Regulatory T cells in spondyloarthropathies: genetic evidence, functional role, and therapeutic possibilities.

Regulatory T cells (Tregs) are a very specialized subset of T lymphocytes: their main function is controlling immune responses during inflammation. T-regs involvement in autoimmune and immune-mediated rheumatic diseases is well-described. Here, we critically review the up-to-date literature findings on the role of Tregs in spondyloarthropathies, particularly in ankylosing spondylitis (AS), a polygenic inflammatory rheumatic disease that preferentially affects the spine and the sacroiliac joints. Genetics discoveries helped in elucidating pathogenic T-regs gene modules and functional involvement. We highlight T-regs tissue specificity as crucial point, as T-regs might have a distinct epigenomic and molecular profiling depending on the different site of tissue inflammation. Furthermore, we speculate about possible therapeutic interventions targeting, or enhancing, Treg cells in spondyloarthropathies.

Balneotherapy in spondyloarthropathy: A systematic review.

AIM OF THE STUDY: To evaluate the effectiveness of balneotherapy on spondyloarthritis. METHODS: Two authors independently searched the CENTRAL, MEDLINE, SCOPUS, EMBASE and WEB OF SCIENCE databases until July 2017, for randomized controlled trials published in French or English, that included participants, and interventions: adults with spondyloarthritis, treated by balneotherapy program or one of its components and compared with any other intervention or no treatment. Internal validity, external validity, quality of the statistical analysis, and publication bias were systematically evaluated. We report the best level of evidence. RESULTS: Nine articles were selected; the internal validity was high in two studies, average in one study, and low in six studies. With high internal validity, one study found a difference for pain between immersion in radon-rich water and tap water for the whole population or rheumatic disease, but the BASFI is not improved for the subgroup of patients with spondyloarthritis. The other study with high validity reported a significant 28-week improvement in quality of life and a composite index. In a study with moderate internal validity involving ankylosing spondylitis patients with associated with inflammatory bowel disease, a balneotherapy program demonstrated a relevant clinical improvement when compared to patients on waiting list. With low internal validity, TNFa inhibitors+spa therapy were found to be superior to a treatment with TNFa inhibitors alone in patients with psoriatic arthritis. CONCLUSIONS: Two trials with high validity demonstrated improvements, but this systematic review is not sufficient to prove the efficacy of balneotherapy in spondyloarthritis. More trials are needed with larger sample size to confirm the preliminary results observed and conclusively determine the benefits of balneotherapy.

2021 EULAR recommendations for the implementation of self-management strategies in patients with inflammatory arthritis.

BACKGROUND: An important but often insufficient aspect of care in people with inflammatory arthritis (IA) is empowering patients to acquire a good understanding of their disease and building their ability to deal effectively with the practical, physical and psychological impacts of it. Self-management skills can be helpful in this regard. OBJECTIVES: To develop recommendations for the implementation of self-management strategies in IA. METHODS: A multidisciplinary taskforce of 18 members from 11 European countries was convened. A systematic review and other supportive information (survey of healthcare professionals (HCPs) and patient organisations) were used to formulate the recommendations. RESULTS: Three overarching principles and nine recommendations were formulated. These focused on empowering patients to become active partners of the team and to take a more proactive role. The importance of patient education and key self-management interventions such as problem solving, goal setting and cognitive behavioural therapy were highlighted. Role of patient organisations and HCPs in promoting and signposting patients to available resources has been highlighted through the promotion of physical activity, lifestyle advice, support with mental health aspects and ability to remain at work. Digital healthcare is essential in supporting and optimising self-management and the HCPs need to be aware of available resources to signpost patients. CONCLUSION: These recommendations support the inclusion of self-management advice and resources in the routine management of people with IA and aim to empower and support patients and encourage a more holistic, patient-centred approach to care which could result in improved patient experience of care and outcomes.

EULAR recommendations for a core data set for pregnancy registries in rheumatology.

