Objective Joint involvement in SLE is the most frequent manifestation and shows a wide heterogeneity. It has not a valid classification and it is often underestimated. Subclinical inflammatory musculoskeletal involvement is not well known. We aim to describe the prevalence of joint and tendon involvement in hand and wrist of SLE patients, either with clinical arthritis, arthralgia or asymptomatic and compare it with healthy subjects using contrasted MRI. Methods SLE patients fulfilling SLICC criteria were recruited and classified as follows: group (G) 1: hand/wrist arthritis, G2: hand/wrist arthralgia, G3: no hand/wrist symptoms. Jaccoud arthropathy, CCPa and RF positivity, hand OA or surgery were excluded. Healthy subjects (HS) were recruited as controls: G4. Contrasted MRI of non-dominant hand/wrist was performed. Images were evaluated following RAMRIS criteria extended to PIP, Tenosynovitis score for RA and peritendonitis from PsAMRIS. Groups were statistically compared. Results 107 subjects were recruited (G1: 31, G2:31, G3:21, G4:24). Any lesion: SLE patients 74.7%, HS 41.67%; p 0.002. Synovitis: G1: 64.52%, G2: 51.61%, G3: 45%, G4: 20.83%; p 0.013. Erosions: G1: 29.03%; G2: 54.84%, G3: 47.62%; G4: 25%; p 0.066. Bone marrow oedema: G1: 29.03%, G2: 22.58%, G3: 19.05%, G4: 0.0%; p 0.046. Tenosynovitis: G1: 38.71%; G2: 25.81%, G3: 14.29%, G4: 0.0%; p 0.005. Peritendonitis: G1: 12.90%; G2: 3.23%, G3: 0.0%, G4: 0.0%; p 0.07. Conclusion SLE patients have a high prevalence of inflammatory musculoskeletal alterations confirmed by contrasted MRI, even if asymptomatic. Not only tenosynovitis but peritendonitis is also present.
BackgroundInterstitial lung disease (ILD) is one of the leading causes of morbidity and premature mortality in rheumatoid arthritis (RA) patients. Some studies have shown that Krebs von den Lungen-6 (KL-6) may be a valuable biomarker for diagnosis and stratifying prognosis in Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD).ObjectivesTo evaluate the diagnostic and prognostic value of serum KL-6 in RA-ILD patients.MethodsWe conducted a retrospective study that included patients with RA (ACR/EULAR 2010 criteria) with available KL-6 data measured in blood serum at study enrolment. Patients were evaluated between February 2017 and October 2019 at a single center. ILD was diagnosed by high-resolution computed tomography (HRCT) and confirmed by a multidisciplinary committee. Serum KL-6 levels were measured by Lumipulse G KL-6 Kit (Fujirebio, Japan), using Chemiluminescent enzyme immunoassay (CLEIA). The reference value for KL-6 in healthy subjects was 118-627 U/mL. The inter-assay variation coefficient of the reagent was ≤ 4.4%. We performed a bivariate analysis according to the presence of ILD and high levels of KL-6. Mortality was assessed in December 2022 by medical chart review.ResultsA total of 166 patients were included (36 RA-ILD and 130 RA-non-ILD). Patient baseline characteristics were as follows: female gender 76.5%, mean age 62.9 ± 12.3 years, mean disease duration 9.1 ± 8.7 years, RF positive 66.3%, anti-CCP positive 85.5%, erosive disease 56.0%, and mean DAS28 3.0. The median follow-up period was 5 years (IQR 4.0–5.0). At baseline, patients with RA-ILD were older (69.9 ± 16.1 vs. 60.9 ± 12.3 years; p<0.001), were more frequently males (36.1% vs. 