of lesion-based criteria with global evaluation by expert readers., Methods: Two independent cohorts A/B of 69/88 consecutive patients with back pain aged ≤50 years, with median symptom duration 1.3/10.0 years, were referred for suspected SpA (A) or acute anterior uveitis plus back pain (B). Patients were classified according to rheumatologist expert opinion based on clinical examination, pelvic radiography and laboratory values as having nr-axSpA (n=51), ankylosing spondylitis (n=34) or non-specific back pain (n=72). Four blinded readers assessed SIJ MRI, recording the presence/absence of SpA by concomitant global evaluation of T1-weighted spin echo (T1SE) and short τ inversion recovery (STIR) scans and, thereafter, whether BMO and/or erosion were present/absent in each SIJ quadrant of each MRI slice. We derived candidate lesion-based criteria based on the number of SIJ quadrants with BMO and/or erosion and calculated mean sensitivity and specificity for SpA., Results: For both cohorts A/B, global assessment showed high specificity (0.95/0.83) compared with the Assessment in SpondyloArthritis international Society (ASAS) definition (0.76/0.74). BMO ≥3 (0.89/0.84) or ≥4 (0.92/0.87) showed comparably high specificity to global assessment. Erosion ≥2 and/or BMO ≥3 or ≥4 were associated with comparably high sensitivity to global assessment without affecting specificity. These combined criteria showed both higher sensitivity and specificity than the ASAS definition., Conclusions: Lesion-based criteria for a positive SIJ MRI based on both BMO and/or erosion performed best for classification of axial SpA, reflecting the contextual information provided by T1SE and STIR sequences., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The purpose of this study is to characterize the MRI changes of the sacroiliac joints (SIJs) during pregnancy and following labor and to correlate them with clinical symptoms. Ninety-three pelvic and hip MRIs of pregnant and ≤6 months postpartum women were retrospectively evaluated (Berlin method), for the presence of acute and structural SIJ changes. A telephone questionnaire focusing on pain characterization, co-morbidities, and clinical outcome was conducted with 52 subjects. Findings were correlated with pregnancy week/postpartum time and clinical parameters. SIJ-bone marrow edema (BME) and subchondral sclerosis were a prevalent peripartum finding (46/26 % subjects, respectively), and their frequency increased with pregnancy age. Also, BME, joint fluid, capsulitis, and enthesitis total score were correlated with pregnancy age/postpartum time (r = 0.2-0.31, P = 0.013-0.036). Significant correlation was noted between BME and subchondral sclerosis scores (r = 0.485, P < 0.0001). A sizable proportion of women showed diffuse SIJ BME (7.6 %) and this correlated with slower resolution of symptoms. Indeed, in half of the cases in which MRI was performed due to pregnancy-induced low-back pain (LBP) and diffuse BME was found-spondyloarthropathy ensued. In conclusion, pregnancy and puerperium are associated with a host of acute findings in and around the SIJ, including BME, capsulitis, and enthesitis, reflecting most probably, mechanical load and hormonal changes. While the vast majority of symptoms abate within weeks to several months postpartum, 3.8 % of women go on to develop spondyloarthropathy. Diffuse SIJ BME and the presence of risk factors for spondyloarthropathy are predictive of a chronic course.

Objectives: Precursor Th17 lineage cells expressing CD161 are implicated in Rheumatoid Arthritis (RA) pathogenesis. CD4+CD161+ T-cells accumulate in RA joints and may acquire a non classical Th1 phenotype. The endogenous ligand for CD161 is lectin-like transcript 1 (LLT1). CD161/LLT1 ligation may co-stimulate T-cell IFN-γ production. We investigated the presence and identity of LLT1-expressing cells in RA synovial fluid (SF) and synovial tissue (ST). We also assessed levels of soluble LLT1 (sLLT1) in different phases of RA development., Methods: Paired samples of peripheral blood mononuclear cells (MC) and SFMC (n = 14), digested ST cells (n = 4) and ST paraffin sections (n = 6) from late-stage RA were analyzed for LLT1 expression by flow cytometry and immunohistochemistry. sLLT1 was measured using a sandwich ELISA. Sera and SF from late-stage RA (n = 26), recently diagnosed RA patients (n = 39), seropositive arthralgia patients (SAP, n = 31), spondyloarthropathy patients (SpA, n = 26) and healthy controls (HC, n = 31) were assayed., Results: In RA SF, LLT1 was expressed by a small proportion of monocytes. In RA ST, LLT1-expressing cells were detected in the lining, sublining layer and in areas with infiltrates. The LLT1 staining pattern overlapped with the CD68 staining pattern. FACS analysis of digested ST confirmed LLT1 expression by CD68+ cells. Elevated systemic sLLT1 was found in all patient groups., Conclusions: In RA joints, LLT1 is expressed by cells of the monocyte/macrophage lineage. Serum levels of sLLT1 were increased in all patient groups (patients with early- and late-stage RA, seropositive arthralgia and spondyloarthropathy) when compared to healthy subjects.

