Discovery of calcite as a new pro-inflammatory calcium-containing crystal in human osteoarthritic synovial fluid.

OBJECTIVE: We aimed to characterize calcium-containing crystals present in synovial fluid from patients with knee osteoarthritis (OA) using Raman spectroscopy, and specifically investigate the biological effects of calcite crystals. DESIGN: Thirty-two synovial fluid samples were collected pre-operatively from knee OA patients undergoing total joint arthroplasty. An integrated Raman polarized light microscope was used for identification of crystals in synovial fluid. Human peripheral blood mononuclear cells (PBMC's), human OA articular chondrocytes (HACs) and fibroblast-like synoviocytes (FLSs) were exposed to calcite crystals. Expression of relevant cytokines and inflammatory genes were measured using ELISA and real-time PCR. RESULTS: Various calcium-containing crystals were identified, including calcium pyrophosphate (37.5 %) and basic calcium phosphate (21.8 %), but they were never found simultaneously in the same OA synovial fluid sample. For the first time, we discovered the presence of calcite crystals in 93.8 % of the samples, while dolomite was detected in 25 % of the cases. Characterization of the cellular response to calcite crystal exposure revealed increased production of innate immune-derived cytokines by PBMC's, when co-stimulated with lipopolysaccharide (LPS). Additionally, calcite crystal stimulation of HACs and FLSs resulted in enhanced secretion of pro-inflammatory molecules and alterations in the expression of extracellular matrix remodeling enzymes. CONCLUSIONS: This study highlights the unique role of Raman spectroscopy in OA crystal research and identified calcite as a novel pro-inflammatory crystal type in OA synovial fluid. Understanding the role of specific crystal species in the OA joint may open new avenues for pharmacological interventions and personalized approaches to treating OA.

Diagnostic Accuracy of Raman Spectroscopy Integrated With Polarized Light Microscopy for Calcium Pyrophosphate-Associated Arthritis.

OBJECTIVE: We studied the performance of integrated Raman polarized light microscopy (iRPolM) for the identification of calcium pyrophosphate (CPP)-associated arthritis (CPPD). METHODS: This is a diagnostic accuracy study including 400 consecutive synovial fluid samples from a single hospital in the Netherlands. Accuracy measures were calculated against polarized light microscopy (PLM) and the 2023 American College of Rheumatology (ACR)/EULAR criteria set for CPPD. RESULTS: The interrater reliability between iRPolM and the 2023 ACR/EULAR criteria set for CPPD was strong (κ = 0.88). The diagnostic performance of iRPolM compared to the 2023 ACR/EULAR criteria set was sensitivity 86.0% (95% confidence interval [CI] 73.3-94.2), specificity 99.1% (95% CI 97.5-99.8), positive likelihood ratio 100.33 (95% CI 32.3-311.3), negative likelihood ratio 0.14 (95% CI 0.07-0.28), positive predictive value 93.5% (95% CI 82.2-97.8), negative predictive value 98.0% (95% CI 82.2-97.8), and accuracy 97.5% (95% CI 95.5-98.8). We allowed rheumatologists to rate the certainty of their microscopic identification of CPP and found a large correspondence between iRPolM and a certain identification (κ = 0.87), whereas only 10% of the uncertain CPP identifications could be confirmed with iRPolM. We identified several novel particle types in synovial fluid analysis, including calcium carbonate crystals, deposited carotenoids, microplastics, and three types of Maltese cross birefringent objects. CONCLUSION: iRPolM can easily identify CPP crystals with a strong diagnostic performance. PLM alone is not specific enough to reliably resolve complicated cases, and the implementation of Raman spectroscopy in rheumatology practice can be of benefit to patients with suspected CPPD.

Test characteristics of Raman spectroscopy integrated with polarized light microscopy for the diagnosis of acute gouty arthritis.

