Spondyloarthritis Research Articles

Pivotal role of the synovioentheseal complex in the imaging of arthritis and rheumatic diseases

Imaging plays a key role in the diagnosis and management of rheumatic diseases. Although joints and periarticular tissue are commonly involved in rheumatic diseases, entheses further away from joints, such as in the Achilles tendon or plantar fascia insertion onto the calcaneus, as well as skin and subcutaneous tissue, are among other -sometimes overlooked- targets. The link of enthesitis, which describes inflammation at the insertions of ligaments, tendons, or joint capsules, with spondyloarthritis (SpA) was established just before the turn of the century as a characteristic feature based on imaging studies with histopathological correspondence. To highlight the association between enthesitis and synovitis in SpA, the anatomical unit of the “synovioentheseal complex” (SEC) and the concepts of “functional enthesis” and “articular enthesis,” apart from the better known “insertional enthesis,” were introduced to encompass other inflammatory lesions associated with SpA. Studies from the last two decades revealed the involvement of the SEC in rheumatic and non-rheumatic disorders with different pathogeneses. Although such involvement is sometimes distinctive, it does not necessarily point to a specific diagnosis at other times. Nevertheless, the potential of SEC inflammation in the differentiation of SpA from other forms of arthritis remains important. The purpose of this review was to provide essential information concerning the involvement of the SEC in the diagnosis of rheumatic diseases and arthritis, focusing on imaging characteristics.

Male fertility is preserved following ixekizumab treatment-a real life pilot study.

Preserving fertility is crucial when managing male patients with spondyloarthritis (SpA) and/or psoriasis (PsO), especially in young men. Chronic inflammation, hormonal dysregulation, and immunosuppressive therapies can negatively impact male fertility. Over the past decades, positive data have emerged regarding the reproductive safety of various therapies in men. Ixekizumab (IXE), a high-affinity monoclonal antibody targeting IL-17A, has shown a safe profile for male fertility in small studies. This pilot study assesses the impact of IXE treatment on sperm parameters in SpA and/or PsO patients in a real-world setting. Consecutive adult male SpA and/or PsO patients eligible for or undergoing IXE treatment were prospectively enrolled. Demographic data, disease characteristics, laboratory assessments, comorbidities, and previous treatments were recorded. Sperm analysis was conducted after a minimum of 6 months of IXE treatment, and also before treatment inititation in a subgroup of patients. Parallel sperm evaluations were performed in a control group of healthy donors. Ten patients were enrolled: 8 with SpA and 2 with PsO. After 6 months of IXE treatment, all patients had normal sperm parameters. One SpA and PsO patient with baseline oligozoospermia showed normal parameters at follow-up and achieved a successful pregnancy post-treatment. Compared with controls, IXE-treated patients had lower sperm concentrations but higher vitality. In our limited size pilot study on SpA and PsO patients, Ixekizumab exposure did not impair male fertility. Sperm parameters remained within normal ranges after a minimum of 6 months of treatment. Early Ixekizumab treatment may preserve or potentially reverse fertility impairment.

Effect of Integrin Blockade on Experimental Spondyloarthritis

Spondyloarthritis (SpA) describes a group of diseases characterized by chronic inflammation in the spine and peripheral joints. While pathogenesis is still unclear, proinflammatory gut-derived immune cells have been identified in the joints of SpA patients. We previously identified an enriched population of integrin-expressing cells in the joints of SpA patients. Entry of gut-derived cells into joints may be mediated by these integrins. In the current study, we used the SKG murine model of SpA to study the impact of integrin blockade. Mice were injected with antibodies against the integrin α4β7 or the β7 monomer twice a week. Treatment with antibodies against α4β7 reduced disease severity in curdlan-injected SKG mice, with disease scores being comparable between treatment initiation times. Targeting the β7 monomer led to reduced arthritis severity compared to targeting the α4β7 dimer. Treatment with antibodies against α4β7 or β7 decreased expression of these integrins in CD4+ T cells, with the frequency of αE+β7+ T cells in the spleen and lymph nodes correlating with disease severity. In summary, we showed that integrin blockade showed potential for ameliorating disease in a murine model of SpA, lending support for further studies testing integrin blockade in SpA.

Unmet Needs in Spondyloarthritis: Pathogenesis, Clinical Trial Design, and Nonpharmacologic Therapy.