Spondyloarthritis (SpA) is a family of inflammatory diseases sharing clinical, genetic, and radiological features. While crucial for tailoring early interventions, validated prognostic biomarkers are scarce in SpA. We analyze the correlation between serum levels of vasoactive intestinal peptide (VIP) and disease activity/severity in patients with early chronic inflammatory back pain. The study population comprised 54 patients enrolled in our early chronic inflammatory back pain register. We collected demographic information, clinical data, laboratory data, and imaging findings. VIP levels were measured by enzyme immunoassay in serum samples from 162 visits. The association between independent variables and VIP levels was analyzed using longitudinal multivariate analysis nested by patient and visit. No significant differences were observed in VIP levels between these two groups. Lower levels of VIP were significantly associated with a higher Bath Ankylosing Spondylitis Disease Activity Index (BASFI) score, presence of bone edema in magnetic resonance imaging (MRI) scan, and lower hemoglobin levels. Coexistence of cutaneous psoriasis was independently associated with lower VIP levels, and similar trend was observed for enthesitis. We conclude that SpA patients with low serum VIP levels had worse 2-year disease outcome, suggesting that serum VIP levels could be a valid prognostic biomarker.

Objective: Although osteopenia is frequent in spondyloarthritis (SpA), the underlying cellular mechanisms and association with other symptoms are poorly understood. This study aimed to characterize bone loss during disease progression, determine cellular alterations, and assess the contribution of inflammatory bowel disease (IBD) to bone loss in HLA-B27 transgenic rats., Methods: Bones of 2-, 6-, and 12-month-old non-transgenic, disease-free HLA-B7 and disease-associated HLA-B27 transgenic rats were examined using peripheral quantitative computed tomography, μCT, and nanoindentation. Cellular characteristics were determined by histomorphometry and ex vivo cultures. The impact of IBD was determined using [21-3 x 283-2]F1 rats, which develop arthritis and spondylitis, but not IBD., Results: HLA-B27 transgenic rats continuously lost bone mass with increasing age and had impaired bone material properties, leading to a 3-fold decrease in bone strength at 12 months of age. Bone turnover was increased in HLA-B27 transgenic rats, as evidenced by a 3-fold increase in bone formation and a 6-fold increase in bone resorption parameters. Enhanced osteoclastic markers were associated with a larger number of precursors in the bone marrow and a stronger osteoclastogenic response to RANKL or TNFα. Further, IBD-free [21-3 x 283-2]F1 rats also displayed decreased total and trabecular bone density., Conclusions: HLA-B27 transgenic rats lose an increasing amount of bone density and strength with progressing age, which is primarily mediated via increased bone remodeling in favor of bone resorption. Moreover, IBD and bone loss seem to be independent features of SpA in HLA-B27 transgenic rats., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Human leucocyte antigen (HLA)-B27 expression is correlated with spondyloarthritis (SpA), but its role in disease pathogenesis remains unclear. The aim of the study was to determine whether HLA-B27 free heavy chain (FHC) contributes to SpA pathogenesis. Flow cytometry was used to analyse the FHC expression on CD3+ and CD14+ cells in the peripheral blood (PB) and synovial fluid (SF) from SpA patients, healthy controls, and rheumatoid arthritis (RA) patients. Human monocytic U937 cell lines stably expressing enhanced green fluorescence protein (EGFP)/HLA-B27, EGFP/HLA-A2 or EGFP alone were created to further investigate the relation between HLA-B27 and FHC expression. The relative FHC level on CD14+ PB cells was significantly higher in SpA patients than in controls, but lower than on the SF cells of SpA patients. No significant correlation was found for relative FHC expression with HLA-B27 or β2-microglobulin expression. HLA-B27-transfected U937 cells expressed higher FHC levels than either EGFP/HLA-A2- or EGFP-transfected cells. HLA class I FHC expression was significantly increased on monocytes of SpA patients and HLA-B27-transfected cells, implying that FHC, perhaps mostly derived from HLA-B27, plays an important role in SpA pathogenesis., (© 2014 John Wiley & Sons Ltd.)