BACKGROUND AND OBJECTIVE: There is an urgent need for robust data on the trajectories and outcomes of pregnancies in women with inflammatory rheumatic diseases (IRD). In particular when rare outcomes or rare diseases are to be investigated, collaborative approaches are required. However, joint data analyses are often limited by the heterogeneity of the different data sources.To facilitate future research collaboration, a European League Against Rheumatism (EULAR) Task Force defined a core data set with a minimum of items to be collected by pregnancy registries in rheumatology covering the period of pregnancy and the 28-day neonatal phase in women with any underlying IRD. METHODS: A stepwise process included a two-round Delphi survey and a face-to-face meeting to achieve consensus about relevant items. RESULTS: A total of 64 multidisciplinary stakeholders from 14 different countries participated in the two rounds of the Delphi process. During the following face-to-face meeting of the EULAR Task Force, consensus was reached on 51 main items covering 'maternal information', 'pregnancy' and 'treatment'. Generic instruments for assessment are recommended for every item. Furthermore, for the five most frequent IRDs rheumatoid arthritis, spondyloarthritis, juvenile idiopathic arthritis, systemic lupus erythematosus and other connective tissue diseases, disease-specific laboratory markers and disease activity measurements are proposed. CONCLUSION: This is the first consensus-based core data set for prospective pregnancy registries in rheumatology. Its purpose is to stimulate and facilitate multinational collaborations that aim to increase the knowledge about pregnancy course and safety of treatment in women with IRDs during pregnancy.

Recommendations by the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on the treatment of patients with inflammatory bowel disease associated with spondyloarthritis. / Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre el tratamiento de pacientes con enfermedad inflamatoria intestinal asociada a espondiloartritis.

Extraintestinal manifestations, in general, and in particular arthropathies, are a common problem in patients with inflammatory bowel disease. In fact, the relationship between those 2entities is close and there are increasingly more data which suggest that the bowel plays a significant role in the aetiopathogenesis of spondyloarthritis. The association of inflammatory bowel disease with any kind of spondyloarthritis represents a challenging clinical scenario. It is therefore necessary that both gastroenterologists and rheumatologists work together and establish a fluent communication that enables the patient to receive the most appropriate treatment for each specific situation. The aim of this review is to make some recommendations about the treatment of patients with inflammatory bowel disease and associated spondyloarthritis, in each different clinical scenario.

Anterior uveitis in patients with spondyloarthropathies in a single US academic center: a retrospective study.

Uveitis may represent an opportunity to diagnose spondyloarthropathies (SpA) earlier and influence treatment decisions. We describe the percentage of acute anterior uveitis (AAU) in a diverse group of SpA patients seen at one academic setting and compare demographic and clinical characteristics according to the presence of uveitis. We conducted a retrospective study of patients with SpA and AAU (January 2016-June 2017). Patients were identified using ICD-10 and administrative claim codes, diagnoses were confirmed through chart review. Extracted data included demographics, laboratory, clinical data, treatment and Routine Assessment of Patient Index Data 3 (RAPID3) scores based on Multidimensional Health Assessment Questionnaire (MDHAQ). Baseline description and comparison between the two groups were performed. We included 190 patients, mostly men (59.5%), with a mean age of 45.9 years: 48% with ankylosing spondylitis (AS), 26% with psoriatic arthritis (PsA), 22% with undifferentiated SpA, and 4% with SpA associated with inflammatory bowel disease (IBD). Uveitis was identified in 17% of patients, ranging from 25% in AS to 4% in PsA. Time from symptom onset to SpA diagnosis was longer in patients with uveitis (10.9 versus 5.9 years, p < 0.001). A higher percentage of patients with uveitis were HLA-B27 positive (85% versus 67%, p = 0.02). The prevalence of uveitis in our population was 17%, slightly lower than previously reported in the literature. There was a diagnostic delay of about 7 years, significantly longer in patients with uveitis. New screening strategies in collaboration with ophthalmology may lead to earlier diagnosis and better outcomes.

Increased incidence of spondyloarthropathies in patients with Takayasu arteritis: a systematic clinical survey.

