Fatigue Assessment Using FACIT-F Scale in Spondyloarthropathy Patients and its Correlation with BASDAI and BASFI Scores.

OBJECTIVE: To measure fatigue in axial spondyloarthropathy patients and find its correlation with the disease activity measures. STUDY DESIGN: Cross-sectional, descriptive study. Place and Duration of the Study: Rheumatology Unit, Federal Government Polyclinic Hospital, from November 2021 to May 2022. METHODOLOGY: This study included 45 patients fulfilling the ASAS criteria for spondyloarthropathy. Bathankylosing spondylitis disease activity (BASDAI), Bath ankylosing spondylitis functional index (BASFI), and functional assessment of chronic illness therapy- fatigue (FACIT-F) scores were measured for each patient. RESULTS: In this study, there were 9 (20%) female patients and 36 (80%) male patients. There were 39 (86.7%) patients who had ankylosing spondylitis, 4 (8.9%) had axial spondyloarthropathy with peripheral arthritis and 2 (4.4%) had enthesitis-related juvenile idiopathic arthritis. The mean duration of the disease was 5.45 ± 4.19 years. Active disease with a BASDAI score of ≥4 was found in 16 (35.6%) patients while 29 (64.4%) had a BASDAI score <4. Severe fatigue with a FACIT-F score of <30 was found in 31 (68.9%) of the patients while less fatigue with FACIT-F score >30 was found in 14 (31.1%). The mean BASFI score of the cohort was 3.23 ± 2.01. Spearman's rho correlation analysis showed a significant strong correlation between the FACIT-F score, BASDAI and BASFI scores (p<0.001). CONCLUSION: Patients with active disease and higher BASFI scores had a lower FACIT-F score suggesting more fatigue, thus correlating with the disease activity. KEY WORDS: Bath ankylosing spondylitis disease activity (BASDAI), Functional assessment of chronic illness therapy-fatigue (FACIT-F), Ankylosing spondylitis (AS), Bath ankylosing spondylitis functional index (BASFI), Assessment in ankylosing spondylitis (ASAS).

Identification of the first signs or symptoms in different spondyloarthritis subtypes and their association with HLA-B27: data from REGISPONSER and RESPONDIA registries.

OBJECTIVE: To describe and analyse the initial symptoms attributable to patients with spondyloarthritis (SpA) and their association with HLA-B27 status. METHODS: This was an observational, cross-sectional and multicentre study with patients who fulfilled the European Spondyloarthropathy Study Group criteria for SpA from the Registry of Spondyloarthritis of Spanish Rheumatology (REGISPONSER) and Ibero-American Registry of Spondyloarthropathies (RESPONDIA) united registries. Differences in the first sign(s) or symptom(s) were compared across diagnoses and between HLA-B27 status. The diagnostic delay between patients who start the disease with musculoskeletal manifestations (MMs) and extra-MMs (EMMs) was compared. RESULTS: A total of 4067 patients were included (2208 from REGISPONSER and 1859 from RESPONDIA) (ankylosing spondylitis (AS): 68.3%, psoriatic arthritis (PsA): 19.9%, undifferentiated SpA: 11.8%). Overall, 3624 (89.1%) patients initiated the disease with MMs and 443 (10.9%) with EMMs. Low back pain (61.7%) and lower-limb arthritis (38.5%) were the most frequent initial symptoms. In AS patients, the absence of HLA-B27 seems to be related to an increase in the probability of starting the disease with cervical pain and peripheral manifestations. In PsA, the onset of arthritis and psoriasis was more prevalent in HLA-B27-negative patients, while initiation with axial manifestations was more predominant in HLA-B27-positive patients. The diagnostic delay was longer in patients with initial MMs than in those with EMMs (7.2 (34.8) vs 4.5 (7.6) years, respectively). CONCLUSION: In this SpA population, MMs were the most prevalent initial symptoms, with differences across diagnoses and depending on the presence of the HLA-B27 antigen.

Advanced practice physiotherapists in Scottish primary care: Axial Spondyloarthropathy epidemiology, time to diagnosis, and referrals to rheumatology.

