Rapid onset pembrolizumab-induced inflammatory arthritis diagnosed using musculoskeletal ultrasound.

Immune checkpoint inhibitors have revolutionised the treatment of cancer. While very effective, they commonly cause a wide spectrum of immune-related adverse events. These immune-related adverse events can be fatal and often have significant effects on quality of life. They therefore require prompt recognition and management. We report the case of a woman presenting with widespread joint pain and stiffness 6 hours after her first pembrolizumab infusion. She had no joint swelling on physical examination but an ultrasound scan revealed widespread musculoskeletal inflammation, confirming the diagnosis of inflammatory arthritis. To the best of our knowledge, this is the fastest reported inflammatory arthritis onset following immune checkpoint inhibitor treatment. It highlights the importance of timely imaging in patients on immune checkpoint inhibitors who present with new non-specific musculoskeletal pain. Her symptoms improved dramatically with intramuscular triamcinolone injection.

Utility of testing for third-generation anticyclic citrullinated peptide (anti-CCP3) antibodies in individuals who present with new musculoskeletal symptoms but have a negative second-generation anticyclic citrullinated peptide (anti-CCP2) antibody test.

OBJECTIVES: To investigate the role of third-generation anticyclic citrullinated peptide (anti-CCP3) antibodies in predicting progression to inflammatory arthritis (IA) in individuals with new musculoskeletal (MSK) symptoms and a negative second-generation anti-CCP antibody test (anti-CCP2-). METHODS: 469 anti-CCP2- individuals underwent baseline anti-CCP3 testing (QUANTA Lite CCP3; Inova Diagnostics) and received a post enrolment 12-month questionnaire. A rheumatologist confirmed or excluded diagnosis of IA. Univariable/multivariable analyses were performed to assess the value of anti-CCP3 in predicting IA development in these anti-CCP2- individuals. RESULTS: Only 16/469 (3.4%) anti-CCP2- individuals had a positive anti-CCP3 test. Of these 16 individuals, 4 developed IA. In addition, 61/469 (13.0%) anti-CCP2- individuals self-reported, to have developed, IA. Progression was confirmed in 43/61 of them (70.5%); of whom 30/43 (69.8%) and 13/43 (30.2%) were given a diagnosis of IA and rheumatoid arthritis (RA), respectively. In qualitative univariable analysis, anti-CCP3 positivity was associated with self-reported progression (p<0.01) and IA (p=0.03), but not with RA. Anti-CCP3 levels differed significantly between progressors and non-progressors (p<0.01) for all three categories. At the manufacturer's cut-off, OR for progression ranged from 2.4 (95% CI 0.5 to 18.6; RA) to 7.5 (95% CI 2.3 to 24.0; self-reported progression). Interestingly, when cut-offs for anti-CCP3 were optimised, lower values (≥5 units) significantly increased the OR for progression in all three categories. In multivariable analysis, anti-CCP3 positivity at the manufacturer's cut-off did not remain associated with IA progression, while this lower cut-off value (≥5 units) was associated with diagnosis of RA (p=0.02). CONCLUSIONS: Anti-CCP3 testing could improve the prediction of IA development in anti-CCP2- individuals with new MSK symptoms.

High prevalence of radiographic erosions in early, untreated PsA: results from the SpARRO cohort.

AIMS: To investigate the prevalence and distribution of bone erosions in an early psoriatic arthritis (PsA) population using conventional radiography (CR) and to explore the agreement between CR and ultrasound (US) detected bone erosions. METHODS: Newly diagnosed, treatment naïve PsA patients fulfilling the ClASsification for Psoriatic Arthritis (CASPAR) classification criteria of ≤5 years symptom duration were recruited as part of the Leeds Spondyloarthropathy Register for Research and Observation and underwent CR and US examination of hands and feet. RESULTS: Overall, 4655 hand and feet joints were assessed in 122 patients. CR erosions were detected in 24.6% (n=30) with lowest prevalence seen below 8 months of symptoms (17.5% vs 24.3%>24 months). The number of erosions was higher on CR (1.55% (63/4,655); US 1.04% (34/3,270)), with 5th metatarsophalangeal (MTP) joint being the most affected site in both CR (5.21% (11/211)) and US (7.14% (15/210)). Erosions in CR were more evenly distributed compared with US where three-quarters of the total number of bone erosions were detected in wrists, second metacarpophalangeal (MCP) and fifth MTP joints. Most joints had almost perfect prevalence-adjusted bias-adjusted kappa values ranging from 0.91 to 1. CONCLUSIONS: Erosions were seen in a quarter of patients with newly diagnosed, untreated PsA with a declining trend around the 8-month symptom duration cut-off. High levels of agreement between CR and US were seen with CR detecting more erosions. A focused US assessment of the wrist, second MCP and fifth MTP joints may be useful to detect bone erosions in early PsA.

