Musculoskeletal Manifestations Research Articles

Evaluation and Pharmacologic Management of Paroxysmal Sympathetic Hyperactivity in Traumatic Brain Injury.

Paroxysmal sympathetic hyperactivity (PSH) can occur in up to 10% of severe traumatic brain injury (TBI) patients and is associated with poorer outcomes. A consensus regarding management is lacking. We provide a practical guide on the multi-faceted clinical management of PSH, including pharmacological, procedural and non-pharmacological interventions. In addition to utilizing a standardized assessment tool, the use of medications to manage sympathetic and musculoskeletal manifestations (including pain) is highlighted. Recent studies investigating new approaches to clinical management are included in this review of pharmacologic treatment options. While studies regarding pharmacologic selection for PSH are limited, this paper suggests a clinical approach to interventions based on predominant symptom presentation (sympathetic hyperactivity, pain and/or muscle hypertonicity) and relevant medication side effects.

Sacroiliitis in inflammatory bowel disease.

This review summarizes the recent evidence regarding the epidemiology of inflammatory bowel disease (IBD) associated sacroiliitis, including the prevalence, pathogenesis, role of imaging, and therapeutic challenges. Sacroiliitis is an underappreciated musculoskeletal manifestation of IBD, a chronic inflammatory condition of the gut affecting the younger population. Untreated sacroiliitis can lead to joint destruction and chronic pain, further adding to morbidity in IBD patients. Recent publications suggest sacroiliitis can be detected on abdominal imaging obtained in IBD patients to study bowel disease, but only a small fraction of these patients were seen by rheumatologists. Early detection of IBD-associated sacroiliitis could be achieved by utilization of clinical screening tools in IBD clinics, careful examination of existing computed tomography and MRI studies, and timely referral to rheumatologist for further evaluation and treatment. Current treatment approaches for IBD and sacroiliitis include several targeted biologic therapies, but IBD-associated sacroiliitis has limited options, as these therapies may not overlap in both conditions. With the advances in imaging, sacroiliitis is an increasingly recognized comorbidity in IBD patients. Future studies focusing on this unique patient population will expand our understanding of complex pathophysiology of IBD-associated sacroiliitis and lead to identification of novel targeted therapies for this condition.

E013 Looking back at back pain: how well do our referrals measure up to available criteria?

Abstract Background/Aims According to the Global Burden of Disease Study 2021, low back pain remains the leading cause of years lived with disability (YLDs) globally affecting about 619 million people as of 2020. Inflammatory back pain affects fewer patients but remains an important referral indication. A previous audit from the early back pain clinic of cases seen between 2015-16 at the Royal National Hospital for Rheumatic Diseases, Bath, identified an axial spondyloarthritis (AxSpA) diagnosis in 21% of patients of whom, two thirds were HLAB27 positive. This follow-up audit aimed to evaluate for interval change in axSpA prevalence and assess the referrals against NICE and ASAS criteria respectively. While the NICE referral guidance is largely clinical, ASAS incorporates extra musculoskeletal manifestations and investigations. Methods We reviewed 100 of the 271 early back pain clinic referrals received between July 2022-23. The completed referral proforma was evaluated against the NICE and ASAS criteria respectively. Electronic medical records and clinic letters of patients were also reviewed including demographics, baseline investigations and imaging. Results The patients were 54% male with an average age of 38.7 ± 13.7years. An axSpA diagnosis was made in 19 patients (19%) of which 12 were HLAB27 positive (63.1%). The median symptom duration was 24 months (6-72) with an appointment delay of 128 days (36-182). Discharge rate was 35% after the first appointment. Overall, 62% of referrals satisfied NICE criteria compared to 71% for ASAS. This was after excluding 21 referrals which did not satisfy the ASAS entry criterion of symptoms > 3months in patients <45 years. Among our cohort, sensitivities were 68.4% for NICE and 73.7% for ASAS while specificities were 39.5% for NICE and 29.6% for ASAS. Three patients all above 45 years with a normal CRP met neither criteria, but were diagnosed with axSpA after MRI while one patient who satisfied both criteria turned out to have lung cancer with bony metastases. Conclusion There has been minimal interval change in AxSpA prevalence from our referrals between 2015-23. The ASAS criteria was easier to satisfy and can serve as an alternative referral indication for patients who do not meet NICE criteria. Both criteria are still very useful in terms of ensuring the quality of referrals received. Improvements in the referral pathway are being planned to reduce primary and secondary care delays thus enhancing earlier diagnosis and treatment. Disclosure A. Akpabio: None. M. Camillieri: None. T. Williams: None. R. Sengupta: None.

