Spondyloarthritis Features Research Articles

Systemic auto-inflammatory manifestations in patients with spondyloarthritis

Objectives(1) characterizing a group of spondyloarthritis (SpA) patients with systemic auto-inflammatory symptoms (S-SpA); (2) comparing SpA features with and without auto-inflammatory symptoms; (3) comparing the auto-inflammatory features of S-SpA and Still's disease (SD). MethodsRetrospective observational study. Clinical data of adult and pediatric patients with S-SpA, SD or SpA were collected retrospectively and analyzed. ResultsForty-one subjects with S-SpA, 39 with SD and 42 with SpA were enrolled. The median latency between systemic and articular manifestations in S-SpA was 4.4 (IQR: 7.2) years. S-SpA and SpA had similar frequency of peripheral arthritis and enthesitis (N.S.), while tenosynovitis was more frequent (P=0.01) and uveitis less frequent (P<0.01) in S-SpA. MRI showed signs of sacroiliac inflammation and damage in both S-SpA and SpA equally (N.S.). S-SpA patients had less corner inflammatory lesions (P<0.05) and inflammation at the facet joints (P<0.01), more interspinous enthesitis (P=0.01) and inter-apophyseal capsulitis (P<0.01). Compared to SD, S-SpA patients had lower-grade fever (P<0.01), less rash (P<0.01) and weight loss (P<0.05), but more pharyngitis (P<0.01), gastrointestinal symptoms (P<0.01) and chest pain (P<0.05). ESR, CRP, WBC, ANC, LDH tested higher in SD (P<0.01). Resolution of systemic symptoms was less frequent in S-SpA than SD on corticosteroid (P<0.01) and methotrexate (P<0.05) treatment. When considering all SD patients, a complete response to corticosteroids in the systemic phase significantly reduced the likelihood of developing SpA (OR=0.06, coefficient −2.87 [CI: −5.0 to −0.8]). ConclusionsSpA should be actively investigated in patients with auto-inflammatory manifestations, including undifferentiated auto-inflammatory disease and SD.

Change in different classes of chronic back pain suspicious of axial spondyloarthritis: a latent transition analysis of the SPACE cohort

ObjectivesTo follow up four previously identified classes ‘pure axial spondyloarthritis’ (axSpA) (‘axial’), ‘axSpA with peripheral signs’ (‘inflammatory back pain+peripheral’), ‘axSpA at risk’ and ‘no spondyloarthritis’ (‘no SpA’). They reflect the...

Imaging of Sacroiliac Pain: The Current State-of-the-Art.

Pain in the sacroiliac (SI) region is a common clinical manifestation, often caused by diseases involving the SI joints. This is typically due to inflammation or degenerative changes, while infections or cancer are less frequent causes. The SI joint is challenging to image accurately because of its distinct anatomical characteristics. For an accurate diagnosis, conventional radiography often needs to be supplemented with more precise methods such as magnetic resonance imaging (MRI) or computed tomography (CT). Sacroiliitis, a common presenting feature of axial spondyloarthritis (axial SpA), manifests as bone marrow edema, erosions, sclerosis, and joint space narrowing. Septic sacroiliitis and repetitive stress injuries in sports can also cause changes resembling inflammatory sacroiliitis. Other conditions, such as osteitis condensans ilii (OCI), can mimic the radiologic characteristics of sacroiliitis. Inflammatory lesions are diagnosed by concurrent erosions, hyperostosis, and ankylosis. Ligament ossifications or mechanical stress can also result in arthritic disorders. Determining the exact diagnosis can be aided by the distribution of the lesions. Inflammatory lesions can affect any part of the articulation, including the inferior and posterior portions. Mechanical lesions, such as those seen in OCI, often occur in the anterior middle region of the joint. In cases of idiopathic skeletal hyperostosis, ligament ossification is found at the joint borders. This pictorial essay describes common SI joint problems, illustrated with multimodal imaging data. We, also, discuss strategies for selecting the best imaging modalities, along with imaging pitfalls, key points, and approaches for treating patients with suspected inflammatory back pain.

Features of Axial Spondyloarthritis in Two Multicenter Cohorts of Patients with Psoriasis, Uveitis, and Colitis Presenting with Undiagnosed Back Pain.