Power Doppler signal at the enthesis and bone erosions are the most discriminative OMERACT ultrasound lesions for SpA: results from the DEUS (Defining Enthesitis on Ultrasound in Spondyloarthritis) multicentre study.

OBJECTIVES: To assess, in spondyloarthritis (SpA), the discriminative value of the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and their associations with clinical features in this population. METHODS: In this multicentre study involving 20 rheumatology centres, clinical and ultrasound examinations of the lower limb large entheses were performed in 413 patients with SpA (axial SpA and psoriatic arthritis) and 282 disease controls (osteoarthritis and fibromyalgia). 'Active enthesitis' was defined as (1) power Doppler (PD) at the enthesis grade ≥1 plus entheseal thickening and/or hypoechoic areas, or (2) PD grade >1 (independent of the presence of entheseal thickening and/or hypoechoic areas). RESULTS: In the univariate analysis, all OMERACT lesions except enthesophytes/calcifications showed a significant association with SpA. PD (OR=8.77, 95% CI 4.40 to 19.20, p<0.001) and bone erosions (OR=4.75, 95% CI 2.43 to 10.10, p<0.001) retained this association in the multivariate analysis. Among the lower limb entheses, only the Achilles tendon was significantly associated with SpA (OR=1.93, 95% CI 1.30 to 2.88, p<0.001) in the multivariate analyses. Active enthesitis showed a significant association with SpA (OR=9.20, 95% CI 4.21 to 23.20, p<0.001), and unlike the individual OMERACT ultrasound lesions it was consistently associated with most clinical measures of SpA disease activity and severity in the regression analyses. CONCLUSIONS: This large multicentre study assessed the value of different ultrasound findings of enthesitis in SpA, identifying the most discriminative ultrasound lesions and entheseal sites for SpA. Ultrasound could differentiate between SpA-related enthesitis and other forms of entheseal pathology (ie, mechanical enthesitis), thus improving the assessment of entheseal involvement in SpA.

Predicting Flare in Patients With Rheumatoid Arthritis in Biologic Induced Remission, on Tapering, and on Stable Therapy.

OBJECTIVE: The tapering of biologic disease-modifying antirheumatic drug (b-DMARD) therapy for patients with rheumatoid arthritis (RA) in stable remission is frequently undertaken, but specific guidance on how to successfully taper is lacking. The objective of this study is to identify predictors of flare in patients in stable b-DMARD-induced clinical remission, who did or did not follow structured b-DMARD tapering. METHODS: Patients with RA receiving b-DMARD treatment who had achieved sustained remission according to a Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) <2.6 for ≥6 months were offered tapering. Clinical, ultrasound (US) (total power Doppler [PD]/grayscale abnormalities), CD4+ T cell subsets, and patient-reported outcomes (PROs) were collected at inclusion. The primary endpoint was the occurrence of flare (loss of DAS28-CRP remission) over 12 months. Logistic regression analyses identified predictors of flare. Dichotomization into high/low-risk groups was based on 80% specificity using the area under the receiving operator curve (AUROC). RESULTS: Of 63 patients choosing tapering, 23 (37%) flared compared with 12 of 60 (20%) on stable treatment (P = 0.043). All patients who flared regained remission upon reinstating treatment. In the tapering group, flare was associated with lower regulatory T cell (Treg) (P < 0.0001) and higher CRP levels (P < 0.0001), erythrocyte sedimentation rate (P < 0.035), and inflammation-related cells (IRCs) (P = 0.054); stepwise modeling selected Tregs (odds ratio [OR] = 0.350, P = 0.004), IRCs (OR = 1.871, P = 0.007), and CRP level (OR = 1.577, P = 0.004) with 81.7% accuracy and AUROC = 0.890. In the continued therapy group, modeling retained the tender joint count, total PD, and visual analog scale pain score, with 82.1% accuracy and AUROC = 0.899. Most patients in the study were considered low risk of flare (80 of 123 patients [65%]). Only 5 of 37 (13.5%) of the low-risk patients who tapered flared, which was notable compared with the continued therapy group (20% flare). CONCLUSION: Flare on tapering b-DMARDs was predicted by lower Tregs and elevated inflammation biomarkers (IRCs/CRP level); flare on continued b-DMARDs was associated with raised pain parameters and US inflammation. Knowledge of these biomarkers should improve outcomes by targeted selection for tapering, and by increased monitoring of those on continued therapy predicted to flare.