OBJECTIVES: Takayasu arteritis and Spondyloarthritis are two distinct inflammatory diseases that affect the same age periods. Increasing number of reports on co-incident Takayasu arteritis-spondyloarthritis cases in literature raised the hypotheses about their association. The purpose of this study is to evaluate the incidence of spondyloarthropathy spectrum diseases in Takayasu arteritis patients. METHODS: Detailed clinical and demographic features of Takayasu arteritis patients were recorded and all were screened meticulously for the presence of spondyloarthropathy features following recommendations of Assessment of SpondyloArthritis international Society. Patients were questioned for inflammatory back pain, enthesitis, uveitis, inflammatory bowel disease, peripheral arthritis, and investigated accordingly with HLA-B27, plain X-rays and sacroiliac magnetic resonance imaging. RESULTS: A total of 69 Takayasu arteritis patients (65 female, 94.2%) were enrolled. After detailed investigation, 14 (20.3%) Takayasu arteritis patients fulfilled the Assessment of SpondyloArthritis international Society criteria for Spondyloarthropathy. Two of 14 (14.2%) spondyloarthropathy patients were positive for HLA-B27. Type 1 and type 2 Takayasu arteritis were more common in patients with diagnosis of both Takayasu arteritis and spondyloarthropathy than those without spondyloarthropathy. Most of patients with diagnosis of both these diseases required biologic therapies than patients with diagnosis of Takayasu arteritis alone (64.3% vs 29.1%, P = 0.014) due to refractory Takayasu arteritis. CONCLUSION: Our results suggest a significant association between Takayasu arteritis and spondyloarthropathy. Possible shared genetic or immunopathogenic processes may explain this association, which merits further investigations.

Traditional Chinese medicine (TCM) collaborative care for patients with axial spondyloarthritis (AcuSpA): protocol for a pragmatic randomized controlled trial.

BACKGROUND: Axial spondyloarthritis (AxSpA) is a chronic disease which results in fatigue, pain, and reduced quality of life (QoL). Traditional Chinese medicine (TCM), especially acupuncture, has shown promise in managing pain. Although a TCM collaborative model of care (TCMCMC) has been studied in cancer, there are no randomized controlled trials investigating TCM in AxSpA. Therefore, we will conduct a pragmatic trial to determine the clinical effectiveness, safety, and cost-effectiveness of TCMCMC for patients with AxSpA. We define TCMCMC as standard TCM history taking and physical examination, acupuncture, and TCM non-pharmacological advice and communications with rheumatologists in addition to usual rheumatologic care. The purpose of this paper is to describe the rationale for and methodology of this trial. METHODS/DESIGN: This pragmatic randomized controlled trial will recruit 160 patients who are diagnosed with AxSpA and have inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs). Simple randomization to usual rheumatologic care or the intervention (TCMCMC) with a 1:1 allocation ratio will be used. Ten 30-min acupuncture sessions will be provided to patients assigned to the TCMCMC arm. All participants will continue to receive usual rheumatologic care. The primary endpoint - spinal pain - will be evaluated at week 6. Secondary endpoints include clinical, quality of life, and economic outcome measures. Patients will be followed up for up to 52 weeks, and adverse events will be documented. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of a TCMCMC for patients with AxSpA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03420404 . Registered on 14 February 2018.

Clinical spinal instability: 10 years since the derivation of a clinical prediction rule. A narrative literature review.

