Higher Levels of SARS-CoV-2 Genetic Variation in Immunocompromised Patients: A Retrospective Case-Control Study.

BACKGROUND: A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection lasts longer in immunocompromised hosts than in immunocompetent patients. Prolonged infection is associated with a higher probability of selection for novel SARS-CoV-2 mutations, particularly in the spike protein, a critical target for vaccines and therapeutics. METHODS: From December 2020 to September 2022, respiratory samples from 444 immunocompromised patients and 234 health care workers positive for SARS-CoV-2, diagnosed at 2 hospitals in Paris, France, were analyzed using whole-genome sequencing using Nanopore technology. Custom scripts were developed to assess the SARS-CoV-2 genetic diversity between the 2 groups and within the host. RESULTS: Most infections were SARS-CoV-2 Delta or Omicron lineages. Viral genetic diversity was significantly higher in infections of immunocompromised patients than those of controls. Minor mutations were identified in viruses sequenced from immunocompromised individuals, which became signature mutations for newer SARS-CoV-2 variants as the epidemic progressed. Two patients were coinfected with Delta and Omicron variants. The follow-up of immunocompromised patients revealed that the SARS-CoV-2 genome evolution differed in the upper and lower respiratory tracts. CONCLUSIONS: This study found that SARS-CoV-2 infection in immunocompromised patients is associated with higher genetic diversity, which could lead to the emergence of new SARS-CoV-2 variants with possible immune evasion or different virulence characteristics.

2023 EULAR recommendations on imaging in diagnosis and management of crystal-induced arthropathies in clinical practice.

OBJECTIVE: To formulate evidence-based recommendations and overarching principles on the use of imaging in the clinical management of crystal-induced arthropathies (CiAs). METHODS: An international task force of 25 rheumatologists, radiologists, methodologists, healthcare professionals and patient research partners from 11 countries was formed according to the EULAR standard operating procedures. Fourteen key questions on the role of imaging in the most common forms of CiA were generated. The CiA assessed included gout, calcium pyrophosphate deposition disease and basic calcium phosphate deposition disease. Imaging modalities included conventional radiography, ultrasound, CT and MRI. Experts applied research evidence obtained from four systematic literature reviews using MEDLINE, EMBASE and CENTRAL. Task force members provided level of agreement (LoA) anonymously by using a Numerical Rating Scale from 0 to 10. RESULTS: Five overarching principles and 10 recommendations were developed encompassing the role of imaging in various aspects of patient management: making a diagnosis of CiA, monitoring inflammation and damage, predicting outcome, response to treatment, guided interventions and patient education. Overall, the LoA for the recommendations was high (8.46-9.92). CONCLUSIONS: These are the first recommendations that encompass the major forms of CiA and guide the use of common imaging modalities in this disease group in clinical practice.

Retention, safety and efficacy of off-label conventional treatments and biologics for chronic calcium pyrophosphate crystal inflammatory arthritis.

OBJECTIVES: Very little is known on the efficacy and safety of drugs for the management of chronic calcium pyrophosphate (CPP) crystal inflammatory arthritis. The objectives of this work were to describe the drugs used in the management of chronic CPP crystal inflammatory arthritis in expert European centres, and to examine treatment retention. METHODS: This was a retrospective cohort study. Charts from patients with a diagnosis of persistent inflammatory and/or recurrent acute CPP crystal arthritis were reviewed in seven European centres. Baseline characteristics were collected, and visits at months 3, 6, 12 and 24 included an assessment of treatment response and safety. RESULTS: One hundred and ninety-four treatments were initiated in 129 patients. Colchicine (used first-line in n = 73/86), methotrexate (used first-line in n = 14/36), anakinra (n = 27) and tocilizumab (n = 25) were the most prescribed treatments, while long-term corticosteroids, hydroxychloroquine, canakinumab and sarilumab were used occasionally. The 24-month on-drug retention was higher for tocilizumab (40%) than anakinra (18.5%) (P < 0.05), while the difference between colchicine (29.1%) and methotrexate (44.4%) was not statistically significant (P = 0.10). Adverse events led to 14.1% of colchicine discontinuations (100% of diarrhoea), 4.3% for methotrexate, 31.8% for anakinra and 20% for tocilizumab; all other discontinuations were related to insufficient response or losses to follow-up. Efficacy outcomes did not differ significantly between treatments throughout follow-up. CONCLUSION: Daily colchicine is the first-line therapy used in chronic CPP crystal inflammatory arthritis, which is considered efficient in a third to half of cases. Second-line treatments include methotrexate and tocilizumab, which have higher retention than anakinra.

Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography in polymyalgia rheumatica: an observational study.

OBJECTIVES: Polymyalgia rheumatica (PMR) is an inflammatory disease with a diagnosis that is sometimes difficult to establish. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) might be helpful. We analysed the usefulness of 18F-FDG PET/CT for the diagnosis of PMR. METHODS: This was an observational retrospective study of individuals with PMR who underwent 18F-FDG PET/CT and a control group. We assessed clinical and 18F-FDG PET/CT characteristics. Sixteen sites were studied. The number of sites with significant FDG uptake, the mean maximum standardised uptake value (SUVmax) and the highest SUVmax value were assessed for each patient. RESULTS: Data for 123 patients with PMR (37 with corticosteroids [CSTs] use) were analysed; 85 had new-onset PMR. As compared with the 75 controls, patients with new-onset PMR had higher mean ± SD number of sites with significant FDG uptake (11.3 ± 3.3 vs. 0.9 ± 1.1, p<0.001) and higher SUVmax scores (p<0.001). A cut-off of 5 hypermetabolic sites provided sensitivity of 96.5% and specificity 100%. For the total SUVmax score, a cut-off of 3 had the best sensitivity (92.6%) and specificity (86.1%). As compared with PMR patients using CSTs, those who were CST-naive had significantly higher CRP level (p<0.001), number of sites with significant FDG uptake (p<0.001) and SUVmax scores (p<0.01). In contrast, large-vessel vasculitis was more frequent in patients receiving CSTs than CST-naive patients (27% vs. 8%, p<0.01). CONCLUSIONS: The number of hypermetabolic sites or SUVmax quantification might be useful for PMR diagnosis, and CSTs might affect the results of 18F-FDG PET/CT.

Screening for spondyloarthritis in patients with inflammatory bowel diseases.

Inflammatory bowel diseases (IBDs) can be associated with various musculoskeletal (IBD-MSK) manifestations that could be difficult to classify for gastroenterologists. We aimed to evaluate the characteristics of patients with IBD-MSK and the prevalence of spondyloarthritis (SpA). In this observational cross-sectional study, we included patients with IBD-MSK complaints (peripheral or back pain). All patients underwent a standardized rheumatology evaluation including clinical, biological and imaging evaluations (MRI of spine and sacroiliac joints and ultrasonography of enthesis). We included 183 IBD patients (60.7% women; median [interquartile range] age 45 [36-56] years); 159 (87%) had joint pain. In 43 (23.5%) and 25/175 (14.3%) patients, enthesis abnormalities were found on ultrasonography and sacroiliitis on MRI, respectively. SpA was diagnosed in 54 (29.5%) patients. IBD-related arthralgia and degenerative spine disease were diagnosed in 105 (57.4%) and 72 (39.3%) patients. Sixteen (29.6%) SpA patients initiated a new conventional synthetic disease modifying anti-rheumatic drug (DMARD). A biologic DMARD was initiated in 10 patients or changed in 3. More than half of IBD-MSK patients had IBD-related arthralgia, and about one-third had definite SpA. Ultrasonography of enthesis and systematic MRI of sacroiliac joints seem useful for SpA classification and differential diagnosis in these patients who often have musculoskeletal pain complaints. Therapeutics were changed in most patients, which highlights the need for a multidisciplinary approach for managing IBD with extra-intestinal symptoms.

Management and outcome of native joint septic arthritis: a nationwide survey in French rheumatology departments, 2016-2017.