'Double target' ultrasound monitoring of biologic therapy in psoriatic arthritis.

OBJECTIVES: We aimed to 1) evaluate by power Doppler (PD) ultrasound (US) the response to therapy of the most inflamed joint and enthesis (target sites) in psoriatic arthritis (PsA) patients starting a biologic disease-modifying anti-rheumatic drug (bDMARD); and 2) to investigate the correlation between the US response and clinical data. METHODS: Consecutive PsA patients with US synovitis and US 'active' enthesitis, starting a bDMARD, were included. The joint with the highest OMERACT-EULAR-US composite score and the enthesis with the highest PD grade (targets) were identified at baseline. The US examination and clinical assessment were performed at 0, 3 and 6 months. The response of OMERACT-EULAR-US synovitis composite score was defined as reaching a grade = 0 at follow-up examination; synovial and entheseal PD responses were defined as a PD=0 and/or a reduction of ≥2 PD grades at follow-up examination. RESULTS: Thirty patients were included. Synovitis composite score, synovial PD and entheseal PD showed significant responses at 3 and 6 months compared to baseline (p<0.01). Synovial PD responses were higher than entheseal PD responses at 3 months (71.4% vs 40.0%, p=0.01) and 6 months (77.8% vs. 46.7%, p=0.02). US synovitis responses were correlated with DAPSA (p<0.01) and MDA responses (p=0.01 for composite score, p=0.02 for PD). CONCLUSIONS: US was found sensitive for monitoring treatment response in PsA patients starting a biologic drug. Entheseal PD was less responsive than synovial PD, suggesting that enthesitis may represent a 'difficult-to-treat' domain in PsA.

Factors associated with resolution of ultrasound subclinical synovitis in anti-CCP-positive individuals with musculoskeletal symptoms: a UK prospective cohort study.

BACKGROUND: Subclinical synovitis occurs in a third of individuals at risk of rheumatoid arthritis. The objective of this study was to assess the reversibility of subclinical synovitis in individuals at risk of rheumatoid arthritis who are positive for anti-cyclic citrullinated peptide (CCP) antibody with musculoskeletal symptoms and investigate factors associated with its resolution within 12 months. METHODS: We conducted a single-centre, prospective, cohort study in the UK, recruiting individuals aged 18 years or older who were anti-CCP-positive with a new non-specific musculoskeletal symptom but no clinical synovitis. Referrals were made through primary or secondary care. Participants attended a baseline visit, which included a clinical assessment, blood tests, patient questionnaires, and a musculoskeletal ultrasound scan (ie, of wrists and metacarpophalangeal, proximal interphalangeal, and metatarsophalangeal joints), and then follow-up visits every 3 months for the first year, with a repeat ultrasound scan every 12 months. Participants with subclinical synovitis (ie, grey scale ≥1 and power Doppler ≥1) in at least one joint at baseline were selected for this analysis. Investigation of good prognostic factors by 12 months was done first using univariable analysis to identify significant factors in participants with no missing data. Then receiver operating characteristic (ROC) curves were used to establish the optimal cutoffs for significant continuous variables. Finally, a modified Poisson regression approach was performed to identify the best prediction model and was adjusted for confounders, using data from all participants, with missing values imputed. This study is registered with ClinicalTrials.gov, NCT02012764. FINDINGS: Between June 30, 2008, and Feb 24, 2020, 451 participants consented to participate in the CCP study and 122 (27%) individuals had subclinical synovitis at baseline, of whom 90 (74%) had data available at 12 months. Mean age was 54·1 years (SD 12·5), and 63 (70%) of 90 participants were women and 27 (30%) were men. Subclinical synovitis resolved in 43 (48%) of 90 participants, whereas subclinical synovitis persisted in 47 (52%) participants, 27 (57%) of whom developed clinical synovitis within 12 months. In the multivariable analysis, low anti-CCP titre (relative risk [RR] 1·52, 95% CI 1·04-2·22), negative rheumatoid factor (1·54, 0·92-2·58), subclinical synovitis in only one joint (1·62, 1·04-2·50), and an erythrocyte sedimentation rate of 15 mm/h or lower (1·82, 1·15-2·87) were predictors of subclinical synovitis resolution within 12 months (ie, good prognostic factors). ROC curve showed an area under the curve of 0·84 (95% CI 0·76-0·92; p<0·0001). Resolution occurred in seven (100%) of seven participants with all four factors present, and in only one (7%) of 14 participants with none of the factors present. INTERPRETATION: In individuals who were anti-CCP-positive, subclinical synovitis disappeared in approximately half of the participants by 12 months and was associated with the presence of good prognostic factors. Subclinical synovitis should be interpreted in the context of these additional factors. FUNDING: National Institute for Health Research Leeds Biomedical Research Centre.

