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A man in his 80s who had a history of diabetes mellitus and aortic valve replacement was referred to our hospital for treatment of early gastric cancer and underwent endoscopic submucosal dissection (ESD). Three days after ESD, the patient presented with low back pain and fever (38.7°). We initially considered adverse events associated with gastric ESD such as delayed perforation. Moreover, thromboembolism and infectious endocarditis were suspected because of his medical history. However, there were no remarkable findings suggestive of these diseases. Finally, based on the results of blood cultures and MRI, the diagnosis of pyogenic spondylitis (PS) was made. We administered antibiotics for 12 weeks, and the patient improved without neurological impairments. This case indicates that bacteraemia and subsequent PS can occur following gastric ESD. Physicians should not overlook the patient’s physical signs related to various adverse events after ESD.

Adults with distal renal tubular acidosis (dRTA) commonly present with hypokalaemia (with/without paralysis), nephrolithiasis/nephrocalcinosis and vague musculoskeletal symptoms. All adults with dRTA should be thoroughly evaluated for systemic diseases, certain medications and toxins. The leading cause of acquired or secondary dRTA in adults is primary Sjögren syndrome (SS); however, other collagen vascular diseases (CVDs) including seronegative spondyloarthropathy (SSpA) may at times give rise to secondary dRTA. Metabolic bone disease is often encountered in adults with dRTA, and the list includes osteomalacia and secondary osteoporosis; sclerotic metabolic bone disease is an extremely rare manifestation of dRTA. Coexistence of dRTA and sclerotic bone disease is seen in primary dRTA due to mutation in CA2 gene and acquired dRTA secondary to systemic fluorosis. Primary SS and SSpA, rarely if ever, may also lead to both secondary dRTA and osteosclerosis. Circulating autoantibodies against carbonic anhydrase II and possibly calcium sensing receptor may explain both these features in patients with CVD.

The Wnt signalling antagonist Dickkopf-1 (DKK1) inhibits osteoblast differentiation and function and has been described to play a central role in promoting bone loss, while blockade of DKK1 increases bone formation. We investigated the effects of DKK1 on periosteal new bone formation in two murine models of inflammatory arthritis, the antigen-induced arthritis (AIA) and K/BxN serum transfer arthritis (STA) models.The flare variant of AIA was induced in wild-type mice and a blocking antibody to DKK1, control rat immunoglobulin G (IgG), or phosphate-buffered saline (PBS) was administered starting on day 14, a time at which inflammation and erosions are known to be established. Knees were assessed for histological inflammation and periosteal new bone formation was quantitated. In addition, STA was generated in transgenic (Tg) mice with osteoblast-specific overexpression ofiDkk1/iand littermate controls. New bone formation around the wrists of these mice was quantified by micro-computed tomography.Blockade of DKK1 in arthritic mice resulted in significantly more periosteal new bone formation compared to mice treated with control rat IgG or PBS. Conversely, in the setting of increasediDkk1/iexpression, arthriticiDkk1/iTg mice developed significantly less periosteal new bone than arthritic controls.DKK1 is a regulator of periosteal bone formation in inflammatory arthritis. Thus, regulation of DKK1 may be considered as a therapeutic approach in inflammatory diseases in which patients suffer from excessive periosteal bone formation, such as spondyloarthritis.

Background MRI is frequently used for early diagnosis of axial spondyloarthritis (axSpA). However, evaluation is time-consuming and requires profound expertise because noninflammatory degenerative changes can mimic axSpA, and early signs may therefore be missed. Deep neural networks could function as assistance for axSpA detection. Purpose To create a deep neural network to detect MRI changes in sacroiliac joints indicative of axSpA. Materials and Methods This retrospective multicenter study included MRI examinations of five cohorts of patients with clinical suspicion of axSpA collected at university and community hospitals between January 2006 and September 2020. Data from four cohorts were used as the training set, and data from one cohort as the external test set. Each MRI examination in the training and test sets was scored by six and seven raters, respectively, for inflammatory changes (bone marrow edema, enthesitis) and structural changes (erosions, sclerosis). A deep learning tool to detect changes indicative of axSpA was developed. First, a neural network to homogenize the images, then a classification network were trained. Performance was evaluated with use of area under the receiver operating characteristic curve (AUC), sensitivity, and specificity.

Spondyloarthropathies, also known as spondyloarthritis, encompasses a spectrum of diseases classified by it's axial and peripheral musculoskeletal manifestations. Extra-articular features are common in SpA making these systemic rheumatologic diseases involve the skin, eye, gut, and other organ systems.Research has identified risk factors for the development of spondyloarthritis, particularly regarding genetic susceptibility and the strong association with HLA-B27. Multiple studies have elucidated clinical risk factors associated with SpA disease activity and severity. In this review, we aim to explore the environmental risk factors for spondyloarthritis.

This study aimed to calculate the healthcare resource utilization and direct medical costs in patients with 2 subtypes of axial spondyloarthritis (axSpA) in a rheumatic care center in Colombia.This is a retrospective cost-of-illness study. Patients with at least 1 medical consultation associated with an axSpA diagnosis between October 2018 and October 2019 were identified. Patients were classified as having radiographic (r-axSpA) or nonradiographic axSpA (nr-axSpA). Direct medical costs were calculated in Colombian pesos and expressed in American dollars using an exchange rate of 3263 Colombian pesos = 1 US dollar ($). Predictors of total direct costs were identified using a generalized linear model with gamma distribution and log-link.A total of 162 patients with a mean age of 49.6 years (± 13.7) were included in the study. Among these, 147 (90.7%) were considered as having r-axSpA and 15 (9.3%) nr-axSpA, with mean costs of $6600 (± 6203) and $843 (± 1135), respectively (P.001). The total direct mean cost was calculated at $6067 (± 6144) per patient. Medication costs were the main driver of total costs (97.6%, $5921), with biologic disease-modifying antirheumatic drugs accounting for nearly 92.0% ($5582) of these costs. Rheumatologist (100%) and physiatrist (64.2%) visits were the most frequently used medical service.The economic burden associated with axSpA in the Colombian setting is substantial. There is a significant difference in direct medical costs between the r-axSpA and the nr-axSpA. Health policies aimed at the comprehensive management of nr-axSpA would have an important role in the reduction of the associated direct medical costs.

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.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.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.The presence of subchondral oedema in active sacroiliitis decreased the diagnostic accuracy of sacroiliac joint erosion detection on T2W Dixon MRI images.

Outcomes of COrona VIrus Disease-19 (COVID-19) in patients with rheumatic diseases (RDs) reported in various studies are heterogenous owing to the influence of age and comorbidities which have a significant bearing on the infection risk, severity, morbidity, and mortality. Diabetes mellitus (DM) and RDs are closely linked with underlying pathobiology and treatment of RDs affecting the risk for DM as well as the glycemic control. Hence, we undertook this narrative review to study the influence of DM on outcomes of COVID-19 in patients with RDs. Additionally, aspects of patient attitudes and immune response to COVID-19 vaccination were also studied. The databases of MEDLINE/PubMed, Scopus, and Directory of Open Access Journals (DOAJ) were searched for relevant articles. Studies from mixed cohorts revealed insufficient data to comment on the influence of DM on the risk of infection, while most studies showed twice the odds for hospitalization and mortality with DM. Specific cohorts of rheumatoid arthritis and systemic lupus erythematosus revealed a similar association. Poor health was noted in patients with spondyloarthritis and DM during the pandemic. The presence of DM did not affect patient attitudes towards vaccination and did not predispose to additional vaccine-related adverse effects. Immune response to inactivated vaccines was reduced but mRNA vaccines were maintained in patients with DM. Detailed assessment of DM with its duration, end-organ damage, and glycemic control along with a focused association of DM with various aspects of COVID-19 like risk, hospitalization, severity, mortality, post-COVID sequelae, immune response to infection, and vaccination are needed in the future. Key Points • Diabetes mellitus is associated with the severity of infection, COVID-19-related hospitalization, and mortality in rheumatic diseases across most studies but studies analyzing its specific role are lacking. • Poor outcomes of COVID-19 in RA and poor health in spondyloarthritis are strongly associated with diabetes mellitus. • Diabetes mellitus may negatively influence the humoral response to inactivated vaccines but does not seem to affect the immune responses to mRNA vaccines. • Diabetes mellitus does not influence the attitude towards vaccination or deviation from the prescribed medications during the pandemic.