We aimed to assess: 1. The frequency of axial spondyloarthritis (axSpA) according to extra-articular presentation and HLA-B27 status; 2. Clinical and imaging features that distinguish axSpA from non-axSpA; 3. The impact of MRI on diagnosis and classification of axSpA. The Screening in Axial Spondyloarthritis in Psoriasis, Iritis, Colitis, (SASPIC) study enrolled patients in two multicenter cohorts. Consecutive patients with undiagnosed chronic back pain attending dermatology, ophthalmology, and gastroenterology clinics with PsO, AAU, or IBD, were referred to a local rheumatologist with special expertise in axSpA for a structured diagnostic evaluation. The primary outcome was proportion of patients diagnosed with axSpA by final global evaluation. Frequency of axSpA was 46.7%, 61.6%, and 46.8% in SASPIC-1 cases (n=212) and 23.5%, 57.9%, and 23.3% in SASPIC-2 cases (n=151) with PsO, AAU, or IBD, respectively. Among B27 positives, axSpA was diagnosed in 70%, 74.5%, and 66.7% in SASPIC-1, and in 71.4%, 87.8%, and 55.6% in SASPIC-2 in patients with PsO, AAU, or IBD, respectively. All musculoskeletal clinical features were non-discriminatory. MRI was indicative of axSpA in 60-80% of patients and MRI in all patients (SASPIC-2) versus on-demand (SASPIC-1) led to 25% fewer diagnoses of axSpA in HLA B27 negatives with PsO or IBD. Performance of the ASAS classification criteria was greater with routine MRI (SASPIC-2) though sensitivity was lower than previously reported. Optimal management of patients presenting with PsO, AAU, IBD, and undiagnosed chronic back pain should include referral to a rheumatologist. Conducting MRI in all patients enhances diagnostic accuracy.

Initiation of vedolizumab did not provoke new-onset spondylarthritis in patients with inflammatory bowel disease: A prospective 24-week study with imaging assessments.

A temporal relationship between vedolizumab and new-onset spondyloarthritis (SpA) has been suggested. We evaluated the relationship between vedolizumab initiation and development of new-onset SpA in patients with inflammatory bowel disease (IBD) through serial clinical evaluation and magnetic resonance imaging (MRI). A single-centre prospective observational study of 24 patients with IBD. Patients were eligible if they had active ulcerative colitis or Crohn's disease (CD), were initiating vedolizumab, had no prior history of arthritis or SpA and were suitable for serial MRI. A rheumatologist performed clinical evaluation prior to the first dose and 8 and 24weeks. Axial MRI was evaluated by a blinded central reader and performed at baseline 8 and 24weeks. Nine tumor necrosis factor (TNF) inhibitor-naïve patients (4 male; mean age 53.2years; 6 UC; 3 CD) and eight TNF inhibitor-experienced patients (7 male; mean age 48years; 3 UC; 5 CD) completed all assessments. No patients developed new features of axial arthritis or features of peripheral SpA (inflammatory oligoarthritis, enthesitis, dactylitis, or psoriasis (nail, body, or scalp)). Both groups demonstrated a good intestinal response. Vedolizumab initiation did not induce new features of axial or peripheral SpA after 24weeks of treatment in TNF inhibitor-experienced or TNF inhibitor-naive patients with IBD.

CHOP-mediated IL-23 overexpression does not drive colitis in experimental spondyloarthritis

HLA-B27 is a major risk factor for spondyloarthritis (SpA), yet the underlying mechanisms remain unclear. HLA-B27 misfolding-induced IL-23, which is mediated by endoplasmic reticulum (ER) stress has been hypothesized to drive SpA pathogenesis. Expression of HLA-B27 and human β2m (hβ2m) in rats (HLA-B27-Tg) recapitulates key SpA features including gut inflammation. Here we determined whether deleting the transcription factor CHOP (Ddit3−/−), which mediates ER-stress induced IL-23, affects gut inflammation in HLA-B27-Tg animals. ER stress-mediated Il23a overexpression was abolished in CHOP-deficient macrophages. Although CHOP-deficiency also reduced Il23a expression in immune cells isolated from the colon of B27+ rats, Il17a levels were not affected, and gut inflammation was not reduced. Rather, transcriptome analysis revealed increased expression of pro-inflammatory genes, including Il1a, Ifng and Tnf in HLA-B27-Tg colon tissue in the absence of CHOP, which was accompanied by higher histological Z-scores. RNAScope localized Il17a mRNA to the lamina propria of the HLA-B27-Tg rats and revealed similar co-localization with Cd3e (CD3) in the presence and absence of CHOP. This demonstrates that CHOP-deficiency does not improve, but rather exacerbates gut inflammation in HLA-B27-Tg rats, indicating that HLA-B27 is not promoting gut disease through ER stress-induced IL-23. Hence, CHOP may protect rats from more severe HLA-B27-induced gut inflammation.