OBJECTIVES: (1) Generate empirical knowledge of a Musculoskeletal (MSK) Advanced Practice Physiotherapist (APP) Service in Scottish Primary Care; (2) Identify the incidence and baseline time to diagnosis of Axial Spondyloarthropathy (AxSpA); (3) Identify APP Rheumatology referral fulfilment of the NICE 2017 Guidelines and Spondylarthritis Diagnosis Evaluation (SPADE) Tool; (4) Calculate APP Rheumatology referral conversion rates for AxSpA diagnosis and further investigation; (5) Contribute towards the current body of literature for informing analysis of MSK APP services within Scottish Primary Care. METHODS: An audit and evaluation approach was undertaken over a 3-year period (May 2019-April 2022). Relevant clinical cases from the whole-service data-set were identified and analysed, using retrospective electronic healthcare record review and descriptive statistical techniques. RESULTS: A total of 37,656 primary care MSK APP consultations took place, with N = 19 suspected AxSpA referrals made to Rheumatology. N = 6 cases of AxSpA were diagnosed by a Rheumatologist (31.6%). The mean age of individuals diagnosed with AxSpA was 39.6 ± 8.8, and 66.7% (4/6) were female. Mean time to diagnosis was 3.4 years, and incidence per-10,000 person-years was 1.6. Compliance of referrals with the NICE 2017 Guidelines and SPADE Tool Criteria was 78.9%. Of those diagnosed with AxSpA, 66.7% met both referral criterion sets. CONCLUSION: Those referred by an MSK APP from primary care had a 5.1 year shorter time to diagnosis than the previous reported UK average of 8.5 years. APPs identified relevant AxSpA features in referring to Rheumatology, and supported effective implementation of the local secondary care pathway.

Monocyte subpopulations display disease-specific miRNA signatures depending on the subform of Spondyloarthropathy.

Spondyloarthropathies (SpA) are a family of rheumatic disorders that could be divided into axial (axSpA) and peripheral (perSpA) sub-forms depending on the disease clinical presentation. The chronic inflammation is believed to be driven by innate immune cells such as monocytes, rather than self-reactive cells of adaptive immune system. The aim of the study was to investigate the micro-RNA (miRNA) profiles in monocyte subpopulations (classical, intermediate and non-classical subpopulations) acquired from SpA patients or healthy individuals in search for prospective disease specific and/or disease subtype differentiating miRNA markers. Several SpA-specific and axSpA/perSpA differentiating miRNAs have been identified that appear to be characteristic for specific monocyte subpopulation. For classical monocytes, upregulation of miR-567 and miR-943 was found to be SpA-specific, whereas downregulation of miR-1262 could serve as axSpA-differentiating, and the expression pattern of miR-23a, miR-34c, mi-591 and miR-630 as perSpA-differentiating markers. For intermediate monocytes, expression levels of miR-103, miR-125b, miR-140, miR-374, miR-376c and miR-1249 could be used to distinguish SpA patients from healthy donors, whereas the expression pattern of miR-155 was identified as characteristic for perSpA. For non-classical monocytes, differential expression of miR-195 was recognized as general SpA indicator, while upregulation of miR-454 and miR-487b could serve as axSpA-differentiating, and miR-1291 as perSpA-differentiating markers. Our data indicate for the first time that in different SpA subtypes, monocyte subpopulations bear disease-specific miRNA signatures that could be relevant for SpA diagnosis/differentiation process and may help to understand SpA etiopathology in the context of already known functions of monocyte subpopulations.

Seronegative spondyloarthropathy-associated inflammatory bowel disease.

Seronegative spondyloarthropathy (SpA) usually starts in the third decade of life with negative rheumatoid factor, human leukocyte antigen-B27 genetic marker and clinical features of spinal and peripheral arthritis, dactylitis, enthesitis and extra-articular manifestations (EAMs). Cases can be classified as ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic arthritis, or juvenile-onset spondyloarthritis. Joint and gut inflammation is intricately linked in SpA and inflammatory bowel disease (IBD), with shared genetic and immunopathogenic mechanisms. IBD is a common EAM in SpA patients, while extraintestinal manifestations in IBD patients mostly affect the joints. Although individual protocols are available for the management of each disease, the standard therapeutic guidelines of SpA-associated IBD patients remain to be established. Nonsteroidal anti-inflammatory drugs are recommended as initial therapy of peripheral and axial SpA, whereas their use is controversial in IBD due to associated disease flares. Conventional disease-modifying anti-rheumatic drugs are beneficial for peripheral arthritis but ineffective for axial SpA or IBD therapy. Anti-tumor necrosis factor monoclonal antibodies are effective medications with indicated use in SpA and IBD, and a drug of choice for treating SpA-associated IBD. Janus kinase inhibitors, approved for treating SpA and ulcerative colitis, are promising therapeutics in SpA coexistent with ulcerative colitis. A tight collaboration between gastroenterologists and rheumatologists with mutual referral from early accurate diagnosis to appropriately prompt therapy is required in this complex clinical scenario.