Back pain (BP) is among the most common reasons for seeking medical attention worldwide. The nature of BP depends on the causative stimulus and its anatomical location. Clinically, BP is manifested by pain, muscle tension, and stiffness. The development of BP is a very complex, multifactorial process in which not only somatic stimuli (anatomical structures), but also psychosocial effects are involved. Using a variety of criteria, BP can be divided into specific where the cause of pain is known, nonspecific wherein the cause remains unclear, or according to its duration (i.e., acute, subacute, and chronic back pain). Simple low back pain must be distinguished from inflammatory BP. Inflammatory BP is one of the symptoms of spondyloarthritides. It is typically a resting pain of insidious onset, peaking at night or in the morning associated with morning stiffness, improved with exercise, and responding to non-steroidal antirheumatic drugs. A red-flag system was developed for the early identification of at-risk patients with a potentially severe disease presenting with BP. Early diagnosis and identification of the cause of complaints often requires multidisciplinary cooperation. The treatment involves pharmacological agents (analgesic and muscle relaxation therapies) and nonpharmacological approaches (rehabilitation, surgical intervention, etc.).

Background and Aims: Changes in body mass composition, such as reduced lean and fat mass, can occur in a patient with rheumatic diseases. However, data about body composition in spondyloarthritis (SpA) showed conflicting results. The aim of the present study was to assess by DXA the distribution of lean and fat mass in SpA patients compared to healthy controls and to in-vestigate the association between body mass composition and disease characteristics. Methods: We conducted a cross-sectional case-control study including 50 SpA patients and 50 con-trols. Sociodemographic data, as well as disease characteristics, were assessed. Body composition measurements and biochemical and inflammatory serum markers were evaluated. Radiographic data (Bath Ankylosing Radiologic Index and the modified Stroke Ankylosing Spondylitis Spine Score) was also recorded. Results: No statistically significant correlation was found between the two groups regarding bone mineral density and body mass distribution. However, a lower weight was observed in the study group compared to the control group (p = 0.043). Male gender and younger age were associated with a higher lean mass (p = 0.05). C-reactive protein (CRP) level was positively correlated with lean mass (r = 0.38, p = 0.023). Similarly, BASFI was higher in patients with lower fat mass (r = -0.42, p = 0.024). A longer duration of NSAIDs intake was associated with a lower lean mass and a higher fat mass. However, no correlations were found between body mass composition and BASRI mSASSS scores as well as bone mineral density and calcium intake. Conclusion: Our findings suggest that younger age, male gender, and axial phenotype were associ-ated with higher lean mass.

Sulfasalazine has been widely used in treatment of rheumatoid arthritis and spondyloarthritis. This study aims to assess persistence with sulfasalazine and also frequency and severity of adverse drug reactions (ADRs) encountered with this very well-established disease-modifying anti-rheumatoid drug.This retrospective study was done in 1,114 patients from medicine and rheumatology outpatient departments of six centers across India. The inclusion criteria was patients taking sulfasalazine. Patients receiving sulfasalazine for rheumatoid arthritis or spondyloarthritis were selected and details on drugs used, duration of taking sulfasalazine, ADRs to sulfasalazine and whether sulfasalazine had to be stopped due to ADRs were analyzed.Of the total of patients included in the study, 10.1% had ADRs with sulfasalazine, and stopped the drug. Gastritis, deranged liver enzymes, hepatitis, skin rashes were the most commonly encountered ADRs. Of the total number of patients recruited for the study, 11% were lost to follow-up, as most of the centers were army hospitals and the officers and staff were posted to other places. Sulfasalazine was taken for less than 1 month by 3.8% patients while 12.5% had taken the drug for less than 6 months. Of the study patients, 28.6% had taken the drug for 24 - 60 months and 4.6% (51 patients) had taken it for more than 5 years. It was found that ADRs were most commonly encountered within the first year of using the drug, and persistence was seen in patients on long-term therapy.Sulfasalazine is a safe option in chronic therapy of rheumatoid arthritis and spondyloarthritis. Although frequency of ADRs with patients taking sulfasalazine is minimal, it did necessitate the stoppage of drug. If not well tolerated, sulfasalazine would not have been continued for more than 12 months as evidenced from this study.

Non-radiographic axial spondyloarthritis (nr-axSpA) data from South America are scarce, especially regarding image features. Objective To estimate the frequency of nr-axSpA and ankylosing spondylitis (AS) in a cohort of Argentinian patients with chronic low back pain (LBP) and to analyze the difference between both, with focus on magnetic resonance imaging (MRI) lesions, at diagnosis.Patients with LBP and a diagnosis of axSpA who participated in a reuma-check program were included. All patients with a suspicion of SpA were evaluated using blood analytics, HLA-B27, and images (MRI). Sociodemographic data, SpA features, diagnostic dela,y and clinimetrics were assessed by an operator who was blinded to the patient's test results. On MRI, the presence of SpA lesions was assessed and a concordance exercise was carried out between rheumatologists and radiologist.Of 198 LBP patients, 97 had axSpA, 54% of whom were nr-axSpA. A positive MRI was found in 50%. No difference in terms of disease activity, functional impact, laboratory or treatments between nr-axSpA and AS were found. Higher frequencies of male sex and chronic lesions on sacroiliac MRI were found in AS patients. In the logistic regression, an independent association with AS diagnosis was found: male (odds ratio [OR] 4.8), MRI fat replacement (OR 4.6), MRI sclerosis (OR 7.6), and diagnostic delay of more than 2 years (OR 10). The concordance between rheumatologists and radiologists was considered good to very good (κ 0.7-0.8).The frequency of nr-axSpA was 54%. We found a higher frequency of being male, more SpA features, and a longer diagnostic delay in patients with AS. Patients with AS had more structural lesions, with a good concordance between rheumatologist and radiologist.

Sacroiliac joint (SJ) imaging is the key point in the diagnosis of ankylosing spondylitis (AS). The curved anatomy of the SJ makes the interpretation of imaging difficult. The aim of this study is to evaluate the interclass and intraclass reliability of specific lesions (bone marrow edema [BME], joint space narrowing, erosions, effusion, ankylosis, bridging, sclerosis, fat deposition, and other additional pathologies) on SJ magnetic resonance imaging (MRI).In a total of 310 randomly chosen patients, 620 SJs were evaluated by three different radiologists with different radiology experiences of specialties other than musculoskeletal radiology.The agreement between readers for BME was fair to substantial, for active sacroiliitis was moderate to substantial, for sacroiliac narrowing was fair at best, for erosions was fair to moderate, for SJ sclerosis was none to slight, for chronic sacroiliitis was slight to fair, for degenerative sacroiliitis was none to slight, for normal SJ was slight, for SJ effusion was none to slight, and for fatty deposition was none. Intraclass correlation for readers 1 and 3 was usually good to excellent and for reader 2 was poor to fair.This study was designed to assess the agreement between radiologists who were not familiar with SJ MRI. The agreement between readers was usually fair to substantial and even intraclass correlation was poor to fair for reader 2. Future studies can be designed for standardization and validation of each MRI lesion for better interpretation of SJ MRI.

The 2014 Update of the Canadian treatment recommendations for the management of spondyloarthritis recommended that patients at risk of peripheral spondyloarthritis, including patients with psoriatic arthritis (PsA), be assessed by a rheumatologist within 6 weeks of referral. This study aimed to: (1) investigate the proportion of PsA patients who were assessed by a rheumatologist within 6 weeks of referral to the PsA Clinic at Toronto Western Hospital and (2) investigate the possible reasons for delays for consult with a rheumatologist. We identified patients with PsA who were seen by rheumatologists at the PsA Clinic between January 2013 and May 2019. We used retrospective chart reviews of medical records and referral letters to determine the number of days between referral and assessment by a rheumatologist. The causes for delays were identified as no spots in the clinic or patient rescheduling their appointment due to their inability to attend the scheduled appointment. Among 168 patients, 43 (25.6%) patients met the recommendation. The median wait time was 78.5 days (IQR 83.5). The most common cause of delay was the lack of available spots in the PsA clinic. The majority of PsA patients at the TWH PsA Clinic were not seen within the wait-time recommendation. The most common factor that prevented a timely consultation with a rheumatologist was the lack of spots in the PsA clinic. Greater access to rheumatologists can improve the timely and effective care of PsA patients.