Background: The objective of this study was to identify leukocyte cell types found within the synovia of patients with seronegative spondylarthropathies (SpA), such as ankylosing spondylitis (AS), using transcription based analyses., Methods: Leukocyte transcriptional profiles obtained from the NCBI's gene expression omnibus and prediction analysis of microarrays (PAM) was used to identify 25-gene leukocyte metagenes. Subsequently, transcriptional profiles from murine and clinical models of AS and SpA were interrogated to characterize the local infiltration of leukocytes in SpA synovia., Results: Analysis of a proteoglycan-induced murine model of AS reveals infiltration of dendritic cells, CD4+ T cells, monocytes, and natural killer cells to the spine. In human SpA and AS patients, transcriptional analysis of synovial biopsies revealed local infiltration of dendritic cells and CD4+ T cells., Conclusions: We identified leukocyte cell types that infiltrated the synovial of SpA patients. Our results imply a role for dendritic cells and CD4+ T cells in the local inflammation that underlies pathogenesis in patients with SpA.

Objective: To assess the sensitivity and specificity of detecting subarticular bone erosion of sacroiliac (SI) joint in patients with spondyloarthritis (SpA) using MRI three-dimensional water selective balanced steady-state free precession sequence (3D-WS-bSSFP) and T1-weighted (T1W) sequence., Materials and Methods: Radiography, CT and MRI of SI joint from 43 SpA patients were retrospectively analyzed. MRI examination sequences include T1W, short tau inversion recovery (STIR) and 3D-WS-bSSFP. Two radiologists, blinded to clinical data, independently determined bone erosion at bilateral sacral and iliac sides of the SI joint on radiography, CT, T1W and 3D-WS-bSSFP respectively. X(2) test was used to compare the sensitivity of detecting bone erosion among different diagnostic methods., Results: Of the 86 sacral and 86 iliac articular surfaces from the 43 cases, radiography, CT, MRI T1W and 3D-WS-bSSFP showed the presence of bone erosion in 40, 74, 50 and 71 articular surfaces respectively. CT and MRI 3D-WS-bSSFP demonstrated similar sensitivity (x(2)=0.11, P=0.74), and both were superior to radiography (x(2)=15.17, P<0.01 and x(2)=12.78, P<0.01, respectively) and T1W (x(2)=7.26, P<0.01 and x(2)=5.62, P<0.05). Using CT diagnosis as the gold standard, the sensitivity and specificity of detecting bone erosion for MRI 3D-WS-bSSFP and T1W sequences were 91.8%, 96.9%, and 60.8%, 94.9% respectively., Conclusion: MRI 3D-WS-bSSFP sequence is associated with short scanning time, zero ionizing radiation, high sensitivity and specificity of displaying the subarticular bone erosion of SI joints in patients with SpA. Therefore, it can be considered an alternative to CT., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To evaluate the clinical courses and outcomes of patients with monoarthritis and to investigate the predictive factors of clinical outcomes., Methods: A retrospective analysis was performed of 171 patients with chronic monoarthritis at a single tertiary hospital between January 2001 and January 2011. Baseline characteristics, radiographic findings and the clinical course were reviewed., Results: The most commonly involved joints were the knees (24.0%), followed by the wrists (22.8%) and ankles (18.7%). A final diagnosis was established in 74 (43.3%) patients. Thirty-one (18.1%) patients were diagnosed with rheumatoid arthritis (RA), 23 (13.5%) with peripheral spondyloarthritis (SpA), and 19 (11.1%) with Behçet's disease (BD). Among 108 patients who were initially undiagnosed, 85 (78.7%) patients remained with undiagnosed monoarthritis, with relatively shorter symptom durations and requiring less treatment. The initially involved joint was a predictive factor for the final diagnosis: the wrist joint for RA (odds ratio [OR] 11.58, P < 0.001), the ankle joint for SpA (OR 6.19, P < 0.001), and the knee joint for BD (OR 3.43, P = 0.014). Bony erosion at baseline was associated with progression to oligo- or polyarthritis (OR 2.88, P = 0.030) and with radiographic progression., Conclusions: In patients presenting with monoarthritis, a final diagnosis was established in less than half of the patients, and a majority of undiagnosed patients showed benign clinical courses. The initially involved joint and the presence of erosion at baseline were predictors of the final diagnosis and of clinical outcomes., (© 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Objective: To compare the utility of radiography and magnetic resonance imaging (MRI) for the diagnosis of juvenile-onset spondyloarthritis in pediatric patients presenting with low back and/or sacroiliac (SI) pain of potentially inflammatory etiology., Methods: Radiographs and MRI studies of the SI joints in 26 patients with juvenile spondyloarthritis (JSpA) and 35 controls were assessed independently by 2 radiologists, with discrepancies arbitrated by a third. Radiographs and MRI were blinded and read in separate batches in random order., Results: Erosion was common and was the most useful diagnostic feature on radiography [positive likelihood ratio (LR) = 3.5] and was especially diagnostic of SpA on MRI (LR = 6.7). Subchondral sclerosis was common but was the least specific feature for both modalities. Joint space narrowing had some utility on radiography (LR = 2.0) and MRI (LR = 2.7) but was uncommon and had poor reader reliability. Bone marrow edema (LR = 3.1) and subarticular fat infiltration (LR = 4.5), detectable only on MRI, were both useful features. Global diagnostic impression of MRI (LR = 9.4) had very high utility for the diagnosis of JSpA, exceeding radiography (LR = 4.4) because of superior specificity. In addition, global diagnosis of SpA is much more reliably made on MRI (κ = 0.80) compared to radiography (κ = 0.30)., Conclusion: Specificity and reliability of MRI of the SI joints are superior to radiography for the diagnosis of juvenile-onset SpA and, where available, MRI should replace radiography as the first line of investigation.

