Articular manifestations related to anti-interleukin-5 therapies in severe asthma: a case series.

Articular manifestations should be screened before and during anti-IL-5/5R biologic treatment in severe asthma. Rigorous multidisciplinary team discussion should be carried out to assess the risk-benefit balance of withholding effective treatment. https://bit.ly/3vfPn4k.

Ankle retinacula abnormalities as features of psoriatic arthritis: An ultrasound study.

OBJECTIVE: To compare the ultrasonography (US) assessment of the retinacula of ankles in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: This cross-sectional study included RA or PsA patients with ankle pain and healthy controls. The following US features were recorded: presence of synovitis, tenosynovitis and abnormalities of two retinacula (the superior peroneal retinaculum [SPR] and the flexor retinaculum [FR] evaluated in mode B and power Doppler). RESULTS: Among the 80 included patients, 37 (46%) and 23 (29%) had RA and PsA; 20 (25%) patients were healthy controls. The FR was thicker in PsA than RA ankles 0.96±0.39 vs. 0.64±0.15, P<0.001 with no difference between RA patients and HCs. Other FR abnormalities such as hypoechogenicity, PD positivity or periostosis were more frequent in PsA than RA patients, P<0.001. On receiver-operating-characteristic curve analysis, a cut-off of 1mm FR thickness provided a sensitivity of 49% and specificity of 97% for the diagnosis of PsA. Overall, 39 and 3% of PsA and RA ankles exhibited retinaculitis of FR (thickness≥1mm with hypervascularization or hypoechogenicity). The two disease groups did not differ in the evaluation of SPR. CONCLUSIONS: US abnormalities of FR were more frequent in PsA than RA and appeared to be specific for PsA. US assessment of FR might be useful to distinguish RA and PsA.

Osteoporosis and risk of fracture in heart transplant patients.

Introduction: Significant bone loss occurs after heart transplantation, predominantly in the first year, with increased risk of incident fractures. The goal of this study was to evaluate the prevalence of fragility fractures in a population of heart transplantation patients and to identify the independent risk factors for fractures. Methods: This was a prospective monocentric study that included patients with heart transplantation occurring < 10 years who were undergoing heart transplantation monitoring. All patients underwent bone mineral density evaluation by dual-energy X-ray absorptiometry and radiographies to establish the presence of vertebral fractures. Results: We included 79 patients (61 men); the mean age was 56.8 ± 10.8 years. The mean time between transplantation and inclusion was 32.3 ± 35.0 months. Incident fractures were diagnosed in 21 (27%) patients after heart transplantation. Vertebral fractures were the most frequent (30 vertebral fractures for 15 patients). Osteoporosis was confirmed in 22 (28%) patients. Mean bone mineral density at the femoral neck and total hip was lower with than without fracture (femoral neck: 0.777 ± 0.125 vs 0.892 ± 0.174 g/cm2, p<0.01; total hip: 0.892 ± 0.165 vs 0.748 ± 0.07 g/cm2, p<0.001), with a significant result on multivariate analysis. The mean time from transplantation to the first fracture was 8.0 ± 7.6 months. Discussion: Our study confirmed a high vertebral fracture risk in heart transplant patients, especially during the first year after transplantation.

CovAID: Identification of factors associated with severe COVID-19 in patients with inflammatory rheumatism or autoimmune diseases.

Introduction: Autoimmune/inflammatory rheumatic diseases (AIRDs) patients might be at-risk of severe COVID-19. However, whether this is linked to the disease or to its treatment is difficult to determine. This study aimed to identify factors associated with occurrence of severe COVID-19 in AIRD patients and to evaluate whether having an AIRD was associated with increased risk of severe COVID-19 or death. Materials and methods: Two databases were analyzed: the EDS (Entrepôt des Données de Santé, Clinical Data Warehouse), including all patients followed in Paris university hospitals and the French multi-center COVID-19 cohort [French rheumatic and musculoskeletal diseases (RMD)]. First, in a combined analysis we compared patients with severe and non-severe COVID-19 to identify factors associated with severity. Then, we performed a propensity matched score case-control study within the EDS database to compare AIRD cases and non-AIRD controls. Results: Among 1,213 patients, 195 (16.1%) experienced severe COVID-19. In multivariate analysis, older age, interstitial lung disease (ILD), arterial hypertension, obesity, sarcoidosis, vasculitis, auto-inflammatory diseases, and treatment with corticosteroids or rituximab were associated with increased risk of severe COVID-19. Among 35,741 COVID-19 patients in EDS, 316 having AIRDs were compared to 1,264 Propensity score-matched controls. AIRD patients had a higher risk of severe COVID-19 [aOR = 1.43 (1.08-1.87), p = 0.01] but analysis restricted to rheumatoid arthritis and spondyloarthritis found no increased risk of severe COVID-19 [aOR = 1.11 (0.68-1.81)]. Conclusion: In this multicenter study, we confirmed that AIRD patients treated with rituximab or corticosteroids and/or having vasculitis, auto-inflammatory disease, and sarcoidosis had increased risk of severe COVID-19. Also, AIRD patients had, overall, an increased risk of severe COVID-19 compares general population.