P163 Low uveitis rates in patients with axial spondyloarthritis treated with bimekizumab: pooled results from phase 2b/3 trials

Abstract Background/Aims Acute anterior uveitis (‘uveitis’) is a common extra musculoskeletal manifestation of axial spondyloarthritis (axSpA). Interleukin (IL)-17 has been implicated in uveitis pathogenesis; however, inhibition of IL-17A alone may not be optimal for uveitis management. We report the incidence of uveitis following IL-17A and IL17F inhibition with bimekizumab (BKZ) in patients with axSpA. Methods Data were pooled for patients randomised to placebo (PBO) or BKZ 160mg every 4 weeks (Q4W) in the double-blind treatment period (DBTP) of the phase (ph)3 studies BE MOBILE 1 (NCT03928704; non-radiographic axSpA) and 2 (NCT03928743; radiographic axSpA [i.e. ankylosing spondylitis]). Data were also pooled for all patients treated with BKZ in BE MOBILE 1, BE MOBILE 2, BE MOVING (NCT04436640; open-label extension [OLE] of BE MOBILE 1 and 2), the ph2b study BE AGILE (NCT02963506; r-axSpA) and its OLE BE AGILE 2 (NCT03355573; data cut-off 4 July 2022). Uveitis events were identified using the preferred terms “autoimmune uveitis,” “iridocyclitis,” “iritis” and “uveitis,” and are reported as exposure adjusted incidence rates (EAIRs) per 100 patient-years (PY) for all patients who received ≥1 BKZ dose. Results Baseline characteristics of the axSpA study populations are shown in the Table. In the DBTP of BE MOBILE 1 and 2, uveitis events occurred in 11/237 (4.6%; EAIR/100 PY [95% CI]: 15.4 [7.7, 27.5]) and 2/349 (0.6%; 1.8 [0.2, 6.7]) patients randomised to PBO and BKZ (percentage difference [95% CI]: 4.1 [1.7, 7.6]), respectively. In 45 PBO-randomised (19.0%) and 52 BKZ-randomised (14.9%) patients with history of uveitis, uveitis occurred in 20.0% (EAIR/100 PY [95% CI]: 70.4 [32.2, 133.7]) and 1.9% (6.2 [0.2, 34.8]) of patients, respectively. In the ph2b/3 pool (N = 848) total BKZ exposure was 2,034.4 PY and 130 (15.3%) patients had history of uveitis. Uveitis occurred in 25 (2.9%; EAIR/100 PY [95% CI]: 1.2 [0.8, 1.8]) and 14 (10.8%; 4.6 [2.5, 7.7]) patients overall and with history of uveitis, respectively. All uveitis events were mild/moderate; one led to discontinuation. Conclusion Incidence of uveitis was lower to Week 16 in patients with axSpA randomised to BKZ 160mg Q4W versus PBO and remained low at 1.2/100 PY in the largest ph2b/3 pool. Disclosure M. Rudwaleit: Consultancies; AbbVie, Eli Lilly, Novartis and UCB Pharma. Member of speakers’ bureau; AbbVie, Boehringer Ingelheim, Chugai, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. M.A. Brown: Consultancies; Clementia, Grey Wolf Therapeutics, Incyte, Ipsen, Pfizer, Regeneron and Xinthera. Member of speakers’ bureau; Novartis and Pfizer. Grants/research support; UCB Pharma. F. van Gaalen: Grants/research support; Jacobus Stichting, Novartis, Stichting ASAS, Stichting Vrienden van Sole Mio and UCB Pharma. Other; fees from Novartis; personal fees from AbbVie, BMS, Eli Lilly and MSD. N. Haroon: Consultancies; AbbVie, Eli Lilly, Janssen, Novartis and UCB Pharma. L.S. Gensler: Consultancies; AbbVie, Acelyrin, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer and UCB Pharma. Grants/research support; Novartis and UCB Pharma paid to institution. C. Fleurinck: Other; Employee of UCB Pharma. A. Marten: Other; Employee of UCB Pharma. U. Massow: Other; Employee of UCB Pharma. N. de Peyrecave: Other; Employee of UCB Pharma. T. Vaux: Other; Employee of UCB Pharma. K. White: Shareholder/stock ownership; UCB Pharma. Other; Employee of UCB Pharma. A. Deodhar: Consultancies; AbbVie, BMS, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer and UCB Pharma. Member of speakers’ bureau; Janssen, Novartis and Pfizer. Grants/research support; AbbVie, BMS, Celgene, Eli Lilly, MoonLake, Novartis, Pfizer and UCB Pharma. D. McGonagle: Consultancies; AbbVie, Celgene, Janssen, Merck, Novartis, Pfizer and UCB Pharma. Honoraria; AbbVie, Celgene, Janssen, Merck, Novartis, Pfizer and UCB Pharma. Member of speakers’ bureau; AbbVie, Celgene, Janssen, Merck, Novartis, Pfizer and UCB Pharma. Grants/research support; AbbVie, Celgene, Janssen, Merck and Pfizer. I. van der Horst-Bruinsma: Consultancies; Abbvie, Eli Lilly, MSD, Novartis and UCB Pharma. Other; unrestricted grants received for investigator-initiated studies from AbbVie, MSD, Pfizer and UCB Pharma; fees received for lectures from AbbVie, BMS, MSD and Pfizer.