20.0%; p=0.044), had a longer disease duration (12.2 ± 1.3 vs. 8.3 ± 8.7 years; p=0.020), had higher RF titers (412.1 ± 120.5 vs. 165.6 ± 221.1; p<0.001), had a higher disease activity (DAS28 3.7 ± 0.2 vs. 2.8 ± 1.1; p<0.001), and higher mortality (33.3% vs. 9.2%; p<0.001). Among RA-ILD patients at baseline, the median FVC and DLco (% predicted value) were 79 (IQR 72.6–87.0) and 60 (IQR 49.0–70.4), respectively. Usual interstitial pneumonia (UIP) was the predominant pattern at HRCT in half of the patients (18/36). The mean serum KL-6 level at baseline was 513.1 ± 480.1 U/mL. KL-6 levels were abnormally elevated in 35 patients (21.0%). Serum levels of KL-6 in the RA-ILD group were significantly higher than those in the RA-non-ILD group (884.0 ± 134.6 vs. 410.4 ± 262.4 U/mL; p<0.001). Patients with high KL-6 had a higher prevalence of RA-ILD (54.3% vs. 13.0%; p<0.001) and UIP pattern at HRCT (22.9% vs. 7.6%; p<0.001), as well as higher mortality (34.3% vs. 9.2%; p<0.001) (Table 1). During follow-up, 24 (14.5%) patients died, mainly due to respiratory infections (62.5%). The median time to death was 20 months (IQR 7.0–29.0).ConclusionOur results suggest that high KL-6 levels might be helpful as a biomarker for diagnosis and prognosis stratification in patients with RA-ILD, especially in patients with UIP pattern at HRCT.References[1]Kim HC, et al.PLoS One.2020[2]Avouac J, et al.PLoS One.2020Table 1.Baseline characteristics in patients with RA according to serum KL-6 status.VariableAll population N=166High KL-6 n=35Normal KL-6 n=131PAge, years62.9 ± 12.368.0 ± 10.061.5 ± 12.50.005Male gender39 (23.5)12 (34.3)27 (20.6)0.090Ever smoking86 (51.8)18 (51.4)68 (51.9)0.871RA duration, years9.1 ± 8.710.7 ± 7.88.7 ± 8.90.250RF, positive110 (66.3)25 (71.4)85 (64.9)0.467RF, titer (IU)219.1 ± 399.5395.5 ± 685.0172.0 ± 263.20.003ACPA, positive142 (85.5)28 (80.0)114 (87.0)0.294ACPA, titer (CU)1201.6 ± 2107.41257.6 ± 1096.21186.7 ± 2306.80.860DAS28-ESR3.0 ± 1.23.3 ± 1.32.9 ± 1.20.094GC, current99 (59.6)27 (77.1)72 (55.0)0.018MTX, current101 (69.8)20 (57.1)81 (61.8)0.614bDMARD, current51 (30.7)9 (25.7)42 (32.1)0.020RA-ILD36 (21.7)19 (54.3)17 (13)<0.001UIP pattern (HRCT)18 (18.8)8 (22.9)10 (7.6)<0.001FVC, % predicted79.7 ± 16.277.1 ± 15.782.8 ± 16.70.289DLco, % predicted63.0 ± 16.659.2 ± 17.367.9 ± 14.80.116Mortality24 (14.5)12 (34.3)12 (9.2)<0.001AcknowledgementsWe want to thank all patients who have participated in the study. Funding: Hospital Clinic of Barcelona (Grant # 37 933) and the Spanish Ministry of Economy and Competitiveness (Grant # RTI2018-094120-B-I00).Disclosure of InterestsJuan C. Sarmiento-Monroy: None declared, Albert Pérez-Isidro: None declared, Raul Castellanos Moreira Employee of: Bristol-Myers Squibb, Virginia Ruiz: None declared, Beatriz Frade-Sosa: None declared, Ana Azuaga: None declared, Julio Ramírez: None declared, Rosa Morlà: None declared, ANDRES PONCE FERNANDEZ: None declared, PATRICIA CORZO GARCIA: None declared, Sandra Myriam Farietta Varela: None declared, Anna Colmenero: None declared, Manuel Morales-Ruiz: None declared, Estíbaliz Ruiz-Ortiz: None declared, Odette Viñas: None declared, Fernanda Hernández-González: None declared, Jacobo Sellarés: None declared, Juan de Dios Cañete: None declared, Raimón Sanmartí: None declared, José A Gómez-Puerta: None declared.