Poly-Refractory Rheumatoid Arthritis: An Uncommon Subset of Difficult to Treat Disease With Distinct Inflammatory and Noninflammatory Phenotypes.

OBJECTIVE: To investigate the prevalence of poly-refractory rheumatoid arthritis (RA) defined as failure of all biological (b)/targeted synthetic (ts)-disease-modifying drugs (DMARDs). To further investigate whether patients with persistent inflammatory refractory RA (PIRRA) and noninflammatory refractory RA (NIRRA), determined by objective ultrasound (US) synovitis, have distinct clinical phenotypes in both EULAR difficult-to-treat RA (D2T-RA) and poly-refractory RA groups. METHODS: A cross-sectional study of 1,591 patients with RA on b/tsDMARDs that evaluated D2T-RA criteria and subclassified as poly-refractory if inefficacy/toxicity to at least one drug of all classes. PIRRA was defined if US synovitis in one or more swollen joint and NIRRA if absent. Univariate tests and multivariate logistic regression were conducted to investigate factors associated with poly-refractory, PIRRA, and NIRRA phenotypes. RESULTS: 122 of 1,591 were excluded due to missing data. 247 of 1,469 (16.8%) had D2T-RA and only 40 of 1,469 (2.7%) poly-refractory RA. This latter group had higher disease activity score 28 C-reactive protein (CRP) (median 5.4 vs 5.02, P < 0.05), CRP levels (median 13 vs 5 mg/l, P < 0.01), and smoking (ever) rates (20% vs 4%, P < 0.01) compared with other D2T patients. Smoking was associated with poly-refractory RA (odds ratio 5.067, 95% CI 1.774-14.472, P = 0.002). Of 107 patients with D2T-RA with recent US, 61 (57%) were PIRRA and 46 (43%), NIRRA. Patients with NIRRA had elevated body mass index (median 30 vs 26, P < 0.001) and higher fibromyalgia prevalence (15% vs 3%, P < 0.05), lower swollen joint count (median: 2 vs 5, P < 0.001), and lower CRP levels (5 vs 10, P < 0.01). CONCLUSION: Only 2.7% of D2T-RA failed all classes of b/tsDMARDs. Among D2T-RA, less than 60% had objective signs of inflammation, representing a target for innovative strategies.

Ultrasound in anti-CCP+ at-risk individuals without clinical synovitis: development of a novel 6-joint protocol for feasible risk prediction.