Screening Tools for Spondyloarthritis in Patients With Psoriasis, Uveitis, and Inflammatory Bowel Disease: A Scoping Review.

Extramusculoskeletal manifestations of spondyloarthritis (SpA) may precede the development of articular features. Patients seen in ophthalmology, dermatology, and gastroenterology clinics with uveitis, psoriasis, or inflammatory bowel disease (IBD) may have undiagnosed SpA. We set out to identify and evaluate screening tools for SpA in patients with psoriasis, uveitis, and IBD and determine factors that influence the performance of these instruments. This scoping review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, and Web of Science were searched from inception to January 2022. We identified 13 screening tools for psoriatic arthritis, 2 SpA screening tools for uveitis, and 3 SpA screening tools for IBD. All screening tools were patient-oriented questionnaires except for the Dublin Uveitis Evaluation Tool, a physician-applied algorithm. The questionnaires varied in length, scoring method, cutoff score, and spectrum of included SpA features. Average completion time was less than five minutes. Across the three patient populations, the sensitivities and specificities of these screening tools were comparable in the primary validation cohorts. Sensitivities and specificities were generally lower in secondary validation studies, with marked variability among cohorts. Our results highlight the heterogeneity and limitations of existing SpA screening tools. Although these tools show promise for use within a specific target population, none are generalizable to all patients with extramusculoskeletal manifestations at risk of SpA. Future studies should explore the utility of a generic patient-oriented SpA screening tool that can be applied to patients with psoriasis, uveitis, or IBD; is easy to use and comprehend; and captures all clinical domains of SpA.

P696 Initiation of Vedolizumab did not provoke new-onset spondylarthritis in patients with inflammatory bowel disease: A Prospective Study Including Rheumatological and Blinded Imaging Assessments

Abstract Background Prior case series indicated a temporal relationship between use of vedolizumab and new-onset spondyloarthritis. Methods We aimed to evaluate the relationship between initiation of vedolizumab and development of new-onset spondyloarthritis in patients with inflammatory bowel disease, through serial clinical evaluation and magnetic resonance imaging. A single-centre prospective observational study of 24 patients with inflammatory bowel disease. Patients were eligible if they had active ulcerative colitis or Crohn’s disease and initiating vedolizumab, had no prior history of arthritis or spondyloarthritis and suitable for undergoing serial magnetic resonance imaging. Clinical evaluation was performed by a rheumatologist prior to first dose of vedolizumab and at weeks 8 and 24 weeks after administration. Axial magnetic resonance imaging was performed at baseline, weeks 8 and 24 and evaluated by a blinded central reader. Results Nine tumour necrosis factor inhibitor-naïve patients (4 male; mean age 53.2 yrs; 6 ulcerative colitis; 3 Crohn’s disease) and eight tumour necrosis factor inhibitor-experienced patients (7 male; mean age 48 yrs; 3 ulcerative colitis; 5 Crohn’s disease) completed all assessments. No patients developed new features of axial arthritis either on clinical or blinded radiological assessment at weeks 8 or 24, nor any features of peripheral spondyloarthritis including inflammatory oligoarthritis, enthesitis, dactylitis, or psoriasis (nail, body, or scalp). Both the tumour necrosis factor inhibitor-naive and tumour necrosis factor inhibitor-experienced patients demonstrated good intestinal response to vedolizumab. Conclusion Initiation of vedolizumab did not induce new features of axial or peripheral spondyloarthritis in tumour necrosis factor inhibitor-experienced or tumour necrosis factor inhibitor-naive patients with inflammatory bowel disease.