Microscopic bowel inflammation is present in up to 60% of all patients with spondyloarthritis (SpA) and appears to be associated with more severe joint disease and a higher risk of developing inflammatory bowel disease (IBD). This study aimed to determine the utility of fecal calprotectin (fCAL) in evaluating endoscopic and histological bowel inflammation in SpA patients.Ileocolonoscopies with biopsies and fCAL measurements were performed in 65 patients with SpA.In 47 (72.3%) patients, the fCAL levels were higher than 50 μg/g, whereas in 20 (30.7%), these levels were greater than 250 μg/g. A total of 38 (58.5%) patients presented with microscopic bowel inflammation, and 13 (20%) presented with signs of endoscopic inflammation. fCAL levels were significantly higher in patients with microscopic bowel inflammation than in those without inflammatory findings (P .001); additionally, these levels were slightly higher in patients with endoscopic signs of bowel inflammation (P = .053). A fCAL cutoff value of 96 μg/g predicted histological bowel inflammation with 73% sensitivity and 67% specificity. No statistically significant difference was observed in the fCAL levels between patients who had been treated or not treated with nonsteroidal anti-inflammatory drugs (NSAIDs).Our findings confirm a high prevalence of microscopic bowel inflammation in SpA patients, regardless of the use of NSAIDs. The evaluation of fCAL levels proved to be useful in the identification of microscopic inflammation and could help in the more judicious indication of ileocolonoscopy. These results support the use of fCAL for the evaluation of microscopic bowel inflammation in SpA patients.

Purpose of Review This review aims to emphasize interesting and important new findings with a focus on the spectrum of spondyloarthritis (SpA) in China. Recent Findings Over the past decade, significant advances have been made in the investigation of SpA epidemiology, the exploration of genetic and environmental risk factors, the identification of clinical features, and the updating of treatment protocols in the Chinese population. The prevalence of ankylosing spondylitis (AS) in China is 0.20–0.42%, and the prevalence of HLA-B27 in AS patients is 88.8–89.4%. HLA-B*2704 is the most common subtype in Chinese AS patients, followed by HLA-B*2705. HLA-A*01, more precisely HLA-A*01:01, may be associated with psoriatic arthritis (PsA). Tumor necrosis factor inhibitors and IL-17A inhibitors have been shown to be effective and safe for AS patients in China. Juvenile-onset AS is relatively rare, accounting for only 9.1% of the AS population. The prevalence of arthritis related to inflammatory bowel disease is 6.9 to 7.2%. A Chinese study showed that the most frequently prescribed medication was methotrexate (66.4%). Biological agents were prescribed in only16.4% of patients with PsA. Summary This review summarizes the latest research in the epidemiology, pathogenesis, clinical manifestations, and management of SpA among Chinese populations. Multiple HLA associations with SpA have also been described, and it is hoped that discoveries of such ethnic-specific risk factor(s) and understanding of their pathological mechanisms may potentially lead to newer targeted therapies for the Chinese populations worldwide.

Pathological roles of macrophage migration inhibitory factor (MIF) have recently been demonstrated in spondyloarthritis (SpA) preclinical models, identifying MIF as a new treatment target for SpA. However, the specific contribution of MIF and therapeutic potential of MIF-targeted therapies to various tissue types affected by SpA are not well delineated.MIF and its cognate receptor CD74 are extensively involved in the pathogenesis of SpA including inflammation in the spine, joint, eyes, skin, and gut. The majority of the current evidence has consistently shown that MIF drives the inflammation in these distinct anatomical sites. In preclinical models, genetic deletion or blockade of MIF reduces the severity of inflammation. Although MIF is generally an upstream cytokine which regulates downstream effector cytokines, MIF also intensifies type 3 immunity by promoting helper T 17 (Th17) plasticity. MIF- or CD74-targeted therapies have also reported to be well tolerated in clinical trials for other diseases. Recent findings suggest that MIF-CD74 axis is a new therapeutic target for SpA to improve various clinical features. Clinical trials for MIF- or CD74-targeted therapies for SpA patients are warranted.

Increased cardiovascular (CV) risk associated with nonsteroidal anti-inflammatory drugs (NSAIDs) is well recognized in the general population. This may limit the use of this effective therapy in patients with spondyloarthritis (SpA), a population already at high CV risk.Increased CV diseases and their risk factors in patients with SpA were consistently shown in recent population-level data. NSAIDs remained commonly prescribed in SpA, though their structural benefit remained controversial and the dispensing practice was variable in different regions in the world. A previous observation study suggested NSAIDs in SpA might be cardio-protective, possibly via their modulation of the chronic inflammatory state. A recent meta-analysis of nonrandomized studies also revealed no increased risk of a CV event. Interestingly, there is growing evidence that different NSAIDs might impose differential CV risk on patients with SpA.Recent evidence suggested NSAIDs were associated with a neutral and possibly lower CV risk in patients with SpA, which provided some reassurance for their use.

We aimed to investigate the relationship between epicardial adipose tissue (EAT) thickness, flow-mediated dilation (FMD), and carotid intima-media thickness (cIMT) in spondyloarthritis (SpA) patients compared to healthy controls.We performed a cross-sectional study including SpA patients aged ≤ 50 years without traditional cardiovascular risk factors and healthy controls matched for age and gender. Baseline characteristics, laboratory data, and SpA-related parameters were recorded. All participants underwent ultrasound examination with measurement of EAT thickness, FMD, and cIMT by both an experienced cardiologist and radiologist blinded to clinical data. The relationships between the ultrasound measurements were analyzed using Spearman's correlation coefficient and Person correlation.The study included 94 subjects (47 SpA and 47 healthy controls). The sex-ratio was 2.35; the median age of patients was 36 years (IQR: 28-46), and the median disease duration was 11 years (IQR: 5-16). Compared to the control group, SpA patients had significantly higher values of EAT thickness (p = 0.001) and cIMT (p 0.0001). FMD values were significantly lower in SpA patients compared to controls (p = 0.008). The univariate analysis detected a significant negative association between EAT thickness and FMD (p = 0.026; r = - 0.325), and between left cIMT and FMD (p = 0.027; r = - 0.322). No association was found between EAT thickness and cIMT.EAT thickness, FMD, and cIMT were significantly impaired in SpA patients compared with healthy controls supporting evidence of accelerated atherosclerosis in SpA. EAT thickness was correlated to endothelial dysfunction suggesting the role of EAT in predicting the early reversible stages of atherosclerosis. Key Points • Spondyloarthritis is associated with impaired subclinical atherosclerosis markers accurately increased epicardial fat and carotid intima-media thickness and endothelial dysfunction. • Increased epicardial fat thickness is correlated with impaired endothelial function in spondyloarthritis patients.

Objectives: to describe the driving difficulties experienced by individuals with axial spondyloarthritis (axSpA), and characterise associated clinical and sociodemographic features, and impact on work.Method: the Scotland Registry for Ankylosing Spondylitis (SIRAS) is a cohort study of patients with a clinical diagnosis of axSpA. Baseline information was collected on clinical and patient‐reported measures, and work participation measures (Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI: SHP)). Patient‐rated difficulties with nine driving tasks were used in a factor analysis, and relationships between driving difficulty and work participation investigated.Results: 718 patients provided data for analysis, of which 642 (89%) had some difficulty with at least one driving task and 72 (10%) had some difficulty with all nine tasks. Three domains of driving difficulty were identified: dynamic driving scenarios, crossing traffic, and the physical act of driving. Chronic widespread pain, knee and back pain, fatigue, high disease activity and anxiety/depression were significantly associated with reporting driving difficulties across all three domains, particularly the physical act of driving. After adjusting for socio‐demographic, disease activity, physical and mental health, driving difficulties in each domain were associated with a 2‐3 times increased likelihood of restricted work productivity and with an increased risk of sickness absence in the past seven days.Conclusion: driving difficulties are common in individuals with axSpA and impact on work, even after adjusting for clinical status. Improving understanding and awareness of driving disability will help direct advice and resources to enable individuals to remain independent and economically active.

ObjectiveTo evaluate the impact of a wearable activity tracker used to encourage physical activity, on disease flares in patients with spondyloarthritis (SpA).MethodsThis randomized controlled trial involved randomizing 108 patients with SpA into tracker and nontracker groups. The participants were then subjected to assessments of disease activity, performance (6-minute walk test), and quality of life (QOL; 36-item Short Form Health Survey) at the 12th, 24th, and 36th week. The primary outcome was the change in the frequency of flare episodes (categorized as no flare, flare in ≤ 3 days, and flare in > 3 days) between baseline and 12 weeks.ResultsThe results of the study showed that at the 12th week, the mean change (∆) of the number of flares improved in both groups: −0.32 (95% CI −0.66 to 0.02) and −0.38 (95% CI −0.68 to −0.09) in the tracker and nontracker group, respectively. However, the between-group differences were insignificant (P = 0.87). Performance scores improved in both groups at the 12th, 24th, and 36th week (all P < 0.01). The different dimensions of QOL also improved at the 12th week (P < 0.01). Conversely, moderate flares (P < 0.01) and performance (P < 0.01) improved over time; however, the influence over time of a wearable activity tracker was not significant (P = 0.29 and P = 0.66, respectively).ConclusionThe use of a wearable activity tracker did not affect the number of flares, performance, or QOL of patients with SpA. Nevertheless, this study confirmed the benefits of physical activity on flares, disease activity, QOL, and physical performance in patients with SpA. (Move Your Spondyl “Better Live Its Rheumatism With the Physical Activity”; ClinicalTrials.gov: NCT03458026)

ObjectiveHealth-related quality of life (HRQOL) is an important aspect in the management of chronic diseases such as spondyloarthritis (SpA). A promising approach to reduce respondent burden when measuring HRQOL is the use of shorter patient-reported outcome measures (PROMs) delivered using computerized adaptive tests (CATs). However, the lack of an item bank that covers the entire continuum of the HRQOL domain impedes the development of CATs to measure HRQOL among patients with SpA. We aimed to develop an item bank for an HRQOL measure among patients with SpA based on the items from existing validated PROMs.MethodsThis study is guided by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) and Patient Reported Outcomes Measurement Information System (PROMIS) standards. Relevant articles were retrieved from PubMed, Embase, and PsycINFO (Ovid) databases. Items from existing PROMs were binned and winnowed according to the facets of HRQOL in the World Health Organization (WHO) quality of life framework.ResultsWe identified 147 relevant articles, from which written permission was obtained for including 31 PROMs into the item bank. PROMs contained 1039 items, which underwent binning and winnowing. This resulted in 968 items covering 23 domains of HRQOL in the WHO framework, with the number of items within each domain ranging from 1 to 453.ConclusionWe created an item bank to measure HRQOL among patients with SpA using items from validated PROMs. This set can provide the foundation for the development of CATs to measure HRQOL among patients with SpA.

To determine the correlations between four quantitative magnetic resonance imaging (MRI) parameters derived from intravoxel incoherent motion diffusion-weighted images (IVIM DWI) and the semi-quantitative Spondyloarthritis Research Consortium of Canada (SPARCC) score of the sacroiliac joint (SIJ) and five clinical activity indices in patients with axial spondyloarthritis (axSpA).A total of 75 patients with axSpA and complete clinical activity indices and SIJ MRI were enrolled to this prospective study. Univariable and multivariable linear regression analyses were performed to evaluate correlations between MRI parameters and clinical activity indices after controlling for confounders. All data were further analysed using Pearson's correlation coefficients (r).Only pure diffusion coefficient (D) and incoherent perfusion related microcirculation (D∗) were found to be independently positively correlated with several clinical activity indices (all p0.05). Positive correlations were observed between D and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), Patient Global Assessment (PGA), extent of influence of pain, with r of 0.605, 0.402, 0.319, and 0.485 (all p0.0125). D∗ correlated positively with BASDAI, BASFI, and PGA (r=0.436, 0.356, 0.301, respectively; all p0.0125).D and D∗ derived from IVIM DWI could be associated with some disease activity indices in patients with axSpA; apparent diffusion coefficient (ADC) and SPARCC scores were not correlated with these indices. IVIM DWI may be a useful tool for the quantitative assessment of disease activity in patients with axSpA.

Spondyloarthritis (SpA) is one of the most common extraintestinal manifestations of inflammatory bowel disease (IBD). Diagnostic delay must be avoided.We assessed the validity of SpA screening criteria (any of the following characteristics: chronic low back pain with onset before 45 years of age; inflammatory lower back pain or alternating buttock pain; arthritis; heel enthesitis; dacylitis; HLA-B27 positivity; sacroiliitis on imaging).This was a multicenter cross-sectional observational study in IBD patients aged ≥18 years. After evaluating the SpA screening criteria, the gastroenterologists referred the participants to the rheumatologists, who determined whether the patient fulfilled the screening criteria and carried out the necessary tests for SpA diagnosis.35 (11.7%) out of 300 patients were diagnosed with SpA. The combination with the best balance between sensitivity and specificity (91.4% and 72.1%, respectively, when applied by the rheumatologists; 80% and 78.9%, when applied by the gastroenterologists) for SpA screening, was fulfillment of any of the following: chronic low back pain with onset before age 45 years, inflammatory low back pain or alternating buttock pain, arthritis, or dactylitis.This is one of the first studies to validate SpA screening criteria in IBD patients in routine clinical practice.

Acknowledgements: The authors thank Lorena Chávez, José Luis Santillán, Simón Guzmán, and Jorge Ramírez for the microarray analysis., To analyze the effect of levofloxacin-induced intestinal microbiota modifications on intestinal, joint, and systemic inflammation in the DBA/1 mice with spontaneous arthritis. The study included two groups of mice, one of which received levofloxacin. The composition and structure of the microbiota were determined in the mice's stool using 16S rRNA sequencing; the differential taxa and metabolic pathway between mice treated with levofloxacin and control mice were also defied. The effect of levofloxacin was evaluated in the intestines, hind paws, and spines of mice through DNA microarray transcriptome and histopathological analyses; systemic inflammation was measured by flow cytometry. Levofloxacin decreased the pro-inflammatory bacteria, including Prevotellaceae, Odoribacter, and Blautia, and increased the anti-inflammatory Muribaculaceae in mice's stool. Histological analysis confirmed the intestinal inflammation in control mice, while in levofloxacin-treated mice, inflammation was reduced; in the hind paws and spines, levofloxacin also decreased the inflammation. Microarray showed the downregulation of genes and signaling pathways relevant in spondyloarthritis, including several cytokines and chemokines. Levofloxacin-treated mice showed differential transcriptomic profiles between peripheral and axial joints and intestines. Levofloxacin decreased the expression of TNF-α, IL-23a, and JAK3 in the three tissues, but IL-17 behaved differently in the intestine and the joints. Serum TNF-α was also reduced in levofloxacin-treated mice. Our results suggest that the microbiota modification aimed at reducing pro-inflammatory and increasing anti-inflammatory bacteria could potentially be a coadjuvant in treating inflammatory arthropathies.

The purpose of this study was to clarify the clinical characteristics of spondyloarthritis (SpA) patients with inflammatory bowel disease (IBD) compared to those without IBD. Furthermore, among patients with SpA and IBD, we aimed to clarify what clinical characteristics lead rheumatologists to diagnose "IBD-related arthritis." Utilizing SpA and psoriatic arthritis (PsA) patients' data from an international, cross-sectional, observational study, we analyzed information on demographics and disease characteristics, dichotomizing patients by IBD status. The presence or absence of IBD was determined based on data collection of treating rheumatologists. Patients with SpA (including PsA) and IBD were also categorized based on treating rheumatologists' definitive diagnosis in regard to SpA type, and compared by whether the patients had IBD-related arthritis or not. Among 4465 SpA patients, 287 (6.4%, 95%CI 5.7-7.2%) were identified with IBD. Compared to SpA patients without IBD, patients with SpA and IBD had a longer diagnostic delay (5.1 vs. 2.9 years, p 0.001). In patients with SpA and IBD, 111 (38.7%, 95%CI 33.0-44.6%) were diagnosed with IBD-related arthritis. Multivariable analyses showed that HLA-B27 positivity [OR = 0.35, (95%CI 0.15-0.80)], psoriasis [OR = 0.14, (95%CI 0.04-0.50)], IBD as first symptom of SpA [OR = 3.32, (95%CI 1.84-6.01)], and need for IBD-specific treatment [OR = 5.41, (95%CI 2.02-14.50)] were independently associated with the definitive diagnosis of IBD-related arthritis. Collaboration with gastroenterologists is needed to shorten the diagnostic delay in patients with SpA and IBD. The recognition of the factors for the diagnosis of "IBD-related arthritis" may lead to the elucidation of the pathogenesis.

Objective The primary goal of this study was to determine the prevalence of peripheral spondyloarthritis (pSpA) in patients with ultrasonography (USG)-confirmed enthesitis. The secondary aim of the study was to reveal the demographic, clinical, and ultrasonographic differences of patients diagnosed with pSpA. Methods Fifty-nine patients with USG-confirmed enthesitis were evaluated by a rheumatologist to evaluate if they met the Assessment of SpondyloArthritis International Society (ASAS) criteria for pSpA. Elementary lesions assessed by USG were based on the definition of the Outcome Measures in Rheumatology in Clinical Trials group which included hypoechogenicity, thickening, Doppler signal within 2 mm of bone, enthesophytes, bone erosions, and calcifications. For all patients, clinical and demographic data included: age, gender, smoking habits, body mass index, comorbid diseases, symptom duration, enthesitis region, the presence of bilateral enthesitis, entheseal pain visual analog scale (0-10), standardized enthesitis count following Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) and SPondyloArthritis Research Consortium Canada (SPARCC) enthesitis index. Results Eight (13.6%, 95% CI 6.0% to 25.0%) of 59 patients were diagnosed with pSpA according to the ASAS classification criteria. Participants diagnosed with pSpA had a longer duration of symptoms (54 vs 12 months), were more likely to present bilateral enthesitis (87.5% vs 49%) with higher SPARCC (11 vs 3) and MASES (6.5 vs 2) scores and higher C-reactive protein (7 vs 3.2 mg/L) concentrations. Entheseal Doppler signal and hypoechogenicity were also more frequently observed (50% vs 0% and 100% vs 49% respectively). Conclusion Peripheral SpA is not uncommon among patients presenting with enthesitis and more likely in cases with prolonged, extensive, and bilateral enthesitis with entheseal hypoechogenicity and Doppler signal. Musculoskeletal ultrasonography can facilitate the diagnosis of pSpA in patients presenting with enthesitis.

Background and Aims Inflammatory bowel disease [IBD] has been associated with spondyloarthritis [SpA], but population-based estimates are scarce. Here we compare the occurrence of SpA before and after a diagnosis of IBD with the general population, overall and by IBD subtype and age. Methods We used a nationwide register-based cohort study of 39 203 patients diagnosed with IBD during 2006-2016, identified from Swedish registers and gastrointestinal biopsy data, and 390 490 matched reference individuals from the general population. Conditional logistic regression models were used to estimate odds ratios [ORs] for a prior [prevalent] SpA diagnosis and conditional Cox regression to calculate hazard ratios [HRs] for a subsequent [incident] SpA diagnosis in IBD patients. Results IBD patients were more likely to have prevalent SpA at IBD diagnosis [2.5%] compared with reference individuals [0.7%] with an OR of 3.48 [95% CI: 3.23, 3.75]. They also more often received an incident diagnosis of SpA; during 23 341 934 person-years of follow-up in IBD patients, there were 1030 SpA events [5.0/1000 person-years] compared with 1524 SpA events in the reference group [0.72/1000 person-years], corresponding to an HR of 7.15 [95% CI: 6.60, 7.75]. In subgroup analyses, associations were most pronounced among patients with Crohn’s disease ([OR = 5.20; 95% CI: 4.59, 5.89], and [HR = 10.55; 95% CI: 9.16, 12.15]) and paediatric onset IBD ([OR = 3.63; 95% CI: 2.35, 5.59] and [HR = 15.03; 95% CI: 11.01, 20.53]). Conclusions IBD patients more frequently experience SpA both before and after the diagnosis of IBD compared with the general population, supporting evidence of a shared pathophysiology. The variation in SpA comorbidity, across IBD subtypes and age groups, calls for targeted approaches to facilitate timely diagnosis and intervention.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease predominantly affecting the axial skeleton. axSpA includes radiographic (i.e., ankylosing spondylitis (AS)) and non-radiographic forms (nr-axSpA). Although recent studies have reported that patients with AS have impaired gait, axSpA’s consequences on gait remain unknown. The present review’s objectives were to identify: 1) how gait is assessed in patients with axSpA, and 2) what the gait characteristics are of patients with axSpA. This systematic review’s protocol was registered in the Prospero database (CRD42020128509). Three databases were systematically searched using keywords related to axSpA and gait. Two independent reviewers selected the articles and extracted the data. The search revealed two hundred titles and abstracts, and two articles were finally included in this review, comprising a total of 132 patients with axSpA. One of the included studies used the 6 m maximum gait velocity test (axSpA: 2.2 ± 0.5 m/s), and the other used the six-minute walk test (axSpA: 414 ± 106 m). Neither study involved a control group to compare gait. Only two published studies assessed the gait performance of patients with axSpA using clinical tests. Furthermore, neither of them compared gait performance to healthy controls or differentiated gait between the AS and nr-axSpA forms of axSPA. The present literature review highlights the need for future research to learn more about how gait is impaired in different types of patients with axSpA.

ObjectiveTo investigate the performance of a health app with respect to usability, adherence, and equivalence of data in daily care of patients with axial spondyloarthritis (axSpA).MethodsConsecutive patients with axSpA were asked to export patient-reported outcomes (PRO) electronically with the AxSpA Live App regularly every 2 weeks over a period of 6 months. The first clinical visit was followed by 2 further personal visits after 3 and 6 months. Patients completed paper-based PRO at every visit; they also completed the Mobile App Rating Scale and the System Usability Scale after 3 and 6 months.ResultsOf 103 patients with axSpA, 69 agreed to participate (67.0%): age 41.5 (11.3) years, 58.0% male, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 4.3 (2.0), and 76.8% treated with biologic disease-modifying antirheumatic drugs. Patients’ adherence to regular app exports was 29.0% and 28.4% after 3 and 6 months, respectively. Significant predictors for good adherence were high disease activity (P = 0.02) and older age (P = 0.04). No systematic differences between digital and paper-based BASDAI scores were found (intraclass correlation coefficients 0.99 [95% CI 0.98-0.99]). Performance of the app was rated as good.ConclusionCollection of digital PROs by AxSpA Live App may be successfully used in patients with axSpA with high disease activity. Our study showed equivalence of digital data, but adherence to the app after 6 months was poor. Higher disease activity and older age resulted in increased adherence to the app. This suggests that the use of health apps like this should concentrate on more severely affected patients.

To evaluate a stratified screening process for the early identification of axial spondyloarthritis (SpA) with consideration of the following: 1) wait times from primary care to rheumatology screen, 2) incremental precision and accuracy from primary care to rheumatology screening, and 3) diagnostic delay.Adults with low back pain attending primary care at low back pain clinics prospectively underwent a primary standardized clinical screening. Patients with low back pain of3 months who experienced symptom onset at age50 years were referred for a comprehensive secondary screening by a physical therapist with advanced rheumatology training. At secondary screening, patients with features of inflammation were classified as being at a low, medium, or high risk for axial SpA versus no risk for axial SpA. Precision and accuracy of this screening strata were measured against a rheumatologist with expertise in axial SpA.Overall, 405 patients underwent primary and secondary screening in the present study. The study cohort had a mean ± SD age of 36.9 ± 9.9 years, and 55% were women. HLA-B27 was present in 14.4% of patients. Median wait time from primary screening to secondary screening was 15 days. Axial SpA risk assignment by rheumatologist was 64.9% for no risk or low risk for axial SpA and 35.1% for medium risk or high risk for axial SpA. The best combination of sensitivity (68%), specificity (90%), positive predictive values (80%), and negative predictive values (84%) was evident in the secondary screening. In this cohort, 15.6% of patients received a final diagnosis of axial SpA. Median low back pain duration from symptom onset to diagnosis was 2 years for nonradiographic axial SpA and 7 years for ankylosing spondylitis.A stratified interprofessional screening process can facilitate rapid diagnosis of persistent low back pain with high precision and accuracy in patients who have axial SpA.

The differences in the epidemiology and management of patients with axial spondyloarthritis (axSpA) among regions and countries largely depend on the positivity of human leukocyte antigen (HLA)-B27 and the health care system. This review article focused on axSpA in Japan, where the prevalence of HLA-B27 is extremely low (0.3%) and the universal health insurance system typically provides a 70% or more copayment by the government.A nationwide survey was conducted in Japan in 2018, which estimated that there were 3200 patients (95% confidence interval [CI]: 2400-3900) with ankylosing spondylitis (AS), a term interchangeable with radiographic axSpA (r-axSpA), and 800 patients (95% CI: 530-1100) had non-radiographic (nr)-axSpA. These data indicate a prevalence of 2.6/100,000 or 0.0026% for AS and 0.6/100,000 or 0.0006% for nr-axSpA. Patients with AS, but not those with nr-axSpA, are designated as suffering from intractable diseases in Japan; thus, their medical expenses are reduced by grant under the Act on Medical Care for Patients with Intractable Diseases. As of February 2022, infliximab, adalimumab, secukinumab, ixekizumab, and brodalumab have been approved for AS, and secukinumab, ixekizumab, and brodalumab have been approved for nr-axSpA. An algorithm for nr-axSpA in Japan has been developed for the proper diagnosis and use of these therapeutic agents. A low prevalence of axSpA, especially that of nr-axSpA, was found in Japan. Early referral and the resultant diagnosis and appropriate treatment of these patients by rheumatologists are crucial issues in Japan, as in other countries.