A program focused on pathogenesis, clinical trial design, and nonpharmacologic mind-body therapy for of spondyloarthritis (SpA) was presented at the Spondylitis Association of America Unmet Needs Conference IV. SpA pathogenesis is incompletely understood but involves a complex set of drivers, including genetics, biomechanical stress, and microbial factors. Affected tissues may include axial and peripheral joints, entheses, skin, uvea, and intestines. The specific role of key cytokines like interleukin (IL)-23, IL-17, and tumor necrosis factor in the phases of this inflammatory process remains unclear. New insights into pathogenesis will continue to generate targets for novel therapeutics. How to optimally evaluate those therapeutics in clinical trials, and for the various manifestations of SpA, remains less clear. Future trials need better generalizability, robust subgroup analyses to assess differential responses for distinct disease manifestations, a focus on comparative efficacy, and outcomes relevant to the clinician and the patient. Additionally, study designs need to leverage available technology to facilitate subject participation in trials. In view of the interplay between biologic, physical, and psychological aspects of disease, there is increasing attention to nonpharmacologic agents, with the aim of maximizing long-term health-related quality of life through the control of symptoms and inflammation. Recent studies provide encouraging evidence that mind-body interventions such as tai chi, qigong, yoga, and meditation have benefits for patients with SpA, particularly those with pain. The advances in our understanding of pathogenesis, novel therapeutics, and nonpharmacologic interventions have revolutionized the management of SpA, but numerous questions around optimal management remain.

Enhancing Equity in Clinical Research: A Multifaceted Proposal for Spondyloarthritis.

Clinical research advances medical knowledge and improves healthcare outcomes. However, disparities in research participation hinder progress. The Unmet Research Needs in Spondyloarthritis Conference IV highlighted critical insights and strategies to enhance equity in clinical research. Talks focused on engaging underrepresented communities and addressing disparities in rheumatic diseases, particularly spondyloarthritis (SpA), to ensure research results are generalizable and inclusive. Disparities in SpA management, such as greater back pain severity among Black and Hispanic Americans and sex-based differences in pain management, emphasize the need for equitable research. Dr. Elizabeth Ferucci discussed the racial disparities in rheumatologic care, highlighting the importance of early access to rheumatologists and culturally informed primary care to improve outcomes. Dr. Hani El-Gabalawy's talk on engaging Indigenous communities stressed the importance of community consent and reciprocal benefits. Dr. Sarfaraz Hasni's presentation on mitigating disparities in research participation underscored the need for inclusive practices and strategies to promote diverse representation. Finally, Dr. Edith Williams emphasized institutional approaches to fostering equity, including diverse recruitment practices and institutional review board alignment with diversity priorities. Strategies to enhance equity in clinical research include community engagement, addressing logistical barriers to participation, and ensuring diverse research teams. These approaches can dismantle barriers for underrepresented communities, making research more accessible and reflective of the broader population. The SpA research community must commit to creating structures that foster inclusivity, ensuring medical advancements benefit all populations, especially historically underrepresented groups. The principles and strategies proposed serve as a roadmap for achieving equity in SpA research.

Prologue: Spondyloarthritis Unmet Research Needs Conference IV.

The Spondylitis Association of America (SAA) and the National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) convened a conference on the campus of the National Institutes of Health (NIH) on September 28 and 29, 2023, to identify unmet needs in spondyloarthritis (SpA) research. The conference featured presentations by experts in areas of disease endotypes, pain, innovative imaging in SpA, health disparities in rheumatic diseases, and therapeutics. Members of the conference planning committee moderated the sessions and led the development of manuscripts summarizing recommendations to address unmet research needs. Early career investigators were invited to submit abstracts, which were presented at a networking session during the conference. Here, we highlight each of the sessions comprising the conference in the form of manuscripts published together as a conference summary.