BACKGROUND: Between 2005 and 2015 significant changes in the clinical decision making paradigm for the treatment of spinal instability occurred. This was largely motivated by a clinical prediction rule (CPR) derivation study that was developed to specifically identify patients with low back pain who are more likely to respond positively to lumbar stabilization exercises. OBJECTIVE: This is a narrative literature review on the recent advances physiotherapy has made in the treatment of clinical spinal instability. METHODS: Literature discussing the conservative treatment of lumbar spinal instability published from 2005-2015 was identified with electronic searches of PubMed (MEDLINE) Advanced search, Web of Science, BIOSIS Previews, MEDLINE (EBSCO), SportDISCUS (EBSCO), CINAHL (EBSCO), PEDro, Scopus and Cochrane and reviewed. RESULTS: Five systematic reviews, 2 with meta-analyses, and 1 systematic review on the quality of systematic reviews were found. There seems to be some benefit from specific stabilization exercise programs in regards to pain reduction, but they might not be more effective than other forms of exercise. The currently existing CPR for stabilization exercises is not far enough developed to use in clinical practice and is not validated as of yet. CONCLUSION: Stabilization exercises seem to decrease chronic low back pain, although it is not clear that this pain has to be caused by clinical spinal instability. Caution should be exercised when using CPRs in the clinic; they are not meant to be strict treatment guidelines, but rather a tool that helps facilitate clinical decision-making.

Enthesitis detection by ultrasound: where are we now?

Over the last 25 years, ultrasound has been used to evaluate involvement at the entheses in spondyloarthritis (SpA) and psoriatic arthritis (PsA). Several studies have been reported indicating its value in detecting active inflammation at entheseal sites using both gray scale and Doppler findings. This review explores the recent literature and appraises the current knowledge and the unmet needs of enthesitis detection by ultrasound in the management of both SpA and PsA.

The impact of axial spondyloarthritis on quality of life (QoL): a comparison with the impact of moderate to end-stage chronic kidney disease on QoL.

PURPOSE: The purpose of the study was to assess the impact of axial spondyloarthritis (axSpA) on patients' quality of life (QoL) compared to patients with moderate to end-stage chronic kidney disease (CKD). METHODS: We conducted secondary analysis of QoL data obtained from patients with axSpA and CKD from 2011 to 2014. QoL was assessed using the SF-36 version 2 and KDQoL-SF for patients with axSpA and CKD, respectively. Patients with CKD were subcategorized to CKD-pre-dialysis, hemodialysis (CKD-HD) and peritoneal dialysis (CKD-PD). Linear regression was used to compare QoL between patients with axSpA and CKD after adjusting for age, gender, ethnicity, education level, and marital status. RESULTS: A total of 765 patients (mean age 54.6, 63.0% males, 69.0% Chinese) were analyzed, of which 188 (24.5%) had axSpA. Patients with axSpA had poorer SF-36 bodily pain (BP) scores (axSpA: reference; CKD-pre-dialysis ß: 11.04, p < 0.001; CKD-HD ß: 9.52, p < 0.001; CKD-PD ß: 10.35, p < 0.001) and higher general health scores (axSpA: reference; CKD-pre-dialysis ß: - 7.87, p < 0.001; CKD-HD ß: - 7.14, p < 0.001, CKD-PD ß: - 7.25, p < 0.001) as compared to patients with CKD. Generally, patients with axSpA had poorer SF-36 scores than patients with CKD-pre-dialysis and similar SF-36 scores compared to patients with CKD-HD or CKD-PD. CONCLUSIONS: The burden of axSpA on QoL is not trivial and is comparable to patients with CKD-HD or CKD-PD.

Adherence to biologic therapy - Does it vary with ethnicity?

BackgroundPoor adherence to therapy remains a significant barrier to improving clinical outcomes in rheumatic diseases and carries a major financial burden. It has been linked to medication related patient beliefs, which were reported to differ between ethnic groups. Little is known about these variations in biologic therapies cohorts. The purpose of this study was to identify potential determinants of adherence to biologic drugs including an assessment of the influence of beliefs about medicines and compare determinants of adherence between patients of Caucasian versus other ethnicities (OE). Relationship of adherence to disease outcome was further explored. MethodsA prospective survey was undertaken of patients with inflammatory arthritis prescribed self-administered subcutaneous biologic therapies at our centre. Data were collected using a) self reported adherence b) five item compliance questionnaire for Rheumatology (CQR5) and c) Beliefs about Medications questionnaire (BMQ) specific-five items each for necessity and concern scales. The replies were assessed against the disease activity score measured on the day of recruitment to the survey. Results80 patients contributed to the survey. 90% were prescribed TNF inhibitors. 40 patients were of Caucasian origin and 40 belonged to OE-predominantly of South Asian descent (85%). Disease activity score (DAS) was significantly higher in OE patients with 3.7 (standard deviation (SD) 1.3) compared to Caucasian patients with a DAS of 2.9 (1.6) (p = 0.031). Negative beliefs (i.e. higher concern scale scores) about therapy were significantly more prevalent (24/40) (60%) in the OE group compared to the Caucasian cohort (14/40 (35%) (p = 0.043). 17/40 (42.5%) of OE patients were poorly adherent to biologic therapy compared to 12/40 (30%) of Caucasian participants (p = 0.308). Most respondents (68/80, 85%) agreed that their biologic therapies were necessary for their health. Amongst 12/80 (15%) who disagreed, only two were in the non-adherent group. ConclusionTo our knowledge, this is the first study to demonstrate ethnic differences in disease activity score and related negative beliefs regarding subcutaneous biologic therapies in people with rheumatic diseases.

