The Role of Advanced Imaging in Gout Management

Gout is a common form of inflammatory arthritis where urate crystals deposit in joints and surrounding tissues. With the high prevalence of gout, the standardized and effective treatment of gout is very important, but the long-term treatment effect of gout is not satisfied because of the poor adherence in patients to the medicines. Recently, advanced imaging modalities, including ultrasonography (US), dual-energy computed tomography (DECT), and magnetic resonance imaging (MRI), attracted more and more attention for their role on gout as intuitive and non-invasive tools for early gout diagnosis and evaluation of therapeutic effect. This review summarized the role of US, DECT, and MRI in the management of gout from four perspectives: hyperuricemia, gout attacks, chronic gout, and gout complications described the scoring systems currently used to quantify disease severity and discussed the challenges and limitations of using these imaging tools to assess response to the gout treatment.

Disease Modification in Gout: A Qualitative Study of Gout Expert Rheumatologists

Objective To examine healthcare provider views of disease modification in gout to potentially derive a provisional set of domains for disease modification in gout. Methods We performed a qualitative nominal group (NG) study with 20 gout experts (15 were authors/expert panel members of the 2012 and/or 2020 ACR gout guidelines, and/or 2015 ACR/EULAR gout classification criteria) about what constitutes “disease modification” in gout – “What sorts of things do you think constitute a change in the course of disease in gout? (positive); What are all the ways in which gout as a disease can be modified?” Results Decrease in gout flares was rated #1 rank in all six NGs as indicative of disease modification in gout, followed by serum urate (SU) lowering, which was rated #1 rank in 1 of the 6 NGs (tied score with flares in one NG). Other components of gout disease modification were to improve quality of life/productivity; restore function; reduce/eliminate pain; reduce tophi burden; and joint preservation or resolution of joint damage. Potential additional components that were not ranked in the top 3 votes within each NG were: Decrease healthcare cost/utilization; cardiovascular/renal morbidity/mortality reduction; and stop urate crystals formation. Conclusion This qualitative study provides a provisional set of domains for disease modification in gout. Future studies for the development of thresholds for disease modification domains, and wider consensus on this definition are needed.

Effectiveness of Messenger Plants (Peperomia Pellucida L.) and Tai Chi Exercise as Modality Therapy for Gout Sufferers: Literature review

Hyperuricemia correlated with an increase in monosodium urate crystals, which was a precipitating factor for gout arthritis. In Indonesia, this disease was more common in individuals over 34 years of age. The elderly who had gout can be associated with metabolic syndrome and increase the risk of cardiovascular disease. Pharmacological therapy of gout, such as allopurinol, had a greater potential to cause side effects in patients than complementary therapy. This article aimed to determine the effectiveness of the messenger plant (Peperomia pellucida) and Tai Chi exercise in overcoming hyperuricemia. The writing method used was a literature review. Articles were obtained through search sites: Google Scholar, Science-Direct, and NCBI, and the criteria used in the search were Indonesian and English with a range of publication years 2014-2020. Eight main journals were used as references; from these journals, it was concluded that Peperomia pellucida could inhibit the formation of uric acid with xanthine oxidase activity through its quercetin-type flavonoid content, while Tai Chi exercise could increase joint flexibility and blood circulation in patients with gout. Therefore, these therapies can be used as a reference for complementary therapy for individuals with hyperuricemia to help manage uric acid levels and reduce the risk of developing gouty arthritis.

Role of fatty acids in inflammation, atherosclerosis, metabolic disorders and gout

Fatty acids (FA) are present in all types of organisms and play an important role in energy metabolism. The length and number of double bonds in the FA of membrane phospholipids determine the viscosity, the activity of transport systems and enzymes, and also the susceptibility to lipid peroxidation. The review discusses the influence of free unsaturated FAs with short and long chains on various inflammatory mechanisms, including atherosclerosis. It has been shown that FAs can reduce endothelial activation and affect the metabolism of eicosanoids. A new model of fundamental factors determining the variability of the timing, degree and duration of acute inflammatory reactions in the deposition of urate crystals in tissues, in which FAs play an important role is considered, using gout as an example. In the future, the study of FAs will expand the understanding of the pathophysiology of chronic inflammation in various diseases, metabolic disorders and atherosclerosis and enable the development of new treatment strategies.