OBJECTIVES: To investigate, in anti-cyclic citrullinated peptide antibody positive individuals with musculoskeletal symptoms but no clinical synovitis (CCP+ at-risk), the additional value of ultrasound (US) for the prediction of inflammatory arthritis (IA). Furthermore, to define a concise US protocol for feasible risk prediction. METHODS: Demographic and clinical data were collected in 417 CCP+ at-risk (Leeds CCP cohort) with a baseline US scan assessing synovitis and bone erosions in 36 joints, and a follow-up duration ≥24 months. Multivariable binary regression models for IA development at 24 months evaluated routine clinical variables associated with IA alone ("clinical" model) and combined with a 36-joint US scanning protocol ("clinical-US extended" model). A "clinical-US short" model was developed. RESULTS: At 24 months, 92/417 (22.1%) CCP+ at-risk developed IA (median time: 7 months, IQR : 3-12). The "clinical-US extended" model performed better than the "clinical" model (AUC 0.788 vs AUC 0.731 respectively, p< 0.001) with an odds ratio for IA development of 3.18 (95% IC 1.80-5.63) for US synovitis and 2.54 (95% IC 1.21-5.37) for bone erosions. The "clinical-US short" model, which retained the wrists, knees and MTP5 joints, performed better (AUC 0.782) than the "clinical" model (p< 0.001) and similarly (difference in Akaike information criteria <2) to the "clinical-US extended" model. CONCLUSIONS: US provides valuable information for predicting progression to IA in CCP+ individuals both alone and in addition to clinical variables. US synovitis was associated with a threefold increase risk of IA development. A concise US protocol of 6 joints provides clinically feasible risk prediction in CCP+ at-risk.

Update on muscle imaging in myositis.

PURPOSE OF REVIEW: Imaging techniques such as MRI, ultrasound and PET/computed tomography (CT) have roles in the detection, diagnosis and management of myositis or idiopathic inflammatory myopathy (IIM). Imaging research has also provided valuable knowledge in the understanding of the pathology of IIM. This review explores the latest advancements of these imaging modalities in IIM. RECENT FINDINGS: Recent advancements in imaging of IIM have seen a shift away from manual and qualitative analysis of the images. Quantitative MRI provides more objective, and potentially more sensitive characterization of fat infiltration and inflammation in muscles. In addition to B-mode ultrasound changes, shearwave elastography offers a new dimension to investigating IIM. PET/CT has the added advantage of including IIM-associated findings such as malignancies. SUMMARY: It is evident that MRI, ultrasound and PET/CT have important roles in myositis. Continued technological advancement and a quest for more sophisticated applications help drive innovation; this has especially been so of machine learning/deep learning using artificial intelligence and the developing promise of texture analysis.

Multimodal ultrasound muscle assessment in patients with rheumatic diseases: a patient-based reliability study.

Objectives: The aim was to explore the inter-reliability of a newly developed US scanning protocol (multimodal US) for the assessment of different aspects of sarcopenia-related muscle involvement, including muscle mass, muscle quality and muscle stiffness [using point shear-wave elastography (SWE)], in patients with rheumatic and musculoskeletal diseases (RMDs). Methods: Quadriceps muscle mass (i.e. muscle thickness), muscle quality (i.e. muscle echogenicity evaluated with both a visual semi-quantitative scale and a dedicated software package for image analysis, ImageJ) and point SWE measurements were obtained by two rheumatologists (blinded to each other's evaluation) in consecutive RMD patients without previous/current myositis or neuromuscular disorders.Inter-reliability was assessed using the intraclass correlation coefficient (ICC) for continuous variables and Cohen's kappa (κ) for categorical variables. Results: A total of 45 RMD patients were enrolled [mean age 54.5 (16.0) years, male-to-female ratio 1:1.5, mean BMI 24.6 (4.6) kg/m2], 10 with PsA, 7 RA, 5 AS, 5 PMR, 4 SLE, 4 gout, 4 OA, 3 FM and 3 SSc. The grade of inter-rater reliability was excellent for muscle mass [ICC = 0.969 (0.953 < ICC < 0.979)]. Regarding muscle echogenicity, the agreement was substantial/almost perfect using the visual semi-quantitative scale (weighted linear = 0.793, weighted squared = 0.878) and excellent using ImageJ analysis [ICC = 0.916 (0.876 < ICC < 0.944)]. Finally, a good agreement was obtained for point SWE measurements [ICC = 0.76 (0.712 < ICC < 0.8)]. Conclusion: Multimodal US is a novel and reliable tool for the evaluation of different aspects of muscle involvement (muscle mass, muscle quality and muscle stiffness) in RMD patients.