'Can you touch your toes?' spondyloarthropathies and acute anterior uveitis for primary eyecare practitioners.

The rheumatological diseases known as spondyloarthropathies (SpAs) are reviewed with respect to the current classifications of SpAs and from the perspective of ophthalmic practitioners. The focus is on the most common spondyloarthropathy, ankylosing spondylitis (AS), and the key symptoms, such as inflammatory back pain. The association with HLA-B27 and acute anterior uveitis (AAU) and the major clinical considerations for primary eye care practitioners are reviewed. An atypical case study illustrates difficulties in the detection and diagnosis of ankylosing spondylitis.

Assessment of plasma microRNA potentials as a non-invasive biomarker in patients with axial spondyloarthropathy.

OBJECTIVE: It is assumed that abnormally expressed MicroRNAs (miRNAs) may be present in the plasma of patients with radiographic axial spondyloarthropathy (rad-AxSpA). Thus, the present study was conducted with the aim of investigating the expression profile of miRNAs in patients with rad-AxSpA. PATIENTS AND METHODS: A total of 15 patients diagnosed with rad-AxSpA according to the Assessment of the SpondyloArthritis International Society (ASAS) classification criteria and nine healthy controls matched for age and gender were included in the study. Demographic data were collected, and disease activity was evaluated using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Peripheral blood samples were collected, and miRNAs were extracted. The expression of microRNAs was analyzed using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) by the miScript miRNA PCR Array Human Inflammatory Response and Autoimmunity. RESULTS: A total of 84 miRNA profiles were evaluated, and expressions in the study and control groups were compared. When compared to the control group, 6 miRNAs (miR-125b-5p, miR-144-3p, miR-19a-3p, miR-20a-5p, miR-29c-3p, miR-30b-5p) were detected to be upregulated, and 42 miRNAs were detected to be downregulated in the rad-AxSpA group. A p-value < 0.05 was accepted as statistically significant. A significant association was found between miR-145-5p and BASDAI (p = 0.04941). MiR-144-3p, miR-302b-3p, miR-381-3p, miR-497-5p, miR-511-5p, and miR-9-5p were found to be significantly upregulated in the HLA-B27+ patients (p = 0.03063). CONCLUSIONS: Abnormal miRNA expressions were detected in the plasma of the patients with rad-AxSpA. It was concluded that comprehensive studies should be continued to define these miRNAs as diagnostic biomarkers for rad-AxSpA in order to detect its association with Ankylosing Spondylitis disease activity.

Coexisting Spine Lesions on Whole Spine T2 Sagittal MRI in Evaluating Spinal Degenerative Disease.

BACKGROUND: Studies have reported on the usefulness of whole spine magnetic resonance imaging (MRI) in evaluating specific diseases such as spinal tuberculosis, spinal trauma, spondyloarthropathies, and multiple myeloma. In studies concerning degenerative spinal disease, sample sizes were small and some did not provide information on how symptomatic coexisting lesions were treated. We evaluated the types and prevalence of coexisting spine lesions found on whole spine T2 sagittal screening performed at the time of routine cervical and lumbar spine MRI and evaluated the efficacy of such screening in degenerative diseases of the cervical and lumbar spine. METHODS: We reviewed 1,757 and 2,266 consecutive cases where whole spine T2 sagittal screening had been performed with routine cervical and lumbar spine MRI, respectively, in patients with cervical and lumbar spinal degenerative diseases. Coexisting spine lesions were documented and statistical analysis was performed to investigate significant differences according to sex, age, and initial diagnosis. Electronic medical records were reviewed to determine whether additional interventions were necessary following such findings. RESULTS: We reviewed 1,252 and 1,689 consecutive cases of routine cervical and lumbar spine MRI respectively, with whole spine T2 sagittal screening. Of the 1,252, 419 (33.5%) patients with cervical spinal degenerative disease had coexisting lesions in the thoracolumbar spine. Patients with ligament ossification disease of the cervical spine showed a higher prevalence of coexisting spine lesions. Sixty of the 419 (14.3%) patients with coexisting spine lesions warranted additional intervention or surgical treatment. Four hundred and eighty-one of 1,689 (28.5%) patients with lumbar degenerative disease had coexisting spine lesions in the cervicothoracic spine. Forty-eight of the 481 (10.0%) patients with coexisting spine lesions warranted additional intervention. In both patient groups, older patients showed a significantly higher prevalence of coexisting spine lesions than younger patients. CONCLUSION: Considering the minimal extra time and cost in performing whole spine screening, its application to routine spine MRI can be considered in evaluating cervical and lumbar spinal degenerative diseases.

