Thermography Detects Subclinical Inflammation in Chronic Tophaceous Gout

Background:Gout is the most prevalent inflammatory arthritis. Gout is chronic inflammatory deposition disease related to an increase of cardiovascular (CV) events and mortality. Subclinical chronic inflammation has been demonstrated in this patients but not its relation with the monosodium urate (MSU) crystal deposit size and the number of CV risk factors.Objectives:To study the subclinical inflammation in intercritical gout patients and its possible relation to the estimated size of the crystal deposition and the number of CV risk factors.Methods:To analyze subclinical inflammation we performed a secretome analysis and a cytokine and adiponektine plasma levels quantification (IL-1β, IL-18, IL-6, sIL-6R, TNFα, CXCL-5, RANTES, leptin, resistin and adiponectin) in a cohort of gout patients. As nowadays it is not feasible to determinate the whole body deposit of MSU crystals we created three different MSU crystal deposit size patient groups using an indirect clinical and analytical classification to estimate it. Then we compared cytokine levels between healthy donors and gout patients. We also compared cytokine levels between the different crystal size deposition groups and studied its association to the number of CV risk factors.Results:Ninety consecutive patients attending a Crystal Arthritis Unit were studied. Mean age was 68.27 (28-101) years. 81.1% were male. Clinical gout evolution was of 10.1±9.8 years. 77.5% were on urate lowering treatment. 24% had tophaceous gout. Mean uric acid was 6.3±2.1 mg/dl with 47.1% of them being on target. Hypertension was present in 68.9%, diabetes mellitus in 18.9%, dislipemia in 48.9%, BMI>30 in 32.9%, abdominal obesity in 50% and 16.1% suffered from ischemic heart disease. From the 102 molecules studied in the secretome analysis in 56 there was at least a 20% difference between donors group and any of the deposition groups. In 74% of them gout patients secreted lower levels. IL-18, sIL-6R, RANTES, leptin and adiponectin were higher in patients than in healthy donors. IL-18, sIL6-R, RANTES and CXCL5 levels were associated to the size of the crystal deposits. IL-18, sIL-6R, RANTES and leptin were higher in gout groups with CV risk factors. IL-18, sIL6-R, RANTES and leptin were higher in gout patients with no risk factors when compared to healthy donors with no risk factors. We found no differences when comparing urate lowering treated and non-treated patients.Conclusion:Our results demonstrate that some proinflammatory cytokines and metabolic proteins are raised in intercritical gout patients. Some of them are different from the flare/inflammasome expected ones. In some cytokines this elevation is related to the size of the monosodium urate crystal deposit and/or to the number of cardiovascular risk factors. This cytokine changes could help to explain the increase of the cardiovascular events in gout patients.Disclosure of Interests:Cesar Diaz-Torne Grant/research support from: Received a grant from Grünenthal, Maria Angels Ortiz: None declared, Sicylle Jeria Navarro: None declared, Andrea Garcia-Gullien: None declared, Lluis Sainz: None declared, Hector Corominas: None declared, Silvia Vidal: None declared

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OP0326 ACPA-INDUCED PAIN-BEHAVIOR, BONE LOSS AND TENDON INFLAMMATION IN MICE: A NOVEL MODEL FOR THE PRE-DISEASE PHASES OF ACPA-POSITIVE RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5583 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 200.2-200

Author(s):