Ultrasound in the Management of Patients With Psoriatic Arthritis: Systematic Literature Review and Novel Algorithms for Pragmatic Use.

OBJECTIVE: In 2015, the European Alliance of Associations for Rheumatology (EULAR) published recommendations for the use of imaging for the diagnosis and management of spondyloarthritis (SpA) in clinical practice. These recommendations included the use of ultrasound (US) in patients with psoriatic arthritis (PsA), but the management was not clearly distinguished from that of SpA. We aimed to systematically review the literature on the role of US for the management of PsA, and to propose pragmatic algorithms for its use in clinical practice. METHODS: A group of 10 rheumatologists, experienced in imaging and musculoskeletal US, met with the objectives of formulating key questions for a systematic literature review (SLR), appraising the available evidence, and then proposing algorithms on the application of US in suspected or established PsA, based on both the literature and experts' opinions following a Delphi process. RESULTS: The SLR included 120 articles, most of which focused on the diagnostic process. The elevated number of articles retrieved suggests the interest of rheumatologists in using US in the management of PsA. After a consensual discussion on literature data and expert opinion, the following 3 algorithms were developed to be used in practical situations: suspicion of PsA, management of PsA with good clinical response, and management of PsA with insufficient clinical response. CONCLUSION: The SLR showed interest by rheumatologists in using US to objectively evaluate PsA for diagnosis and management. We propose 3 practical algorithms to guide its use in the clinical management of patients, from diagnosis to the assessment of treatment response. Further studies are needed to define remission and to assess the ability of US to predict disease severity.

Antibodies to leukotoxin A from the periodontal pathogen Aggregatibacter actinomycetemcomitans in patients at an increased risk of rheumatoid arthritis.

Objectives: Periodontitis and underlying bacteria have been linked to the development of rheumatoid arthritis (RA). One suggested pathogen is Aggregatibacter actinomycetemcomitans (A.a.), which expresses leukotoxin A (LtxA) that can citrullinate human proteins, providing a possible trigger for the production of anti-citrullinated protein antibodies (ACPA). In this study, we seek to determine the presence of antibodies toward LtxA in patients at risk of developing RA. Methods: Two prospective observational patient cohorts (one Swedish and one British) with symptomatic at-risk patients were studied. Anti-LtxA antibodies were analyzed by a cell-based neutralization assay in baseline serum and compared to 100 Swedish blood donors that served as controls. Results: Serum anti-LtxA levels or positivity did not differ between patients and blood donors. In the British cohort, anti-LtxA was more prevalent among ACPA-positive arthralgia patients compared with ACPA-negative arthralgia cases (24% vs. 13%, p < 0.0001). In the Swedish at-risk cohort, anti-LtxA positive patients were at increased risk of progression to arthritis (hazard ratio (HR) 2.10, 95% CI 1.04-4.20), but this was not confirmed in the UK at-risk cohort (HR 0.99, CI 0.60-1.65). Conclusion: Serum anti-LtxA is not elevated before RA diagnosis, and associations with disease progression and ACPA levels differ between populations. Other features of the oral microbiome should be explored in upcoming periodontitis-related RA research.

Predicting Inflammatory Arthritis in At-Risk Persons: Development of Scores for Risk Stratification.