Construct validity of the ASAS health index in psoriatic arthritis: a cross-sectional analysis.

OBJECTIVES: The Assessment of SpondyloArthritis international Society health index (ASAS-HI) was designed to assess the global health of patients with spondyloarthritis, but its performance in psoriatic arthritis (PsA) is hardly known. We addressed the clinimetric properties of this instrument in patients with PsA. METHODS: This was a cross-sectional observational study that included 90 consecutive patients with PsA. The measurement properties of ASAS-HI were analysed against the Disease Activity index for PSoriatic Arthritis (DAPSA) and the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire. A multivariate analysis was performed to weigh the ASAS-HI items associated with DAPSA active disease and PsAID high impact. RESULTS: Mean ASAS-HI was 5.8 (4.3). Convergent validity was high both against DAPSA (ρ 0.78, P < 0.0001) and PsAID (ρ 0.80, P < 0.0001). ASAS-HI showed a high discriminant capacity for both DAPSA remission [optimal criterion ≤ 2, area under the receiver operating characteristic curve (AUC) 0.92 (95% CI: 0.85, 0.97), P < 0.0001], and low activity [optimal criterion ≤6, AUC 0.87 (95% CI: 0.79, 0.94), P < 0.0001]. The ASAS-HI items significantly associated with DAPSA active disease were: 'I find it hard to stand for long' (ß 4.48, P < 0.0001), 'I find it hard to concentrate' (ß 2.94, P = 0.042) and 'I sleep badly at night' (ß 1.86, P = 0.044). As for PsAID, the only item significantly associated with a high impact was 'I sleep badly at night' (ß -3.29, P = 0.015). CONCLUSION: We demonstrated construct validity of ASAS-HI, a spondyloarthritis instrument, for the assessment of global health in patients with PsA.

Which Magnetic Resonance Imaging Lesions in the Sacroiliac Joints Are Most Relevant for Diagnosing Axial Spondyloarthritis? A Prospective Study Comparing Rheumatologists' Evaluations With Radiologists' Findings.

OBJECTIVE: Pathologic sacroiliac (SI) joint changes on magnetic resonance imaging (MRI) are important for the classification of axial spondyloarthritis (SpA). In daily practice, radiologists play a major role in interpreting imaging findings. This study was undertaken to evaluate the impact of MRI SI joint findings on the identification of axial SpA by radiologists, in comparison to diagnosis by rheumatologists. METHODS: Patients age ≤45 years were prospectively included when referred for clinical suspicion of axial SpA and underwent a complete diagnostic evaluation including STIR- and T1-weighted MRI of the SI joint. Diagnosis made by an experienced rheumatologist with access to all relevant information was considered the gold standard. MRIs were evaluated by 2 experienced radiologists who were unaware of the clinical data, who indicated which MRI lesions were "critical" to the decision for or against axial SpA. RESULTS: Of the 300 patients included, 132 (44%) were diagnosed as having axial SpA. Mean age was comparable between the 2 groups, but patients with axial SpA and those with non-axial SpA differed with regard to symptom duration (58.6 ± 69.5 versus 33.9 ± 45.1 months, respectively; P = 0.003) and HLA-B27 positivity (75.6% versus 19%, respectively; P < 0.001). Rheumatologists and radiologists agreed on the diagnosis in 262 cases (87.3%), while 34 patients (11.3%) were diagnosed as having axial SpA by rheumatologists only (clinically), and 4 cases (1.3%) were judged as suggestive of axial SpA by radiologists only. Bone marrow edema (BME) and sclerosis showed the highest sensitivity, while erosions and fatty lesions showed the highest specificity, for axial SpA diagnosis. The combination of BME with erosions had the highest positive predictive value (86.5%). CONCLUSION: The MRI findings with the highest diagnostic value in patients in whom axial SpA is suspected are structural changes in the SI joint, alone or in combination with BME. Our findings indicate that while the absence of BME is usually not compatible with a diagnosis of axial SpA, the presence of BME does not necessarily confirm a diagnosis of axial SpA.