OBJECTIVES: We studied the performance of Raman spectroscopy integrated with polarized light microscopy (iRPolM) as a next-generation technique for synovial fluid analysis in gout. METHODS: This is a prospective study, including consecutive synovial fluid samples drawn from any peripheral swollen joint. Diagnostic accuracy was compared to the 2015 ACR/EULAR Gout classification criteria as a reference test and to polarized light microscopy (PLM) analysis by a rheumatologist. Synovial fluid was analysed with iRPolM after unblinding the PLM results. RESULTS: Two hundred unselected consecutive patient samples were included in this study. Validation against clinical criteria: 67 patients were classified as gout according to 2015 ACR/EULAR classification criteria. Compared to the 2015 ACR/EULAR gout classification criteria, iRPolM had a sensitivity of 77.6% (95% CI: 65.8-86.9), specificity of 97.7% (95% CI: 93.5-99.5), positive predictive value (PPV) of 94.5% (95% CI: 84.9-98.2), negative predictive value (NPV) of 89.7% (95% CI: 84.7-93.1), an accuracy of 91.0% (95% CI: 86.2-94.6), a positive likelihood ratio of 34.4 (95% CI: 11.16-106.10) and a negative likelihood ratio of 0.23 (95% CI: 0.15-0.36). Validation against PLM: 55 samples were positive for MSU according to PLM. The interrater agreement between PLM and iRPolM was near perfect (к=0.90). The sensitivity of iRPolM to identify MSU in PLM-positive samples was 91.2% (95% CI: 80.7-97.1), the specificity was 97.6% (95% CI: 93.0-99.5), the PPV was 94.6% (95% CI: 85.0-98.2), NPV was 96.0% (95% CI: 91.2-98.2) and the accuracy was 95.6% (95% CI: 91.4-98.2). The positive likelihood ratio was 37.4 (95% CI: 12.20-114.71), and the negative likelihood ratio was 0.09 (95% CI: 0.04-0.21). CONCLUSION: iRPolM is a promising next-generation diagnostic tool for rheumatology by diagnosing gout with high specificity, increased objectivity, and a sensitivity comparable to PLM.

The 2023 ACR/EULAR Classification Criteria for Calcium Pyrophosphate Deposition Disease.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease. METHODS: Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. RESULTS: Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score >56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). CONCLUSION: The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.

The 2023 ACR/EULAR classification criteria for calcium pyrophosphate deposition disease.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease. METHODS: Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. RESULTS: Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score>56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). CONCLUSION: The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.

Association of Gout Polygenic Risk Score With Age at Disease Onset and Tophaceous Disease in European and Polynesian Men With Gout.

OBJECTIVE: To determine whether a gout polygenic risk score (PRS) is associated with age at gout onset and tophaceous disease in European, East Polynesian, and West Polynesian men and women with gout. METHODS: A 19-variant gout PRS was produced in 7 European gout cohorts (N = 4,016), 2 East Polynesian gout cohorts (N = 682), and 1 West Polynesian gout cohort (N = 490). Sex-stratified regression models were used to estimate the relationship between the PRS and age at gout onset and tophaceous disease. RESULTS: The PRS was associated with earlier age at gout onset in men (ß = -3.61 in years per unit PRS [95% confidence interval (95% CI) -4.32, -2.90] in European men; ß = -6.35 [95% CI -8.91, -3.80] in East Polynesian men; ß = -3.51 [95% CI -5.46, -1.57] in West Polynesian men) but not in women (ß = 0.07 [95% CI -2.32, 2.45] in European women; ß = 0.20 [95% CI -7.21, 7.62] in East Polynesian women; ß -3.33 [95% CI -9.28, 2.62] in West Polynesian women). The PRS showed a positive association with tophaceous disease in men (odds ratio [OR] for the association 1.15 [95% CI 1.00, 1.31] in European men; OR 2.60 [95% CI 1.66, 4.06] in East Polynesian men; OR 1.53 [95% CI 1.07, 2.19] in West Polynesian men) but not in women (OR for the association 0.68 [95% CI 0.42, 1.10] in European women; OR 1.45 [95% CI 0.39, 5.36] in East Polynesian women). The PRS association with age at gout onset was robust to the removal of ABCG2 variants from the PRS in European and East Polynesian men (ß = -2.42 [95% CI -3.37, -1.46] and ß = -6.80 [95% CI -10.06, -3.55], respectively) but not in West Polynesian men (ß = -1.79 [95% CI -4.74, 1.16]). CONCLUSION: Genetic risk variants for gout also harbor risk for earlier age at gout onset and tophaceous disease in European and Polynesian men. Our findings suggest that earlier gout onset involves the accumulation of gout risk alleles in men but perhaps not in women, and that this genetic risk is shared across multiple ancestral groups.

