ObjectivesTo update the Assessment of SpondyloArthritis international Society (ASAS)-EULAR recommendations for the management of axial spondyloarthritis (axSpA).MethodsFollowing the EULAR Standardised Operating Procedures, two systematic literature reviews were conducted on non-pharmacological and pharmacological treatment of axSpA. In a task force meeting, the evidence was presented, discussed, and overarching principles and recommendations were updated, followed by voting.ResultsFive overarching principles and 15 recommendations with a focus on personalised medicine were agreed: eight remained unchanged from the previous recommendations; three with minor edits on nomenclature; two with relevant updates (#9, 12); two newly formulated (#10, 11). The first five recommendations focus on treatment target and monitoring, non-pharmacological management and non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice pharmacological treatment. Recommendations 6–8 deal with analgesics and discourage long-term glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for pure axial involvement. Recommendation 9 describes the indication of biological DMARDs (bDMARDs, that is, tumour necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i)) and targeted synthetic DMARDs (tsDMARDs, ie, Janus kinase inhibitors) for patients who have Ankylosing Spondylitis Disease Activity Score ≥2.1 and failed ≥2 NSAIDs and also have either elevated C reactive protein, MRI inflammation of sacroiliac joints or radiographic sacroiliitis. Current practice is to start a TNFi or IL-17i. Recommendation 10 addresses extramusculoskeletal manifestations with TNF monoclonal antibodies preferred for recurrent uveitis or inflammatory bowel disease, and IL-17i for significant psoriasis. Treatment failure should prompt re-evaluation of the diagnosis and consideration of the presence of comorbidities (#11). If active axSpA is confirmed, switching to another b/tsDMARD is recommended (#12). Tapering, rather than immediate discontinuation of a bDMARD, can be considered in patients in sustained remission (#13). The last recommendations (#14, 15) deal with surgery and spinal fractures.ConclusionsThe 2022 ASAS-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.

BackgroundDepression is common among patients with axial spondyloarthritis (axSpA), but reports of its prevalence are highly variable. We performed a systematic review to (i) describe the prevalence of depression in axSpA, (ii) compare its prevalence between axSpA, ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA) cohorts, and (iii) compare disease activity and functional impairment between those with and without depression.MethodsWe searched Medline, PubMed, Web of Science, PsycINFO, CINAHL Plus, the Cochrane library and conference abstracts of the European League Against Rheumatism, British Society for Rheumatology and American College of Rheumatology using a predefined protocol in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Meta-analysis was performed using quality-effects model.ResultsFifteen original articles and one abstract were included for analysis; 14 studies described AS cohorts and two nr-axSpA. Three screening criteria and one diagnostic criterion were used to define depression. Prevalence ranged from 11 to 64% depending on criteria and thresholds used. Pooled prevalence of at least moderate depression was 15% using the Hospital Anxiety and Depression Scale (HADS) threshold of ≥ 11. The prevalence of depression was similar between axSpA, AS and nr-axSpA cohorts. Patients with depression had significantly worse disease activity, including higher BASDAI by 1.4 units (95% CI 1.0 to 1.9), ASDAS by 0.5 units (95% CI 0.3 to 0.7) and ESR by 3.5 mm/h (95% CI 0.6 to 6.4). They also had greater functional impairment with higher BASFI and BASMI by 1.2 units (95% CI 0.6 to 1.8) and 0.6 units (95% CI 0.3 to 0.8), respectively. Mean age of each study cohort inversely correlated with depression prevalence.ConclusionsDepression is common among axSpA patients and is associated with more severe disease activity and functional impairment. Identifying and managing depression should form part of their holistic care. Further longitudinal studies are needed to explore the impact of depression on treatment outcomes and axSpA treatment on symptoms of depression.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1644-6) contains supplementary material, which is available to authorized users.

Though pain in neuromyelitis optica (NMO) has been described in two recent reports, the proportion with true neuropathic pain (NP), its features, impact on activities of daily living (ADL) and quality of life has not been well characterised. A cross-sectional study of 50 NMO patients with transverse myelitis was performed using Douleur Neuropathique 4, Brief Pain Inventory, Extended Disability Status Scale and Short Form 36. NP was identified in 62% of patients. Pain was constant in 68% affecting most ADL. Pain was associated with significant reduction of the SF36 Mental Composite Score. The high prevalence of NP and associated disability necessitates an in-depth enquiry in patients with NMO.