OBJECTIVES: To describe current management and outcome of native joint septic arthritis (NJSA) in French rheumatology departments. METHODS: For this retrospective, nationwide multicentric study, 127 French rheumatology departments were contacted to report up to 12 cases of NJSA that occurred between 1 January 2016 and 31 December 2017. Characteristics, diagnosis procedures, therapeutic management and outcome were recorded. RESULTS: Overall, 362 patients were included (mean age 64.0±18.6 years, median Charlson comorbidity index 3.5 (0-14)). Knee was the most frequent site (n=160 (38.9%)), and Staphylococcus sp (n=185 (51.4%)), the most frequent pathogen. All patients received antibiotics for a mean duration of 46.8 (±22.0) days, including intravenous route for a mean of 17.2 (±15.4) days. Management was heterogeneous. Surgical procedure was performed in 171 (48.3%), joint immobilisation in 128 (43.8%). During follow-up, 91 (28.3%) patients have had serious complications and 28 (9.2%) of them died. Factors associated with 1-year mortality were age (OR 1.08, 95% CI 1.04 to 1.13; p<0.001), Charlson's index (OR 1.30, 95% CI 1.06 to 1.58; p=0.012), presence of bacteraemia (OR 4.02, 95% CI 1.35 to 11.99; p=0.008), antibiotic use in the previous 3 months (OR 3.32, 95% CI 1.11 to 9.87; p=0.029) and Staphylococcus aureus NJSA compared with Streptococcus sp. NJSA (OR 7.24, 95% CI 1.26 to 41.68, p=0.027). The complete recovery with no adverse joint outcome at 1 year was observed in n=125/278 patients (55.0%). CONCLUSION: Prognosis of NJSA remained severe with a high rate of morbimortality. Its management was very heterogeneous. This study highlights the importance of the new French recommendations, published after the completion of the study, in order to facilitate NJSA management.

Salivary gland ultrasonography in patients with connective tissue diseases: a multi-centre observational study.

OBJECTIVE: US of salivary glands (SGUS) is a non-invasive tool that allows for diagnosing primary SS (pSS) or secondary SS (sSS). However, little is known about the prevalence of US findings of SS in other CTDs. The aim of this multi-centre observational study was to evaluate, in CTD patients with or without SS, the prevalence of abnormal SGUS findings and the possible association of the findings with clinical or biological phenotypes. METHODS: B-Mode SGUS was performed by one operator blinded to clinical data. Each SG was semi-quantitatively rated on a scale from 0 to 4 according to the Jousse-Joulin score; a score ≥2 was considered pathological. RESULTS: Data for 194 patients were analysed (pSS, n = 30; sSS, n = 39; other CTDs, n = 77; controls, n = 48). SGUS findings were abnormal in 80%, 67%, 25% and 2% of patients, respectively. Independent of the underlying disease, age and sex, abnormal SGUS findings were significantly associated with presence of anti-SSA antibodies (P < 0.001), pSS (P < 0.001) and sSS (P < 0.01). Among SS patients, abnormal SGUS findings were associated with the presence of hypergammaglobulinemia, anti-SSA antibodies, objective eye dryness and increased anti-nuclear antibody level, with no difference in EULAR SS Disease Activity Index. CONCLUSION: Abnormal SGUS findings were associated with anti-SSA antibody positivity independent of the underlying disease. In SS patients, abnormal findings were associated with immunologic features and mouth involvement. Among CTD patients, SGUS changes may be associated with a particular immune profile.

Musculoskeletal Tuberculosis: New Insights on Diagnosis Strategy and Treatment.