Development and usability of a web-based patient-tailored tool to support adherence to urate-lowering therapy in gout.

BACKGROUND: The aim of this study is to develop and assess usability of a web-based patient-tailored tool to support adherence to urate-lowering therapy (ULT) among gout patients in a clinical setting. METHODS: The content of the tool was based on the Integrated Change (I-Change) model. This model combines various socio-cognitive theories and assumes behavioral change is a result of becoming aware of the necessity of change by integrating pre-motivational, motivational, and post-motivational factors. An expert group (five gout experts, three health services researchers, and one health behavior expert) was assembled that decided in three meetings on the tool's specific content (assessments and personalized feedback) using information from preparatory qualitative studies and literature reviews. Usability was tested by a think aloud approach and validated usability questionnaires. RESULTS: The I-Change Gout tool contains three consecutive sessions comprising 80 questions, 66 tailored textual feedback messages, and 40 tailored animated videos. Navigation through the sessions was determined by the patients' intention to adapt suboptimal ULT adherence. After the sessions, patients receive an overview of the personalized advices and plans to support ULT adherence. Usability testing among 20 gout patients that (ever) used ULT and seven healthcare professionals revealed an overall score for the tool of 8.4 ± 0.9 and 7.7 ± 1.0 (scale 1-10). Furthermore, participants reported a high intention to use and/or recommend the tool to others. Participants identified some issues for further improvement (e.g. redundant questions, technical issues, and text readability). If relevant, these were subsequently implemented in the I-Change Gout tool, to allow further testing among the following participants. CONCLUSION: This study provides initial support for the usability by patients and healthcare professionals of the I-Change Gout tool to support ULT adherence behavior.

[Gout: an overview of diagnostics and treatment]. / Jicht.

Gout is characterized by acute arthritis due to the deposition of urate crystals in joints in a state of hyperuricemia. Gout is a clinical diagnosis and can be confirmed with a joint aspiration to examine the synovial fluid with a polarized light microscopy. If a joint aspiration is not feasible or inconclusive, ultrasound or Dual Energy Computed Tomography (DECT) can be considered. Pharmacological treatment of gout consists of treating acute flares with anti-inflammatory drugs and, if indicated, of urate lowering therapies (ULT). (Inter)national rheumatology guidelines recommend the use of ULT indefinite by a treat-to-target approach, but there is discussion whether (certain) patients might also be treated by a treat-to-avoid-symptoms approach. Two large Dutch trials are comparing these strategies in gout patients. Most gout patients have cardiovascular and metabolic comorbidities and therefore an indication for cardiovascular risk assessment.

Erosive Hand OsteoArthritis (EHOA): analysis of consecutive patients presenting with EHOA in a hospital-based rheumatology practice and its implications for an upcoming interventional study.