Effectiveness of N-3 fatty acids supplementation on spondyloarthritis: A systematic review and meta-analysis

Background & AimsThe study aims to systematically review and meta-analyze randomized controlled trials (RCTs) assessing the effects of n-3 fatty acids (FA) supplementation on spondyloarthritis (SpA) disease activity, inflammatory markers, and imaging. MethodsThe study protocol was developed and registered online in advance. The PubMed, SCOPUS, and Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases were systematically searched for RCTs up to April 2024. Two independent reviewers screened, assessed for eligibility, and extracted data from the eligible RCTs. The revised Cochrane Risk of Bias tool was used to assess the quality of trials. The random-effects model was used to calculate the pooled estimates. ResultsWe included four RCTs, involving 245 patients with SpA. Supplementation with n-3 FA did not improve physician-reported outcomes [number of tender joints (four trials, standardized mean difference (SMD): -0.22; 95% confidence interval (CI): -0.74 to 0.29; I2=61%), number of swollen joints (two trials, SMD: -0.13; 95% CI: -0.42 to 0.15; I2=0%)], and patient-reported outcomes [pain (three trials, SMD: -0.16; 95% CI: -1.03 to 0.70; I2=74%), Health Assessment Questionnaire (three trials, SMD: -0.04; 95% CI: -0.78 to 0.70; I2=71%). The other nine pre-specified outcomes were not analyzed due to lack of information from the original RCTs which were evaluated as «some concerns» or «high risk» of bias. ConclusionsIn the present systematic review and meta-analysis including placebo-controlled RCTs, n-3 FA supplementation did not show improvement in the reported outcomes. Future RCTs should be conducted with homogenous intervention, placebo, and outcomes to re-examine possible beneficial effects.

Familial mediterranean fever in a patient with ankylosing spondylitis: could familial mediterranean fever explain a typical eight-year ankylosing spondylitis?

Patients with familial mediterranean fever (FMF) often present with musculoskeletal involvement typical of spondyloarthropathy (SpA) or ankylosing spondylitis (AS), posing a diagnostic challenge for medical practitioners and leading to the description of the FMF-related SpA/AS clinical spectrum. Currently, the available data focuses on SpA diagnosis in patients with known FMF, while the contrary is rarely reported in the medical literature. We describe an unusual case of concomitant FMF diagnosis in a patient with an eight-year long history of typical, human leukocyte antigen-B27 positive AS on adalimumab treatment, who presented with recurrent febrile attacks and abdominal pain. The laboratory work-up revealed high titres of serum amyloid A while genetic testing was positive for the pathogenic M694V heterozygous variant in the MEFV gene. The patient was promptly treated with colchicine, showing complete remission of clinical symptoms and normalisation of inflammatory markers to date. We also performed a review of the available literature elaborating on the interrelationship of AS and FMF in terms of pathogenesis and clinical characteristics. Our case highlights the need for reporting of similar cases and further explores the association of AS and FMF as distinct clinical entities or as constituents of the same disease continuum model.

Efficacy and safety of the biosimilar etanercept in the treatment of patients with rheumatoid arthritis and spondyloarthritis

Objective: to evaluate the efficacy and safety of the biosimilar etanercept (ETC, Altebrel) in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) in clinical practice.Material and methods. The study included 20 patients with a confirmed diagnosis of RA and 8 with SpA: 5 with axial SpA with radiological signs of sacroiliitis (r-axSpA), 3 with peripheral psoriatic arthritis (PsA). The mean age of the patients with RA was 47.7±12.3 years, and the mean age of SpA patients was 40.4±15.9 years. Patients with RA had moderate or high disease activity: mean DAS28-ESR index 5.2±1.0, median CDAI – 22.5 [15.5; 35.0], SDAI – 31.9 [24.4; 38.6], CRP level – 11 [0.9; 32.5] mg/L. Patients with r-axSpA had high activity and functional impairment, the median BASDAI was 5.5 [3.5; 8.0], BASFI – 6 [4; 6], CRP level – 17.5 [12.5; 27] mg/L. In PsA, the average DAS28 was 6.25±0.71. All patients were prescribed Altebrel at a dose of 50 mg subcutaneously weekly against a background of disease-modifying antirheumatic drugs. Patients were examined at baseline and then after 3 and 6 months of treatment.Results and discussion. During treatment with the biosimilar ETC, all patients with RA showed a decrease in inflammatory activity markers: after 3 and 6 months of therapy, the mean DAS28-ESR value decreased to 3.5±1.2 and 2.3±0.7 (p <0.001) the median SDAI value to 19.6 [6.9; 32.5] and 8.4 [4.7; 15.6] (p<0.001), CDAI value to 9.5 [4; 13.0] and 4.5 [3.0; 7.5] (p <0.001), the CRP level – to 5.0 [0.7; 21.9] and 5.0 [2.0; 10.9] mg/L (p<0.001), respectively. Patients with SpA showed a decrease in disease activity and an improvement in functional status: the median BASDAI decreased to 1.0 [0; 2.5] and 0 [0; 1.5], BASFI to 0 [0; 1] and 0 [0; 0], CRP level to 4.5 [2.5; 6.5] and 2.0 [2.0; 2.5] mg/L, respectively. In patients with PsA, DAS28 decreased on average to 2.92±0.12 after 3 months, and after 6 months the values were 1.74 and 2.29 in 2 patients.All patients completed the study and no adverse events were observed during treatment. According to EULAR criteria, a good response was achieved in 40% of patients with RA after 3 months, and in 80% after 6 months, and a satisfactory response in 20%. Patients with r-axSpA showed statistically significant positive dynamics of BASDAI and BASFI indices as well as normalization of laboratory activity parameters.Conclusion. The results of the study demonstrate the high efficacy of Altebrel in rheumatic diseases, including RA and SpA.