Arthritic lesions have been frequently diagnosed in the fossil record, with spondyloarthropathy (a type of erosive and pan-mammalian arthritis) being one of the most common types described to date for mammals, though not restricted to this group. Here, we identify spondyloarthropathy in fossil bones from the late Pleistocene in Brazil assignable to a large glyptodont individual. Bone erosions in the peripheral joints (viz., the ulna, radius, left femur and tibiae-fibulae) associated with osteosclerosis allow the diagnosis of spondyloarthropathy. The presence of osteophytes in seven bones of the forelimbs (viz., the ulna and radius) and hind limbs (viz., the tibiae-fibulae, left femur and patellae) and a subchondral cyst in one element (viz., the left femur) indicate secondary osteoarthritis. A calcified deposition on the articular surface of the left patella indicates the presence of calcium pyrophosphate deposition disease, which, like the observed osteoarthritic alterations, likely represents a complication of spondyloarthropathy. This is the first report of spondyloarthropathy for xenarthrans.

Alterations of vertebral endplates have long been a subject of interest, but are of unclear clinical significance. The vertebral columns of a cohort-based sample of 850 individuals were therefore evaluated for vertebral endplate defects, noting adjacent vertebral size and shape variation, bone density and associated pathologies. Defects were found in the vertebral endplates of 458 individuals (Schmorl's nodes in 52.0% and linear defects in 10.6%). Vertebral centra osteophytes and diffuse idiopathic skeletal hyperostosis were more common; vertebral compression, less common in vertebrae with defects. Linear defects were more disseminated throughout the vertebral column, with individual defects more commonly affected either the interior half or the posterior quarter of the endplate or extended across all quarters form anterior to posterior. Individual Schmorl's nodes were predominantly limited to a single quarter. An inverse relationship was identified with tuberculosis. Spondyloarthropathy was more common in individuals with Schmorl's nodes, but not linear defects. Schmorl's nodes and linear endplate defects should be independently assessed, although they do share implications. Paradoxically, they are associated with phenomena which seem to mark increased ossification potential (osteophytes and diffuse idiopathic skeletal hyperostosis), but not with osteoporosis. Similarly, presence of Schmorl's nodes correlation with spondyloarthropathy, another disorder characterized by increased ossification potential. While correlation is not causality, inverse relationship to tuberculosis is intriguing, given the known relationship of spondyloarthropathy to tuberculosis and its antigens. Previously undescribed surface elevations were commonly associated with the presence of Schmorl's nodes and also correlated with disease, especially inflammatory arthritis, hypertrophic osteoarthropathy.