OA09 Significant association between disease duration in axial spondyloarthritis and the occurrence of uveitis and inflammatory bowel disease, with no such association found for psoriasis

Abstract Background/Aims Axial spondyloarthritis is a chronic inflammatory condition primarily impacting the spine and sacroiliac joints. In addition to spinal inflammation and peripheral symptoms, it frequently presents with extra-musculoskeletal manifestations such as inflammatory bowel disease, psoriasis, and anterior uveitis, collectively adding to the overall disease burden. Although existing research has explored the heightened risk of ophthalmological manifestations with prolonged disease duration, there is a paucity of literature examining the association between disease duration in axial spondyloarthritis and the onset of inflammatory bowel disease and psoriasis. Aim: To investigate the relationship between axial spondyloarthritis disease duration and the development of extra-musculoskeletal manifestations. Methods This is a retrospective cohort study with data obtained from the Ankylosing Spondylitis Registry of Ireland (ASRI), which is a large cross-sectional, multicentre cohort study. Using both univariate and multivariate regression analyses, we examined the relationship between axial spondyloarthritis disease duration and extra musculoskeletal manifestations. In the multivariate analysis, several covariates including gender, body mass index, smoking, and HLA-B27 status were considered to account for their potential influence on the observed associations. Results Demographic details were available for 912 patients included at the time of analysis. The median disease duration in years for our cohort was 16. Table 1 presents relevant general characteristics of the ASRI cohort and the results of our regression analysis. Uveitis exhibited a highly significant association (P < 0.001) with AxSpA duration in both univariate and multivariate analyses, even after accounting for covariates. Inflammatory bowel disease also showed a significant association with AxSpA duration in both univariate and multivariate analyses (P < 0.003). In our analysis, psoriasis showed no significant relationship with AxSpA disease duration in both univariate (P = 0.298) and multivariate analyses (P1 = 0.249). Conclusion Our study, using a large data set, reveals distinct patterns of association between axial spondyloarthritis disease duration and inflammatory bowel disease and uveitis. Conversely, psoriasis demonstrates no significant link to disease duration when considering confounding factors. Clinically, these insights are crucial for tailored management strategies, emphasising the need for improved diagnostic time and multidisciplinary care to address the diverse manifestations of AxSpA and optimise patient outcomes. Disclosure B. Dinneen: None. M. Kenyon: None. F. O'Shea: None.

Prevalence of spondyloarthritis in inflammatory bowel disease according ASAS and ultrassonography and its correlation with plasma calprotectin

BackgroundEnteropathic spondyloarthritis is underdiagnosed and inflammatory biomarkers and ultrasonography (US) could be useful for screening inflammatory bowel disease (IBD) patients. The objective of this study was to evaluate the prevalence of spondyloarthritis (SpA) in IBD patients, according to the Assessment of SpondyloArthritis International Society (ASAS) criteria and the correlation of results of US of entheses and joints with plasma calprotectin levels.MethodsThis was an observational cross-sectional study. Patients from the IBD outpatient clinic of a reference center were evaluated according to ASAS criteria classification, results of US of entheses and joints, and inflammatory biomarker measurements (erythrocyte sedimentation rates, C-reactive protein levels, fecal and plasma calprotectin levels). A p value lower than 0.05 was considered significant.ResultsA total of 30.5% of the studied sample (n = 118) of patients with IBD presented at least one inflammatory musculoskeletal manifestation. The overall prevalence of enteropathic SpA was 13.55%, with 10.16% axial SpA and 4.23% peripheral SpA according to the ASAS criteria. A total of 42.1% of patients had an MASEI score greater than 18, 35.2% had synovitis, and 14.7% had tenosynovitis on US, increasing the frequency of diagnosis of enteropathic SpA to 22.8%. Plasma calprotectin levels were similar to those in healthy controls, and correlated only with the fecal calprotectin level (p 0.041).ConclusionsA total of 13.5% of patients met the criteria in accordance with the ASAS criteria for enteropathic SpA, which increased to 22.8% with the addition of US. The prevalence of enthesitis, synovitis and tenosynovitis by US of symptomatic joints and entheses were 42%, 35% and 14.7% respectively. Plasma calprotectin was correlated with fecal calprotectin but not with inflammatory biomarkers or US or ASAS criteria.

VEXAS syndrome: Focus on dermatological manifestations and their histopathological correlate

AbstractBackgroundVEXAS ‘Vacuoles, E1 Enzyme, X‐linked, Autoinflammatory, Somatic syndrome’ is a rare autoinflammatory syndrome, first described in October 2020 by Beck et al. It is caused by somatic mutations in the UBA1 gene, coding for the E1 enzyme, responsible for ubiquitination. It manifests in adulthood, mainly in men, with constitutional symptoms, haematological abnormalities and often skin lesions with neutrophilic dermatoses most frequently reported. Since skin lesions are a frequent and early manifestation, recognising these may prove very useful for diagnosis.ObjectivesTo focus on the dermatological manifestations of VEXAS and their histopathological correlate.MethodsWe retrospectively collected data and revised skin biopsies of VEXAS patients diagnosed in our tertiary care centre, and compared those with the literature.ResultsWe identified nine men between 62 and 84 years old. The most frequently encountered UBA1 mutation was p.Met41Thr. Skin manifestations occurred in all patients; mostly as erythematous to purpuric papules/plaques, often with annular pattern. Histopathological, early VEXAS lesions showed a gradient in infiltrate with neutrophils being concentrated in the superficial interstitium and lymphocytes situated deeper around the blood vessels. Later in the disease course, the pattern became more variable and less specific with more nuclear debris, histiocytes, neutrophils and ulceration. Haematological and constitutional manifestations were present in all patients, followed by musculoskeletal (88.8%), eye (77.7%) and cardiovascular manifestations (66.6%). Polychondritis was present in 6/9 (66.6%) patients, as were respiratory symptoms, though only 33.3% had proven lung disease. The mortality rate was 22% 10 months after diagnosis.ConclusionsThis is the first cohort which describes in detail VEXAS skin manifestations with revision of all available skin biopsies, which led to the conclusion that early histopathological abnormalities in VEXAS syndrome may be easy to recognise, while the histopathological image becomes less specific over time and mimics other diseases as VEXAS progresses.

Antinuclear antibodies may predict the development of immune-related adverse events in asymptomatic patients treated with immune checkpoint inhibitors: results from a single-center cohort

We aim at investigating the association between subclinical autoimmunity and immune-related adverse events (irAEs) in a cohort of patients treated by immune checkpoint inhibitors for solid metastatic cancer. In the context of an oncology/rheumatology outpatient clinic, we evaluated patients treated with anti-PD-1 or anti-PD-L1. Before treatment, each patient underwent a physical evaluation and a blood sample to identify the presence of a set of autoantibodies. Indeed, all the patients were followed during treatment to identify irAEs and to assess the association with autoantibodies. Fifty-one patients (M/F 16/35; median age 70 years, IQR 16.5) were evaluated; 34.8% of patients showed ANA positivity, 6.5% ENA positivity (anti-SSA), 4.3% Ratest positivity, and 2.1% (one patient) ACPA positivity. During a median period of 21 months (IQR 38.75), 39.2% of patients developed irAEs. Musculo-skeletal manifestations, in particular arthritis, were the most frequent. We found a significant association between the positivity for ANA and the development of irAES (p = 0.03, RR 2.01, 95% CI 1.03–3.92). Furthermore, the progression-free survival was significantly longer in patients developing irAEs compared to those who are not experiencing these events (p = 0.007). This study underlines the potential role of ANA positivity as a predictive biomarker for the development of irAEs.