A. Krishnamurthy ◽

Y. Kisten ◽

A. Circiumaru ◽

K. Sakurabas ◽

P. Jarvolli ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Bone Loss ◽

Joint Inflammation ◽

Tendon Sheath ◽

Joint Involvement ◽

Subclinical Inflammation ◽

Core Motif ◽

Dixon Method ◽

Hind Limbs ◽

Predicting Factor

Background:In rheumatoid arthritis (RA), anti-citrullinated protein antibodies (ACPAs) are associated with bone loss and pain. Recently, tenosynovitis has been suggested as a predicting factor for arthritis progression in individuals at-risk for RA.Objectives:We aimed to investigate if transfer of human ACPAs into mice could induce tenosynovitis and/or subclinical inflammation.Methods:Monoclonal ACPA (1325:04C03 and 1325:01B09) and control (1362:01E02) antibodies (mAbs) were generated from synovial plasma or memory B cells of RA patients. 2mg of combination of monoclonal ACPAs or control antibody were injected in BALB/c female mice (age 12-16 weeks) (n= 9). Pain-like behavior was monitored by measuring mechanical hypersensitivity using von Frey filaments every 3 days and estimation by up-down Dixon method. Bone morphometrics was analyzed by micro-CT. Using specially designed mobilization casts, dedicated mouse MRI coils, and gadolinium enhanced contrast medium, the hind limbs of these mice were scanned in a 9.4 T scanner and resulting T1-weighted images were evaluated for signs of soft tissue joint inflammation. The MRI images were scored for the presence of joint involvement and tendon inflammatory changes by 3 readers in a blinded manner.Figure 1.NAPA performed on healthy donor mo-DCs incubated with native, PAD2-citrullinated, and PAD4-citrullinated fibrinogen. Alpha, beta, and gamma chains of fibrinogen are shown separately. Each colored line represents a unique peptide. Nested peptides with a common core motif are shown in the same color. Grey bar denotes peptides with identical core motif between samples.Results:ACPAs (1325:04C03 and 1325:01B09) induced pain-like behavior (lasting for at least 4 weeks) and reduction of the trabecular and cortical bone thickness in the hind limbs as compared to control monoclonal antibodies (p<0.05). While no macroscopic or MRI signs of synovial inflammation were detected, MRI subclinical inflammation of the tendon sheaths was present in mice injected with ACPAs, but not in those injected with control mAb. Semi-quantitative scoring of the inflammatory tendon changes showed significant higher values in mice injected with ACPA (median of 1, range 0 to 2) than those injected with control mAb (median of 0, range 0 to 1).Conclusion:We show that ACPA induces pain-like behavior, bone loss and tendon sheath inflammation in mice, a model that mimics the preclinical state of ACPA positive RA.References:[1]Harre, U. et al. J Clin Invest (2012)[2]Krishnamurthy, A. et al. Ann Rheum Dis (2016, 2019), JI 2019[3]Wigerblad, G. et al. Ann Rheum Dis (2016, 2019)[4]KleyerA, Seminars in Arthritis and Rheumatism (2016)Disclosure of Interests:Akilan Krishnamurthy: None declared, Yogan Kisten: None declared, Alexandra Circiumaru: None declared, Koji Sakurabas: None declared, Patrik Jarvolli: None declared, Juan Jimenez Jimenez Andrade: None declared, Peter Damberg: None declared, Heidi Wähämaa: None declared, Vivianne Malmström Grant/research support from: VM has had research grants from Janssen Pharmaceutica, Lars Klareskog: None declared, Camilla Svensson: None declared, Bence Réthi: None declared, Anca Catrina: None declared

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POS1120 PRESENCE OF TOPHI IS ASSOCIATED WITH A RAPID DECLINE IN THE RENAL FUNCTION IN PATIENTS WITH GOUT

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.50 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 839.1-839

Author(s):

Y. J. Oh ◽

K. W. Moon

Keyword(s):

Renal Function ◽

Renal Dysfunction ◽

Clinical Characteristics ◽

Multivariate Logistic Regression Analysis ◽

Joint Involvement ◽

Rapid Decline ◽

Symptom Duration ◽

Tophaceous Gout ◽

Duration Of Symptoms ◽

Increased Risk

Background:Gout is the most common inflammatory arthritis resulting from a chronic deposition of MSU crystals in the joints and other soft tissues. After the process of repeated tissue damage and repair due to gout, tophi could be formed around the affected joints. Intra-articular tophi may sometimes result in bone destruction, joint deformities, and dysfunction which can adversely affect the patient’s quality of life. Furthermore, early-onset tophaceous gout patients are more likely to develop renal dysfunction, however, few studies have investigated if the presence of tophi is related with the progression of renal dysfunction in gout patients.Objectives:We aimed to compare clinical characteristics of patients with and without tophi at the time of the diagnosis of gout and investigate the effect of tophi on the renal function in gout patients.Methods:Data of 257 patients who were first diagnosed with gout at the Kangwon National University Hospital from January 2012 to December 2018 were retrospectively studied. Patients were divided into 2 groups according to the presence of tophi at the diagnosis. We compared clinical characteristics and the progression of renal dysfunction between the two groups.Results:Of all patients, 66 (25.5%) initially presented with tophi. Patients with tophi were older, had a longer duration of symptoms, and had a higher prevalence of multiple joint involvement than those without tophi. The decline in the eGFR was more prominent in patients with tophi than in those without (-4.8±14.5 ml/min/1.73m2vs. -0.7±11.9 ml/min/1.73m2, respectively; P=0.039). In multivariate logistic regression analysis, a prolonged symptom duration (odds ratio [OR], 1.010; 95% confidence interval [CI], 1.004–1.017; P=0.001) and multiple joint involvement (OR, 3.027; 95% CI, 1.831–5.004; P<0.001) were significantly associated with increased risk of formation of tophi. The presence of tophi was significantly associated with a rapid decline in the eGFR (β=-0.141; P=0.035).Conclusion:A prolonged symptom duration and multiple joint involvement were independent risk factors for tophi as the presenting symptom in gout patients. The presence of tophi was associated with a declining renal function. Therefore, an early diagnosis and active treatment are important in tophaceous gout.References:[1]Bardin T, Richette P. Definition of hyperuricemia and gouty conditions. Curr Opin Rheumatol 2014;26:186-91.[2]Liu F, Du GL, Song N, Ma YT, Li XM, Gao XM, et al. Hyperuricemia and its association with adiposity and dyslipidemia in Northwest China: results from cardiovascular risk survey in Xinjiang (CRS 2008-2012). Lipids Health Dis 2020;19:58.[3]Dalbeth N, Merriman TR, Stamp LK. Gout. Lancet 2016;388:2039-52.[4]Ruoff G, Edwards NL. Overview of Serum Uric Acid Treatment Targets in Gout: Why Less Than 6 mg/dL? Postgrad Med 2016;128:706-15.[5]Bieber A, Schlesinger N, Fawaz A, Mader R. Chronic tophaceous gout as the first manifestation of gout in two cases and a review of the literature. Semin Arthritis Rheum 2018;47:843-8.Disclosure of Interests:None declared.

