Tophus Formation Research Articles

From Patents to Progress: Unraveling Gout's Journey Through Clinical Trials and Advancements.

Gout, an inflammatory arthritis form, is renowned for its historical association with affluence. This review delves into its pathophysiology, exploring hyperuricemia, urate crystal formation, and the ensuing inflammatory response. The epidemiology of gout is examined, focusing on its rising prevalence and impact on public health. In this study, progress in gout management is discussed, involving pharmacological interventions, dietary changes, and emerging therapies. Genetic predisposition and triggers like alcohol, temperature, and diet are highlighted in this study. Prevention strategies, including serum urate-lowering therapy and lifestyle modifications, aim to reduce recurrent flares and complications. The inflammatory response in acute gout attacks is elucidated, involving immune cells, cytokines, and the NLRP3 inflammasome. Chronic gout manifestations, such as gouty tophus formation, are explored for their destructive impact on surrounding tissues. Recent advancements in gout treatment, including nanotherapies and novel compounds, are discussed, along with promising urate-lowering drugs. Cutting-edge research on zinc ferrite nanoparticles, dimethyl fumarate, and myricetin/nobiletin hybrids addresses oxidative stress and inflammation in gout. Additionally, the potential therapeutic role of methanolic leaf extract of Euphorbia milii and tip-loaded CLC-Soluplus® MAPs is explored as natural and transdermal alternatives for gout management. The review also covers the development status of new urate-lowering drugs, providing insights into promising candidates and their mechanisms. Patents on gout and recent diagnostic advancements using techniques like laser confocal micro Raman spectrometer, FTIR, and THz-TDS offer a more accurate approach for gout stone analysis, enabling early detection and targeted treatment.

Mechanism of Reactive Oxygen Species-Guided Immune Responses in Gouty Arthritis and Potential Therapeutic Targets.

Gouty arthritis (GA) is an inflammatory disease caused by monosodium urate (MSU) crystals deposited in the joint tissues causing severe pain. The disease can recur frequently and tends to form tophus in the joints. Current therapeutic drugs for the acute phase of GA have many side effects and limitations, are unable to prevent recurrent GA attacks and tophus formation, and overall efficacy is unsatisfactory. Therefore, we need to advance research on the microscopic mechanism of GA and seek safer and more effective drugs through relevant targets to block the GA disease process. Current research shows that the pathogenesis of GA is closely related to NLRP3 inflammation, oxidative stress, MAPK, NET, autophagy, and Ferroptosis. However, after synthesizing and sorting out the above mechanisms, it is found that the presence of ROS is throughout almost the entire spectrum of micro-mechanisms of the gout disease process, which combines multiple immune responses to form a large network diagram of complex and tight connections involved in the GA disease process. