Spondyloarthritis Features Research Articles

Diagnosing axial spondyloarthritis by multidiciplinary team conference at 3.5 years’ follow-up in a cohort of patients with disease features according to the ASAS criteria

Objectives During the past two decades, magnetic resonance imaging (MRI) has increasingly been used diagnostically in axial spondyloarthritis (axSpA), and in 2009 MRI was introduced in the Assessment of SpondyloArthritis Society (ASAS) classification criteria. In clinical practice, there is a risk of overdiagnosis if MRI findings are not related to clinical and biochemical findings. The aim of this study was to provide an estimate of the prevalence of axSpA in a cohort of clinical patients with low back pain and findings suggestive of axSpA according to ASAS through consensus diagnosis at a multi-disciplinary team (MDT) conference, and to describe the performance of the features included in the ASAS criteria. Method Consensus diagnoses of axSpA at MDT conferences were retrospectively established at 3.5 years’ follow-up in a cohort of 84 patients, initially referred with disease features according to the ASAS criteria. Patients were examined clinically regarding spondyloarthritis features, and biochemical tests and MRI of the sacroiliac joints and entire spine were performed at baseline and after a mean of 3.5 years. Results According to the MDT consensus, 25 patients (30%) of the total cohort had axSpA at follow-up; 40% of individuals who fulfilled the ASAS criteria at baseline had axSpA, and 37% at follow-up; 96% of axSpA patients according to the MDT consensus met the ASAS criteria at baseline and 92% at follow-up. Conclusion Approximately one-third of the included patients had axSpA when evaluated at the MDT conference. The ASAS criteria had low predictive value, but high sensitivity at both baseline and follow-up.

The Role of the IL-23/IL-17 Axis in Disease Initiation in Spondyloarthritis: Lessons Learned From Animal Models.

Spondyloarthritis (SpA) is a spectrum of chronic inflammatory joint diseases that frequently presents with inflammation of the axial skeleton, peripheral joints, entheses, skin, and gut. Understanding SpA pathogenesis has been proven challenging due to the limited availability of human target tissues. In recent years, the interleukin (IL)-23/IL-17 pathway has been implicated in the pathogenesis of SpA, in addition to the Tumor Necrosis Factor Alpha (TNF-α) cytokine. The underlying molecular mechanisms by which the IL-23/IL-17 pathway triggers disease initiation, both in the joints as well as at extra-musculoskeletal sites, are not precisely known. Animal models that resemble pathological features of human SpA have provided possibilities for in-depth molecular analyses of target tissues during various phases of the disease, including the pre-clinical initiation phase of the disease before arthritis and spondylitis are clinically present. Herein, we summarize recent insights gained in SpA animal models on the role of the IL-23/IL-17 pathway in immune activation across affected sites in SpA, which include the joint, entheses, gut and skin. We discuss how local activation of the IL-23/IL-17 axis may contribute to the development of tissue inflammation and the onset of clinically manifest SpA. The overall aim is to provide the reader with an overview of how the IL-23/IL-17 axis could contribute to the onset of SpA pathogenesis. We discuss how insights from animal studies into the initiation phase of disease could instruct validation studies in at-risk individuals and thereby provide a perspective for potential future preventive treatment.

Subclinical entheseal involvement in patients with rheumatoid arthritis

BackgroundEnthesopathy is a common feature of Spondyloarthritis (SpA) but can also be found in rheumatoid Arthritis (RA). Recognizing enthesopathy could be challenging because of low sensitivity and specific clinical testing. To detect enthesopathy, The European League Against Rheumatism (EULAR) recommends magnetic resonance imaging (MRI) or ultrasonography (US). Aim of the workTo investigate the frequency and distribution of entheseal involvement in RA patients and its relation to disease activity. Patients and methods100 RA patients with any symptom in foot and ankle were enrolled. Disease activity score (DAS28), Visual analogue scale (VAS), Health assessment questionnaire-Disability index (HAQ-DI) and Glasgow Ultrasound Enthesitis Scoring System (GUESS) were assessed. ResultsThe mean age of patients was 44.1 ± 12.2 years, disease duration was 7 ± 5.8 years and 86% were females. The mean DAS28 score was 4.3 ± 1.2 and GUESS score was 7.2 ± 4.2; all patients had variable degrees of enthesitis: 30% of patients had mild enthesitis, 42% had moderate enthesitis and 28% had marked enthesitis. GUESS was significantly higher in patients with moderate (7.8 ± 4.9) and high (7.2 ± 3.2) disease activity than in patients with low disease activity (5.2 ± 3.9) and those in remission (6.5 ± 1.9) (p = 0.015). HAQ, Age and ESR significantly correlated with GUESS score (r = 0.19, p = 0.049; r = 0.23, p = 0.023; r = 0.33, p = 0.001 respectively). ConclusionSubclinical enthesitis is remarkable in RA patients. Quadriceps tendon enthesis was mostly affected. Enthesitis is significantly related to age, ESR and HAQ. The presence of enthesitis in RA may represent a potential marker for disease activity.

Similarities and Differences Between Juvenile and Adult Spondyloarthropathies.

Spondyloarthritis (SpA) encompasses a broad spectrum of conditions occurring from childhood to middle age. Key features of SpA include axial and peripheral arthritis, enthesitis, extra-articular manifestations, and a strong association with HLA-B27. These features are common across the ages but there are important differences between juvenile and adult onset disease. Juvenile SpA predominantly affects the peripheral joints and the incidence of axial arthritis increases with age. Enthesitis is important in early disease. This review article highlights the similarities and differences between juvenile and adult SpA including classification, pathogenesis, clinical features, imaging, therapeutic strategies, and disease outcomes. In addition, the impact of the biological transition from childhood to adulthood is explored including the importance of musculoskeletal and immunological maturation. We discuss how the changes associated with adolescence may be important in explaining age-related differences in the clinical phenotype between juvenile and adult SpA and their implications for the treatment of juvenile SpA.

Spinal mobility in radiographic axial spondyloarthritis: criterion concurrent validity of classic and novel measurements

BackgroundLimitations in spinal mobility are a characteristic feature of Axial Spondyloarthritis. Current clinical measurements of spinal mobility have shown low criterion-concurrent validity. This study sought to evaluate criterion-concurrent validity for a clinically feasible measurement method of measuring spine mobility using tri-axial accelerometers.MethodsFifteen radiographic-Spondyloarthritis patients were recruited for this study. Two postural reference radiographs, followed by three trials in forward, left and right lateral bending were taken. For all trials, three measurements were collected: tape (Original Schober’s, Modified Schober’s, Modified-Modified Schober’s, Lateral Spinal Flexion Test and Domjan Test), followed immediately by synchronized radiograph and accelerometer measurements at end range of forward and bilateral lateral flexion. The criterion-concurrent validity of all measurement methods was compared to the radiographic measures using Pearson’s correlation coefficients. A Bland-Altman analysis was conducted to assess agreement.ResultsIn forward bending, the accelerometer method (r = 0.590, p = 0.010) had a stronger correlation to the radiographic measures than all tape measures. In lateral bending, the Lateral Spinal Flexion tape measure (r = 0.743, p = 0.001) correlated stronger than the accelerometer method (r = 0.556, p = 0.016). The Domjan test of bilateral bending (r = 0.708, p = 0.002) had a stronger correlation to the radiographic measure than the accelerometer method.ConclusionsAccelerometer measures demonstrated superior criterion-concurrent validity compared to current tape measures of spinal mobility in forward bending. While a moderate correlation exists between accelerometer and radiographs in lateral bending, the Lateral Spinal Flexion Test and Domjan Test were found to have the best criterion-concurrent validity of all tests examined in this study.

Comparative Analysis of Clinical and Imaging Features of Osteomalacia and Spondyloarthritis.

Aim: To compare the clinical and radiological characteristics of osteomalacia and spondyloarthritis/ankylosing spondylitis (SpA/AS) in order to provide a basis for differential diagnosis.Methods: We carried out a retrospective analysis of patients who were diagnosed with osteomalacia at the First Medical Center of 301 Hospital (Beijing, China) from January 2012 to January 2019. The clinical and radiological data of all patients were collected; at the same time, we selected age- and gender-matched patients with SpA/AS for comparison.Results: We enrolled a total of 76 patients, 38 with osteomalacia, and 38 with SpA/AS. The mean ages of the two groups were, respectively 44.62 ± 14.90 years and 44.85 ± 9.76 years (P > 0.05). Of patients with osteomalacia, 65.79% (n = 25) had previously been misdiagnosed with SpA/AS. In the osteomalacia and SpA/AS groups, there were, respectively 31 and 33 patients with low back pain, 22 and 13 patients with peripheral arthralgia, and 13 and 3 patients with heel pain. Alkaline phosphatase (ALP) level was significantly higher in the osteomalacia than in the SpA/AS group (P < 0.05). Serum phosphorus levels, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, and bone mineral density (BMD) were significantly lower in the osteomalacia group than the SpA/AS group (P < 0.05). Twenty-five patients in the osteomalacia group underwent sacroiliac-joint magnetic-resonance imaging (SIJ–MRI); abnormalities were found in 10 of these patients, seven of whom met the definition for positive SIJ–MRI according to 2009 Assessment of SpondyloArthritis international Society (ASAS) criteria. All seven presented with bilateral sacral involvement. Logistic-regression analysis found that the odds ratio (OR) for bone erosion score was 0.551; the higher this score, the lower the possibility of osteomalacia.Conclusion: Clinical and radiological presentations of patients with osteomalacia could highly simulate those of patients with spondyloarthritis; identifying the differences between these two diseases could effectively decrease the misdiagnosis rate.

Inflammatory back pain: a concept, not a diagnosis.

The concept of inflammatory back pain (IBP) describes a cohort of patients with chronic back pain (CBP) who have distinct clinical characteristics, rather than being a diagnosis in and of itself. IBP is a common and important feature of axial spondyloarthritis (axSpA) but this is not the only differential. This review examines the utility of IBP in both primary and secondary care settings. There are a number of suggested referral strategies for patients with suspected axSpA that include IBP. These strategies attempt to strike a balance between ensuring potential axSpA patients are not overlooked, whilst simultaneously not overwhelming secondary care services. Their success relies on the clinicians who first encounter these patients being familiar with IBP as a concept; however, it is still poorly recognized by many healthcare professionals. IBP may be helpful as part of a referral strategy; however, other clinical features, laboratory investigations and radiology must be incorporated for the final diagnostic outcome in axSpA. Delayed diagnosis is a major clinical problem in axSpA and is associated with worse clinical outcomes. When recognized and utilized correctly, IBP can be a useful tool to promote prompt referral to rheumatology services.

P183 Osteitis condensans ilii or axial spondyloarthritis: a diagnostic challenge!

Abstract Background/Aims Osteitis condensans ilii (OCI) is a rare cause of chronic non-inflammatory axial lower back pain. It has become an important differential diagnosis of axial spondyloarthritis. Bone marrow oedema can be present in 48% of patients. Although 'aunt minnie' appearance on MRI is pathognomonic, specialised imaging like SPECT/PET CT can be considered in difficult cases to confirm the diagnosis. We reviewed case notes of patients with incidental diagnosis of OCI on imaging and followed their clinical progression to see if the diagnosis was modified later. Methods Retrospective radiological database analysis was performed to find imaging reported as OCI or osteitis from 2015-2020. Electronic patient records were analyzed and data was compiled through Microsoft Excel. Results Data from 24 patients was reviewed. Most patients were females (91.7%), with a median age of 43 years (range 19-79 years). CT and MRI were the chief modalities of imaging (46% and 38% respectively) while 20% had plain x-rays of the pelvis. The main indications for imaging were pelvic or hip girdle pain (58.3%), cancer surveillance (25%), abdominal pain (6%), and infection (6%). 20% had an underlying rheumatological diagnosis of which 8% had spondyloarthritis. 12.5% of patients had seronegative features of spondyloarthritis and 8.3% were HLA B27 positive. Approximately 40% of patients were seen by the Rheumatology team for further assessment after imaging and 12.5% of patients were diagnosed with axial spondyloarthritis and remained under follow-up. Conclusion OCI can mimic sacroiliitis on imaging. Although only a minority of patients with OCI reported on initial imaging were subsequently diagnosed with axial spondyloarthritis, thorough clinical assessment and multidisciplinary discussion can reduce the chance of a missed axial spondyloarthritis diagnosis. Further large-scale studies are required to find the exact incidence of spondyloarthritis in patients with imaging features of OCI. Disclosure S. Saeed: None. M. Jamal: None. D. Ostry: None. G. Robinson: None. R. Sengupta: None.

Recent Updates in the Immunopathology of Type 3 Immunity-Mediated Enthesitis.

Enthesitis is a cardinal feature of spondyloarthritis (SpA). Despite increasing available treatments, challenges remain in adequately controlling inflammation and subsequent new bone formation (NBF) in entheses; thus, a better understanding of the immunopathogenesis is warranted. Increasing evidence has identified immune cells playing key roles in enthesitis such as γδ T cells and group 3 innate lymphoid cells (ILC3), possibly with site-specific regulatory systems. The presence of T cells producing interleukin (IL)-17 independent of IL-23 in human spinal entheses was recently reported, which may corroborate the discrepancy between recent clinical trials and pre-clinical studies. In addition, the contribution of myeloid cells has also been focused in both human and pre-clinical SpA models. Moreover, not only the IL-23/IL-17 signaling, but other key type 3 immunity mediators, such as IL-22 and granulocyte-macrophage colony-stimulating factor (GM-CSF), have been reported as pivotal cytokines in inflammation and NBF of entheses. Immune cells demonstrating distinct features orchestrate entheses, leading to the complex landscape of enthesitis. However, recent advances in understanding the immunopathogenesis may provide new therapeutic targets and future research directions.

Is Treatment in Patients With Suspected Nonradiographic Axial Spondyloarthritis Effective? Six‐Month Results of a Placebo‐Controlled Trial

ObjectiveTo investigate the efficacy of 16‐week treatment with etanercept (ETN) in patients with suspected nonradiographic axial spondyloarthritis (SpA).MethodsTumor necrosis factor inhibitor–naive patients with inflammatory back pain with at least 2 SpA features and high disease activity (Bath Ankylosing Spondylitis Disease Activity Index score ≥4), without the requirement of a positive finding on magnetic resonance imaging (MRI) of the sacroiliac (SI) joint and/or elevated C‐reactive protein (CRP) level, were randomized (1:1) to receive ETN (n = 40) or placebo (n = 40) for 16 weeks and subsequently were followed up for a further 8 weeks (to 24 weeks from baseline) without study medication. The primary end point was the Assessment of SpondyloArthritis international Society 20 (ASAS20) response at 16 weeks. Secondary end points included the Ankylosing Spondylitis Disease Activity Score (ASDAS) and changes in disease parameters, including the Bath Ankylosing Spondylitis Metrology Index (BASMI), CRP level, erythrocyte sedimentation rate (ESR), and Spondyloarthritis Research Consortium of Canada index scores (MRI of the SI joint), after 16 and 24 weeks.ResultsPatient characteristics at baseline were comparable between the ETN and placebo groups. At 16 weeks, there was no significant difference in the percentage of patients exhibiting ASAS20 response between the ETN group (6 patients [16.7%]) and the placebo group (4 patients [11.1%]) (relative risk 0.7 [95% confidence interval 0.2–2.2], P = 0.5). Only the ESR showed more improvement in the ETN group compared to the placebo group at 16 weeks (decreases of 2.2 mm/hour and 1.4 mm/hour, respectively), but the difference did not reach statistical significance. Between 16 and 24 weeks, without study medication, the BASMI, CRP level, and ESR had worsened to a greater extent in the ETN group compared to the placebo group, with the difference being significant for the CRP level.ConclusionThis study shows that in patients with suspected nonradiographic axial SpA with high disease activity but without the requirement of a positive finding on SI joint MRI and/or elevated CRP level, treatment with ETN is not effective.

Enthesitis is a clue to the diagnosis of spondyloarthritis, focus on psoriatic arthritis

Enthesitis is a common clinical feature of spondyloarthritis (SpA), characterized by inflammation of the tendon or ligament attachment site to a bone or joint capsule. The importance of detecting enthesitis for the diagnosis of SpA is confirmed by its inclusion in the classification criteria for psoriatic arthritis (PsA) – CASPAR – and in the classification criteria for SpA of the international group for the study of spondyloarthritis – ASAS. Enthesitis may be the first clinical sign of SpA, as well as the leading symptom that significantly influences the therapeutic choice. Enthesitis occurs in 30–50% of patients with SpA and is associated with high disease activity, more severe pain and worse quality of life. The frequency of enthesitis detected by ultrasound in patients with PsA is approximately 4 times higher than in patients with ankylosing spondylitis and is associated with the severity of the disease. The review presents current data on the pathophysiology, diagnosis and treatment of enthesitis. Recent studies emphasize the role of imaging methods for the diagnosis of enthesitis due to their higher sensitivity and specificity compared to clinical examination. There is very limited information on the effect of synthetic disease-modifying antirheumatic drugs on enthesitis, while targeted drugs and biologic therapy have shown high efficacy in its treatment compared to placebo. Preliminary evidence suggests that targeting interleukin (IL) 17 or IL12/23 may be more effective in enthesises inflammation suppression than tumor necrosis factor α inhibition.

Spondyloarthritis in North Africa: an update.

Spondyloarthritis (SpA) has been less well studied than rheumatoid arthritis in North Africa, due to a belief that it is rare and benign in certain populations. The main genetic trait of SpA is its association with human leukocyte antigen (HLA)-B27. The distribution of this allele largely explains the prevalence and severity of SpA. The prevalence of HLA-B27 in the general population of North Africa is estimated at about 4%, and rises to about 60% among people affected with SpA. Coxitis is one of the main features of North African SpA, but the response to treatment is comparable to the literature from the West. The major challenge in North Africa remains accessibility to specialized care and means of early diagnosis. Prevalent infections in North Africa do not seem to be a major obstacle to optimal treatment strategies.

"Reuma-Check": Performance of a Comprehensive Fast-Track Program for the Diagnosis of Axial Spondyloarthritis in South America.

The aim of this study was to evaluate the performance of a comprehensive diagnosis program called "Reuma-check" for the diagnosis of axial spondyloarthritis (SpA) in patients with low back pain (LBP). This is a cross-sectional study. Patients with LBP aged 18 years or older were preselected, and those with at least 1 SpA feature completed the circuit. They were referred after 2 strategies: education for orthopedists and a campaign on social networks. All patients underwent a clinical evaluation, laboratory testing, and imaging (including human leukocyte antigen B27 evaluation and magnetic resonance imaging). The diagnosis of axial SpA was established by an expert rheumatologist opinion. Time from onset of symptoms to "Reuma-check," time from patient referral to admission of the checkup, and time from "Reuma-check" to diagnosis were evaluated. A total of 175 of 246 patients were included, most of them came from the social media campaign (55%). Seventy-five (43%) of 175 patients were diagnosed as axial SpA. The median time from referral (or self-referral) to access to the program was 1.3 months. The median time from symptoms onset to access to the program was 31.7 months, and the median time from the performance of "Reuma-check" to final diagnosis was 2 weeks. Features associated with a diagnosis of axial SpA were as follows: inflammatory LBP (odds ratio [OR], 6.64; 95% confidence interval [CI], 1.6-28), clinical enthesopathy (OR, 4.56; 95% CI, 1.1-18.4), positive human leukocyte antigen B27 (OR, 23.02; 95% CI, 3.5-58), and positive magnetic resonance imaging (OR, 14.34; 95% CI, 3.5-58). "Reuma-check" allowed a high frequency of axial SpA diagnosis and improved access to rapid diagnosis, shortening the time from referral to diagnosis with a shorter acquisition time for the ancillary studies. Patients with a final diagnosis of axial SpA presented distinctive features.

Enhanced BMP-2/BMP-4 ratio in patients with peripheral spondyloarthritis and in cytokine- and stretch-stimulated mouse chondrocytes

BackgroundExcessive bone formation in the entheses is one of the features of peripheral spondyloarthritis (SpA). Complex pathological mechanisms connecting inflammation, mechanical stress, and ossification are probably involved. We focused on bone morphogenetic protein (BMP)-2, -4, and -7 as possible mediators of this process.MethodsBMP-2, -4, and -7 concentration was measured by ELISA in synovial fluids (SFs) of SpA (n = 56) and osteoarthritic (n = 21) patients. Mouse organotypic ankle cultures were challenged by a pro-inflammatory cocktail. Mouse primary chondrocytes, osteoblasts, or tenocytes were treated with TNF-α, interleukin (IL)-17, or IL-22 and/or subjected to cyclic stretch, or with recombinant BMP-2 or -4.ResultsIn SpA SFs, if BMP-7 was barely detectable, BMP-2 concentration was higher and BMP-4 was lower than in osteoarthritic samples, so that BMP-2/BMP-4 ratio augmented 6.5 folds (p < 0.001). In SpA patients, TNF-α, IL-6, and IL-17 levels correlated this ratio (n = 21). Bmp-2/Bmp-4 ratio was similarly enhanced by cytokine treatment in explant and cell cultures, at mRNA level. In particular, simultaneous application of TNF-α and cyclical stretch induced a 30-fold increase of the Bmp-2/Bmp-4 ratio in chondrocytes (p = 0.027). Blockade of prostaglandin E2 and IL-6 production had almost no effect on the stretch-induced regulation of Bmp-2 or -4. Osteoinductive effects of BMP-4, and to a lesser extend BMP-2, were identified on cultured chondrocytes and tenocytes.ConclusionsOur results first settle that BMP factors are locally deregulated in the SpA joint. An unexpected decrease in BMP-4 could be associated to an increase in BMP-2, possibly in response to mechanical and/or cytokine stimulations.

Ectopic bone formation and systemic bone loss in a transmembrane TNF-driven model of human spondyloarthritis

BackgroundThe transmembrane-TNF transgenic mouse, TgA86, has been shown to develop spontaneously peripheral arthritis with signs of axial involvement. To assess similarity to human spondyloarthritis, we performed detailed characterization of the axial, peripheral, and comorbid pathologies of this model.MethodsTgA86 bone pathologies were assessed at different ages using CT imaging of the spine, tail vertebrae, and hind limbs and characterized in detail by histopathological and immunohistochemical analysis. Cardiac function was examined by echocardiography and electrocardiography and bone structural parameters by μCT analysis. The response of TgA86 mice to either early or late anti-TNF treatment was evaluated clinically, histopathologically, and by μCT analysis.ResultsTgA86 mice developed with 100% penetrance spontaneous axial and peripheral pathology which progressed with time and manifested as reduced body weight and body length, kyphosis, tail bendings, as well as swollen and distorted hind joints. Whole-body CT analysis at advanced ages revealed bone erosions of sacral and caudal vertebrae as well as of sacroiliac joints and hind limbs and, also, new ectopic bone formation and eventually vertebral fusion. The pathology of these mice highly resembled that of SpA patients, as it evolved through an early inflammatory phase, evident as enthesitis and synovitis in the affected joints, characterized by mesenchymal cell accumulation, and neutrophilic infiltration. Subsequently, regression of inflammation was accompanied by ectopic bone formation, leading to ankylosis. In addition, both systemic bone loss and comorbid heart valve pathology were evident. Importantly, early anti-TNF treatment, similar to clinical treatment protocols, significantly reduced the inflammatory phase of both the axial and peripheral pathology of TgA86 mice.ConclusionsThe TgA86 mice develop a spontaneous peripheral and axial biphasic pathology accompanied by comorbid heart valvular dysfunction and osteoporosis, overall reproducing the progression of pathognomonic features of human spondyloarthritis. Therefore, the TgA86 mouse represents a valuable model for deciphering the role of transmembrane TNF in the pathogenic mechanisms of spondyloarthritis and for assessing the efficacy of human therapeutics targeting different phases of the disease.

Enhanced BMP-2/BMP-4 ratio in patients with peripheral spondyloarthritis and in cytokine- and stretch-stimulated mouse chondrocytes

Excessive bone formation in the entheses is one of the features of peripheral spondyloarthritis (SpA). Complex pathological mechanisms connecting inflammation, mechanical stress, and ossification are probably involved. We focused on bone morphogenetic protein (BMP)-2, -4, and -7 as possible mediators of this process. BMP-2, -4, and -7 concentration was measured by ELISA in synovial fluids (SFs) of SpA (n = 56) and osteoarthritic (n = 21) patients. Mouse organotypic ankle cultures were challenged by a pro-inflammatory cocktail. Mouse primary chondrocytes, osteoblasts, or tenocytes were treated with TNF-α, interleukin (IL)-17, or IL-22 and/or subjected to cyclic stretch, or with recombinant BMP-2 or -4. In SpA SFs, if BMP-7 was barely detectable, BMP-2 concentration was higher and BMP-4 was lower than in osteoarthritic samples, so that BMP-2/BMP-4 ratio augmented 6.5 folds (p < 0.001). In SpA patients, TNF-α, IL-6, and IL-17 levels correlated this ratio (n = 21). Bmp-2/Bmp-4 ratio was similarly enhanced by cytokine treatment in explant and cell cultures, at mRNA level. In particular, simultaneous application of TNF-α and cyclical stretch induced a 30-fold increase of the Bmp-2/Bmp-4 ratio in chondrocytes (p = 0.027). Blockade of prostaglandin E2 and IL-6 production had almost no effect on the stretch-induced regulation of Bmp-2 or -4. Osteoinductive effects of BMP-4, and to a lesser extend BMP-2, were identified on cultured chondrocytes and tenocytes. Our results first settle that BMP factors are locally deregulated in the SpA joint. An unexpected decrease in BMP-4 could be associated to an increase in BMP-2, possibly in response to mechanical and/or cytokine stimulations.

Enthesitis may be one of the signs of severe disease in familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an auto-inflammatory disease that is also characterized with some of the common musculoskeletal features of spondyloarthritis (SpA). Enthesitis is the hallmark of SpA. Recently, it was postulated that exertional leg pain is a possible sign of lower extremity enthesitis associated with FMF severity. In this study, we have evaluated the association between the enthesitis, enthesitis score and disease severity in FMF patients. We enrolled 238 FMF patients that fulfilled the modified Tel-Hashomer criteria. We assessed the presence of enthesitis at the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) defined sites with standard palpation method. Then, FMF patients dichotomised two groups as enthesitis group and controls. Herein, we evaluated the enthesis extensity with MASES. FMF disease severity was determined via the international severity scoring system for FMF (ISSF). Firstly, we have compared demographic properties, disease-related features and ISSF scores of the groups. Then, we have correlated ISSF with MASES in enthesitis group. We showed that 54 (22.6%) of 238 patients had enthesitis. The demographic features were similar between the groups. The enthesitis group had higher ISSF scores (p < 0.001); higher frequency of fever (p = 0.004), exertional leg pain (p < 0.001), myalgia (p < 0.001) and arthritis (p = 0.01); and more intense, widespread, frequent and longer attacks compared with controls. Moreover, there was a weak correlation between ISSF and MASES in the patients with enthesitis. Enthesitis may be a sign of more severe FMF phenotype and frequently associated with other musculoskeletal manifestations resemble SpA. Key points •More than one-fifth of the patients with FMF would suffer from enthesitis. •The FMF patients with enthesitis had higher ISSF scores; higher frequency of fever, exertional leg pain, myalgia and arthritis; and more intense, widespread, frequent and longer attacks as compared with controls. •Enthesitis may be a sign of more severe FMF phenotype and frequently associated with other SpA-like musculoskeletal feature.

Evaluation Effects of Laser Therapy and Extracorporeal Shock Wave Therapy with Clinical Parameters and Magnetic Resonance Imaging for Treatment of Plantar Fasciitis in Patients with Spondyloarthritis: A Randomized Controlled Trial.

Objective Low-level laser therapy (LLLT) and extracorporeal shock wave therapy (ESWT) is applied in the conservative treatment of inflammatory plantar fasciitis, which is also a characteristic feature of spondyloarthritis (SpA) (Gill, 1997 and Roxas, 2005). We determined and compared the effectiveness of LLLT and ESWT using magnetic resonance imaging (MRI). Methods This study is a prospective, randomized, comparative, single-blind clinical study. Voluntarily followed 40 patients with the diagnosis of SpA and having pain at the heels at least for 6 months. Patients were divided randomly into two treatment groups. One group undertook 14 sessions of infrared Ga-Al-As LLLT, and the other group undertook 3 sessions ESWT. Feet functions of the patients were evaluated by American Orthopaedic Foot and Ankle Society (AOFAS) and Roles and Maudsley Scoring; VAS was evaluated for foot pain and function. In clinical assessment, disease activity was carried out by applying the BASDAI, the functional assessment was evaluated through the BASFI, and the patient quality of life was evaluated through the ASQoL; enthesitis was scored according to MASES assessment, performed before and at 1 month after treatment. The thickness of the plantar fascia was measured with MRI before and 1 month after treatment. Results Compared with the pretherapy, progress in the feet function by AOFAS and Roles-Maudsley scoring and decrease in VAS levels were statistically significant in both groups (p < 0.001). Only the VAS exercise score was superior to LLLT (p < 0.05). The thickness of the plantar fascia had decreased significantly on MRI in all two groups. Conclusion The treatment of plantar fasciitis with LLLT and ESWT was more successful in pain improvement and functional outcomes with the dose, frequency, and duration used in our study.

Assessing rheumatologists' attitudes and utilization of classification criteria for ankylosing spondylitis and axial spondyloarthritis: a global effort.

This study aims to assess rheumatologists' perceptions, utilization patterns, and attitudes towards the modified New York (mNY) criteria for ankylosing spondylitis (AS) and Assessment of SpondyloArthritis International Society (ASAS) criteria for axial spondyloarthritis (axSpA). Members of the national rheumatology societies in five countries (United States of America (USA), Canada, India, Turkey, and Brazil) were invited to participate in a survey containing questions regarding rheumatologists' familiarity, and use of AS and axSpA classification criteria in daily practice, perceived specificity of spondyloarthritis features in making the diagnosis, patterns of imaging tests performed in daily practice, and their opinion about the need for modification of current classification criteria. The responses were analyzed by gender, age, years in practice, as well as by country of practice. Descriptive statistics, t test, and chi-square test were used for comparison of groups. Approximately 6% rheumatologists (478 out of 8021 professional association members) from five countries completed the survey. The country-specific response rates were Brazil 4%, USA 4.3%, India 11%, Canada 14%, and Turkey 29%, though the overall contributions from individual countries were USA 47%, India 14.9%, Brazil 13.8%, Turkey 12.8%, and Canada 8.8%. The mean age of respondents was 50years (± 11.8), 31% were females and 90% spent majority (> 75%) of their time in clinical practice. The mNY and ASAS criteria were regularly used in clinical practice by 44 and 66% of responders, respectively. Those reporting "always" using ASAS criteria were more likely to be women (p = 0.006), and within 5years of completing rheumatology training. Vast majority (74%) regarded Inflammatory Back Pain (IBP) as a specific feature for axSpA. Majority (50 and 60%, respectively) regarded uveitis and dactylitis as "very specific" features helping them make the diagnosis of axSpA, whereas heel enthesitis, peripheral inflammatory arthritis, and response to NSAIDs were considered "somewhat specific" by 50% of the responders. Less than half (47%) of the responders used the mNY grading for X-ray of SI joints. In the case of normal X-ray of SI joint, the use of MRI was more frequent than CT scan (83.6 vs. 10.9%) in assessing for sacroiliitis. If sacroiliitis was not seen on X-rays, the likelihood of ordering MRI was significantly higher among rheumatologists completing training within < 15years versus > 25years prior (90 vs. 75%, p = 0.007). Overall, 70% thought that ASAS criteria were adequately specific for clinical trials. However, 42% respondents still felt a need to modify ASAS classification criteria for axSpA. Also, 46% respondents felt that mNY criteria should be modified. In the absence of diagnostic criteria, majority of rheumatologists are using the classification criteria for diagnosis of axSpA. Though axSpA classification criteria are perceived to be specific for clinical trials, 40% rheumatologists feel the need to modify these criteria. Key Points • This study informs how rheumatologists in five countries spread over four different continents diagnose axSpA in clinical practice. • Since majority rheumatologists among survey respondents across the countries use ASAS criteria for diagnosis of axSpA, more specific criteria may be required to avoid overdiagnosis. • MRI is commonly used to rule out sacroiliitis in case of normal X-ray of sacroiliac joints.

Transmembrane TNF drives osteoproliferative joint inflammation reminiscent of human spondyloarthritis.

TNF plays a key role in immune-mediated inflammatory diseases including rheumatoid arthritis (RA) and spondyloarthritis (SpA). It remains incompletely understood how TNF can lead to different disease phenotypes such as destructive peripheral polysynovitis in RA versus axial and peripheral osteoproliferative inflammation in SpA. We observed a marked increase of transmembrane (tm) versus soluble (s) TNF in SpA versus RA together with a decrease in the enzymatic activity of ADAM17. In contrast with the destructive polysynovitis observed in classical TNF overexpression models, mice overexpressing tmTNF developed axial and peripheral joint disease with synovitis, enthesitis, and osteitis. Histological and radiological assessment evidenced marked endochondral new bone formation leading to joint ankylosis over time. SpA-like inflammation, but not osteoproliferation, was dependent on TNF-receptor I and mediated by stromal tmTNF overexpression. Collectively, these data indicate that TNF can drive distinct inflammatory pathologies. We propose that tmTNF is responsible for the key pathological features of SpA.