BACKGROUND/ OBJECTIVE: Skeletal tuberculosis (TB) is rare. We aimed to report on diagnostic strategy and treatment of skeletal TB. METHODS: In this multidisciplinary single-center medical records review study, all adult patients admitted between January 2009 and December 2019 with microbiologically proven skeletal TB were included. Demographic, medical history, laboratory, imaging, pathologic findings, treatment, and follow-up data were extracted from medical records. RESULTS: Among 184 patients identified with TB, 21 (16 women, 42 years [27, 48 years]) had skeletal involvement. Skeletal TB included spondylitis (n = 11), lytic bone lesions (n = 7), sacroiliitis (n = 5), arthritis (n = 3), osteitis (n = 2), and diffuse muscle abscesses without bone lesion (n = 1). Lytic lesions involved both axial and peripheral skeleton at multiple sites in most cases. 18F-fluorodeoxyglucose positron emission tomography was performed in 13 patients and helped to detect multifocal asymptomatic lesions and to target biopsy. All patients were treated with anti-TB therapy for 7 to 18 months. Fifteen patients (71.4%) received steroids as an adjunct therapy. Eleven patients needed an orthopedic immobilization corset, and 3 patients underwent surgery. All patients clinically improved under treatment, but 2 relapsed over a median follow-up of 24 months (12-30 months). No patient died or suffered long-term disabilities. CONCLUSION: Our study emphasizes the diversity of skeletal involvement in TB. 18F-fluorodeoxyglucose positron emission tomography scanner at diagnosis is key to assess the extension of skeletal involvement and guide extraskeletal biopsy. Neurological complications might be prevented by adding corticosteroids to anti-TB therapy.

MRI Features Associated With the Detection of Microbial Pathogens by CT-Guided Biopsy in Septic Spondylodiscitis.

OBJECTIVE: The aim of this study was to assess the magnetic resonance imaging (MRI) features associated with microbial pathogen detection by computed tomography (CT)-guided biopsy in patients with suspected septic spondylodiscitis. METHODS: For the last 10-year period, we analyzed the medical records of patients who underwent MRI and CT-guided biopsy for suspected septic spondylodiscitis. Clinical characteristics were recorded. The following MRI features were assessed: edema or contrast enhancement of the intervertebral disc, adjacent vertebrae, epidural and paravertebral space, presence of abscess, and paravertebral edema size. A positive biopsy was defined by pathogen identification on bacterial analysis or the presence of granuloma on histology. Predictors of a positive biopsy were assessed with a logistic regression model. RESULTS: We examined data for 61 patients (34 [56%] male; mean age, 59.9 ± 18.0 years); for 35 patients (57%), CT-guided biopsy was positive for a pathogen. The 4 MRI findings significantly associated with a positive biopsy were epiduritis, greater than 50% vertebral endplate edema, loss of intradiscal cleft, and abscess. The size of paravertebral edema was greater with a positive than negative biopsy (median, 15.9 [interquartile range, 11.3-21.3] vs 7.3 [4.6-12.9] mm; p = 0.004). On multivariable analysis, epiduritis was the only independent predictor of a positive biopsy (adjusted odds ratio, 7.4 [95% confidence interval, 1.7-31.4]; p = 0.006). CONCLUSIONS: Epiduritis and the size of paravertebral edema on MRI are associated with detection of a microbial pathogen in suspected septic spondylodiscitis. For patients without these MRI signs, the need for further investigations such as enriched or prolonged cultures, a second CT-guided biopsy, or even surgical biopsy need to be discussed.

MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease.

BACKGROUND: Given the phenotypic similarities between rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that the strongest risk factor for the development of idiopathic pulmonary fibrosis, the gain-of-function MUC5B promoter variant rs35705950, would also contribute to the risk of ILD among patients with RA. METHODS: Using a discovery population and multiple validation populations, we tested the association of the MUC5B promoter variant rs35705950 in 620 patients with RA-ILD, 614 patients with RA without ILD, and 5448 unaffected controls. RESULTS: Analysis of the discovery population revealed an association of the minor allele of the MUC5B promoter variant with RA-ILD when patients with RA-ILD were compared with unaffected controls (adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.8 to 5.2; P=9.7×10-17). The MUC5B promoter variant was also significantly overrepresented among patients with RA-ILD, as compared with unaffected controls, in an analysis of the multiethnic case series (adjusted odds ratio, 5.5; 95% CI, 4.2 to 7.3; P=4.7×10-35) and in a combined analysis of the discovery population and the multiethnic case series (adjusted odds ratio, 4.7; 95% CI, 3.9 to 5.8; P=1.3×10-49). In addition, the MUC5B promoter variant was associated with an increased risk of ILD among patients with RA (adjusted odds ratio in combined analysis, 3.1; 95% CI, 1.8 to 5.4; P=7.4×10-5), particularly among those with evidence of usual interstitial pneumonia on high-resolution computed tomography (adjusted odds ratio in combined analysis, 6.1; 95% CI, 2.9 to 13.1; P=2.5×10-6). However, no significant association with the MUC5B promoter variant was observed for the diagnosis of RA alone. CONCLUSIONS: We found that the MUC5B promoter variant was associated with RA-ILD and more specifically associated with evidence of usual interstitial pneumonia on imaging. (Funded by Société Française de Rhumatologie and others.).