Axial Spondyloarthritis is a rheumatic condition affecting young patients with social and occupational consequences. Diagnosis delay is associated with functional impairment and impact on quality of life, requiring a multidisciplinary approach.To develop a set of recommendations based on the best available evidence for early detection, diagnosis, treatment and monitoring adult patients with axial spondyloarthritis.A working group was established, questions were developed, outcomes were graded, and a systematic search for evidence was conducted. A multidisciplinary panel of members was established (including patient representatives), minimizing bias in relation to conflicts of interest. The GRADE approach "Grading of Recommendations Assessment, Development and Evaluation" was used to assess the quality of the evidence as well as the direction and strength of recommendations. In total, 11 recommendations with regard to diagnosis (n = 2), pharmacological treatment (n = 6), non-pharmacological treatment (n = 2) and monitoring (n = 1) are presented.Sacroiliac joint radiography as the first diagnostic method, and the use of disease activity scales for patient monitoring (ASDAS or BASDAI), are recommended. Nonsteroidal anti-inflammatory drugs are the first treatment option; in case of intolerance or residual pain, acetaminophen or opioids are recommended. In patients with axial involvement, it is recommended not to use conventional disease-modifying antirheumatic drugs or systemic or local glucocorticoids. In patients with failure to non-steroidal anti-inflammatory drugs, anti-TNF or anti-IL17A is recommended. In those patients presenting with anti-TNF failure, starting an anti-IL17A is recommended. Exercise, physical and occupational therapy are recommended as part of treatment. It is recommended not to use unconventional therapies as the only treatment option.This set of recommendations provides an updated guide on the diagnosis, treatment and monitoring of patients with axial spondyloarthritis.

To review the effectiveness of secukinumab (SEC) in patients with juvenile idiopathic enthesitis related arthritis (ERA), who had partial or no response on anti-TNF therapy.We conducted a retrospective monocentric chart review of patients with ERA, who were treated with SEC, until March 15th 2019. We used the JADAS10 and the Juvenile Spondyloarthritis Disease Activity Index (jspADA) to evaluate response. We analysed the onset of AE and SAE.We analysed 17 patients with ERA. The mean age at the start of the treatment was 19.5 years (SD 4.9, range 13-34 years, median 18.2). The mean disease duration was 6.3 years (SD 3.3, range 2-12 years). The patients received in average 1.9 (SD1.0) different anti-TNF'́s before switching to SEC. SEC was applied at the start of the treatment with 150 mg per dose (n=13, 76.5%) and 300 mg per dose (n=4, 23.5%). The dose of 150 mg was increased in 11 patients (85% of 13) after baseline. The mean follow-up of patients was 18.2 months (SD 7.2) accounting to 25.8 years under exposure to SEC. The jspADA (mean change of -1.3; p0.001; 95%CI: -1.9 to -0.7) and JADAS10 (mean change of -2.4; p=0.021; 95%CI: -4.5 to -0.4) signi cantly improved between baseline and the 24-month follow-up. There was no serious adverse event observed.In our anti-TNF non-responder patients SEC showed good effectiveness. The 150 mg dose seems to be insufficient in anti-TNF non-responder patients and most patients had to be escalated to the 300 mg/dose.

ObjectiveFactors predicting axial spondyloarthritis (axSpA) among first-degree relatives (FDRs) of ankylosing spondylitis (AS) patients need to be defined. We investigated the predictive value of the probands’ HLA-B27 and radiographic sacroiliitis status on disease occurrence among their FDR. We also assessed the predictive value of features of the clinical history, including chronic inflammatory back pain (CIBP) and acute anterior uveitis (AAU), among the FDR and how they can be used to improve classification and diagnosis of axSpA.MethodsIn 1985, we studied 363 AS probands and 806 FDR who underwent rheumatologic examination, completed questionnaires, provided blood samples for HLA-typing and underwent radiography of sacroiliac joints. At follow-up in 2018–2019, 125 patients and 360 FDR were available for study, and completed a postal questionnaire about axSpA features. FDRs were asked to report whether after 1985 they had been diagnosed by Swiss rheumatologists as having axSpA.ResultsAmong HLA-B27(+) FDR, axSpA occurred in 25.4%–26.3%, independent of the radiographic sacroiliitis status of the proband. AAU occurred in 13/34 (38.2%) FDR with axSpA vs 29/251 (11.6%) FDR without axSpA (p=0.00004, OR=4.74 95% CI 2.15 to 10.47). The presence of CIBP at baseline did not predict later occurrence of axSpA but combining CIBP and pain/discomfort at the thoracic spineandat anterior (ventral) chest wall ever, assessed at follow-up in 2018–2019, provided 83.1% sensitivity and 87.2% specificity for current axSpA.ConclusionOccurrence of AAU among FDR of axSpA probands should prompt screening for axSpA. Moreover, co-occurrence of CIBP and pain/discomfort in the thoracic spine and at anterior chest wall as a three-question tool may further enhance clinical suspicion of axSpA among these FDR.

Diagnosis and management of axial spondyloarthritis (axSpA) has vastly improved over the past two decades. With advances in the discernment of immunopathogenesis of this disease, new therapies have become available, which are associated with substantial improvement in symptoms, signs and quality of life. The four broad categories of approved treatment options are physical therapy and exercise (which have been known to be beneficial for millennia), NSAIDs (since the 1950s), TNF inhibitors (first FDA approval in 2003) and IL-17 inhibitors (first FDA approval in 2016). In addition, there have been a host of new developments in the axSpA field, including new treatment guidelines, the FDA approval of three biologic DMARDs to treat non-radiographic axSpA, the FDA and EMA approval of Janus kinase (JAK) inhibitors for ankylosing spondylitis, new data on the effect of biologic DMARDs on structural progression in ankylosing spondylitis, strategy trials on tapering or stopping TNF inhibitors in patients in remission, trials of treat-to-target strategy in axSpA, and several new molecules in phase III studies. This Review explores the developments in the management of axSpA.

BACKGROUND: Axial spondyloarthritis (axSpA) is an inflammatory rheumatic disease primarily affecting the axial skeleton. OBJECTIVE: To evaluate the short-term effects of locoregional water-filtered infrared A radiation (sl-wIRAR) in the treatment of lower back pain in patients with axSpA. METHODS: Patients with active axSpA with non-steroidal anti-inflammatory drug (NSAID) therapy undergoing a 7-day multimodal rheumatologic complex treatment in an in-patient setting were eligible. Patients were randomly assigned to the intervention group (IG) receiving sl-wIRAR treatment of the back (2 treatments/day for 30 min each for 6 days) or to the control group (CG) receiving no treatment. Primary outcome was a between-group difference in pain after sl-wIRAR therapy measured on a numeric rating scale (NRS) (0 = no pain, 10 = worst pain). Secondary outcomes included an assessment of i) the onset and development of analgesic effects and an evaluation of whether sl-wIRAR ii) improved axSpA-specific well-being and iii) influenced serum cytokine levels. RESULTS: Seventy-one patients were enrolled, completed the trial and were analyzed (IG: 36 patients, CG: 35 patients). In the IG, there was a statistically significant change (p< 0.0005) in pain level [NRS] (1.6 ± 1.9 [5; 2]) from baseline (4.1 ± 2.4 [0; 8]) to trial completion (2.6 ± 2.0 [0; 7]) and a significant difference to the CG (p= 0.006). In the IG there was a significant improvement in axSpA-specific well-being (BAS-G) (p= 0.006). A physiologically relevant change in serum cytokine levels could not be observed. CONCLUSION: sl-wIRAR treatment can be useful in the treatment of patients with active axSpA as it leads to a rapid reduction of pain.

Structural lesion evaluation in axial spondyloarthropathy (SpA) can improve accuracy of diagnosis. However, structural lesions (bone erosions) are difficult to be assessed using conventional MRI compared to computed tomography (CT).To evaluate the diagnostic performance of ultrashort echo time (UTE) for detecting bone erosion in axial SpA compared to T1WI and three-dimensional double-echo steady-state (3D DESS) imaging using CT as the reference standard.Retrospective.Fourteen patients (eight females, 57.1%) and 14 healthy controls (seven females, 50.0%) who underwent sacroiliac (SI) joint MRI and CT.3 T; TSE T1WI, 3D DESS, 2D UTE.The bilateral SI joints were assessed for bone erosion. Three observers scored bone erosion for all three sequences of MRI. CT was used as the gold standard. Diagnostic confidence in axial SpA was measured based on a four-point confidence score.Correlation of erosion scores between CT and MRI were evaluated using Spearman's correlation test. Sensitivity, specificity, and positive-negative predictive values were calculated. Confidence scores were compared using the Wilcoxon sum rank test. Statistical significance was set at P 0.05.Compared with erosion scores of CT, the correlation coefficients for each MRI sequence showed significant low-to-high positive correlations (0.39-0.72). UTE imaging showed the highest correlation coefficients for all observers (0.70, 0.72, and 0.67, respectively). The specificity of UTE imaging was equal or higher than those of T1WI and 3D DESS for all observers (0.86 vs. 0.71 vs. 0.57; 0.93 vs. 0.71 vs. 0.57; 0.79 vs. 0.79 vs. 0.43). All observers had the highest confidence in interpreting UTE imaging for detecting bone erosion among the three sequences (3.5, 3.4, and 3.3 for UTE; 3.1, 3.0, and 2.6 for T1WI; and 3.2, 2.7, and 2.4 for DESS).UTE imaging can detect bone erosions in patients with axial SpA and show higher specificity than conventional T1WI and 3D DESS.4 TECHNICAL EFFICACY: Stage 2.