BACKGROUND: Inflammatory arthritis (IA) is an immune-related condition defined by the presence of clinical synovitis. Its most common form is rheumatoid arthritis. OBJECTIVE: To develop scores for predicting IA in at-risk persons using multidimensional biomarkers. DESIGN: Prospective observational cohort study. SETTING: Single-center, Leeds, United Kingdom. PARTICIPANTS: Persons with new musculoskeletal symptoms, a positive test result for anticitrullinated protein antibodies, and no clinical synovitis and followed for 48 weeks or more or until IA occurred. MEASUREMENTS: A simple score was developed using logistic regression, and a comprehensive score was developed using the least absolute shrinkage and selection operator Cox proportional hazards regression. Internal validation with bootstrapping was estimated, and a decision curve analysis was done. RESULTS: Of 455 participants, 32.5% (148 of 455) developed IA, and 15.4% (70 of 455) developed it within 1 year. The simple score identified 249 low-risk participants with a false negative rate of 5% (and 206 high-risk participants with a false-positive rate of 72%). The comprehensive score identified 119 high-risk participants with a false-positive rate of 29% (and 336 low-risk participants with a false-negative rate of 19%); 40% of high-risk participants developed IA within 1 year and 71% within 5 years. LIMITATIONS: External validation is required. Recruitment occurred over 13 years, with lower rates of IA in later years. There was geographic variation in laboratory testing and recruitment availability. CONCLUSION: The simple score identified persons at low risk for IA who were less likely to need secondary care. The comprehensive score identified high-risk persons who could benefit from risk stratification and preventive measures. Both scores may be useful in clinical care and should also be useful in clinical trials. PRIMARY FUNDING SOURCE: National Institute for Health and Care Research Leeds Biomedical Research Centre.

Efficacy of orofacial myofunctional therapy combined with myofascial release in patients with mild obstructive sleep apnoea: a randomized controlled trial.

BACKGROUND: Obstructive sleep apnoea (OSA) is characterized by repetitive narrowing and collapse of pharyngeal airway during sleep, leading to apnoea or hypopnoea. In this context, myofunctional therapy and myofascial release might be effective, despite the literature on the combination of these approaches is still scarce. OBJECTIVES: This randomized controlled trial aimed to assess the efficacy of oro-facial myofunctional therapy combined with myofascial release in terms of functioning in patients with mild OSA. METHODS: Patients aged from 40 to 80 years with diagnosis of mild OSA were randomly allocated into intervention group (oro-facial myofunctional therapy plus myofascial release) and control group (only oro-facial myofunctional therapy). At the baseline (T0), after 4 weeks (T1), and after 8 weeks (T2), the following outcomes were assessed: apnoea/hypopnoea index (AHI), average oxygen saturation (SpO2 ), sleep time spent with oxygen saturation < 90% (T90), snoring index, and Pittsburgh Sleep Quality Index (PSQI). RESULTS: Out of the 60 patients enrolled, 28 (aged 61.46 ± 8.74 years) complete the treatment in the intervention group and 24 (aged 60.42 ± 6.61 years) in the control group. There were no significant differences in AHI between groups. A significant difference was reported for ΔT0-T1 SpO2 (p = .01), T90 (p = .030), ΔT0-T1 and ΔT0-T2 snoring index (p = .026 and <.001 respectively), and ΔT0-T1 and ΔT0-T2 Pittsburgh Sleep Quality Index (p = .003 and <.001 respectively). CONCLUSION: Taken together, a combination of oro-facial myofunctional therapy and myofascial release showed a potential treatment for sleep quality in patients with mild OSA. Future studies are necessary to better investigate the role of these interventions in OSA patients.

Early and Late Response and Glucocorticoid-Sparing Effect of Belimumab in Patients with Systemic Lupus Erythematosus with Joint and Skin Manifestations: Results from the Belimumab in Real Life Setting Study-Joint and Skin (BeRLiSS-JS).

AIM: To assess the efficacy of belimumab in joint and skin manifestations in a nationwide cohort of patients with SLE. METHODS: All patients with skin and joint involvement enrolled in the BeRLiSS cohort were considered. Belimumab (intravenous, 10 mg/kg) effectiveness in joint and skin manifestations was assessed by DAS28 and CLASI, respectively. Attainment and predictors of DAS28 remission (<2.6) and LDA (≥2.6, ≤3.2), CLASI = 0, 1, and improvement in DAS28 and CLASI indices ≥20%, ≥50%, and ≥70% were evaluated at 6, 12, 24, and 36 months. RESULTS: DAS28 < 2.6 was achieved by 46%, 57%, and 71% of patients at 6, 12, and 24 months, respectively. CLASI = 0 was achieved by 36%, 48%, and 62% of patients at 6, 12, and 24 months, respectively. Belimumab showed a glucocorticoid-sparing effect, being glucocorticoid-free at 8.5%, 15.4%, 25.6%, and 31.6% of patients at 6, 12, 24, and 36 months, respectively. Patients achieving DAS-LDA and CLASI-50 at 6 months had a higher probability of remission at 12 months compared with those who did not (p = 0.034 and p = 0.028, respectively). CONCLUSIONS: Belimumab led to clinical improvement in a significant proportion of patients with joint or skin involvement in a real-life setting and was associated with a glucocorticoid-sparing effect. A significant proportion of patients with a partial response at 6 months achieved remission later on during follow-up.