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.

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.

A Risk Score to Detect Subclinical Rheumatoid Arthritis-Associated Interstitial Lung Disease.

OBJECTIVE: Patients at high risk of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) would benefit from being identified before the onset of respiratory symptoms; this can be done by screening patients with the use of chest high-resolution computed tomography (HRCT). Our objective was to develop and validate a risk score for patients who have subclinical RA-ILD. METHODS: Our study included a discovery population and a replication population from 2 prospective RA cohorts (ESPOIR and TRANSLATE2, respectively) without pulmonary symptoms who had received chest HRCT scans. All patients were genotyped for MUC5B rs35705950. After multiple logistic regression, a risk score based on independent risk factors for subclinical RA-ILD was developed in the discovery population and tested for validation in the replication population. RESULTS: The discovery population included 163 patients with RA, and the replication population included 89 patients with RA. The prevalence of subclinical RA-ILD was 19.0% and 16.9%, respectively. In the discovery population, independent risk factors for subclinical RA-ILD were presence of the MUC5B rs35705950 T allele (odds ratio [OR] 3.74 [95% confidence interval (95% CI) 1.37, 10.39]), male sex (OR 3.93 [95% CI 1.40, 11.39]), older age at RA onset (for each year, OR 1.10 [95% CI 1.04, 1.16]), and increased mean Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (for each unit, OR 2.03 [95% CI 1.24, 3.42]). We developed and validated a derived risk score with receiver operating characteristic areas under the curve of 0.82 (95% CI 0.70-0.94) for the discovery population and 0.78 (95% CI 0.65-0.92) for the replication population. Excluding MUC5B rs35705950 from the model provided a lower goodness of fit (likelihood ratio test, P = 0.01). CONCLUSION: We developed and validated a risk score that could help identify patients at high risk of subclinical RA-ILD. Our findings support an important contribution of MUC5B rs35705950 to subclinical RA-ILD risk.

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.

Synovial fluid analysis with leukocyte esterase reagent strip test.

To determine whether leukocyte esterase reagent strip test (LERST) analysis could help distinguish inflammatory arthritis from mechanical joint effusion. We analyzed synovial fluid (SF) from consecutive patients with a non-traumatic joint effusion during a 6-month period. Inflammatory SF was defined by white blood cell (WBC) count ≥ 2000/mm3. The LERST was performed with both semi-quantitative visual analysis (VA) and automated colorimetric reader (ACR) analysis. Leukocytes ≥ 1+ was considered a positive LERST result and WBC count was the reference. We obtained 100 SF samples (87 knees, 7 ankles, 5 hips, and 1 elbow) from 100 patients (mean ± SD age 61 ± 17 years, 59% men). The laboratory analyzed 88 SF samples (37 mechanical and 51 inflammatory). The remaining 12 SF samples were 10 hemarthrosis not allowing LERST analysis and 2 samples with coagulum not allowing WBC count. As compared with the laboratory analysis, the LERST had sensitivity and specificity 55% and 89% with VA and 47% and 92% with ACR analysis. The positive and negative predictive values were 87.5% and 59% with VA and 89% and 55% with ACR analysis. We found almost perfect agreement between VA and ACR results (kappa 0.70 [95% CI 0.50-0.90]). The WBC count increased with number of + observed after VA. Our results confirm that the LERST is able to detect inflammation in SF of native joints, thereby representing a useful and cheap tool in primary care. Its low sensitivity limits its use for ruling out inflammatory disorders. Key Points • Reagent strip tests can detect inflammation in synovial fluid. • In primary care practice, this method is cheap and easy to do.