INTRODUCTION: Erosive Hand OsteoArthritis (EHOA) is a common rheumatological problem. We aim to determine characteristics of EHOA patients: comorbidities, radiographic erosivity and pain experienced after being diagnosed, in order to find which of these are potentially relevant in upcoming interventional trials. METHOD: Retrospective analysis of EHOA patients within the electronic database in one centre, with a telephone interview on pain as experienced even exceeding 12 months after being diagnosed. RESULTS: Eighty-four non-academic EHOA patients were found: 89% females (median age 69 years), 11% males (similar age distribution). Kellgren-Lawrence (KL) erosivity scores in both sexes were comparable; DIPs scored higher than PIP's. Comorbid conditions were crystal-induced arthritis, rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in 8%, 5% and 1%, respectively; seropositivity for rheumatoid factor and anti-citrullinated protein antibodies in 8% and 1% respectively. Pain worst experienced often exceeded a visual analogue score of 5.0, but was unrelated to the total KL score. Some pain reduction was reached with non-steroidals (perorally/transcutaneously) as deduced from continued use in 1 in 3. CONCLUSIONS: In many EHOA patients, there is an unmet need regarding the treatment of pain, which per se was not directly correlated with erosivity score. Future studies may be designed considering the aforementioned characteristics, acting on the inflammatory process resulting in PIP/DIP erosions, with the exclusion of RA and PsA in order to get a clean study on EHOA. Several studies with monoclonal antibodies have been performed but demonstrated ineffectivity on the outcome of pain. Hope glooms with the arrival of innovative small molecules that may reach EHOA target cells. Key Points • Erosive handOA is a common problem in non-academic rheumatology; it is often associated with significant pain in both sexes exceeding a VASpain of 5.0 even years after being diagnosed; 1 in 3 found some relief in non-steroidals perorally/transcutaneously. • Future studies will have to focus on (episodic) inflammatory hand OA resulting in proven erosivity (EHOA) located in PIP plus DIP joints and may have to exclude comorbid active crystal-induced arthritis as well as rheumatoid/psoriatic arthritis and possibly even RF/ACPA seropositivity in order to get a clean study on EHOA. • As several big monoclonals have failed in EHOA, we may have to search for promising new drugs within the group of small molecules. These will have to show a significant pain-reducing effect and preferably also a disease-modifying osteoarthritis drug (DMOAD) effect.

Identifying Potential Classification Criteria for Calcium Pyrophosphate Deposition Disease: Item Generation and Item Reduction.

OBJECTIVE: Classification criteria for calcium pyrophosphate deposition (CPPD) disease will facilitate clinical research on this common crystalline arthritis. Our objective was to report on the first 2 phases of a 4-phase process for developing CPPD classification criteria. METHODS: CPPD classification criteria development is overseen by a 12-member steering committee. Item generation (phase I) included a scoping literature review of 5 literature databases and contributions from a 35-member combined expert committee and 2 patient research partners. Item reduction and refinement (phase II) involved a combined expert committee meeting, discussions among clinical, imaging, and laboratory advisory groups, and an item-rating exercise to assess the influence of individual items toward classification. The steering committee reviewed the modal rating score for each item (range -3 [strongly pushes away from CPPD] to +3 [strongly pushes toward CPPD]) to determine items to retain for future phases of criteria development. RESULTS: Item generation yielded 420 items (312 from the literature, 108 from experts/patients). The advisory groups eliminated items that they agreed were unlikely to distinguish between CPPD and other forms of arthritis, yielding 127 items for the item-rating exercise. Fifty-six items, most of which had a modal rating of +/- 2 or 3, were retained for future phases. As numerous imaging items were rated +3, the steering committee recommended focusing on imaging of the knee and wrist and 1 additional affected joint for calcification suggestive of CPP crystal deposition. CONCLUSION: A data- and expert-driven process is underway to develop CPPD classification criteria. Candidate items comprise clinical, imaging, and laboratory features.

Outcomes of Care Among Patients With Gout in Europe: A Cross-sectional Survey.