The Efficacy of Tai Chi and Yoga in Rheumatoid Arthritis and Spondyloarthropathies: A narrative biomedical review.

Rheumatoid arthritis (RA) and spondyloarthropathies (SpA) are among the most common inflammatory rheumatic diseases, which might induce chronic pain for their sufferers. Mind-body interventions like Tai Chi and yoga are among the many alternative therapies for combatting chronic pain. This review aims to overview the articles about their effectiveness in RA and SpA. We searched PubMed/MEDLINE, Scopus, and Web of Science for English-language sources from their inception through September 2017. Case-control studies, interventional studies, and case series that included more than three cases and randomized crossover studies were included. The literature search retrieved 133 non-duplicate records, and 15 of them were eligible and were included in this review. The influence of Tai Chi remains debatable in RA, while there is only one study that investigated its efficacy in SpA. Yoga seems effective in decreasing pain and inflammation while increasing quality of life. There are no data available about its effect on SpA. Even after a thorough research, the number of articles is quite limited on the effectiveness of Tai Chi and yoga in RA and SpA. While these complementary approaches still show some promise as alternative therapies in RA and SpA, the literature lacks long-term studies with larger patient groups.

Role of Stem Cells in Pathophysiology and Therapy of Spondyloarthropathies-New Therapeutic Possibilities?

Considerable progress has been made recently in understanding the complex pathogenesis and treatment of spondyloarthropathies (SpA). Currently, along with traditional disease modifying anti-rheumatic drugs (DMARDs), TNF-α, IL-12/23 and IL-17 are available for treatment of such diseases as ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Although they adequately control inflammatory symptoms, they do not affect the abnormal bone formation processes associated with SpA. However, the traditional therapeutic approach does not cover the regenerative treatment of damaged tissues. In this regards, stem cells may offer a promising, safe and effective therapeutic option. The aim of this paper is to present the role of mesenchymal stromal cells (MSC) in pathogenesis of SpA and to highlight the opportunities for using stem cells in regenerative processes and in the treatment of inflammatory changes in articular structures.

Spine Conditions: Mechanical and Inflammatory Low Back Pain.

Mechanical low back pain (LBP) is an injury or derangement of an anatomic structure in the low back. When evaluating patients with LBP, clinicians should maintain clinical suspicion for vertebral fracture, cancer, and cauda equina syndrome. Management includes patient education focused on exercise, massage, and behavioral approaches such as cognitive behavioral therapy. Acupuncture can be an effective alternative and specific herbal supplements may provide short-term pain relief. The prognosis for patients with mechanical LBP is good. Inflammatory LBP is pain resulting from a systemic inflammatory condition, often referred to as axial spondyloarthritis. Ankylosing spondylitis is chronic inflammatory LBP characterized by early onset (mean age 24 years), with a higher prevalence in men. Five clinical parameters can help identify inflammatory LBP: improvement with exercise, pain at night, insidious onset, onset at younger than 40 years, and no improvement with rest. Management of inflammatory LBP typically includes nonsteroidal anti-inflammatory drugs and structured exercise programs, with emphasis on the involvement of a rheumatology subspecialist. Spondyloarthritis is associated with other rheumatic or autoimmune conditions, including rheumatoid arthritis, inflammatory bowel disease, and psoriasis. These should be considered when evaluating patients with inflammatory LBP.