Impact of Janus Kinase Inhibition on the Treatment of Axial Spondyloarthropathies.

Many immune cells and effector molecules (e.g. cytokines, Interferons, growth factors) utilize different combinations of Janus kinase (JAK) and signal transducer and activator of transcription (STAT) molecules to transduce signals from the cell surface to the nucleus, where they regulate transcription. This pathway is basically involved in almost all inflammatory diseases and also in the interleukin (IL)-23/IL-17 cascade, which is an essential part of the pathogenesis of spondyloarthropathies (SpA). Upon evidence from in vitro and in vivo experiments indicating disease-modifying effects of JAK inhibition in inflammatory joint disease, numerous inhibitors of the JAK/STAT pathway (= JAKinibs) with different selectivity against the four members of the JAK family [JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2)] were developed. Trials in rheumatoid arthritis were successful with respect to efficacy and safety, and currently, three JAKinibs are approved for the treatment of rheumatoid arthritis in the European Union. Although new treatment options (anti-IL-23, anti-IL-17, and phosphodiesterase 4 inhibitors) have become available for spondyloarthritis and especially psoriatic arthritis (PsA) within the last years, most of them are biologics and do not address all disease manifestations equally. Therefore, multiple trials were initiated to evaluate JAKinibs in PsA and axial spondyloarthritis (axSpA). A trial of Tofacitinib (OPAL) was successful in PsA and has led to the inclusion of JAKinibs into the treatment algorithm. Currently many trials with JAKinibs are ongoing for PsA and axSpA, with one phase III trial of upadacitinib (selective JAK1 inhibitor) showing good therapeutic response in active radiographic axSpA.

Osteitis condensans ilii: current knowledge and diagnostic approach.

Osteitis condensans ilii is a noninflammatory condition of an uncertain etiology, characterized by sclerotic bone lesions located mainly in the iliac region of the sacroiliac joints. In many patients, osteitis condensans ilii remains an incidental imaging finding; however, it has been associated with lower back pain and may mimic inflammatory rheumatic conditions such as axial spondyloarthritis. The diagnosis is based on the presence of the characteristic sclerotic lesions on radiographs and the exclusion of other conditions that are associated with back pain. Management is usually conservative with the use of physical therapy and analgesics, and it is associated with a favorable prognosis. Herein, we conducted a narrative literature review using the terms osteitis condensans ilii, and we identified case reports, case series, reviews, and original studies associated with the condition. The aim of this article is to raise the awareness of this underrecognized clinicoradiological condition and to enable the health-care providers to recognize clinical and radiological features that should raise suspicion of the osteitis condensans illi, and to describe the treatment options.

Immunoglobulin A antibodies to oxidized collagen type II as a potential biomarker for the stratification of spondyloarthritis from rheumatoid arthritis.

OBJECTIVES: The discovery of diseased tissue-specific neoantigens offers the opportunity to develop important disease tissue-specific biomarkers that can help in the prediction, diagnosis, and stratification of diseases. This opportunity is specifically significant for autoimmune diseases where diagnostic biomarkers are not available. Inflammatory autoimmune diseases are commonly associated with local generation of large amounts of reactive oxidants. We have previously identified oxidative post-translationally modified (oxPTM) tissue-specific neoantigens in rheumatoid arthritis (RA) and type 1 diabetes that elicit an immune response. In the current study, we studied the presence and clinical significance of antibodies to oxPTM collagen type II (CII) in patients with spondyloarthritis (SpA). METHOD: Levels of antibodies specific to native CII and oxPTM-CII were assessed by enzyme-linked immunosorbent assay. RESULTS: Immunoglobulin G (IgG) binding to oxPTM-CII was observed in 52%, 83%, and 28% of serum samples from patients with axial spondyloarthritis (axSpA), RA, and psoriatic arthritis (PsA), respectively. Importantly, while strong IgA anti-oxPTM-CII responses were detected in axSpA and PsA patients, with 47% and 84% respective binders, no IgA anti-oxPTM-CII was detected in RA patients. IgA anti-oxPTM-CII reactivity in axSpA patients treated with biologics was higher and more frequent, with 85% binders compared to 9% binders in patients treated with synthetic disease-modifying anti-rheumatic drugs. CONCLUSION: Our data imply that SpA and PsA are associated with the presence of antibodies to oxPTM-CII, suggesting that there may be a humoral component that may distinguish patients with SpA from RA. Our approach could be adapted to other diseases, particularly to inflammatory autoimmune diseases.