Methotrexate and rheumatoid arthritis associated interstitial lung disease.

QUESTION ADDRESSED BY THE STUDY: Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Fibrotic interstitial lung disease (ILD) is a common complication of RA. Whether MTX exposure increases the risk of ILD in patients with RA is disputed. We aimed to evaluate the association of prior MTX use with development of RA-ILD. METHODS: Through a case-control study design with discovery and international replication samples, we examined the association of MTX exposure with ILD in 410 patients with chronic fibrotic ILD associated with RA (RA-ILD) and 673 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques. RESULTS: Analysis of the discovery sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted OR 0.46, 95% CI 0.24-0.90; p=0.022), which was confirmed in the replication samples (pooled adjusted OR 0.39, 95% CI 0.19-0.79; p=0.009). The combined estimate using both the derivation and validation samples revealed an adjusted OR of 0.43 (95% CI 0.26-0.69; p=0.0006). MTX ever-users were less frequent among patients with RA-ILD compared to those without ILD, irrespective of chest high-resolution computed tomography pattern. In patients with RA-ILD, ILD detection was significantly delayed in MTX ever-users compared to never-users (11.4±10.4 years and 4.0±7.4 years, respectively; p<0.001). ANSWER TO THE QUESTION: Our results suggest that MTX use is not associated with an increased risk of RA-ILD in patients with RA, and that ILD was detected later in MTX-treated patients.

Efficacy of tocilizumab in patients with hand osteoarthritis: double blind, randomised, placebo-controlled, multicentre trial.

OBJECTIVE: To evaluate the efficacy of tocilizumab, an antibody against IL-6 receptor, in patients with hand osteoarthritis. METHODS: This was a multicentre, 12-week, randomised, double-blind, placebo-controlled study from November 2015 to October 2018. Patients with symptomatic hand osteoarthritis (pain ≥40 on a 0-100 mm visual analogue scale (VAS) despite analgesics and non-steroidal anti-inflammatory drugs; at least three painful joints, Kellgren-Lawrence grade ≥2) were randomised to receive two infusions 4 weeks apart (weeks 0 and 4) of tocilizumab (8 mg/kg intravenous) or placebo. The primary endpoint was changed in VAS pain at week 6. Secondary outcomes included the number of painful and swollen joints, duration of morning stiffness, patients' and physicians' global assessment and function scores. RESULTS: Of 104 patients screened, 91 (45 to tocilizumab and 46 to placebo; 82% women; mean age 64.4 (SD 8.7) years) were randomly assigned and 79 completed the 12-week study visit. The mean change between baseline and week 6 on the VAS for pain (primary outcome) was -7.9 (SD 19.4) and -9.9 (SD 20.1) in the tocilizumab and placebo groups (p=0.7). The groups did not differ for any secondary outcomes at weeks 4, 6, 8 or 12. Overall, adverse events were slightly more frequent in the tocilizumab than placebo group. CONCLUSION: Tocilizumab was no more effective than placebo for pain relief in patients with hand osteoarthritis.