BackgroundStudies have shown an association between active synovitis measured by ultrasound (US) with plasma calprotectin in rheumatoid arthritis (RA) patients [1]. Neutrophil extracellular traps (NETs) may play a pathogenetic role in RA [2]. Elevated plasma NETs have been observed in RA patients, although their association with disease activity is unclear. No studies have analyzed the association between NETs remnants and US synovitis in RAObjectivesTo analyse whether plasma calprotectin and NETs remnants are associated with synovial inflammation measured by US in patients with established RA treated with biological therapies or JAK inhibitors (JAKi).MethodsObservational cross-sectional study. RA patients (ACR/EULAR 2010) receiving treatment with biologic DMARDs (IL6 inhibitors (IL6i), TNF inhibitors (antiTNF), rituximab (RTX)) or JAKi) were consecutively included regardless of disease activity and previous therapy. Clinical disease activity indexes and laboratory parameters of inflammation were evaluated. Plasma calprotectin was analysed. Plasma levels of elastase-DNA (EN-DNA) and histone-DNA complex (H3-DNA) (NETs remnants) were examined using a home-made ELISA test. Joint US of both hands was evaluated and graded according to Szudlarek’s score. The synovial hypertrophy (SH), power Doppler (PD) and the total score (SH+PD) was calculated. US active synovitis as previously defined (3) was calculated (SH ≥ 2 + PD ≥1). A correlation study between neutrophilic markers and US scores was made.Results101 RA patients (91% female, 86% seropositive (RF and/or ACPA) were included. Mean age was 55.4 ±12.1 yrs and the mean RA duration was 15.4 ±9.5 yrs. 78 received treatment with biologics (45 IL6i, 30 antiTNF and 3 RTX) and 23 JAKi. Mean DAS28, CDAI and SDAI were 3.19, 12 and 13 respectively. Low disease activity or remission (CDA<10) were found in 56 patients (54.5%). Mean total US score was 12.7 ±13.7 and US active synovitis was found in 69 patients (69.8%). Means levels of plasma calprotectin were 0.98 μg/ml ±1.4 and plasma NETs remnants were 1.1 ±0.4 (EN-DNA) and 0.9 ±0.08(H3-DNA) [Table 1]. Plasma NETs remnants were not correlated with any US scores. Calprotectin correlated moderately with US scores (ρ between 0.54 and 0.60, p<0.001). There was no correlation between both NETs remnants and calprotectin levels. Mean calprotectin levels were significantly higher in patients with US active synovitis (1.28 vs 0.35 μg/ml, p<0.001) but NETs remnants were not (data not shown). The lack of correlation between NETs and US scores was observed in all therapeutic groups.Table 1.Clinical and laboratory characteristicsIL6in 45JAKin 23AntiTNFn 30RTXn 3Totaln101Age56.4±11.353.9±12.555.4±13.150.9±14.355.4±12.1Female42(93.3)20 (87)27(90)3(100)92(91.1)Seropositive (ACPA/ RF)39(86.7)22(95.7)23(76.7)3(100)101(86.1)Disease duration (years)16.4±8.112.2±9.316.5±11.614.6±8.515.4±9.5128TJC4.1±5.83.7±5.42.3±3.714.3±2.13.8±5.428SJC1.6±2.32.0±2.72.2±0.59,3±0.51.8±2.7DAS282.8±1.23.7±1.43.1±1.16.3±0.63.2±1.3CDAI12.0±10.612.4±9.39.9±9.440.1±0,812.3±10.1SDAI12.4±10.713.1±9.611.03±11.142.8±3.0813.04±11.6hs PCR (mg/dL)0.1± 0.20.4±0.430.7± 2.52.3±2.60.45±1.4Plasma calprotectin (μg/ml)0.73±0.640.93±1.021.25±2.242.47±1.450.98±1.45EN-DNA1.1±0.41.1±0.31,1±0.60,9±0.11.1±0.4H3-DNA1.1±0.31.1±0.21,1±0.20,8±0.51.1±0.4SH score6.20±5.67.6±7.66.83±6.632.7±8.17.5±7.8PD score4.9±5.05.0±6.14.35±6.020.0±10.55.2±6.2Total US score11.1±10.312.6±13.411.1±12.452.7±15.812.7±13.6Results are mean ±standard deviation or number of patients (%)ConclusionPlasma calprotectin but not NET remnants were associated with synovial inflammation measured by US in established RA patients receiving biologic or JAKi therapy. The two markers may play a different pathogenetic role in RA.References[1]Frade- Sosa.Ther Adv Musculoskelet Dis 2022.[2]Song Frontiers in Immunology 2021.[3]Ramirez Arthritis Res Ther 2014Acknowledgements:NIL.Disclosure of InterestsNone Declared.