Effect of whole-body cryotherapy on the rheological parameters of blood in older women with spondyloarthrosis.

BACKGROUND: Cryotherapy is a physiotherapy method used to treat back pain in older persons. OBJECTIVE: This study aims to evaluate the changes in the rheological parameters of blood in older women with spondyloarthrosis, who underwent whole-body cryotherapy. METHODS: The experimental group comprised 69 older women with lumbar spondyloarthrosis, aged between 65 and 70 years. Due to the methodology of the procedure, the experimental group was randomly divided into three groups. Each group underwent two weeks of different types of physiotherapy: only whole-body cryotherapy (22 women); only kinesitherapy (23 women); and both cryotherapy and kinesitherapy (24 women). The control group comprised 25 women who did not undergo any form of therapy. The evaluation of the rheological properties of the blood encompassed measurements of the plasma viscosity, the erythrocyte elongation and aggregation indices, and the level of fibrinogen. RESULTS: The conducted rheological tests revealed a significant decrease in the erythrocyte elasticity and aggregation indices only in the group of women who had undergone both whole-body cryotherapy and kinesitherapy. CONCLUSIONS: Applying whole-body cryotherapy to older women with spondyloarthrosis decreases the elasticity of erythrocytes and, despite favourable changes in the aggregation parameters, problems with perfusion may still appear. For this reason, the benefit of using whole-body cryotherapy in these persons is debatable.

Biologic Therapy for HLA-B27-associated Ocular Disorders.

The treatment of articular and extra-articular manifestations associated with HLA-B27 has undergone dramatic changes over the past two decades, mainly as a consequence of the introduction of biologic agents and in particular anti-tumor necrosis factor α (anti-TNFα) agents. Uveitis is known to be the most frequent extra-articular feature in HLA-B27-associated spondyloarthritides. Topical corticosteroids and cycloplegic agents remain the cornerstones of treatment. However, biologic therapy may be effective in the management of refractory or recurrent forms of uveitis. This review gives an update on the management of HLA-B27-associated ocular disorders with biologics, including anti-TNFα agents and non-anti-TNFα biologic modifier drugs. There is an emerging role for newer biologics targeting interleukin-12/23 and interleukin-17 for the treatment of spondyloarthritides but data on their efficacy on anterior uveitis are sparse.

Telerheumatology: A technology appropriate for virtually all.

BACKGROUND/PURPOSE: Telerheumatology services were developed at Dartmouth-Hitchcock Medical Center (DHMC) to bring specialty care to New Hampshire (NH) and Vermont (VT) where a large proportion of the population lives in rural areas (60%) with limited resources and access to care. We sought to learn what challenges and accomplishments our early telemedicine program has encountered since inception. METHODS: As part of a quality improvement initiative we performed an IRB-exempt retrospective review of patients seen in the telerheumatology clinic at DHMC from October 2011 to December 2014. We also interviewed the participants; including providers, presenters, and patients regarding their experience of care. We assessed both patient and provider satisfaction with the experience. RESULTS: Between October 2011 and December 2014, 176 patients were seen via telerheumatology between two clinical sites over the course of 244 telerheumatology patient visits. The top diagnosis for patients during the telerheumatology visits was inflammatory arthritis (n = 156, 63.9%). We found 19% of patients to be inappropriate for the visit type for the following two main reasons: the underlying diagnosis was unclear or the disease was too complex. CONCLUSION: The use of telerheumatology has successfully increased access to specialty care in rural regions of NH and VT with good patient and provider satisfaction. While telerheumatology improved the access to specialty care, consideration should be given to selecting the appropriate patient for this visit type given that 19% of patients were deemed inappropriate. We propose a triage mechanism to ensure that patients are appropriately paired to the proper visit type in the future.