Screening of dental and sinus infections in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is associated with increased risk of infections. Screening for oral (dental and/or sinus) infection could be proposed before biologic disease-modifying antirheumatic drugs (bDMARDs) initiation but is not systematically recommended. The aim of our study was to assess the prevalence of oral infection in RA patients requiring bDMARDs. MATERIALS AND METHODS: This was a monocentric retrospective study. We included patients with RA and active disease requiring bDMARDs. Dental infection and sinusitis were assessed by a stomatologist and otorhinolaryngologist after clinical, panoramic dental X-ray and sinus CT evaluation. Factors associated with oral infections were analysed in uni- and multivariate models, estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We included 223 RA patients (79.4% women, mean disease duration 8.9 ± 8.6 years). The mean age was 54.4 ± 10.9 years and mean Disease Activity Score in 28 joints 5.5 ± 2.6. Systematic dental screening revealed infection requiring treatment before bDMARDs initiation in 46 (20.9%) patients. Sinusitis was diagnosed by the otorhinolaryngologist in 33 (14.8%) patients. Among the 223 patients, 69 (30.9%) had dental and/or sinus infection. On univariate analysis, active smoking was associated with increased probability of oral infection (OR = 2.16 [95% CI 1.02-4.57], P = .038) and methotrexate with reduced probability (OR = 0.43 [95% CI 0.23-0.81], P = .006). On multivariate analysis, no RA variables were associated with oral infection. CONCLUSION: In our study, asymptomatic oral infection was confirmed in one third of RA patients.

Ultrasound shoulder assessment of calcium pyrophosphate disease with suspected polymyalgia rheumatica.

OBJECTIVES: Polymyalgia rheumatica (PMR) is characterised by inflammatory pain of shoulders and the pelvic girdle that affects older people. Conditions that can mimic PMR include rheumatoid arthritis (RA), spondyloarthritis (SpA) and calcium pyrophosphate disease (CPPD). In this study, we aimed to define the prevalence of CPPD among patients with polymyalgic syndrome with suspected PMR according to recent ACR/EULAR criteria. METHODS: This was an observational study in which we included patients with polymyalgic syndrome (inflammatory pain of shoulders, elevated C-reactive protein (CRP) level, and age >50 years). All patients were tested for RA antibodies and underwent ultrasonography (US) of shoulders [gleno-humeral effusion, biceps tenosynovitis, sub-acromiodeltoid (SAD) bursitis, synovitis and CPPD of the acromio-clavicular (AC) joint and humeral bone erosion]. RESULTS: We included 94 patients with polymyalgic syndrome (mean age 69.4±11.3 years, 67% female); 27 had a diagnosis of RA and 14 SpA. The remaining 52 were considered to have PMR according to ACR/EULAR criteria for PMR; 25 had a diagnosis of CPPD. As compared with PMR patients without CPPD, those with CPPD more frequently had humeral bone erosion (p=0.003), synovitis and CPPD of the AC joint (p<0.0001 for both) and less frequently SAD bursitis (p=0.0098). For PMR diagnosis, the most sensitive US features were SAD bursitis (96.3%) and biceps tenosynovitis (85.2%), despite low specificity. For CPPD diagnosis, CPPD of the AC joint had the best ratio of sensitivity to specificity (sensitivity: 85.2%; specificity: 97.1%). CONCLUSIONS: Detection of CPPD is relatively frequent with suspected PMR. Adding US assessment of the AC joint to usual US screening might help the clinician better distinguish PMR from other conditions, notably CPPD.

Ultrasound evaluation in follow-up of urate-lowering therapy in gout: the USEFUL study.

OBJECTIVES: We aimed to determine the ability of ultrasonography (US) to show disappearance of urate deposits in gouty patients requiring urate-lowering therapy (ULT). METHODS: We performed a 6-month multicentre prospective study including patients with: proven gout; presence of US features of gout (tophus and/or double contour sign) at the knee and/or first metatarsophalangeal joints; and no current ULT. US evaluations were performed at baseline and at months 3 and 6 (M3, M6) after starting ULT. Outcomes were: the change in US features of gout at M6 according to final (M6) serum urate (SU) level (high, > 360 µmol/l, i.e. > 6 mg/dl; low, 300-360 µmol/l, i.e. 5-6 mg/dl; very low, < 300 µmol/l, i.e. < 5 mg/dl); and correlation between changed US features and final SU level. RESULTS: We included 79 gouty patients (mean ± s.d., age 61.8 (14) years, 91% males, disease duration 6.3 (6.1) years). Baseline SU level was 530 ± 97 µmol/l (i.e. 8.9 mg/dl ± 1.6mg/dl). At least one US tophus and double contour sign was observed in 74 (94%) and 68 (86%) patients, respectively. Among the 67 completers at M6, 18 and 39 achieved a very low and low SU level, respectively. We found a significant decrease in US features of gout among patients with the lowest SU level (P < 0.001). Final M6 SU level was positively correlated with decreased size of tophus (r = 0.54 [95% CI: 0.34, 0.70], P < 0.0001), and inversely correlated with proportion of double contour sign disappearance (r=-0.59 [-0.74, -0.40]). CONCLUSION: US can show decreased urate deposition after ULT, which is correlated with decreased SU level. The responsiveness of US in gout is demonstrated and can be useful for gout follow-up and adherence to ULT.