Thrombocytosis in patients with spondyloarthritis: a case–control study

ObjectiveThis study aimed to investigate the clinical and laboratory as well as radiological features of spondyloarthritis (SpA) patients with thrombocytosis and to explore risk factor for thrombocytosis in SpA patients and to assess the effect of antitumor necrosis factor-α (anti-TNF-α) therapy on platelet count in SpA patients with thrombocytosis.MethodsA total of 145 patients with SpA were included in this study, and non-thrombocytosis was identified in 76 patients while thrombocytosis was found in 69 patients, 38 out of the 69 patients received anti-TNF-α therapy. Logistic regression analysis was performed to investigate risk factors that associated with thrombocytosis. The platelet count of patients in the thrombocytosis group treated with anti-TNF-α therapy on week 0, week 6 and week 12 were collected and compared with conventional therapy group.ResultsThe proportion of hip involvement (60.86% vs 36.84%, p = 0.004), bath ankylosing spondylitis disease activity index score (4.24 ± 0.55 vs 3.69 ± 0.67, p < 0.001), erythrocyte sedimentation rate (62.22 ± 41.97 mm/hour vs 27.00 ± 25.93 mm/hour, p < 0.001), C-reactive protein (53.45 ± 47.45 mg/L vs 18.91 ± 31.09 mg/L, p < 0.001), fibrinogen (5.77 ± 1.48 g/L vs 4.01 ± 1.32 g/L, P < 0.001), white blood cells (8.15 ± 1.90 × 109/L vs 6.85 ± 2.39 × 109/L, p < 0.001) and neutrophils (5.08 ± 1.55 × 109/L vs 4.01 ± 2.04 × 109/L, p = 0.001) are higher in thrombocytosis group, but hemoglobin and albumin are lower compared to non-thrombocytosis group (122.88 ± 17.25 g/L vs 131.51 ± 16.03 g/L, p = 0.002; 37.19 ± 4.73 g/L vs 39.67 ± 3.99 g/L, p = 0.001, respectively). Multivariable logistic regression analysis indicated that higher white blood cells (OR, 1.644; 95% CI, 1.045–2.587; P = 0.032) and fibrinogen (OR, 2.169; 95% CI, 1.237–3.804; P = 0.007) were independently associated with thrombocytosis in SpA patients. The platelet count in the thrombocytosis group treated with anti-TNF-α therapy on week 6 and week 12 were statistically lower than week 0 (225.05 ± 60.58 × 109/L vs 368.26 ± 54.34 × 109/L, p < 0.001; 201.26 ± 51.48 × 109/L vs 368.26 ± 54.34 × 109/L, p < 0.001) and conventional therapy (week 6, 225.05 ± 60.58 × 109/L vs 370.00 ± 74.05 × 109/L, p < 0.001; week 12, 201.26 ± 51.48 × 109/L vs 303.13 ± 71.49 × 109/L, p < 0.001).ConclusionSpA patients with thrombocytosis have a higher proportion of hip involvement and disease activity compared to non-thrombocytosis SpA patients. The potential risk factors for thrombocytosis in SPA patients were higher white blood cells and fibrinogen. Anti-TNF-α therapy can reduce the increased platelets more effectively and rapidly than conventional treatments in SpA patients with thrombocytosis.

Spondyloarthritis Associated with Uveitis: A Review.

Spondyloarthritis (SpA) is a group of chronic inflammatory rheumatism characterized by common clinical, radiological, and biological manifestations occurring on a predisposing genetic background dominated by the HLA-B27 antigen. Acute anterior uveitis is the most common extra-articular feature of SpA. The objective of this review is to describe the prevalence, demographic characteristics, factors favoring the occurrence of uveitis in patients with SpA, clinical manifestations, and their therapeutic management.

Longitudinal Follow-Up Using the Heel Enthesitis Magnetic Resonance Imaging Scoring System (HEMRIS) Shows Minimal Changes in Heel Enthesitis Assessed in Spondyloarthritis and Psoriasis Patients.

Enthesitis is a common clinical feature of spondyloarthritis (SpA). For reliable assessment of enthesitis the Heel Enthesitis Magnetic Resonance Imaging Scoring System (HEMRIS) was developed. The aims of this study were to evaluate changes in HEMRIS over time and to evaluate whether these changes correlated with changes in clinical parameters. This single-center observational study followed patients with SpA and psoriasis, regardless of presence of clinical heel enthesitis, for two years. Clinical evaluation and ankle MRIs were performed annually. Changes in HEMRIS were compared at one-year intervals using the Wilcoxon signed-rank test. The association between changes in the HEMRIS with changes in clinical parameters was evaluated using Spearman's correlation coefficient. In total, 38 patients were included. An increase in the inflammatory and structural HEMRIS was identified in, respectively, 12 (17.9%) and 4 (6.0%) patients in one-year intervals. We found non-significant changes in the HEMRIS during longitudinal follow-up. Changes in the HEMRIS did not correlate with changes in local or general disease activity. Our results show that MRI-findings of enthesitis assessed with HEMRIS changed in a small number of patients in a one-year interval in an observational setting. Changes in HEMRIS were not associated with changes in clinical disease activity.