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Impact of HLA Mismatching on Early Subclinical Inflammation in Low-Immunological-Risk Kidney Transplant Recipients

Journal of Clinical Medicine ◽

10.3390/jcm10091934 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1934

Author(s):

Domingo Hernández ◽

Teresa Vázquez ◽

Juana Alonso-Titos ◽

Myriam León ◽

Abelardo Caballero ◽

...

Keyword(s):

Risk Factor ◽

Kidney Transplant ◽

Graft Function ◽

Human Leukocyte ◽

Subclinical Inflammation ◽

Kidney Transplant Recipients ◽

Protocol Biopsy ◽

Recipient Age ◽

The Impact ◽

Hla Mismatches

The impact of human leukocyte antigen (HLA)-mismatching on the early appearance of subclinical inflammation (SCI) in low-immunological-risk kidney transplant (KT) recipients is undetermined. We aimed to assess whether HLA-mismatching (A-B-C-DR-DQ) is a risk factor for early SCI. As part of a clinical trial (Clinicaltrials.gov, number NCT02284464), a total of 105 low-immunological-risk KT patients underwent a protocol biopsy on the third month post-KT. As a result, 54 presented SCI, showing a greater number of total HLA-mismatches (p = 0.008) and worse allograft function compared with the no inflammation group (48.5 ± 13.6 vs. 60 ± 23.4 mL/min; p = 0.003). Multiple logistic regression showed that the only risk factor associated with SCI was the total HLA-mismatch score (OR 1.32, 95%CI 1.06–1.64, p = 0.013) or class II HLA mismatching (OR 1.51; 95%CI 1.04–2.19, p = 0.032) after adjusting for confounder variables (recipient age, delayed graft function, transfusion prior KT, and tacrolimus levels). The ROC curve illustrated that the HLA mismatching of six antigens was the optimal value in terms of sensitivity and specificity for predicting the SCI. Finally, a significantly higher proportion of SCI was seen in patients with >6 vs. ≤6 HLA-mismatches (62.3 vs. 37.7%; p = 0.008). HLA compatibility is an independent risk factor associated with early SCI. Thus, transplant physicians should perhaps be more aware of HLA mismatching to reduce these early harmful lesions.

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Tophaceous gout as a squamous cell carcinoma mimicker

JAAD Case Reports ◽

10.1016/j.jdcr.2021.01.021 ◽

2021 ◽

Vol 10 ◽

pp. 11-13

Author(s):

Kelly A. Mueller ◽

Molly R. Marous ◽

Kathleen A. Mannava ◽

Franki Lambert Smith

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Tophaceous Gout

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Polyarticular, ulcerated tophaceous gout

Journal of Osteopathic Medicine ◽

10.1515/jom-2020-0316 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Cara M. Borelli ◽

Brendan T. Doherty

Keyword(s):

Tophaceous Gout

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EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-220884 ◽

2021 ◽

pp. annrheumdis-2021-220884

Author(s):

Kulveer Mankia ◽

Heidi J Siddle ◽

Andreas Kerschbaumer ◽

Deshire Alpizar Rodriguez ◽

Anca Irinel Catrina ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factors ◽

At Risk ◽

Clinical Trials ◽

Observational Studies ◽

Task Force ◽

Musculoskeletal Symptoms ◽

Subclinical Inflammation ◽

Consensus Statements ◽

Clinical Arthritis

BackgroundDespite growing interest, there is no guidance or consensus on how to conduct clinical trials and observational studies in populations at risk of rheumatoid arthritis (RA).MethodsAn European League Against Rheumatism (EULAR) task force formulated four research questions to be addressed by systematic literature review (SLR). The SLR results informed consensus statements. One overarching principle, 10 points to consider (PTC) and a research agenda were proposed. Task force members rated their level of agreement (1–10) for each PTC.ResultsEpidemiological and demographic characteristics should be measured in all clinical trials and studies in at-risk individuals. Different at-risk populations, identified according to clinical presentation, were defined: asymptomatic, musculoskeletal symptoms without arthritis and early clinical arthritis. Study end-points should include the development of subclinical inflammation on imaging, clinical arthritis, RA and subsequent achievement of arthritis remission. Risk factors should be assessed at baseline and re-evaluated where appropriate; they include genetic markers and autoantibody profiling and additionally clinical symptoms and subclinical inflammation on imaging in those with symptoms and/or clinical arthritis. Trials should address the effect of the intervention on risk factors, as well as progression to clinical arthritis or RA. In patients with early clinical arthritis, pharmacological intervention has the potential to prevent RA development. Participants’ knowledge of their RA risk may inform their decision to participate; information should be provided using an individually tailored approach.ConclusionThese consensus statements provide data-driven guidance for rheumatologists, health professionals and investigators conducting clinical trials and observational studies in individuals at risk of RA.

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