OBJECTIVE: To assess health- and patient-centered outcomes in gout across Europe, and explore patient-, care-, and country-level characteristics associated with these outcomes. METHODS: Patients with self-reported physician-diagnosed gout from 14 European countries completed an online survey. Multivariable mixed-effect logistic and linear regressions were computed for health outcomes (gout flare recurrence) and patient-centered outcomes (patient satisfaction with current medication, and unaddressed goals), accounting for clustering within countries. The role of patient-, care-, and country-level factors was explored. RESULTS: Participants included 1029 patients, predominantly diagnosed by a general practitioner (GP). One or more gout flares were reported by 70% of patients and ≥ 3 flares by 32%. Gout patients reported 1.1 ± 1.2 unaddressed goals, and 80% were satisfied with current medication. Patients with ≥ 3 and ≥ 1 flares were less likely to be treated with urate-lowering therapy (ULT) (OR 0.52, 95% CI 0.39-0.70 and OR 0.38, 95% CI 0.28-0.53, respectively), but more likely to have regular physician visits (OR 2.40, 95% CI 1.79-3.22 and OR 1.77, 95% CI 1.30-2.41). Three or more gout flares were also associated with lower satisfaction (OR 0.39, 95% CI 0.28-0.56) and more unaddressed goals (ß 0.36, 95% CI 0.19-0.53). Notwithstanding, the predicted probability of being satisfied was still between 57% and 75% among patients with ≥ 3 flares but who were not receiving ULT. Finally, patients from wealthier and Northern European countries more frequently had ≥ 3 gout flares. CONCLUSION: Across Europe, many patients with gout remain untreated despite frequent reported flares. Remarkably, a substantial proportion of them were still satisfied with gout management. A better understanding of patients' satisfaction and its role in physicians' gout management decisions is warranted to improve quality of care and gout outcomes across Europe.

Emerging and New Treatment Options for Knee Osteoarthritis.

Osteoarthritis (OA) is the most prevalent type of arthritis worldwide, resulting in pain and often chronic disability and a significant burden on healthcare systems globally. Non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, intra-articular corticosteroid injections are of little value in the long term, and opioids may have ominous consequences. Radiotherapy of knee OA has no added value. Physical therapy, exercises, weight loss, and lifestyle modifications may give pain relief, improve physical functioning and quality of life. However, none of them has articular cartilage regenerating potential. Due to a better understanding of osteoarthritis, innovative new treatment options have been developed. In this narrative review, we focus on emerging OA knee treatments, relieving symptoms, and regenerating damaged articular cartilage that includes intra-articular human serum albumin, conventional disease-modifying anti-rheumatic drugs (DMARDs), metformin, lipid-lowering agents (statin), nerve growth factors antagonists, bone morphogenetic protein, fibroblast growth factors, Platelet-Rich Plasma (PRP), Mesenchymal Stem Cells (MSC), exosomes, interleukin-1 blockers, gene-based therapy, and bisphosphonate.

Sex Differences in the Clinical Profile Among Patients With Gout: Cross-sectional Analyses of an Observational Study.

OBJECTIVE: Research findings in gout result predominantly from studies about men and might not be generalizable to women. To improve insight into sex differences in gout, our study compared clinical characteristics and comorbidities of female and male patients with gout, and explored the influence of menopause on these differences. METHODS: Data from patients referred to 2 rheumatology clinics and diagnosed with gout were used. Clinical characteristics and comorbidities of each sex were compared univariately. Sex difference in comorbidities were further explored in multivariate logistic regression analyses adjusting for age, BMI, smoking, and alcohol consumption in both the total group and in those with gout onset ≥ 55 years (as a surrogate for menopausal state). RESULTS: There were 954 patients, including 793 (83%) men, included. Women were on average older (65 vs 62 yrs), were more often obese (54% vs 36%), had a higher serum uric acid (sUA) level (0.53 vs 0.49 mmol/L), used diuretics more often (60% vs 30%), and consumed alcohol less frequently (47% vs 72%). Additionally, women more frequently had reduced renal function (64% vs 31%), hypertension (78% vs 56%), heart failure (23% vs 12%), and type 2 diabetes (39% vs 17%; all P < 0.05). In those with gout onset ≥ 55 years, differences in comorbidities were less pronounced and disappeared after adjusting for lifestyle. CONCLUSION: Our study confirmed sex differences in clinical characteristics and comorbidities among newly diagnosed patients with gout, and revealed that sex differences in comorbidities among those with gout onset beyond the age of female menopause were strongly attenuated and fully explained by lifestyle.