Increased Serum Apelin Levels in Patients with Inflammatory Bowel Disease

Apelin has been implicated in the pathogenesis of several chronic inflammatory diseases through mechanisms related to endothelial cells dysfunction. There is evidence of increased apelin levels in mesenteric adipose tissue and colonic epithelium in patients with inflammatory bowel disease (IBD), but their significance remains unclear. We aimed to measure serum apelin (SA) levels in patients with IBD and to evaluate an association with disease characteristics. SA levels of 104 IBD patients and age and sex matched healthy controls (HCs) in a 1:1 ratio were compared. SA-13 levels were measured using an enzyme-linked immunosorbent assay (ELISA). Mean SA levels were increased in IBD patients compared to HCs (1996.29 ± 1592.96 pg/mL vs. 1552.99 ± 809.64 pg/mL, p = 0.012). Both patients without and with cardiovascular disease (CVD) had increased SA levels (2076.44 ± 1714.74 pg/mL vs. 1525.75 ± 818.74 pg/mL, p = 0.011 and 1743.01 ± 1116.26 pg/mL vs. 1283.92 ± 726.85 pg/mL, p = 0.035, respectively). An inverse association between mean SA levels and a history of musculoskeletal extraintestinal manifestations in the subgroup of IBD patients without CVD was found (p = 0.043). The present study—the first to evaluate SA levels in patients with IBD—showed that IBD patients have higher levels of SA compared to HCs. The potential role of SA in IBD merits further investigation in larger studies.

Neurological, cardiac, musculoskeletal, and renal manifestations of scleroderma along with insights into its genetics, pathophysiology, diagnostic, and therapeutic updates.

Scleroderma, also referred to as systemic sclerosis, is a multifaceted autoimmune condition characterized by abnormal fibrosis and impaired vascular function. Pathologically, it encompasses the persistent presence of inflammation, abnormal collagen buildup, and restructuring of blood vessels in various organs, resulting in a wide range of clinical symptoms. This review incorporates the most recent scientific literature on scleroderma, with a particular emphasis on its pathophysiology, clinical manifestations, diagnostic approaches, and treatment options. A comprehensive investigation was carried out on numerous databases, such as PubMed, MEDLINE, Scopus, Web of Science, and Google Scholar, to collect pertinent studies covering diverse facets of scleroderma research. Scleroderma presents with a range of systemic manifestations, such as interstitial lung disease, gastrointestinal dysmotility, Raynaud's phenomenon, pulmonary arterial hypertension, renal complications, neurological symptoms, and cardiac abnormalities. Serological markers, such as antinuclear antibodies,anti-centromere antibodies,and anti-topoisomerase antibodies,are important for classifying diseases and predicting their outcomes. The precise identification of scleroderma is crucial for promptly and correctly implementing effective treatment plans. Treatment approaches aim to improve symptoms, reduce complications, and slow down the progression of the disease. An integrated approach that combines pharmacological agents, including immunosuppressants, endothelin receptor antagonists, and prostanoids, with nonpharmacological interventions such as physical and occupational therapy is essential for maximizing patient care. Through the clarification of existing gaps in knowledge and identification of emerging trends, our goal is to improve the accuracy of diagnosis, enhance the effectiveness of therapeutic interventions, and ultimately enhance the overall quality of life for individuals suffering from scleroderma. Ongoing cooperation and creative research are necessary to advance the field and achieve improved patient outcomes and new therapeutic discoveries.

Mean Platelet Volume Is Related to Cumulative Disease Damage in Patients with Systemic Lupus Erythematosus.

Mean platelet volume (MPV), which represents the average platelet size in femtoliters, has emerged as a reliable biomarker in several systemic and chronic disorders. However, its relationship with disease characteristics in large series of patients with systemic lupus erythematosus (SLE) has not been exhaustively studied to date. In the present work, we aimed to analyze how disease characteristics, including disease activity and cumulative damage, relate to MPV in a well-characterized series of SLE patients. In total, 179 patients with SLE and 181 age- and sex-matched healthy controls were recruited. Complete blood counts including MPV were assessed. Linear multivariable analysis was performed to evaluate the relationship between MPV and SLE disease characteristics, including composite scores of disease activity and damage. MPV was significantly lower in patients with SLE compared to controls after multivariable analysis (beta coefficient, -0.7 [95% confidence interval, -1.1 to -0.3)] fL, p < 0.001). Although the SLEDAI disease activity index was not related to MPV, the SLICC score measuring cumulative disease damage was significantly associated with lower MPV values after adjustment for covariates. Elements of the SLICC score that were associated with lower MPV levels were those pertaining to the kidney, peripheral vascular, and musculoskeletal manifestations of the disease. In conclusion, MPV is lower in patients with SLE compared to matched controls. This MPV downregulation is primarily due to the renal, peripheral vascular and musculoskeletal manifestations of the disease. MPV may represent a biomarker of accrual disease damage in SLE.

Morquio A Syndrome: Identification of Differential Patterns of Molecular Pathway Interactions in Bone Lesions.

Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) is a rare autosomal recessive lysosomal storage disease (LSD) caused by deficiency of a hydrolase enzyme, N-acetylgalactosamine-6-sulfate sulfatase, and characterized clinically by mainly musculoskeletal manifestations. The mechanisms underlying bone involvement in humans are typically explored using invasive techniques such as bone biopsy, which complicates analysis in humans. We compared bone proteomes using DDA and SWATH-MS in wild-type and MPS IVA knockout mice (UNT) to obtain mechanistic information about the disease. Our findings reveal over 1000 dysregulated proteins in knockout mice, including those implicated in oxidative phosphorylation, oxidative stress (reactive oxygen species), DNA damage, and iron transport, and suggest that lactate dehydrogenase may constitute a useful prognostic and follow-up biomarker. Identifying biomarkers that reflect MPS IVA clinical course, severity, and progression have important implications for disease management.

Musculoskeletal symptoms and their impact on health-related quality of life in chronic nonbacterial osteomyelitis patients

IntroductionChronic non-bacterial osteomyelitis (CNO) is a rare, non-infection- related inflammatory disorder that affects children and teens. Clinical manifestations of CNO range widely from moderate, time-limited, monofocal inflammation of the bone to extreme multifocal or chronically active inflammation of the bone.ObjectivesThe main aim of this study was to explore the correlation between musculoskeletal (MSK) symptoms and health-related quality of life (HRQoL) in patients with CNO.MethodsChildren and adults with CNO and their parents were asked to answer a web-based survey. The survey consisted of multiple questions centered around demographic, clinical and therapeutic data, MSK discomfort form based on the Nordic MSK Questionnaire and HRQoL based on Pediatric Quality of Life Inventory-4 (PedsQL-4) and PedsQL rheumatology module. The inclusion criteria included diagnosis of CNO before the age of 18. Patients who had malignancies or any chronic rheumatic, MSK, neurological disease prior to CNO onset were excluded.ResultsThere was a total of 68 participants, mostly females (66.2%), with median age 14 years and median disease duration 4.75 years. The median number of bones affected by CNO was 5 and ranged from 1 to 24 bones. Among the studied patients, 45 patients (66.2%) had MSK manifestations at the last month. The most commonly affected part was ankle and feet (26.5%). Regarding HRQoL, patients with MSK manifestations had lower scores than did patients without in PedsQL-4 (p < 0.001) including domains of physical functioning (p < 0.001), emotional functioning (p = 0.033), social functioning (p < 0.001) and school functioning (p = 0.007) in addition to lower scores in PedsQL rheumatology module (p < 0.001) including domains of pain and hurt (p < 0.001), daily activities (p < 0.001), treatment (p = 0.035), worry (p = 0.001) and communication (p < 0.001).ConclusionMSK manifestations have a negative impact on HRQoL in CNO patients. So, early identification and treatment are highly recommended.

Cytotoxic Tph subset with low B-cell helper functions and its involvement in systemic lupus erythematosus

T peripheral helper (Tph) cells are thought to contribute to extra-follicular B cell activation and play a pathogenic role in autoimmune diseases. However, the role of Tph subsets is not fully elucidated. Here, we investigate the immunological functions of Tph subsets and their involvement in systemic lupus erythematosus (SLE). We have defined four Tph subsets (Tph1: CXCR3+CCR6−, Tph2: CXCR3−CCR6−, Tph17: CXCR3−CCR6+, and Tph1-17: CXCR3+CCR6+) and performed RNA sequencing after cell sorting. Tph1 and Tph17 subsets express substantial levels of IL21, indicating B cell helper functions. However, Tph2 and Tph1-17 subsets express low IL21. Interestingly, we have found Tph2 subset express high levels of CX3CR1, GZMB, PRF1, GLNY, S1PR5, TBX21, EOMES, ZNF863, and RUNX3, indicating a feature of CD4+ cytotoxic T lymphocytes. In SLE patients, the frequency of Tph1 and Tph2 subsets are significantly increased and positively correlated with SLE disease activity indexes. Tph1 cells expansion has been observed in patients with cutaneous and musculoskeletal manifestations. On the other hand, Tph2 cell expansion has been found in patients with lupus nephritis in addition to the above manifestations. Our findings imply that Tph1 and Tph2 subsets exert distinct immunological functions and are contributed to the complexity of clinical manifestations in SLE.