Oral dextran sulfate sodium administration induces peripheral spondyloarthritis features in SKG mice accompanied by intestinal bacterial translocation and systemic Th1 and Th17 cell activation

BackgroundSpondyloarthritis (SpA) is an autoimmune and autoinflammatory musculoskeletal disease characterised by systemic enthesitis. Recent research has focused on subclinical inflammatory bowel disease (IBD) in SpA pathogenesis. SKG mice, harbouring the Zap70 W163C mutation, increase autoreactive Th17 cells intrinsically, and in a conventional environment, they exhibit spontaneous arthritis with fungal factors. Under SPF conditions, they show SpA features, including enteritis, after peritoneal injection of β-1,3-glucan. This study aimed to clarify whether oral dextran sulfate sodium (DSS) administration, utilised in IBD model mice, can provoke SpA features in SKG mice under SPF conditions, focusing on the relationship between gut microorganisms and SpA pathogenesis.MethodsBALB/c and SKG mice were administered oral DSS, and their body weights, arthritis, and enthesitis scores were recorded. In another cohort, antibiotics (meropenem and vancomycin) or an anti-fungal agent (amphotericin B) was administered orally before DSS administration. The splenic Th1 and Th17 cell populations were examined before and after DSS administration using flow cytometry. Furthermore, the amount of circulating bacterial DNA in whole blood was measured by absolute quantitative polymerase chain reaction (qPCR), and the number and characteristics of bacterial species corresponding to these circulating DNA were analysed by next-generation sequencing (NGS).ResultsAnkle enthesitis as a peripheral SpA feature was elicited in half of DSS-administered SKG mice, and none of the BALB/c mice. Pre-administration of antibiotics suppressed enthesitis, whilst an anti-fungal agent could not. Th1 and Th17 cell levels in the spleen increased after DSS administration, and this was suppressed by pre-administration of antibiotics. SKG mice have a larger amount of bacterial DNA in whole blood than BALB/c mice before and 1 day after the initiation of DSS administration. The number of bacterial species in whole blood increased after DSS administration in BALB/c and SKG mice. Some genera and species significantly specific to the DSS-treated SKG mouse group were also detected.ConclusionOral DSS administration alone elicited peripheral enthesitis in SKG mice with bacterial translocation accompanied by increased splenic Th1 and Th17 cell levels. Pre-administration of antibiotics ameliorated these DSS-induced SpA features. These findings suggest that intestinal bacterial leakage plays a pivotal role in SpA pathogenesis.

Improvement of early diagnosis of axial spondyloarthritis in intestinal infectious diseases

Introduction. Despite numerous fundamental clinical studies on the frequency, pathogenesis, clinical features of spondyloarthritis (SpA) in intestinal infectious diseases (IID) and intestinal damage in SpA, there are currently a number of unresolved problems, one of which is the problem of early diagnosis of arthropathies, especially associated with IID, which makes it necessary to continue the research in the scientific problem. Purpose of the study. Appreciation of the features of early manifestations of axial arthropathies in intestinal infectious diseases in order to improve their early diagnosis. Objectives of the study. Identification of clinical variants of axial arthropathies in patients with infectious intestinal diseases and instrumental description of axial lesion by conducting comparative analysis of clinical and laboratory parameters in these patients depending on the presence of axial arthropathies. Development of an algorithm for the early detection of axial spondyloarthritis in intestinal infectious diseases. Material and methods. During 2015-2021, 141 patients were analyzed retrospectively, out of which 50 patients with SpA from the Republican Clinical Hospital „Timofei Moşneaga” and 91 patients with infectious intestinal diseases from the gastro-enterology and hepatology departments of the Republican Clinical Hospital „Timofei Moşneaga”. Depending on the etiology of IID, subjects were divided into 2 groups: the first group included patients with Yersinia enterocolitica or Campylobacter jejuni (Y±C), the second with Salmonella enteritidis or Shigella flexneri (S±Sh). Results. In patients with IID, the following clinical variants of arthropathies have been identified: axial lesion (spinal inflammatory pain according to ASAS criteria (2009) in 42.9%, axial spondyloarthritis (axSpA) in 28.6%, AS in 15.4%), arthralgia - 38.5%, arthritis - 13.2%. Conventional radiography imaging and magnetic resonance imaging (MRI) of the sacroiliac joints (SI) increased the incidence of SpA from 6.6% (n = 6) to 28.6% (n = 26). Conclusions. In patients with IID, the following clinical variants of arthropathies have been identified: axial lesion (spinal inflammatory pain according to ASAS criteria (2009) in 42.9%, axSpA in 28.6%, ankylosing spondylitis in 15.4%), arthralgia – 38.5%, arthritis – 13.2%. Imaging in the form of conventional radiography and MRI of SI joints increased the incidence of SpA from 6.6% (n = 6) to 28.6% (n = 26). Axial arthropathies, arthralgia, arthritis, and uveitis are encountered more frequently. At the same time, the possibility of detecting axSpA is greater if arthritis, arthralgia, inflammatory back pain, uveitis is present. Patients with S±Sh have a higher chance of developing axSpA compared to patients with Y±C.