Dynamic assessment of the double contour sign by ultrasonography helps to distinguish between gout and calcium pyrophosphate deposition disease.

OBJECTIVE: To test whether the double contour (DC) sign has a different dynamic behaviour in gout and calcium pyrophosphate deposition (CPPD) and whether the dynamic assessment of the DC sign increases its accuracy in gout diagnosis. METHODS: This cross-sectional analysis included patients with gout meeting the 2015 ACR/EULAR classification criteria and patients with crystal-proven diagnosis of CPPD. Hyaline cartilages were explored by ultrasound (US) to detect the DC sign (ie, abnormal hyperechoic band over the superficial margin of hyaline cartilages) and its dynamic behaviour during joint movement was evaluated ((ie, movement of the DC sign together with subchondral bone (DC sign), or in the opposite direction (pseudo DC sign)). RESULTS: Eighty-one patients with gout and 84 patients with CPPD underwent US assessment. Among them, 47 patients with gout and 9 patients with CPPD had evidence of the DC sign. During dynamic assessment, in all 47/47 patients with gout there was a DC sign. Conversely, in 7/9 (77.8%) patients with CPPD, there was a pseudo DC sign (p<0.01).The presence of DC sign during static assessment had a sensitivity, specificity and accuracy of 58.0% (95% CI 46.5% to 68.9%), 89.3% (95% CI 80.6% to 95.0%) and 73.9% (95% CI 66.5% to 80.5%) for gout, respectively. The dynamic evaluation improved the DC sign's diagnostic performance (p=0.01) as the specificity (97.6% (95% CI 91.7% to 99.7%)) and the accuracy (78.2% (95% CI 71.1% to 84.2%)) increased without loss in sensitivity. CONCLUSION: The dynamic US assessment of the DC sign may help to differentiate the DC sign due to MSU crystals from the pseudo DC sign seen in CPPD, as they move in opposite directions.

Doppler Signal and Bone Erosions at the Enthesis Are Independently Associated With Ultrasound Joint Erosive Damage in Psoriatic Arthritis.

OBJECTIVE: To explore the association of the Outcome Measures in Rheumatology ultrasound (US) entheseal abnormalities with the presence of US joint bone erosions in psoriatic arthritis (PsA). METHODS: Consecutive patients with PsA were included in this cross-sectional study. Demographic and clinical variables were collected. A bilateral US assessment was carried out at the following entheses: plantar fascia, and the quadriceps, patellar (proximal and distal), and Achilles tendons. The following US entheseal abnormalities were registered: hypoechogenicity, thickening, Doppler signal < 2 mm from the bony cortex, calcification/enthesophyte, and bone erosion. The presence of US joint bone erosions was investigated at the second and fifth metacarpophalangeal joints, ulnar head, and fifth metatarsophalangeal (MTP) joint, bilaterally, as well as at the level of the most inflamed joint on physical examination. Multiple linear regression analysis was performed to identify clinical and/or US variables associated with US-detected joint bone erosions. RESULTS: A total of 104 patients with PsA were enrolled. At least 1 joint bone erosion was found in 47 of 104 patients (45.2%). Bone erosions were most frequently detected at the fifth MTP joint level (42/208 joints [20.2 %] in 32/104 patients [30.8%]). In the multivariate model, only a power Doppler (PD) signal at the enthesis (P < 0.001, standardized ß = 0.51), bone erosions at the enthesis (P = 0.02, standardized ß = 0.20), PsA disease duration (P = 0.04, standardized ß = 0.17), and greyscale joint synovitis (P = 0.03, standardized ß = 0.42) were associated with US-detected joint bone erosions. CONCLUSION: PD signal and bone erosions at the enthesis represent sonographic biomarkers of a more severe subset of PsA in terms of US-detected joint erosive damage.