Celecoxib in rheumatic diseases: possibilities and prospects. Brief descriptive survey

Chronic pain is the main manifestation of rheumatic diseases (RD), it determines the main complaints and worsens the quality of life of patients. The problem of effective control of chronic pain in rheumatology remains a current issue despite the successes in the development of new drugs for pathogenetic therapy, especially in immunoinflammatory RD. For example, 40-50% of patients with rheumatoid arthritis (RA), even those receiving biologic disease-modifying antirheumatic drugs and Janus kinase inhibitors, require analgesics. According to several population studies, about 50% of patients with the most common RD, osteoarthritis (OA) are forced to take various analgesics on a regular basis.The most popular class of analgesics with proven efficacy in RA, spondyloarthritis (SpA) and OA are non-steroidal anti-inflammatory drugs (NSAIDs). As has been shown in several meta-analyses, NSAIDs are superior to placebo and paracetamol in their therapeutic effect, are not inferior to opioids and are better tolerated overall. However, the use of NSAIDs can be associated with the development of dangerous adverse events (AEs), which requires careful monitoring of the patient's condition, considering comorbid diseases and risk factors. It is very important to choose a drug with a balanced ratio of efficacy and low risk of gastrointestinal and cardiovascular AEs. One such drug is celecoxib, whose therapeutic potential and relative safety have been confirmed in RA, SpA and OA. A differentiated approach to celecoxib prescription makes it possible to achieve a maximum therapeutic result with a minimum risk of AEs. For severe pain, treatment starts with a dose of 400 mg/day, followed by a switch to a maintenance dose of 200 mg/day.

Muscle ultrasound in Spondyloarthritis patients receiving biologic disease-modifying anti-rheumatic drugs early in treatment

Objective: This study evaluated muscle ultrasound in spondyloarthritis (SpA) patients receiving biologic disease-modifying anti-rheumatic drugs (b-DMARDs) early in treatment. Methods: A prospective study was conducted with 110 b-DMARD-naive SpA patients. The baseline and control muscle strength, physical performance tests, ultrasonographic muscle parameters, and disease activity scores of 67 controlled patients were examined. Results: During the follow-up period, there were significant improvements in the thickness of the gastrocnemius medialis (GM) muscle (p<0.001), the length of the GM fascicle (p=0.031), the thickness of the rectus femoris (RF) muscle (p<0.001), the cross-sectional area of the RF (RFCSA) muscle (p<0.001), the thickness of the rectus abdominis (RA) muscle (p<0.001), the thickness of the transverse abdominis (TA) muscle (p=0.004), and the thickness of the external oblique (EO) muscle (p=0.042). Besides, ASDAS-CRP scores were related to GM muscle thickness, RFCSA, and TA muscle thickness percent changes in patients whose disease activity regressed from high to moderate (respectively; p=0.030, p=0.040, p=0.002). Conclusion: Muscle ultrasound examination can show muscle mass improvement in SpA patients during treatment.

Relationship Between Ultrasound and Physical Examination in the Assessment of Enthesitis in Patients With Spondyloarthritis: Results From the DEUS Multicenter Study.