Overweight and obesity affect clinical assessment of synovitis in rheumatoid arthritis: comparison of ultrasonography and clinical exam.

OBJECTIVES: Body mass index (BMI) might affect rheumatoid arthritis (RA) outcomes. Clinical assessment of swollen joint count (SJC) might also be affected by obesity in terms of obesity-related excess adipose tissue. In this study, we compared ultrasonography (US) and clinical examination in assessing the effect of BMI on RA disease activity assessment. METHODS: This was a single-centre study including RA (ACR/EULAR criteria) patients. US assessment was performed by one trained rheumatologist blinded to clinical data. US synovitis was defined as grey-scale score ≥2 and/or power Doppler score ≥1. The primary outcome measure was difference in SJC (ΔSJC) between clinical and US assessment (US-clinical examination). The secondary outcome was to evaluate the difference between clinical and US assessment of the Disease Activity Score in 28 joints (ΔDAS28) in the 3 BMI subgroups according to the WHO classification. RESULTS: We included 76 RA patients (mean age 53.8 ± 11.8 years; 67% female). Overall, 28 (36.8%), 33 (43.4%) and 15 (19.7%) were normal weight, overweight and obese, respectively. Baseline characteristics did not differ between the 3 BMI subgroups. US-determined SJC was significantly higher than clinical-determined SJC for overweight and obese RA patients: p=0.001 and p=0.049, respectively. The DAS28 was higher with US than clinical examination within the overweight group only (p=0.002). One-way analysis of variance (ANOVA) revealed a significant difference between ΔDAS28 among the 3 BMI subgroups (p=0.046). CONCLUSIONS: In high BMI RA patients both SJC and DAS28 seem to be undervalued by clinical assessment when compared to US.

Tophus size is associated with hallux valgus deformity in gout.

OBJECTIVE: Hallux valgus (HV) and gout are common pathologies of the first metatarsophalangeal joint (MTP1) leading to pain and deformation. In this study, we aimed to determine the correlation between tophus size and characteristics of HV in gouty patients. METHODS: In this case-control study, we included patients with gout (the presence of monosodium urate crystals in synovial fluid) and control patients with spondyloarthritis, without crystal disease disorders. Radiographic assessment and ultrasound (US) assessment were performed by two blinded operators. US features of gout (double contour [DC] sign and/or tophus) were collected. HV was defined by hallux abductus (HA) angle ≥20° and/or intermetatarsal angle (IM) ≥10°. Correlation between US findings and HV angles was estimated by Spearman correlation coefficient. RESULTS: We included 56 gouty patients (87.5% males, mean age of 63.9 ± 12.2 years) and 41 control patients (90% males, mean age of 59.0 ± 12.8 years). HV was more frequent in patients with gout than controls (62% vs 37%, P = .0007). Regardless of HV status, correlations were found between the size of US tophi and IM (r = .3381, P = .003) and HA angles (r = .2344, P = .043). CONCLUSIONS: Our results confirm a high prevalence of HV in gouty patients. We also observed a correlation between the size of the US tophus and the angles defining HV, which suggests a link between urate deposition load and HV. Early urate-lowering therapy for gout could limit the occurrence of HV.

Increased rate of lumbar spondylolisthesis in rheumatoid arthritis: A case-control study.