A Comparative Clinical Study of Trikarshika Kwatha with and without Lifestyle Modification in the Management of Vatarakta with Special Reference to Hyperuricaemia

Nowadays, people are more vulnerable to metabolic disorders due to their faulty dietary and behavioural habits. One such disorder is Vatarakta which causes functional impairment due to involvement of Sandhi (joints). It is manifested by Ruk, Toda, Sparsha asahatva, Shopha, Raga, Daha and Stabdhata in Sandhi. Vatarakta can be correlated with Hyperuricaemia or Gout due to similarity in their clinical features. Hyperuricaemia is defined as abnormally high level of uric acid in blood (i.e. >6mg/dl in female and >7mg/dl in male). On the other hand, Gout is an inflammatory response to monosodium urate crystals formed secondary to hyperuricaemia. Aims and objectives: 1. To evaluate the effectiveness of Trikarshika kwatha and lifestyle modification in the management of Vatarakta. 2. To compare the effects of Trikarshika kwatha with and without lifestyle modification in the management of Vatarakta. Materials and methods: Raw herbs of the research formulation were collected after proper identification and Kwatha was prepared for oral administration. For the clinical study, total 60 patients were selected on the basis of selection criteria. Selected patients were randomly divided into two groups. (i) Group A: 30 patients were treated with Trikarshika kwatha. (ii) Group B: 30 patients were treated with Trikarshika kwatha along with Lifestyle modification. Individual patient was treated for 45 days along with follow up at the interval of every 15 days. To assess the effectiveness of treatment, scoring pattern was followed for subjective and objective parameters. They were assessed before and after treatment. The collected data were analysed statistically by using Paired t-test. Results: On the basis of all statistical data, it can be said that patients of Group B showed better results in all parameters in comparison to patients of Group A. Conclusion: Both Trikarshika kwatha and Lifestyle modification are affective but Trikarshika kwatha with Lifestyle modification is more effective than Trikarshika kwatha without Lifestyle modification in the management of Vatarakta.

The Association between Clonal Hematopoiesis and Gout

Background: Gout is a highly prevalent arthritis associated with debilitating joint pain and functional impairment. It is caused by elevated serum uric acid levels (hyperuricemia) and triggered by precipitation of urate crystals in and around joints. Urate crystals are ingested by macrophages and provoke an innate immune response with subsequent secretion of inflammatory cytokines including interleukin 1 beta (IL-1B). Clonal hematopoiesis of indeterminate potential (CHIP) is a precursor to hematologic malignancies defined by somatic mutations in hematopoietic cells that drive clonal expansion and inflammation. Specifically, CHIP is associated with an increased risk of cardiovascular events and can accelerate atherosclerosis. Mutations in TET2, one of the most commonly mutated genes in CHIP, lead to increased expression of IL-1B through inflammasome activation. Here we investigate the role of CHIP in the development of gout using a combination of human genetic studies and mouse models of CHIP. Methods: To determine the clinical association between CHIP and gout, we analyzed exome sequencing and clinical data from >50,000 individuals included in the UK Biobank (UKB) and Mass General Brigham Biobank (MGBB). To test whether mutant blood cells can promote gout, Tet2- and Dnmt3a-deficient mouse models were used. Results: CHIP was more prevalent in individuals with gout than without gout (MGBB: 12.3% vs. 7.9%, P=0.017; UKB: 8.2% vs. 5.8%, P=0.011) and individuals with CHIP were at increased risk of developing gout (UKB: hazard ratio [HR], 1.59; 95% confidence interval [CI], 1.27-2.00; P<0.001). In multivariable analyses, CHIP with variant allele fraction (VAF) ≥10% was associated with higher risk of incident gout compared to no CHIP after adjusting for common gout risk factors (UKB: HR, 1.46; 95% CI, 1.07-2.01; P=0.019). To determine if somatically mutated blood cells directly contribute to the aberrant immune response in gout, we utilized a mouse model of MSU-mediated peritonitis. Compared to control animals, mice with hematopoietic-specific Tet2 deficiency demonstrated markedly increased IL-1B serum levels after injection with MSU (P<0.05). To study gene-specific contributions to joint tissue injury, we established an in vivo model that closely represents the clinical phenotype of gout. Following MSU treatment in situ, Tet2-deficient animals developed exacerbated paw edema compared to wild-type controls (P<0.05). We next generated bone-marrow derived macrophages (BMDM) from Tet2- and Dnmt3a-deficient mice to specifically investigate the MSU-induced cytokine profile in mutant macrophages. Consistent with our in vivo data, IL-1B was the most differentially secreted cytokine after MSU treatment in both Tet2-deficient and Dnmt3a-deficient BMDM compared to wild-type cells (P<0.05). RNA-sequencing confirmed a strong pro-inflammatory gene expression signature of MSU-treated Tet2- and Dnmt3a-deficient macrophages. Finally, we found that pharmacologic inhibition or genetic loss of inflammasome abrogated IL-1B secretion in Tet2- and Dnmt3a-deficient macrophages treated with MSU. Conclusion: CHIP is associated with an increased risk of having and developing gout in human cohorts and distinct mouse models confirm a direct influence of mutant hematopoietic cells on gout-induced inflammation and arthropathy. CHIP may provide a mechanistic explanation for the heterogeneity in clinical symptoms and inflammation due to gout. Our findings substantiate the biologic rationale for interventional strategies directed at CHIP-associated inflammatory conditions beyond cardiovascular disease and thereby define a path for clinical evaluation of targeted therapies for patients with CHIP-positive gout. Disclosures Miller: Foundation Medicine: Consultancy. Neuberg: Pharmacyclics: Research Funding; Madrigal Pharmaceuticals: Other: Stock ownership. Natarajan: Amgen: Research Funding; Apple: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Boston Scientific: Research Funding; Blackstone Life Sciences: Consultancy; Genentech: Consultancy; Foresite Labs: Consultancy. Rao: Janssen: Honoraria, Research Funding; Pfizer: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; GlaxoSmithKline: Honoraria; Merck: Honoraria; Scipher Medicine: Honoraria.