We aimed to investigate muscle physical properties, strength, mass, physical performance, and the prevalence of sarcopenia in patients with axial spondylarthritis (axSpA) compared to the healthy controls (HC).We performed a cross-sectional study on 54 participants: 27 patients with axSpA and 27 HC, matched by age, gender, and level of physical activity. Muscle physical properties (stiffness, tone and elasticity), muscle strength (five-times sit-to-stand [5STS] test), muscle mass, physical performance (measured through gait speed) and sarcopenia were compared between the groups. Linear regression models were conducted allowing adjustment for relevant variables.Patients with axSpA (mean age 36.5 (SD 7.5) years, 67% males, mean disease duration 6.5 (3.2) years) had no significant difference in segmental muscle stiffness, tone or elasticity, compared with the HC, despite showing a slight numerically higher lower lumbar (L3-L4) stiffness [median 246.5 (IQR 230.5-286.5) vs. 232.5 (211.0-293.5), p=0.38]. No participants presented sarcopenia. Patients with axSpA, compared to the HC, had lower total strength [B=1.88 (95% CI 0.43;3.33)], as well as lower strength in the upper (B=-17.02 (-27.33;-6.70)] and lower limbs [B=-11.14 (-18.25;-4.04)], independently of muscle physical properties. Patients had also significantly lower gait speed than the HC [B=-0.11 (-0.21;-0.01)], adjusted for muscle mass, strength and muscle physical properties.Young axSpA patients with a relatively short disease duration presented similar segmental muscle physical properties as the HC and had no sarcopenia. Patients with axSpA had reduced physical performance and lower strength compared to the HC, despite normal muscle mass, suggesting a possible muscle dysfunction. Gait characteristics may be a potential biomarker of interest in axSpA.

In 2009, the Assessment of SpondyloArthritis international Society (ASAS) published a definition of ‘active sacroiliitis on magnetic resonance imaging (MRI) for classification of axial spondyloarthritis’. This new definition of an ‘ASAS-positive MRI’ was integral to new classification criteria for axial spondyloarthritis that were published in the same year. The ASAS MRI definition had the considerable advantage of simplicity and the definition gained popularity as guidance for interpreting MRI of the sacroiliac joints in clinical practice. However, classification criteria are not designed for use in clinical practice with the consequence that overreliance on the presence of bone marrow edema, which is the principal determinant of an ‘ASAS-positive MRI’, may result in a tendency to overcall inflammatory sacroiliitis in the clinical setting. This article aims to inform the reader about the rationale behind the ASAS definition of a positive MRI and ASAS classification criteria, their proper use in research and why they should not be used in clinical practice. The article also contains guidance for an updated imaging protocol and interpretation of images including typical imaging findings, differential diagnosis, and common pitfalls.

Objective To evaluate response rates at week 16 with ixekizumab in patients with radiographic axial SpA (r-axSpA) and elevated or normal/low baseline inflammation measured by serum CRP or spinal MRI using data from two randomized, double-blind, placebo (PBO)-controlled phase III trials. Methods Biologic-naïve (COAST-V) or TNF inhibitor-experienced (COAST-W) adults with active r-axSpA received 80 mg ixekizumab every 2 weeks (IXEQ2W) or 4 weeks (IXEQ4W) or PBO or active reference [40 mg adalimumab every 2 weeks (ADAQ2W) in COAST-V. At week 16, patients receiving ixekizumab continued as assigned and patients receiving PBO or ADA were rerandomized 1:1 to IXEQ2W or IXEQ4W through week 52. Assessment of SpondyloArthritis international Society 40% (ASAS40) response rates were examined by baseline CRP (≤5 or >5 mg/l) and Spondyloarthritis Research Consortium of Canada (SPARCC) MRI spine inflammation score ( Results In the COAST-V/W integrated dataset (N = 567), significantly more patients treated with ixekizumab achieved ASAS40 response at week 16 by CRP ≤5 mg/l (27% IXEQ4W, P 5 mg/l (39% IXEQ4W, P Conclusion Ixekizumab demonstrated efficacy in the treatment of AS/r-axSpA in patients with and without elevated CRP or evidence of spinal inflammation on MRI. Trial registration ClinicalTrials.gov (https://clinicaltrials.gov): NCT02696785, NCT02696798

People with axial spondyloarthritis (AS) have an inflammatory profile, increasing the risk of hypertension, type 2 diabetes, obesity, and dyslipidaemia. Consequently, AS is linked with co-morbidities such as cardiovascular disease (CVD). Physical inactivity, diet, smoking, alcohol consumption, and obesity influence inflammation, but knowledge of the interaction between these with inflammation, disease activity, and CVD risk in AS is dominated by cross-sectional research.A review of the literature was conducted between July 2020 and December 2021. The focus of the scoping review is to summarise longitudinal and randomised control trials in humans to investigate how tracking or modifying lifestyle influences inflammation and disease burden in patients with AS.(1) Lifestyle modifications, especially increased physical activity (PA), exercise, and smoking cessation, are critical in managing AS. (2) Smoking is negatively associated with patient reported outcome measures with AS, plus pharmaceutical treatment adherence, but links with structural radiographic progression are inconclusive. (3) Paucity of data warrant structured studies measuring inflammatory cytokine responses to lifestyle modification in AS.Increased PA, exercise, and smoking cessation should be supported at every given opportunity to improve health outcomes in patients with AS. The link between smoking and radiographic progression needs further investigation. Studies investigating the longitudinal effect of body weight, alcohol, and psychosocial factors on disease activity and physical function in patients with AS are needed. Given the link between inflammation and AS, future studies should also incorporate markers of chronic inflammation beyond the standard C-reactive protein and erythrocyte sedimentation rate measurements.

To describe the observations of studies that have explored the effects of exercise on inflammation and tissue remodeling in animal models of inflammatory arthropathies including Rheumatoid Arthritis and Spondyloarthritis.A search was performed at Pubmed, Scopus and Web of Science databases from 2010 to 2021. The selected articles were classified into those who reported positive and negative effects of exercise, and the characteristics of their experimental designs, including the animal model, the study groups, the exercise intervention and the evaluation techniques, were detailed.Thirteen original articles that met the selection criteria were included. The effects of exercise on the joint biology of mice with inflammatory arthritis were controversial. Although exercise benefits have been observed in some experimental designs, the majority of them have shown that exercise leads to exacerbation of inflammation, tissue remodeling, and processes associated with arthritis such as oxidative stress and hypoxia.Further research is necessary as the existing guidelines do not consider the negative effects of the exercise evidenced in animal models. The potential risks of exercise for patients should be considered.

To determine the prevalence and risk factors for uveitis in spondyloarthritis (SpA) patients.A total of 225 patients who fulfilled Assessment of Spondyloarthritis International Society classification criteria for axial and peripheral SpA were enrolled. The diagnosis of uveitis was confirmed by an ophthalmologist. From medical records and from clinical evaluation associated information like disease duration, and human leukocyte antigen B27 was collected. Relevant laboratory tests were done and disease severity was assessed using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score - erythrocyte sedimentation rate and C-reactive protein. Characteristics of uveitis positive and uveitis negative groups were compared. Multivariate logistic regression analysis was done for the risk factors, and P values.05 were considered significant.Prevalence of uveitis was 18.7%. The disease duration was 9.3 ± 7 years and 5.4 ± 4.5 years in uveitis and no uveitis groups respectively (P ≤ .001). Family history of SpA was positive in 45.2% in the uveitis group (P ≤ .001). The frequency of axial SpA was 92.9% and 73.8% in the uveitis and no uveitis groups respectively (P ≤ .008). The mean BASDAI was 2.4 ± 1.9 and 3.3 ± 2.8 in uveitis and no uveitis groups respectively (P = .050). In multivariate logistic regression analysis, among the selected variables, family history of SpA (odds ratio [OR] =3.697; 95% CI =1.616-8.457; P = .002) and duration of disease (OR =1.089; 95% CI =1.004-1.181; P = .039) were independently associated with the occurrence of uveitis.The prevalence of uveitis was 18.7%. The family history and the disease duration of SpA were independently associated with uveitis.

