Managing Gout in Patients with Metabolic Syndrome.

Gout is characterized by monosodium urate (MSU) crystal deposition secondary to hyperuricemia. Gout is associated with metabolic syndrome (MetS) and its related comorbid conditions such as cardiovascular disease (CVD). Major advances have been made in the comprehension of the link between MetS and gout. Despite observational studies suggesting an association between MetS-related conditions and hyperuricemia, there is no proof of causality. Most studies using Mendelian randomization did not find hyperuricemia as a causal factor for MetS-related conditions. In contrast, these conditions were found associated with hyperuricemia, which suggests a reverse causality. Among patients with gout, this high CVD risk profile implies the need for systematic screening for MetS-related conditions. Most international guidelines recommend systematic screening for and care of CVD and related risk factors in patients with gout. Some anti-hypertensive agents, such as losartan and calcium channel blockers, are able to decrease serum urate (SU) levels. However, there are potential interactions between gout management therapies and the treatment of metabolic diseases. Some data suggest that anti-inflammatory drugs used for gout flare treatment, such as colchicine or canakinumab, might have benefits for CVD. Regarding the impact of urate-lowering therapies on CVD risk, recent studies found a similar CVD safety profile for allopurinol and febuxostat. Finally, sodium-glucose cotransporter-2 inhibitors are promising for gout because of their ability to decrease SU levels and risk of recurrent flares. In this review, we focus on the clinical challenge of managing MetS in patients with gout, particularly older patients with co-medications.

Polymyalgia rheumatica and giant cell arteritis following COVID-19 vaccination: Results from a nationwide survey.

We conducted a national in-depth analysis including pharmacovigilance reports and clinical study to assess the reporting rate (RR) and to determine the clinical profile of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in COVID-19-vaccinated individuals. First, based on the French pharmacovigilance database, we estimated the RR of PMR and GCA cases in individuals aged over 50 who developed their initial symptoms within one month of receiving the BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines. We then conducted a nationwide survey to gather clinical profiles, therapeutic management, and follow-up data from individuals registered in the pharmacovigilance study. A total of 70 854 684 COVID-19 vaccine doses were administered to 25 260 485 adults, among which, 179 cases of PMR (RR 7. 1 cases/1 000 000 persons) and 54 cases of GCA (RR 2. 1 cases/1 000 000 persons) have been reported. The nationwide survey allowed the characterization of 60 PMR and 35 GCA cases. Median time to the onset of first symptoms was 10 (range 2-30) and 7 (range 2-25) days for PMR and GCA, respectively. Phenotype, GCA-related ischemic complications and -large vessel vasculitis as well as therapeutic management and follow-up seemed similar according to the number of vaccine shots received and when compared to the literature data of unvaccinated population. Although rare, the short time between immunization and the onset of first symptoms of PMR and GCA suggests a temporal association. Physician should be aware of this potential vaccine-related phenomenon.

Limb arteries involvement assessed by FDG/PET CT at diagnosis of giant cell arteritis and risk of relapse: An observational study.

INTRODUCTION: Steroids and anti-IL6 biotherapy are highly effective in obtaining remission in patients with giant cell arteritis (GCA) but the risk of relapses remains high. We aimed to identify predictors of relapse in GCA. METHODS: All consecutive patients admitted with a new diagnosis of GCA - according to the 2022 American College of Rheumatology/EULAR (ACR/EULAR) classification criteria - between May 2011 and May 2022 were eligible for this study. The primary outcome was the GCA relapse rate over the 36-months follow up. Factors associated with the primary outcome and time to first relapse were analyzed. RESULTS: One hundred and eight patients (74 [69-81] years, 64.8% women) with a new diagnosis of GCA were studied. GCA was biopsy-proven in 65 (60.2%) cases. Ninety-eight (90.7%) FDG/PET CT scans performed at diagnosis were available for review. All patients received steroids given for 21.0 [18.0-28.5] months, associated with methotrexate (n=1, 0.9%) or tocilizumab (n=2, 1.9%). During a median follow-up of 27.5 [11.4-35.0] months, relapse occurred in 40 (37%) patients. Multivariable Cox regression model, including general signs, gender, aortic wall thickness, FDG uptake in arterial wall and IV steroid pulse as covariates, showed that both general signs (HR 2.0 [1.0-4.0, P<0.05) and FDG uptake in limb arteries (HR 2.7 [1.3-5.5], P<0.01) at diagnosis were associated with GCA relapse. CONCLUSION: FDG uptake in limb arteries at diagnosis is a predictor of relapse in newly diagnosed GCA.