Extracellular matrix (ECM) production is critical to preserve the function and integrity of mature blood vessels. Toward the engineering of blood vessels, studies have centered on ECM production by supporting cells, whereas few studies implicate endothelial cells (ECs) with ECM synthesis. Here, we elucidate variations between cultured human arterial, venous, and progenitor ECs with respect to ECM deposition assembly, composition, and response to biomolecular and physiological factors. Our studies reveal that progenitor ECs, endothelial colony-forming cells (ECFCs), deposit collagen IV, fibronectin, and laminin that assemble to an organized weblike structure, as confirmed by decellularized cultures. Mature ECs only express these ECM proteins intracellularly. ECFC-derived ECM is abrogated in response to TGFβ signaling inhibition and actin cytoskeleton disruption. Hypoxic (1%) and physiological (5%) O(2) tension stimulate ECM deposition from mature ECs. Interestingly, deposition of collagen I is observed only under 5% O(2) tension. ECM production from all ECs is found to be regulated by hypoxia-inducible factors 1α and 2α but differentially in the different cell lines. Collectively, we suggest that ECM deposition and assembly by ECs is dependent on maturation stage and oxygen supply and that these findings can be harnessed to advance engineered vascular therapeutics.

ObjectivesThis systematic review and meta-analysis will describe the prevalence of concomitant FM in adults with inflammatory arthritis and quantify the impact of FM on DAS.MethodsCochrane library, MEDLINE, Psychinfo, PubMed, Scopus and Web of Science were searched using key terms and predefined exclusion criteria. As appropriate, proportional and pairwise meta-analysis methods were used to pool results.ResultsForty articles were identified. In RA the prevalence of FM ranged from 4.9 to 52.4% (21% pooled). In axSpA the range was 4.11–25.2% (13% pooled in AS only). In PsA the range was 9.6–27.2% (18% pooled). The presence of concomitant FM was related to higher DAS in patients with RA and AS (DAS28 mean difference 1.24, 95% CI: 1.10, 1.37 in RA; BASDAI mean difference 2.22, 95% CI: 1.86, 2.58 in AS). Concomitant FM was also associated with higher DAS in existing PsA studies. Self-reported, rather than objective, components of DAS appear to be raised in the presence of FM (e.g. tender joint count and Visual Analogue Scale (VAS) pain scores).ConclusionFM is common in RA, AxSpA and PsA. Comorbid FM appears to amplify DAS and could therefore influence management of these rheumatic conditions.

Background Delay to diagnosis in axial SpA (axSpA) is longer than in many other rheumatic diseases. Prolonged delay is associate with poorer outcomes, including functional impairment and quality of life. Our aims were to describe global variation in delay to diagnosis, factors associated with delay, and delay compared with PsA. Methods We searched MEDLINE, PubMed, Embase and Web of Science using a predefined protocol. Diagnostic delay was defined as years between the age at symptom onset and at diagnosis. We pooled the mean delay using random effects inverse variance meta-analysis. We examined variations in pooled estimates using prespecified subgroup analyses and sources of heterogeneity using meta-regression. Results A total of 64 studies reported the mean diagnostic delay in axSpA patients. The pooled mean delay was 6.7 years (95% CI 6.2, 7.2) with high levels of heterogeneity. Delay to diagnosis did not improve over time when stratifying results by year of publication. Studies from high-income countries (defined by the World Bank) reported longer delays than those from middle-income countries. Factors consistently reported to be associated with longer delays were lower education levels, younger age at symptom onset and absence of extra-articular manifestations (EAMs). The pooled estimate for diagnostic delay from 8 PsA studies was significantly shorter, at 2.6 years (95% CI 1.6, 3.6). Conclusion For axSpA patients, delay to diagnosis remains unacceptably prolonged in many parts of the world. Patient factors (e.g. education) and disease presentation (onset age and EAMs) should inform campaigns to improve delay.

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