Inflammatory Arthritis in Systemic Sclerosis: Its Epidemiology, Associations, and Morbidity.

To describe the epidemiology, associations, and impact of inflammatory arthritis (IA) in systemic sclerosis (SSc). Patients with SSc prospectively enrolled in the Australian Scleroderma Cohort Study were included. IA was defined clinically as the presence of synovitis on examination. Logistic regression was used to determine the associations of IA with SSc manifestations and serological parameters. Patient-reported outcome measures were used to capture physical function and health-related quality of life (HRQoL). IA was a common SSc manifestation affecting one-third (33.3%) of patients over a median follow-up of 4.3 (1.7-8.4) years. Associations of IA included diffuse SSc (odds ratio [OR] 1.33, 95% confidence interval [95% CI] 1.01-1.74, P = 0.042), concurrent musculoskeletal manifestations (joint contractures and tendon friction rubs, OR 1.70, 95% CI 1.34-2.15, P < 0.001); myositis (OR 2.11, 95% CI 1.39-3.20, P < 0.001), and sicca symptoms (OR 1.57, 95% CI 1.14-2.16, P = 0.006), whereas IA was negatively associated with pulmonary arterial hypertension (OR 0.52, 95% CI 0.35-0.78, P = 0.002). Neither the presence of rheumatoid factor nor U1 small nuclear RNP were associated with IA (OR 1.13, 95% CI 0.88-1.44, P = 0.331, OR 1.46, 95% CI 0.89-2.39, P = 0.129 respectively). Positive anticyclic citrullinated protein antibodies, although at low frequency, were more common in those with IA compared with those without IA (7.5% vs 1.5%, P < 0.001). IA was associated with significantly lower HRQoL score (P < 0.001) and more physical disability than in those without IA (P < 0.001). IA is a common disease manifestation that is more frquently seen in diffuse disease. IA is associated with poor HRQoL and physical disability. Further research is needed into the effective management of IA in SSc.

Psoas Abscess in a Snowboarder: A Musculoskeletal Manifestation of Crohn's Disease.

Psoas Abscess in a Snowboarder: A Musculoskeletal Manifestation of Crohn's Disease.

Mechanisms of musculoskeletal consequences of COVID-19

Introduction A coronavirus, SARS-CoV-2, called COVID-19 by the WHO has caused a pandemic of respiratory illness killed more than 6 million people. The severe infection has a significant negative impact on the entire musculoskeletal system.The objective was to summarize literature data on the mechanisms of the condition and identify musculoskeletal symptoms of COVID-19.Material and methods An internet search of PubMed, MedLine and eLIBRARY library databases using the search terms: COVID-19, aseptic osteonecrosis, post-COVID-19 syndrome, arthropathy, musculoskeletal system, spondylitis, osteoporosis was performed.Results and discussion Musculoskeletal symptoms of COVID-19 are reported in 31-59% of cases. Mechanisms of musculoskeletal involvement of coronavirus infection include cytotoxic effect of the virus on osteogenesis cells, vascular inflammation and coagulopathy, “cytokine storm”, side effects of drug therapy and hypoxia. According to an etiological factor, musculoskeletal manifestations of SARS-CoV-2 include autoimmune (reactive arthritis, sacroiliitis, ankylosing spondylitis, axial spondyloarthritis, psoriatic arthritis) conditions caused by impaired circulation of bone tissue (aseptic osteonecrosis), infectious (septic arthritis, spondylitis, spondylodiscitis) and metabolic (osteopenia, osteoporosis) conditions.Conclusion It has been established that COVID-19 infection has a negative impact on the musculoskeletal, endocrine and immune systems increasing the risk of degenerative diseases of the musculoskeletal system and infectious complications in orthopaedic patients early post surgery.

Peripheral joint and enthesis involvement in patients with newly diagnosed inflammatory bowel disease: symptoms, clinical and ultrasound findings - a population-based cohort study.