OBJECTIVE: The aim of this study was to compare the prevalence of lumbar spondylolisthesis (SPL) in patients suffering from low back pain (LBP) with or without rheumatoid arthritis (RA) and to identify potential factors associated with SPL in patients with RA. METHODS: We performed a case-control study. Cases and control patients had chronic LBP (more than 4 weeks). Patient with RA fulfilled the 2010 ACR/EULAR criteria. The main outcome was the presence of lumbar SPL on lumbar X-ray. The prevalence of SPL between RA and control patients was compared using chi-squared test. Potential factors associated with SPL in patients with RA were investigated by univariate and multivariate analysis, estimating odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: A total of 67 cases and 83 controls were included. Median [interquartile range] age of patients with RA was 60.0 years [51.0-72.0]; 80.6% were females; and 92.5% and 83.6% were positive for anti-citrullinated protein antibodies (ACPAs) or rheumatoid factor, respectively. Mean RA disease duration was 11.2 ± 8.7 years. SPL was more frequent in patients with RA than controls (41.8% versus 18.1%, P = 0.001). Adjusted to gender, RA was associated with increased prevalence of SPL (OR 3.15 [95% CI 1.48-6.70], P = 0.003). Among patients with RA, SPL was mainly Grade 1 (85.7%). Multivariate analysis revealed SPL is associated with increased age in patients with RA (OR 1.06 [1.02-1.11], P = 0.004). CONCLUSION: In a population of patients with chronic LBP, the prevalence of lumbar SPL was higher with than without RA. SPL might be explained by synovitis of lumbar facet joints.

Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis.

Despite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern of interstitial pneumonia and common environmental risk factors, we hypothesised that the two diseases might share additional risk factors, including FPF-linked genes. Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a discrete number of FPF-linked genes and performed a burden test to assess the excess number of mutations in RA-ILD patients compared to controls.Among the 101 RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations in the TERT, RTEL1, PARN or SFTPC coding regions. The burden test, based on 81 RA-ILD patients and 1010 controls of European ancestry, revealed an excess of TERT, RTEL1, PARN or SFTPC mutations in RA-ILD patients (OR 3.17, 95% CI 1.53-6.12; p=9.45×10-4). Telomeres were shorter in RA-ILD patients with a TERT, RTEL1 or PARN mutation than in controls (p=2.87×10-2).Our results support the contribution of FPF-linked genes to RA-ILD susceptibility.

Patient phenotypes in fibromyalgia comorbid with systemic sclerosis or rheumatoid arthritis: influence of diagnostic and screening tests. Screening with the FiRST questionnaire, diagnosis with the ACR 1990 and revised ACR 2010 criteria.

OBJECTIVES: Fibromyalgia (FM) may occur with rheumatoid arthritis (RA) and systemic sclerosis (SSc), and debate remains about its diagnosis. We aimed to use three FM tools (a screening tool (FiRST), diagnostic criteria (ACR 1990 and revised 2010), to compare FM prevalence between RA and SSc patients, to describe the phenotypes of patients with comorbid FM, and to analyze links between FM and secondary Sjögren's syndrome (SS). METHODS: Consecutive adult patients with confirmed RA or SSc from four university hospitals were tested with the three FM tools. RESULTS: FiRST detected FM in 22.6% of the 172 RA patients, with confirmation in 22.1% (ACR1990) and 19.1% (ACR2010). ACR1990FM+ RA patients had more diffuse pain, whereas ACR2010FM+ RA patients had higher BMI and pain intensity, more diffuse pain, active disease, disability, and associated SS. FiRST detected FM in 27.8% of the 122 SSc patients, with confirmation in 30.3% (ACR1990) and 23.7% (ACR2010). ACR1990FM+ SSc patients had greater disability and pain intensity, and more diffuse pain, whereas ACR2010FM+ SSc patients had higher BMI, pain intensity, more disability and diffuse pain, and associated SS. Correlations between FM diagnostic and screening tool results were modest in both conditions. Secondary SS was associated with comorbid FM. CONCLUSIONS: The prevalence of FM is high in SSc and RA, whatever the FM diagnostic tool used. Secondary SS is associated with FM in both RA and SSc. The revised ACR 2010 FM criteria and FiRST screening tool reveal specific phenotypes potentially useful for improving disease management.