The study objectives were (i) to explore the agreement between the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and physical examination in assessing enthesitis in patients with spondyloarthritis (SpA) and (ii) to investigate the prevalence and clinical relevance of subclinical enthesitis in this population. Twenty rheumatology centers participated in this cross-sectional study. Patients with SpA, including axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), underwent both ultrasound scan and physical examination of large lower limb entheses. The OMERACT ultrasound lesions of enthesitis were considered, along with a recently proposed definition for "active enthesitis" by our group. Subclinical enthesitis was defined as the presence of "active enthesitis" in ≥1 enthesis in patients with SpA without clinical enthesitis (ie, number of positive entheses on physical examination and Leeds Enthesitis Index score = 0). A total of 4,130 entheses in 413 patients with SpA (224 with axSpA and 189 with PsA) were evaluated through ultrasound and physical examination. Agreement between ultrasound and physical examination ranged from moderate (ie, enthesophytes) to almost perfect (ie, power Doppler and "active enthesitis"). Patellar tendon entheses demonstrated the highest agreement, whereas Achilles tendon insertion showed the lowest. Among 158 (38.3%) of 413 patients with SpA with clinical enthesitis, 108 (68.4%) exhibited no "active enthesitis" on ultrasound. Conversely, of those 255 without clinical enthesitis, 39 (15.3%) showed subclinical enthesitis. Subclinical enthesitis was strongly associated with local structural damage. However, no differences were observed regarding the demographic and clinical profiles of patients with SpA with and without subclinical enthesitis. Our study underscores the need for a comprehensive tool integrating ultrasound and physical examination for assessing enthesitis in patients with SpA.

Successful treatment of Crohn's disease-related peripheral spondyloarthritis with upadacitinib: two case reports and case-based review.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease (CD), not only causes significant intestinal inflammation but also leads to extra-intestinal manifestations such as spondyloarthritis (SpA). Although the efficacy of tumor necrosis factor (TNF) inhibitors has been reported for IBD-related SpA, some cases still encounter treatment failure, highlighting the need for novel therapeutic alternatives. Recently, Janus kinase inhibitors have demonstrated their efficacy in IBD and SpA, yet their impact on CD-related SpA remains unexplored. Here we present the first two cases of CD-related peripheral SpA successfully treated with upadacitinib. Additionally, our literature review identified a reported case of CD-related peripheral SpA treated with tofacitinib. All cases achieved clinical remission of both CD and peripheral SpA with Janus kinase inhibitors, and no adverse events or disease relapses were reported during the observation period. Our cases and literature review highlight the promising potential of Janus kinase inhibitors as a novel treatment not only for intestinal inflammation of CD, but also for CD-related peripheral SpA.

Prevalence and incidence of uveitis in patients with spondyloarthritis: the impact of the biologics era. Data from International ASAS-COMOSPA Study.

Uveitis is a common extra-musculoskeletal manifestation in Spondyloarthritis (SpA). The aim of this study was to analyze the prevalence of uveitis in SpA patients, its association with geographical areas and to determine whether its incidence was different before and after the biological era. ASAS-COMOSPA is a retrospective study that includes patients fulfilling ASAS SpA classification criteria from 22 countries. The overall prevalence of uveitis was calculated, and factors associated with the onset of a first episode of uveitis were evaluated using a Cox regression. A Log-Rank test was performed to compare the new onset of uveitis in the no biological era (SpA onset before 2000) vs biological era (SpA onset after 2000). 3984 patients were included. The likelihood of presenting a first uveitis episode increased over time, from a prevalence of 10.5% (95%CI 9.5%-11.4%) at the time of the SpA diagnosis to 46.6% (41.6%-51.5%) after 30 years since the SpA diagnosis. HLA-B27 positivity, family history of uveitis, peripheral enthesitis and IBD were associated with higher risk of uveitis. Patients with SpA disease onset after year 2000 showed a lower prevalence of uveitis compared with disease onset before year 2000 (8.2% vs 25.5%, p< 0.01), as well as a lower incidence (2.8 per 100 PY vs 6.1 per 100 PY, respectively). In our study the risk of having suffered from at least one episode of uveitis ranged from 10% at the time of the diagnosis of axSpA to 47% after 30 years of disease duration. Patients with disease onset after biologic therapy introduction showed a significantly lower prevalence and incidence of first episodes of uveitis.

South African Rheumatism and Arthritis Association 2024 guidelines for the management of peripheral spondyloarthritis.

Peripheral spondyloarthritis (SpA) includes psoriatic arthritis (PsA), inflammatory bowel disease (IBD)-associated arthritis, reactive arthritis and undifferentiated peripheral SpA. These South African guidelines offer information on diagnosis, assessment and therapy of peripheral SpA. Emphasis is placed on a multidisciplinary team, and a treat-to-target strategy with escalation of therapy if the target of minimal or very low disease activity is achieved. Screening for and treatment of comorbidities are paramount.