Recommendations of the French Society of Rheumatology for the management in current practice of patients with polymyalgia rheumatica.

OBJECTIVE: To develop recommendations for the routine management of patients with polymyalgia rheumatica (PMR). METHODS: Following standard procedures, a systematic review of the literature by five supervised junior rheumatologists, based on the questions selected by the steering committee (5 senior rheumatologists), was used as the basis for working meetings, followed by a one-day plenary meeting with the working group (15 members), leading to the development of the wording and determination of the strength of the recommendations and the level of agreement of the experts. RESULTS: Five general principles and 19 recommendations were drawn up. Three recommendations relate to diagnosis and the use of imaging, and five to the assessment of the disease, its activity and comorbidities. Non-pharmacological therapies are the subject of one recommendation. Three recommendations concern initial treatment based on general corticosteroid therapy, five concern the reduction of corticosteroid therapy and follow-up, and two concern corticosteroid dependence and steroid-sparing treatments (anti-IL-6). CONCLUSION: These recommendations take account of current data on PMR, with the aim of reducing exposure to corticosteroid therapy and its side effects in a fragile population. They are intended to be practical, to help practitioners in the day-to-day management of patients with PMR.

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.

Anti-mutated citrullinated vimentin antibodies are increased in IPF patients.

INTRO: An increased prevalence of serum anti-MCV antibody is observed in the serum of patients with idiopathic pulmonary fibrosis (IPF) but the clinical relevance of these antibodies is unknown. METHODS: Patients from our center with a diagnosis of IPF according to the 2018 ATS/ERS/JRS/ALAT guidelines and at least one anti-MCV assay available were selected. All patients were part of the prospective cohort European IPF registry and selected between 03/2010 and 03/2018. We constituted two groups of patients according to the anti-MCV status at baseline to compare their characteristics at baseline and the evolution of lung function, survival and/or transplantation status. RESULTS: Anti-MCV data were available for 101 patients, of whom 86 had complete clinical data available. Twenty-nine (34 %) patients had a positive anti-MCV assay (MCV+), at a low level in most patients (29 UI/mL [IQR 25-40]), and 57 (66 %) patients a negative assay (MCV-). MCV+ patients were 20 men and 9 women, with a median age of 73 years [IQR 67-78]. MCV- patients were 49 men and 8 women with a median age of 72 years [IQR 64-77]. Sixty-two (75 %) patients were ex-smokers and 5 (6 %) were active smokers. Median cumulative tobacco smoke exposure was 22.5 (15.0-38.6) and was similar in both groups. Lung function test results and HRCT pattern distribution was similar in both groups at baseline. The median duration of follow-up was 3.5 years [IQR 2.1-5.0]. Lung function decline was similar in both groups. During the study period, 31 (36 %) patients died or have been transplanted with no difference in transplant-free survival status between the two groups. CONCLUSION: Low level anti-MCV autoimmunity was prevalent in IPF patients.

Diagnosis and treatment of Tropheryma whipplei infection in patients with inflammatory rheumatic disease: Data from the French Tw-IRD registry.

OBJECTIVES: Tropheryma whipplei infection can manifest as inflammatory joint symptoms, which can lead to misdiagnosis of inflammatory rheumatic disease and the use of disease-modifying antirheumatic drugs. We investigated the impact of diagnosis and treatment of Tropheryma whipplei infection in patients with inflammatory rheumatic disease. METHODS: We initiated a registry including patients with disease-modifying antirheumatic drugs-treated inflammatory rheumatic disease who were subsequently diagnosed with Tropheryma whipplei infection. We collected clinical, biological, treatment data of the inflammatory rheumatic disease, of Tropheryma whipplei infection, and impact of antibiotics on the evolution of inflammatory rheumatic disease. RESULTS: Among 73 inflammatory rheumatic disease patients, disease-modifying antirheumatic drugs initiation triggered extra-articular manifestations in 27% and resulted in stabilisation (51%), worsening (34%), or improvement (15%) of inflammatory rheumatic disease. At the diagnosis of Tropheryma whipplei infection, all patients had rheumatological symptoms (mean age 58 years, median inflammatory rheumatic disease duration 79 months), 84% had extra-rheumatological manifestations, 93% had elevated C-reactive protein, and 86% had hypoalbuminemia. Treatment of Tropheryma whipplei infection consisted mainly of doxycycline plus hydroxychloroquine, leading to remission of Tropheryma whipplei infection in 79% of cases. Antibiotic treatment of Tropheryma whipplei infection was associated with remission of inflammatory rheumatic disease in 93% of cases and enabled disease-modifying antirheumatic drugs and glucocorticoid discontinuation in most cases. CONCLUSIONS: Tropheryma whipplei infection should be considered in inflammatory rheumatic disease patients with extra-articular manifestations, elevated C-reactive protein, and/or hypoalbuminemia before disease-modifying antirheumatic drugs initiation or in inflammatory rheumatic disease patients with an inadequate response to one or more disease-modifying antirheumatic drugs. Positive results of screening and diagnostic tests for Tropheryma whipplei infection involve antibiotic treatment, which is associated with complete recovery of Tropheryma whipplei infection and rapid remission of inflammatory rheumatic disease, allowing disease-modifying antirheumatic drugs and glucocorticoid discontinuation.