The frequency of sacroiliitis on MRI in subjects over 55years of age.

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

NON-IMMUNE MEDIATED MUSCULOSKELETAL DISEASE IN CROHN’S DISEASE PATIENTS BEING EVALUATED FOR INFLAMMATORY SPONDYLOARTHRITIS - A PILOT STUDY

BACKGROUNDMusculoskeletal (MSK) disease is the most common extra-intestinal manifestation of inflammatory bowel disease (IBD). The emphasis in the published literature has been on the inflammatory arthritis associated with IBD, spondyloarthritis (SpA). There is a lack of data regarding common, non-inflammatory MSK diseases such as osteoarthritis and fibromyalgia. This distinction is important, as these two conditions have different prognoses, require different clinical approaches and management.OBJECTIVETo evaluate the prevalence of non-inflammatory MSK disease in a cohort of Crohn’s disease (CD) patients.METHODSThis was a cross-sectional study of a validated CD cohort from a single center registry in New York City conducted from 9/2019 - 1/2021. Recruitment was limited due to the COVID-19 Pandemic. Patients were sent a four question MSK survey (Figure 1) addressing peripheral joint and back symptoms. Those who answered positively to any question were considered to have MSK symptoms. All patients underwent one study visit with a rheumatologist that included: 66/68 tender/swollen joint count (TJC/SJC), Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC), Bath Ankylosing Spondylitis Metrology Index (BASMI), American College of Rheumatology fibromyalgia criteria, ESR and CRP. Disease activity was measured via a modified Ankylosing Spondylitis Disease Activity Score (ASDAS), Harvey Bradshaw Index (HBI), and Inflammatory Bowel Disease Questionnaire (IBD-Q).RESULTS26 CD patients participated. Median age was 45.6±17.7 years, 35% were male, median disease duration was 17.7±14.2 years and 73% were on immunomodulatory agents for CD. Median values (range) for the following physical exam and disease features were: TJC 10.8±13.2 (0-68), SJC 0.9±2.2 (0-66), SPARCC 2.8±3.1 (0-16), BASMI 1.5±1.0 (0-10, higher values: more motion limitation) ASDAS 1.5±0.9 (<1.3: inactive disease, >2.1: high disease activity), HBI 6.8±3.5 and IBD-Q 159±36. Median ESR and CRP were 18.9±22.2 mm/hr (normal 0-22) and 0.6±0.5 mg/dL (normal<0.7), respectively. 16/26 (62%) reported MSK symptoms. 7/16 (43.8%) had features of SpA, while 9/16 (56.3%) did not have evidence by history or exam of SpA and were therefore determined to have non-inflammatory MSK disease. 13/26 (50%) met fibromyalgia diagnostic criteria.CONCLUSIONMSK conditions were very common in this pilot cohort. Though features of SpA were present in almost half of patients, non-inflammatory MSK disease was present in the majority of those with MSK symptoms. While both rheumatologists and gastroenterologists need to recognize the importance of SpA, it is additionally essential to understand that the most common MSK disease in IBD may be non-inflammatory, which has distinct implications for management. Future studies should examine the prevalence of these conditions in larger cohorts of IBD patients.

Australian Consensus Statements for the Assessment and Management of Non-radiographic Axial Spondyloarthritis.