BackgroundJoint involvement in SLE is the most frequent manifestation and shows a wide heterogeneity1. It has not a valid classification and it is often underestimated. Subclinical inflammatory musculoskeletal involvement is not well known2.ObjectivesWe aim to describe the prevalence of joint and tendon involvement in hand and wrist of SLE patients, either with clinical arthritis, arthralgia or asymptomatic and compare it with healthy subjects using contrasted MRI.MethodsSLE patients fulfilling SLICC criteria were recruited and classified as follows: group (G) 1: hand/wrist arthritis, G2: hand/wrist arthralgia, G3: no hand/wrist symptoms. Jaccoud arthropathy, CCPa and RF positivity, hand OA or surgery were excluded. Healthy subjects (HS) were recruited as controls: G4. Contrasted MRI of non-dominant hand/wrist was performed. Images were evaluated following RAMRIS criteria extended to PIP, Tenosynovitis score for RA and peritendonitis from PsAMRIS. Groups were statistically compared.Results107 subjects were recruited (G1: 31, G2:31, G3:21, G4:24). Any lesion: SLE patients 74.7%, HS 41.67%; p 0.002. Synovitis: G1: 64.52%, G2: 51.61%, G3: 45%, G4: 20.83%; p 0.013. Erosions: G1: 29.03%; G2: 54.84%, G3: 47.62%; G4: 25%; p 0.066. Bone marrow edema: G1: 29.03%, G2: 22.58%, G3: 19.05%, G4: 0.0%; p 0.046. Tenosynovitis: G1: 38.71%; G2: 25.81%, G3: 14.29%, G4: 0.0%; p 0.005. Peritendonitis: G1: 12.90%; G2: 3.23%, G3: 0.0%, G: 0.0%; p 0.07.ConclusionSLE patients have a high prevalence of inflammatory musculoskeletal alterations by contrasted MRI, even if asymptomatic. Not only tenosynovitis but peritendonitis is also present.References[1]Ceccarelli F et al. Joint involvement in systemic lupus erythematosus: From pathogenesis to clinical assessment. Semin Arthritis Rheum. 2017;47:53-64[2]Di Matteo A et al. Imaging of Joint and Soft Tissue Involvement in Systemic Lupus Erythematosus. Curr Rheumatol Rep. 2021;23:73AcknowledgementsThis work has been granted by GSK and Societat Catalana de Reumatologia and we want to acknowledge them for their collaborationDisclosure of InterestsPATRICIA CORZO GARCIA Grant/research support from: GSK, Ivan Garcia-Duitama: None declared, Anna Agustí Claramunt: None declared, Irene Carrión Barberà: None declared, Salvatore Marsico: None declared, Jordi Monfort Grant/research support from: GSK, Tarek Carlos Salman Monte Grant/research support from: GSK
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.