Objectives: To report an unusual case of lipoma aborescens (LA) presented in a patient with treatment-responsive juvenile spondyloarthropathy (JSPA) and to summarize the clinical manifestations, therapy and prognosis of LA by literature review., Methods: We report an atypical case of a 17-year-old patient with an initial presentation of juvenile spondyloarthropathy, whose inflammatory condition was improved successfully by traditional anti-rheumatic drugs and an anti-TNF alpha agent but developed progressive swelling of bilateral knees. Lipoma arborescens were diagnosed in each knee by synovial biopsy obtained by arthroscopic surgery. Fifty-one cases of LA have been reported and are reviewed in detail., Results: Clinically, LA could present as monoarthritis or oligoarthritis. The lateral compartment of the knee is the most common site of involvement. Several cases were reported as a comorbidity of inflammatory diseases, but were not improved by anti-inflammatory therapy. Most patients were diagnosed by classic MRI and biopsy findings. The lesions can be managed by open or arthroscopic surgery, but a minority of the cases may have reoccurrence in the same or opposite joint., Conclusions: LA is a very rare lesion of the synovial and bursal tissue with an unknown etiology. It is considered to be a benign proliferation of the synovial fat associated with trauma, degenerative or inflammatory conditions. LA should be considered as a secondary or comorbid condition in inflammatory arthropathies if other joints respond well to intensive therapy and one or more do not., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Activation of caspase-1 by NALP3 inflammasomes has been shown to be important in initiating acute gouty arthritis. The objectives of this study were to measure the levels of caspase-1 in synovial fluid in gout and various arthritides, and to elucidate the clinical significance of caspase-1 levels in synovial fluid. Caspase-1, IL-1β, IL-18, and uric acid were measured in synovial fluid from 112 patients with gout and other arthritides, such as rheumatoid arthritis, osteoarthritis, and spondyloarthropathy. Caspase-1 in synovial fluid from patients with crystal-induced arthritis, inflammatory arthritis, osteoarthritis, and spondyloarthropathy was 35.9 ± 86.7, 49.7 ± 107.7, 2.1 ± 7.0, and 152.6 ± 155.7 pg/mL, respectively. The mean level and the frequency of high levels (≥125 pg/mL) of caspase-1 in spondyloarthropathy were significantly higher than those in the other arthritides including gout. Caspase-1 was detectible in the synovial fluid of patients with the various arthritides. Contrary to our hypothesis, the caspase-1 level in the synovial fluid of patients with gout was not higher than in that of other arthritides. High levels of caspase-1 may be helpful in differentiating spondyloarthropathy from other arthritides.

The sacroiliac joints are involved in most cases of axial spondyloarthropathy, the first manifestation usually being sacroiliitis. A finding of sacroiliitis at radiography is the classic diagnostic hallmark of axial spondyloarthropathy. However, radiographic changes reflect structural damage rather than active inflammation, which may delay the diagnosis by several years. In the past decade, the field of spondyloarthropathy has undergone major changes, largely driven by the development of new drugs for the treatment of ankylosing spondylitis. In recent years, the Assessment of SpondyloArthritis international Society has focused on the reassessment of existing classification criteria and the development and validation of diagnostic tools to facilitate early diagnosis and assessment of treatment response. Magnetic resonance (MR) imaging is the most recent innovation and the important change with respect to the previously established classification criteria. This modality has become an integral part of managing patients with sacroiliitis. MR imaging can serve as a biomarker of disease activity, allows monitoring, and can provide guidance for the treatment of affected patients, and it will likely become even more central to the care of these patients. Familiarity with the anatomy, anatomic variants, and physiologic changes of the sacroiliac joints is important for correctly interpreting findings and avoiding misdiagnosis., (© RSNA, 2013.)