BackgroundThe understanding of non-radiographic axial spondyloarthritis (nr-axSpA) has accelerated over the last decade, producing a number of practice-changing developments. Diagnosis is challenging. No diagnostic criteria exist, no single finding is diagnostic, and other causes of back pain may act as confounders.AimTo update and expand the 2014 consensus statement on the investigation and management of non‐radiographic axial spondyloarthritis (nr-axSpA).MethodsWe created search questions based on our previous statements and four new topics then searched the MEDLINE and Cochrane databases. We assessed relevant publications by full-text review and rated their level of evidence using the GRADE system. We compiled a GRADE evidence summary then produced and voted on consensus statements.ResultsWe identified 5145 relevant publications, full-text reviewed 504, and included 176 in the evidence summary. We developed and voted on 22 consensus statements. All had high agreement. Diagnosis of nr-axSpA should be made by experienced clinicians, considering clinical features of spondyloarthritis, blood tests, and imaging. History and examination should also assess alternative causes of back pain and related conditions including non-specific back pain and fibromyalgia. Initial investigations should include CRP, HLA-B27, and AP pelvic radiography. Further imaging by T1 and STIR MRI of the sacroiliac joints is useful if radiography does not show definite changes. MRI provides moderate-to-high sensitivity and high specificity for nr-axSpA. Acute signs of sacroiliitis on MRI are not specific and have been observed in the absence of spondyloarthritis. Initial management should involve NSAIDs and a regular exercise program, while TNF and IL-17 inhibitors can be used for high disease activity unresponsive to these interventions. Goals of treatment include improving the frequent impairment of social and occupational function that occurs in nr-axSpA.ConclusionsWe provide 22 evidence-based consensus statements to provide practical guidance in the assessment and management of nr-axSpA.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00416-7.

Overexpression of Transmembrane TNF Drives Development of Ectopic Lymphoid Structures in the Bone Marrow and B Cell Lineage Alterations in Experimental Spondyloarthritis.

TNF is important in immune-mediated inflammatory diseases, including spondyloarthritis (SpA). Transgenic (tg) mice overexpressing transmembrane TNF (tmTNF) develop features resembling human SpA. Furthermore, both tmTNF tg mice and SpA patients develop ectopic lymphoid aggregates, but it is unclear whether these contribute to pathology. Therefore, we characterized the lymphoid aggregates in detail and studied potential alterations in the B and T cell lineage in tmTNF tg mice. Lymphoid aggregates developed in bone marrow (BM) of vertebrae and near the ankle joints prior to the first SpA features and displayed characteristics of ectopic lymphoid structures (ELS) including presence of B cells, T cells, germinal centers, and high endothelial venules. Detailed flow cytometric analyses demonstrated more germinal center B cells with increased CD80 and CD86 expression, along with significantly more T follicular helper, T follicular regulatory, and T regulatory cells in tmTNF tg BM compared with non-tg controls. Furthermore, tmTNF tg mice exhibited increased IgA serum levels and significantly more IgA+ plasma cells in the BM, whereas IgA+ plasma cells in the gut were not significantly increased. In tmTNF tg × TNF-RI-/- mice, ELS were absent, consistent with reduced disease symptoms, whereas in tmTNF tg × TNF-RII-/- mice, ELS and clinical symptoms were still present. Collectively, these data show that tmTNF overexpression in mice results in osteitis and ELS formation in BM, which may account for the increased serum IgA levels that are also observed in human SpA. These effects are mainly dependent on TNF-RI signaling and may underlie important aspects of SpA pathology.

MRI and spondyloarthropathy: diagnostic performance compared to long-term clinical follow-up with evaluation of gadolinium chelates injection.

To evaluate MRI performance on both initial and long-term rheumatologic diagnosis of spondyloarthritis (SpA), taking into account clinical evolution and treatment response, and the impact of gadolinium injection. In this single-center study, patients who underwent both spinal and sacroiliac (SI) joint MRI were prospectively recruited between May 2013 and January 2014 and followed for 7 years until 2020. Clinical, biological, and radiologic parameters were collected. At 7-year follow-up (2020), two independent readers reevaluated the initial MRI datasets for specific radiological features of SpA with a 5-point Likert scale to record the estimation of confidence. The centralized MRI interpretations were compared to the established rheumatologic diagnoses in 2013 and 2020. In total, 145 patients (52 men and 93 women) were included. During the 7-year follow-up, the number of patients with positive SpA diagnosis decreased from 93 to 58. Mean sensitivity, specificity, and accuracy of non-contrast MRI were 18, 97, and 49% and 27, 97, and 69% considering 2013 and 2020 rheumatologic diagnoses, respectively. Mean sensitivity, specificity, and accuracy values of gadolinium-enhanced MRI were 26, 97, and 54% and 38, 97, and 73% considering 2013 and 2020 diagnoses, respectively. Post-contrast MRI enabled identification of a subgroup of enthesis-only lesions, without any bone lesions, corresponding to 14% of the pathological cohort. It confirmed uncertain diagnoses in an additional 8.5% of pathological cases. MRI performance for SpA diagnosis is higher when long-term clinical follow-up is considered than when compared to initial diagnosis. Gadolinium injection increases MRI diagnostic performance and may demonstrate a pure enthesic form of the disease, without bone abnormality. • Compared to the rheumatologist's diagnosis over long-term clinical follow-up, MRI performance for SpA is higher than usually estimated. • Gadolinium injection increases diagnostic performance of MRI as it may identify a purely enthesis form of the disease. • Gadolinium injection should be discussed in patients for whom the diagnostic suspicion is strong and whose initial non-injected examination is normal or doubtful.