Dapansutrile, an oral selective NLRP3 inflammasome inhibitor, for treatment of gout flares: an open-label, dose-adaptive, proof-of-concept, phase 2a trial.

BACKGROUND: Gout flares are driven by interleukin (IL)-1ß. Dapansutrile inhibits the NLRP3 inflammasome and subsequent activation of IL-1ß. In this study we aimed to investigate the safety and efficacy of orally administered dapansutrile in patients with a gout flare. METHODS: In this open-label, proof-of-concept, phase 2a trial, adult patients (aged 18-80 years) with a monoarticular monosodium urate crystal-proven gout flare were enrolled at an outpatient clinic in the Netherlands and sequentially assigned using a dose-adaptive design to receive 100 mg/day, 300 mg/day, 1000 mg/day, or 2000 mg/day oral dapansutrile for 8 days. The coprimary outcomes were change in patient-reported target joint pain from baseline to day 3 and from baseline to day 7, assessed in the per-protocol population (all patients who received at least 80% of the study drug and had no major protocol deviations). Safety was assessed in the intention-to-treat population. This trial is registered with the EU Clinical Trials Register, EudraCT 2016-000943-14, and is completed. FINDINGS: Between May 18, 2017, and Jan 21, 2019, 144 patients were assessed for eligibility, of whom 34 were enrolled and 29 were included in the per-protocol population (three patients were excluded due to receiving <80% of study drug and two had major protocol deviations): eight patients received 100 mg/day, seven received 300 mg/day, six received 1000 mg/day, and eight received 2000 mg/day. Between baseline and day 3, there was a mean reduction in patient-reported target joint pain of 52·4% (SD 32·94; p=0∙016) for the 100 mg/day group, 68·4% (34·29; p=0∙016) for the 300 mg/day group, 55·8% (44·90; p=0∙063) for the 1000 mg/day group, and 57·6% (38·72; p=0∙016) for the 2000 mg/day group. At day 7, there was a mean reduction of 82·1% (22·68; p=0∙031) for the 100 mg/day group, 84·2% (16·33; p=0∙016) for the 300 mg/day group, 68·9% (34·89; p=0∙031) for the 1000 mg/day group, and 83·9% (15·44; p=0∙008) for the 2000 mg/day group, compared to baseline. 25 (73·5%) of 34 patients reported a total of 45 treatment-emergent adverse events, most of which were metabolism and nutrition disorders (17 [37·8%]) and gastrointestinal disorders (ten [22·2%]). Two serious adverse events occurred during the study, admission to hospital because of worsening of gout flare at day 3, and admission to hospital because of coronary stenosis 18 days after the patient received their last dose; these were considered moderate in severity and unrelated to the study drug. INTERPRETATION: Dapansutrile is a specific NLRP3 inflammasome inhibitor with a satisfactory safety profile and efficacy in the reduction of target joint pain in this study. Future studies are needed to confirm the clinical potential of dapansutrile.

Lessons and pitfalls from the 2020 Gout Clinical Practice Guideline presented in Atlanta at the ACR 2019.

Gout is the most common type of arthritis and is evoked by arousal of the inflammasome in the presence of urate crystals superponed on a dysmetabolism with urate accumulation. Gout can be cured in most patients but still treatment is suboptimal in the majority of patients. Quality guidelines for management from experts such as from American College of Rheumatology aim to give guidance to US physicians and their own rheumatologists but have a value worldwide. We should know about the updates that were recently made publicly, with their strong and conditional recommendations, as we may learn and improve from their updated guideline.