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.

UltraSound evaluation in follow-up of urate-lowering therapy in gout phase 2 (USEFUL-2): Duration of flare prophylaxis.

OBJECTIVES: To determine whether changes in ultrasonography (US) features of monosodium urate crystal deposition is associated with the number of gouty flares after stopping gout flare prophylaxis. METHODS: We performed a 1-year multicentre prospective study including patients with proven gout and US features of gout. The first phase of the study was a 6-month US follow-up after starting urate-lowering therapy (ULT) with gout flare prophylaxis. After 6 months of ULT, gout flare prophylaxis was stopped, followed by a clinical follow-up (M6 to 12) and ULT was maintained. Outcomes were the proportion of relapsing patients between M6 and M12 according to changes of US features of gout and determining a threshold decrease in tophus size according to the probability of relapse. RESULTS: We included 79 gouty patients [mean (±SD) age 61.8±14 years, 91% males, median disease duration 4 (IQR 1.5;10) years]. Among the 49 completers at M12, 23 (47%) experienced relapse. Decrease in tophus size ≥50% at M6 was more frequent without than with relapse (54% vs. 26%, P=0.049). On ROC curve analysis, a threshold decrease of 50.8% in tophus size had the best sensitivity/specificity ratio to predict relapse [AUC 0.649 (95% confidence interval 0.488; 0.809)]. Probability of relapse was increased for patients with a decrease in tophus size <50% between M0 and M6 [OR 3.35 (95% confidence interval 0.98; 11.44)]. CONCLUSION: A high reduction in US tophus size is associated with lower probability of relapse after stopping gout prophylaxis. US follow-up may be useful for managing ULT and gout flare prophylaxis.

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.

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.).

Enthesopathy in rheumatoid arthritis and spondyloarthritis: An ultrasound study.

OBJECTIVE: We aimed to compare the prevalence of enthesopathy seen on ultrasonography (US) in spondyloarthritis (SpA) and rheumatoid arthritis (RA) and compared it to healthy controls. METHODS: All included patients with RA (2010 ACR/EULAR criteria) and SpA (ASAS criteria) and healthy controls underwent clinical and US evaluation of enthesis at seven sites (quadriceps, proximal and distal patellar, Achilles and triceps tendons, plantar aponeurosis and lateral epicondyle enthesis). The Glasgow Ultrasound Enthesitis Scoring System (GUESS) and the Madrid Sonographic Enthesitis Index (MASEI) scores were determined by two sonographers blinded to clinical data. RESULTS: We included 30 patients with RA (mean age: 55.7±14.8 years, mean disease duration 10.5±7.9years); 41 with SpA (mean age: 45.3±15.4 years, mean disease duration 9.2±8.7years) and 26 healthy controls (HC) (mean age: 50.4±17.3years). Patients with SpA and RA had similar prevalence of painful enthesis of examined sites (17% vs. 14%, non-significant [ns]), but more than among in healthy controls (3%, P<0.05 for RA and SpA comparison). Comparison between SpA and RA patients revealed that at least one US enthesis abnormality was found with similar frequency (46% and 48% sites [ns]) but both rheumatic diseases had higher frequency of US enthesis abnormality than HC (31%, P<0.05 for RA and SpA comparison). The mean MASEI score was 8.5±7.3 for RA patients, 7.8±6.5 for SpA patients (ns) and 3.4±2.8 for healthy controls (P<0.05 for RA and SpA comparison). Overall, 6 RA (20%) and 4 SpA (10%) patients had a MASEI score≥18 (ns). None of the healthy controls had a MASEI score≥18 (P<0.05 for RA and SpA comparison). The mean GUESS score was 5.8±3.1 and 6.3±3.9 for RA and SpA patients (ns), and 4.0±3.1 for healthy controls (P<0.01 vs. SpA and <0.05 vs. RA). CONCLUSIONS: RA and SpA patients did not differ in entheseal abnormalities seen on US. Such US features may have low specificity in inflammatory conditions affecting joints and enthesis such as SpA and RA.