The role of pulmonary rehabilitation in improving lung functions in patients with ankylosing spondylitis

Background Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by axial and peripheral entheseal inflammation and new bone production(1). The development of syndesmophytes, enthesophytes, and spinal fusion along the course of the disease is linked to chronic pain, functional impairment, and disability(2). Fibrosis of the upper lobes of the lungs (interstitial lung disease) and chest wall abnormalities are two of the emerging forms of pulmonary involvement in AS. (3). Pulmonary rehabilitation is a multifaceted program of education, counselling, breathing exercises, and other modalities that can increase the patient’s independence and ease of functioning(4). Aim To estimate the role of pulmonary rehabilitation in enhancing lung function in AS individuals in relation to disease activity, clinical, and functional parameters. Patients and methods This study was an interventional study: single-arm group (prospective randomized clinical study). Thirty people (30) participated in that study from those presented to Physical Medicine, Rheumatology and Rehabilitation inpatient and outpatient clinic at Ain Shams University hospitals, diagnosed as radiographic axial spondyloarthropathy (SPA) from 02/2022 to 12/2022. All patients underwent pulmonary rehabilitation program and were exposed to a detailed history, clinical, and pulmonary function testing. Disease activity was evaluated by Ankylosing Spondylitis Disease Activity Score C-reactive protein (ASDAS-CRP), Valuation of function by using Bath Ankylosing Spondylitis Functional index (BASFI), 6-Minute walk test (6MWT), the Modified Borg Dyspnoea Scale (MBS), and Timed Up and Go (TUG) test. All function and clinical scores were done at baseline and repeated after completing pulmonary rehabilitation program. Result The mean age of patients was 36.57 ± 7.83 years (23–45 years), with a median disease duration of (5 (3–9) years). In total, there were 19 out of the studied patients with restrictive pattern. With comparison between pre- and postintervention of pulmonary rehabilitation, there was a significant statistical difference in all, disease activity (ASDAS and BASFI) and functional (MBS, TUG, and 6MWT) parameters (P &lt;0.001), except for occiput to the wall. Regarding pulmonary function tests, including forced vital capacity (FVC), expiratory volume in one second (FEV1), and peaked expiratory flow (PEF), there was a statistically significant change at baseline and at the end of exercise (P &lt;0.001). Conclusion Improved respiratory function and disease activity and overall functional activity are possible outcomes of pulmonary rehabilitation programs in combination with other rehabilitation interventions.

Neuropathic pain in spondyloarthritis: Decoding its prevalence, risk factors, and impact on disease activity

ObjectivesThis study aimed to evaluate the prevalence and characteristics of neuropathic pain in patients with various subtypes of spondyloarthritis (SpA), including axial SpA (axSpA), psoriatic arthritis (PsA), and undifferentiated peripheral SpA (p-SpA). Additionally, the study sought to identify potential risk factors associated with the presence or severity of neuropathic pain and to investigate its impact on clinical disease activity assessment. MethodsWe conducted a cross-sectional study at two tertiary rheumatology centers, enrolling patients diagnosed with SpA. Data on demographic and clinical characteristics, comorbidities, and current therapies were collected. Neuropathic pain was assessed using the PainDETECT Questionnaire (PD-Q) and the Neuropathic Pain Symptom Inventory (NPSI). Statistical analyses included descriptive statistics, t-tests, and Pearson's correlations to evaluate the relationships between neuropathic pain scores and clinical disease activity indices. ResultsThe study included 177 patients. Of these, 22.2% had a PD-Q score ≥19, showing a high likelihood of neuropathic pain, while 64.9% scored ≤12, suggesting the absence of significant neuropathic components. The mean PD-Q score was 11.5 ± 10.1. Subgroup analyses showed that females had significantly higher scores for paroxysmal and evoked pain (p < 0.05), and obese patients had significantly higher scores across all NPSI subscores (p < 0.05). Moderate positive correlations were found between neuropathic pain scores and clinical disease activity indices, such as DAPSA (r = 0.46, p < 0.0001) and ASDAS-CRP (r = 0.42, p < 0.01). ConclusionsNeuropathic pain is prevalent among patients with SpA and is significantly associated with disease activity assessments and management. This study highlights the importance of integrating neuropathic pain evaluation into the clinical assessment of SpA to tailor treatment approaches effectively and improve patient outcomes.