Musculoskeletal manifestations in patients with inflammatory bowel disease (IBD) are common and associated with poorer outcomes. Hence, early detection is important to optimally tailor treatment. We aimed to determine the prevalence and distribution of inflammatory lesions in peripheral joints and entheses in newly diagnosed IBD patients. Patients with newly diagnosed IBD from a prospective population-based inception cohort were consecutively included. Data on musculoskeletal symptoms were collected by questionnaires and by structured rheumatological interview. Peripheral joints and entheses were assessed clinically and by ultrasound (US), using standardized definitions. Of 110 included patients (mean age: 42 years, 40% male, 70 with ulcerative colitis (UC), 40 with Crohn's disease (CD)), history of ≥1 musculoskeletal symptoms was reported by 49%. Clinical examination revealed peripheral musculoskeletal manifestations in 56 (52.3%) patients; 29 (27.1%) had ≥1 tender and/or swollen joints and 49 (45.8%) ≥1 tender entheses. Small peripheral joints were predominantly affected. US found inflammation in ≥1 joint or enthesis in 52 (49.5 %) patients; 29 (27.4 %) had US synovitis in ≥1 joint, while 36 (34%) US enthesitis. Fibromyalgia classification criteria were fulfilled in seven (7.9%) patients. There was no difference in clinical or US findings between patients with UC and CD, nor between patients with active and inactive IBD. Half of patients with newly diagnosed IBD had inflammation in their peripheral joints and/or entheses, documented by rheumatological clinical and ultrasound evaluations. This indicates a need for multidisciplinary collaboration to ensure an optimal therapeutic strategy for suppressing inflammation in all disease domains.

Neuromuscular manifestations of wild type transthyretin amyloidosis: a review and single center's experience.

Transthyretin amyloidosis (ATTR) is a condition defined by accumulation of insoluble transthyretin amyloid deposits in multiple organs, especially in the peripheral nerve and heart muscle. ATTR may result from transthyretin mutations (variant ATTR or ATTRv) or may occur with normal transthyretin genotype (wild type ATTR or ATTRwt). ATTRwt was previously known as "senile amyloidosis" and causes cardiomyopathy which may lead to heart failure with a preserved ejection fraction, affecting predominantly elderly men. The exact prevalence of ATTRwt in the general population remains unclear, but its occurrence may be underestimated in women. It was observed that a proportion of ATTRwt cardiomyopathy patients may develop slowly progressing neuropathy that is milder and indolent in comparison with typical progressive neuropathy associated with ATTRv. Furthermore, the causality of neuropathy is often uncertain in patients with ATTRwt. Neuropathy symptoms, including distal sensory loss, unsteadiness and (neuropathic) pain are common in elderly patients with multiple potential causes, and as ATTRwt patients are typically older, relatively high prevalence of peripheral neuropathy is expected with frequent comorbidities. Relatively high prevalence of ATTRwt in elderly population contrasts few documented cases of neuropathy caused by ATTRwt, and there is uncertainty whether ATTRwt neuropathy is an infrequent occurrence or a significant manifestation of multisystemic ATTRwt. We review neurologic and musculoskeletal manifestations of ATTRwt and present clinical features of a single center cohort of ATTRwt patients with suspected peripheral neuropathy.

The Diagnostic Odyssey in Children and Adolescents With X-linked Hypophosphatemia: Population-Based, Case–Control Study

Abstract Context X-linked hypophosphatemia (XLH) is a rare genetic disorder causing renal phosphate wasting, which predicates musculoskeletal manifestations such as rickets. Diagnosis is often delayed. Objective To explore the recording of clinical features, and the diagnostic odyssey of children and adolescents with XLH in primary care electronic healthcare records (EHRs) in the United Kingdom. Methods Using the Optimum Patient Care Research Database, individuals aged 20 years or younger after January 1, 2000, at date of recorded XLH diagnosis were identified using Systematized Nomenclature of Medicine Clinical Terms (SNOMED)/Read codes and age-matched to 100 controls. Recording of XLH-related clinical features was summarized then compared between cases and controls using chi-squared or Fisher's exact test. Results In total, 261 XLH cases were identified; 99 met the inclusion criteria. Of these, 84/99 had at least 1 XLH-related clinical feature recorded in their primary care EHR. Clinical codes for rickets, genu varum, and low phosphate were recorded prior to XLH diagnosis in under 20% of cases (median of 1, 1, and 3 years prior, respectively). Rickets, genu varum, low phosphate, nephrocalcinosis, and growth delay were significantly more likely to be recorded in cases. Conclusion This characterization of the EHR phenotypes of children and adolescents with XLH may inform future case-finding approaches to expedite diagnosis in primary care.