Complement C3d is not associated with axial spondyloarthritis and magnetic resonance imaging changes at the sacroiliac joint

Objective: To investigate the associations between complement C3d and inflammatory and structural changes by magnetic resonance imaging (MRI) at the sacroiliac joints (SIJ) suggestive of axial spondyloarthritis, according to the Assessment of SpondyloArthritis international Society (ASAS) criteria, in patients with low back pain.Method: This was a cross-sectional study of patients referred to the Spine Centre of Southern Denmark owing to unspecified low back pain (Spines of Southern Denmark cohort). The patients were divided into three groups: group 1: patients fulfilling the ASAS criteria for axial spondyloarthritis (axSpA, n = 96); group 2: patients with either a positive MRI of the SIJ and no spondyloarthritis features, or a negative MRI of the SIJ but positive human leucocyte antigen-B27 and one spondyloarthritis feature (non-axSpA, n = 38); group 3: patients with unspecified low back pain for > 3 months (control group, n = 82). Complement C3d was measured with double-decker rocket immunoelectrophoresis and evaluated in relation to the group division and baseline findings by SIJ MRI.Results: In total, 184 C3d analyses were performed. The mean ± sd level of C3d was 33.8 ± 8.1 AU/mL. There were no differences in C3d levels between the three patient groups, mean values being: axSpA = 34.3 ± 7.9 AU/mL, non-axSpA = 33.5 ± 6.9 AU/mL, and controls = 33.4 ± 9.2 AU/mL. The level of C3d was not related to MRI findings.Conclusions: In these patients, complement C3d was not associated with active or structural SIJ changes on MRI suggestive of axial spondyloarthritis.

Incidence of anterior uveitis in patients with axial spondyloarthritis treated with anti-TNF or anti-IL17A: a systematic review, a pairwise and network meta-analysis of randomized controlled trials

BackgroundAnterior uveitis (AU) is the most frequent extra-articular feature of axial spondyloarthritis (axSpA). We aimed to assess and compare the incidence of AU in axSpA patients treated with anti-TNF or anti-IL17A.MethodsWe systematically reviewed PubMed, EMBase, and Cochrane from inception to May 3, 2020, and searched for placebo-controlled and head-to-head randomized controlled trials (RCTs) assessing anti-TNF monoclonal antibodies (mAb) or soluble receptor fusion protein or anti-IL17A in patients with axSpA according to ASAS criteria and reporting safety data on AU. Data were extracted following a predefined protocol. We did pairwise and network meta-analyses for the primary outcome of AU flares (relapse or de novo) incidence and estimated summary odds ratios (ORs). We assessed the quality of evidence using the Cochrane risk-of-bias 2.0 tool. We ranked treatments according to their effectiveness in preventing AU flare using the P-score.ResultsWe identified 752 citations and included 33 RCTs, comprising 4544 treated patients (anti-TNF mAb 2101, etanercept [ETN] 699, anti-IL17A 1744) and 2497 placebo-receiving patients. Incidence of uveitis was lower with anti-TNF mAb versus placebo (OR = 0.46; CI 95% [0.24; 0.90]) and versus anti-IL17A (OR = 0.34; CI 95% [0.12; 0.92]. According to the P-score, the ranking from the most to the least preventive treatment of uveitis flare was as follows: anti-TNF mAb, ETN, placebo, and anti-IL17A.ConclusionIn RCTs assessing anti-TNF and anti-IL17A in axSpA, incident uveitis are rare events. However, this network meta-analysis demonstrates that anti-TNF mAb are associated with a lower incidence of uveitis compared to placebo and anti-IL17A.