Systemic lupus erythematosus induced by anti-tumor necrosis factor α therapy in inflammatory rheumatic diseases: a case series.

This case series aims to characterize the development of systemic lupus erythematosus (SLE) induced by anti-tumor necrosis factor α (anti-TNFα) therapy in patients with inflammatory rheumatic diseases, namely rheumatoid arthritis (RA), spondylarthritis (SpA), and psoriatic arthritis (PsA). Patients with a diagnosis of SLE induced by anti-TNFα therapy and registered on the Rheumatic Diseases Portuguese Register (Reuma.pt) who started their first anti-TNFα between 2001 and 2020 were included. Demographic, clinical, and laboratory data were obtained by consulting Reuma.pt. The diagnosis of SLE induced by anti-TNFα was considered if there was a temporal relationship between the onset of anti-TNFα therapy and manifestations (clinical and immunological) in accordance with the American College of Rheumatology/European League Against Rheumatism criteria (2019). A total of 607 patients with inflammatory rheumatic diseases and six cases of SLE induced by anti-TNF-α therapy were reviewed: two patients were affected by RA, three patients by SpA, and one by PsA. All these patients had articular and constitutional symptoms that improved after discontinuation of the anti-TNFα agent. After switching to a second anti-TNFα agent, there was no recurrence of SLE over time. The development of SLE secondary to anti-TNFα agents in inflammatory rheumatic patients is rare. In this case series, all patients had a mild disease that improved after therapy discontinuation without recurrence of the disease. SLE induced by anti-TNFα should be considered in the follow-up of RA, SpA, and PsA patients.

Diagnosis and Management of Inflammatory Bowel Disease-Associated Spondyloarthritis.

Inflammatory bowel disease (IBD)-associated spondyloarthritis (SpA) is common but remains poorly understood. In this review article, we aimed to provide guidance regarding the diagnosis and management of this condition. For diagnosis of IBD-associated peripheral SpA (IBD-pSpA), we recommend collaboration with rheumatology for incorporation of clinical symptoms, physical examination findings, joint imaging if applicable, and available diagnostic criteria. For the management of IBD-pSpA, we first recommend assessment and treatment of underlying luminal IBD disease activity. We provide guidance regarding positioning of advanced therapies for IBD in patients with IBD-pSpA based on the limited available literature. For diagnosis of IBD-associated axial SpA, we recommend rheumatology referral to make the diagnosis based on incorporation of symptoms, laboratory data, imaging findings (sacroiliitis), and available diagnostic criteria. For the management of axial SpA, we recommend comanagement with rheumatology and use of either antitumor necrosis factor agents or Janus kinase inhibitors, when applicable.

Intestinal epithelial expression of human TNF is sufficient to induce small bowel inflammation and sacroiliitis mimicking human Spondyloarthritis.

Gut and joint disease commonly co-occur in spondyloarthritis (SpA). Up to 50% of SpA-patients show signs of subclinical gut inflammation and 10% evolves into inflammatory bowel disease (IBD). However, the mechanisms underlying this gut-joint axis are still unclear. Here we tested the hypothesis whether restricted expression of a pro-inflammatory cytokine in the intestine may trigger onset of combined gut and joint inflammation. Intestinal expression of human TNF (hTNF) was achieved by driving hTNF gene expression under control of the rat FAPB2 promoter, creating a new animal model, the TNFgut mice, which expresses hTNF in the proximal intestinal tract. Intestinal-specific TNFgut mice were examined for pathological changes in the intestine and extra-intestinal tissues by means of histology, qPCR and flow cytometry, along with 16S sequencing on stools. Local expression of hTNF in the epithelium of the small intestine induces a pro-inflammatory state of the proximal intestinal tract with epithelial alterations and induction of members of the S100 family, as well as local upregulation of T helper 17 and regulatory T cells, but no obvious signs of dysbiosis. Curiously, TNFgut mice develop sacroiliitis (p< 0.05) in addition to small bowel inflammation (p< 0.05). However, no signs of peripheral arthritis nor enthesitis could be documented. Intestinal expression of hTNF is sufficient to initiate a pro-inflammatory cascade culminating in small bowel inflammation and sacroiliitis. Thus, gut-derived cytokines are sufficient to induce spondyloarthritis.