Evaluating the safety and short-term equivalence of colchicine versus prednisone in older patients with acute calcium pyrophosphate crystal arthritis (COLCHICORT): an open-label, multicentre, randomised trial.

BACKGROUND: Acute calcium pyrophosphate crystal arthritis causes intense joint pain mainly affecting older people. Because guidance and evidence remain scarce, management of this disease relies on expert opinion. We therefore aimed to compare the safety and short-term equivalence of low-dose colchicine with oral prednisone in older patients with acute calcium pyrophosphate crystal arthritis. METHODS: We did an open-label, multicentre, randomised, trial (COLCHICORT) at six hospitals in Paris and northern France. We enrolled patients who were admitted to hospital who were 65 years or older and who presented with acute calcium pyrophosphate crystal arthritis with a symptom duration of less than 36 h. Diagnosis of calcium pyrophosphate crystal arthritis was made by the identification of calcium pyrophosphate crystals on synovial fluid analysis or typical clinical presentation (onset of joint pain and swelling). Key exclusion criteria included absence of calcium pyrophosphate crystals on synovial fluid analysis or a history of gout. Participants were randomly allocated (1:1), using a centralised electronic treatment group allocation module, to receive either colchicine 1·5 mg on day 1 and 1 mg on day 2 (ie, the colchicine group) or oral prednisone 30 mg on days 1 and 2 (ie, the prednisone group). The primary outcome was change in joint pain (measured by visual analogue scale [VAS] from 0 mm to 100 mm) at 24 h. Equivalence was determined whether the 95% CI of the between-group difference at 24 h was within the -13 mm to +13 mm margin in the per-protocol analysis. Adverse events were recorded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). This trial is completed and is registered with ClinicalTrials.gov, NCT03128905. FINDINGS: Between Feb 5, 2018, and May 7, 2022, 111 patients who were admitted to hospital were randomly assigned (57 [51%] to the colchicine group and 54 [49%] to the prednisone group). 95 (86%) of 111 patients were included in the per-protocol analysis (49 [52%] in the colchicine group and 46 [48%] in the prednisone group). The median age was 88·0 years (IQR 82·0-91·0) and 69 (73%) of 95 participants were women and 26 (27%) were men. Acute calcium pyrophosphate crystal arthritis affected mainly the knee in 46 (48%) of 95 participants, the wrist in 19 (20%), and the ankle in 12 (13%). Pain VAS at baseline was 68 mm (SD 17). At 24 h, change in pain VAS was -36 mm (SD 32) in the colchicine group and -38 mm (SD 23) in the prednisone group. The between-group difference in change in pain VAS at 24 h was -1 mm (95% CI -12 to 10), showing equivalence between the two drugs. In the colchicine group, 12 (22%) of 55 patients had diarrhoea, one (2%) had hypertension, and none had hyperglycaemia. In the prednisone group, three (6%) of 54 had diarrhoea, six (11%) had hypertension, and three (6%) had hyperglycaemia. No deaths occurred in the colchicine group; two deaths occurred in the prednisone group, which were deemed unrelated to prednisone (one due to infectious valvular endocarditis leading to heart failure, and one due to a stroke). INTERPRETATION: Colchicine and prednisone exhibit equivalent short-term efficacy for the treatment of acute calcium pyrophosphate crystal arthritis, with different safety profiles in the older population. FUNDING: French Inter-regional Hospital Program of Clinical Research.