Natural ACTH Relieves Acute Inflammation of Gout by Changing the Function of Macrophages

Objective: Gout is a common arthritis caused by deposition of monosodium urate crystals. Macrophage is crucial in the process of monosodium urate (MSU) -induced inflammation. Although it has been reported that adrenocorticotropic hormone (ACTH) in nature can be used to cure urarthritis, the mechanism concerning macrophage is still not clear. This study aims to explore how natural ACTH can alleviate urarthritis through functional changes in macrophage. Methods: We analysed the variations in VAS pain scores of five patients, knowing the time of action, and detecting the level of cortisol and ACTH in patients 24 hours after the application of ACTH. The effect of natural ACTH on joint inflammation and the level of cortisol in blood in mouse model was evaluated by studies in vivo. In vitro studies we evaluated the effect of natural ACTH on macrophage and revealed different functions of ACTH and dexamethasone on macrophage in the transcriptional level. Results: In patients with acute gout, natural ACTH can quickly alleviate pain and has no effect on the level of cortisol and ACTH. Natural ACTH is able to ease the swelling and inflammatory cell infiltration caused by arthritis, without changing the level of cortisol. Besides, natural ACTH in vitro can alleviate acute gouty inflammation by regulating phagocytosis and polarization of macrophage, which also exert different effects on the transcription of some related genes.Conclusion: Natural ACTH is able to alleviate acute gouty inflammation by regulating macrophage, and this effect differs from that of dexamethasone in the transcriptional level.

SYSTEMATIC REVIEW ON UNDERSTANDING AND MANAGEMENT OF VATARAKTA: A REVIEW ARTICLE

BACKGROUND: In today’s modern period, the lifestyle of people has changed, food habits also has changed, it is going more towards sedimentary lifestyle. People nowadays preferred to have instant, junk, and spicy fast food than a normal healthy diet. Hence nowadays more and more people are developing so many metabolic disorders due to inactive, sluggish, seated lifestyles. Among so many metabolic disorders gout is the one that commonly occurs in today’s modern manner of living. Purine metabolism causes hyperuricemia and deposition of monosodium urate crystals in joints. In Ayurveda, Vatarakta shows so much resemblance with gouty arthritis. Vatarakta is mainly an Avaranajanya Vata Pradhan Tridoshaja Vyadhi where Rakta is main Dushya.Vatarakta is more distressing. Due to the desk-bound lifestyle, many people are affected constantly by this severe disease. Currently, in modern science NSAIDS, allopurinol, colchicine, the corticosteroid is being used to treat gout. But these drugs have many adverse effects and disadvantages Panchkarma induced Shodhana and Shamana is not only an important component of Ayurvedic treatment but also the elemental basis of Ayurvedic treatment. Different procedures like Swedana, Va- mana, Virechana, Basti, Raktamokshana focuses on purification which detoxifies the patient's body and thus helps in correcting metabolism at the molecular level. Hence the Panchkarma is a quirky approach in the management of Vatarakta. Shamana refers to all the Ayurvedic procedures and protocols that reduce suppress and eliminate thedisease. Shamana Chikitsa is planned to make the patient recover and feel healthier by suppressing the disease symptoms. Hence while the inherent disease might still be present the patient going through Shamana Chikitsa can control the symptoms. Keywords: Ayurveda, Cataract, Vata, Rakta, Gouty arthritis.

Contrasting role of NLRP12 in autoinflammation: evidence from a case report and mouse models

ObjectiveTo explore at the molecular level the phenotype of a patient suffering an autoinflammatory syndrome which was diagnosed as familial cold autoinflammatory syndrome type 2 (FCAS-2). To explore the functions of Nlrp12 in inflammation using mouse models.MethodsWhole exome sequencing and Nlrp12 targeted resequencing were performed on DNA isolated from the patient and her family members. In vivo and ex vivo models of inflammation (urate crystals-dependent acute joint inflammation and urate crystals-induced peritonitis) were analysed in Nlrp12-deficient and Nlrp12-competent mice.ResultsA rare missense NLRP12 variant (c.857C>T, p.P286L) was identified in the patient and her healthy relatives. Nlrp12-deficient mice exhibit reduced systemic inflammation and neutrophilic infiltration.ConclusionNlrp12 mediates proinflammatory functions in mice. In humans, the identification of Nlrp12 variants must be cautiously interpreted depending on clinical and paraclinical data to diagnose FCAS-2.