To determine among patients with axial spondyloarthritis (SpA) the factors associated with decreased spinal mobility and to determine whether poor mobility is a predictor of response to anti-tumor necrosis factor (anti-TNF) therapy.This was a prospective UK cohort study of persons meeting Assessment of Spondylarthritis international Society (ASAS) criteria for axial SpA. At recruitment, clinical and patient-reported factors independently associated with spinal mobility (measured by the Bath Ankylosing Spondylitis Metrology Index [BASMI]) were determined. Among those commencing anti-TNF therapy, factors that were independent predictors of response were determined using ASAS criteria, quality of life, and Ankylosing Spondylitis Disease Activity Score (ASDAS) response criteria.A total of 1,960 participants were eligible; 70% were male, the median age was 48 years (interquartile range [IQR] 37, 59), and the median BASMI score 3.6 (IQR 2.2, 5.3). Factors independently associated with poor spinal mobility were poorer function, meeting radiographic criteria for AS, longer symptom duration, higher levels of inflammation (measured by C-reactive protein level), older age, male sex, not being currently employed, and lower levels of education. For 51% of participants, the measured BASMI score was within 1 of that estimated. Poorer mobility (higher BASMI score) was an independent predictor of not meeting response criteria for ASAS 20% improvement (odds ratio [OR] per increasing score 0.80 [IQR 0.66, 0.98]), ASAS 40% improvement (OR 0.69 [IQR 0.50, 0.95]), and quality of life (measured by the Ankylosing Spondylitis Quality of Life Questionnaire) (β = 0.64 [IQR 0.26, 1.02]), but was not related to meeting ASDAS response criteria.The BASMI score was estimated moderately well by other routinely measured factors in patients with axial SpA and was an independent predictor of response to biologic therapy for some, but not all, commonly used measures. Consensus around its role in disease monitoring and clinical decisions, particularly in the likely context of face-to-face consultations becoming less frequent, remains to be established.

Objective The aim of this study was to develop a deep learning algorithm for detection of active inflammatory sacroiliitis in short tau inversion recovery (STIR) sequence MRI. Methods A total of 326 participants with axial SpA, and 63 participants with non-specific back pain (NSBP) were recruited. STIR MRI of the SI joints was performed and clinical data were collected. Region of interests (ROIs) were drawn outlining bone marrow oedema, a reliable marker of active inflammation, which formed the ground truth masks from which ‘fake-colour’ images were derived. Both the original and fake-colour images were randomly allocated into either the training and validation dataset or the testing dataset. Attention U-net was used for the development of deep learning algorithms. As a comparison, an independent radiologist and rheumatologist, blinded to the ground truth masks, were tasked with identifying bone marrow oedema in the MRI scans. Results Inflammatory sacroiliitis was identified in 1398 MR images from 228 participants. No inflammation was found in 3944 MRI scans from 161 participants. The mean sensitivity of the algorithms derived from the original dataset and fake-colour image dataset were 0.86 (0.02) and 0.90 (0.01), respectively. The mean specificity of the algorithms derived from the original and the fake-colour image datasets were 0.92 (0.02) and 0.93 (0.01), respectively. The mean testing dice coefficients were 0.48 (0.27) for the original dataset and 0.51 (0.25) for the fake-colour image dataset. The area under the curve of the receiver operating characteristic (AUC-ROC) curve of the algorithms using the original dataset and the fake-colour image dataset were 0.92 and 0.96, respectively. The sensitivity and specificity of the algorithms were comparable with the interpretation by a radiologist, but outperformed that of the rheumatologist. Conclusion An MRI deep learning algorithm was developed for detection of inflammatory sacroiliitis in axial SpA.

The spondyloarthritides are a diverse group of distinct yet interrelated disease processes with overlapping clinical features. They are ankylosing spondylitis, reactive arthritis, inflammatory bowel disease-associated arthritis, and psoriatic arthritis. Genetically, these disease processes have been linked by the presence of HLA-B27. They manifest with axial and peripheral symptoms, such as inflammatory back pain, enthesitis, oligoarthritis, and dactylitis. The onset of symptoms can begin before the age of 45; however, because of the wide range of signs and symptoms, diagnosis can be delayed, leading to unchecked inflammation, structural damage, and later, restriction in physical mobility.

Introduction: Hip involvement in patients with spondyloarthritis is responsible for disability and functional impairment. Its treatment is not codified. Our study aimed to determine the associated factors with moderate and severe hip involvement in spondyloarthritis patients. It also aimed to assess the efficacy of tumour necrosis factor inhibitors (TNFi) on hip disease. Methods: We conducted a cross-sectional study, including 44 spondyloarthritis patients with hip involvement. Hip involvement was diagnosed based on radiographic findings. We assessed the following parameters: Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Radiology Index (BASRI), patient global assessment (PGA), and Lequesne index. We compared these parameters and the mean radiographic joint space width between the time of the study to those right before the use of TNFi. Results: Hip involvement was bilateral in 31 patients. The mean age was 44.56±12.21 years. There were 29 men. Severe and moderate involvement (BASRI-hip>3) was reported in 21 hips from 75 affected. These patients were older and had longer diagnosis delays than patients with BASRI- hip Conclusion : Our study showed that higher body mass and Lequesne indexes are associated with moderate and severe hip involvement. TNFi may improve both the Lequesne index and PGA and stabilize the radiological findings.

To evaluate the frequency of sacroiliitis in older subjects.Consecutive MRI examinations of the sacroiliac joints (SIJs) performed for suspected sacroiliitis (2005-2019) in patients ≥ 18 years were retrospectively evaluated for the presence of active/structural lesions and were categorized for the presence/absence of sacroiliitis. Clinical and imaging parameters were compared between subjects with sacroiliitis according to age groups 40 years, 40-55, and 55 years. Clinical parameters including inflammatory back pain (IBP) and other spondyloarthritis (SpA) features were retrieved from the medical records.A total of 431 patients with SIJs MRI were evaluated: median age, 44 [IQR 35-54]; female:male 267(62%):164(38%). Sacroiliitis was diagnosed in 89 (20.6%) subjects-median age, 41 years [IQR 32-54], 52% females- and was equally prevalent among the different age groups: 40 years old, 23.6%; 40-55, 20%; and 55 years old, 17%, p = 0.43, with active/structural lesions equally dispersed. Older patients ( 55) started suffering from back pain at an older age and had a longer delay in diagnosis. Gender distribution, the presence of IBP, and other SpA features were no different in patients 45 and 55 years of age.The frequency of sacroiliitis on SIJs-MRI in subjects 55 years is similar to its frequency in younger subjects and is associated with the same type and magnitude of active and structural MRI lesions. Clinical parameters such as IBP and additional SpA features are similarly prevalent in older and younger subjects suggesting they suffer from the same disease and differing only in age of presentation.

Enthesitis-related arthritis (ERA) could be considered the pediatric equivalent of ankylosing spondylitis in adults albeit with certain significant differences. We aim to evaluate the sensitivity and specificity of the International League of Associations for Rheumatology (ILAR), the Assessment of Spondyloarthritis International Society (ASAS), and the preliminary Pediatric Rheumatology International Trials Organization (PRINTO) classification criteria in ERA patients.The medical records of ERA patients who were followed up between January 2005 and September 2020 have been analyzed. The control group consisted of patients with oligoarticular JIA (n = 146), polyarticular JIA (n = 55), and psoriatic arthritis (n = 20).This retrospective study included 108 ERA (73.1% male) and 221 control patients (25.8% male). The median age at diagnosis for ERA and control patients were 12.5 and 4.0 years, respectively (p 0.001). Arthritis was observed more frequently in the control group at diagnosis and in the follow-up (p 0.001 for both), while enthesitis, sacroiliac joint tenderness, and inflammatory back pain were more common in the ERA group both at diagnosis and in the follow-up (p 0.001 for all). In sacroiliac imaging, 70.1% of ERA patients had positive findings suggestive of sacroiliitis at diagnosis and 78% in the follow-up. The sensitivities of ILAR, PRINTO, ASAS criteria for axial SpA, and peripheral SpA at diagnosis were 74.0%, 57.4%, 21.3%, and 85.1%, respectively which increased to 82.4%, 78.7%, 35.1%, and 92.5%, respectively at follow-up. The specificities were 100%, 100%, 99.1%, and 90.9%, respectively at both diagnosis and follow-up.The ASAS criteria for peripheral SpA were the most sensitive while ILAR and the preliminary PRINTO criteria were the most specific criteria for classifying ERA patients.The ASAS criteria for peripheral SpA were the most sensitive criteria for classifying ERA patients. The use of ASAS axial SpA criteria may provide early detection of axial involvement.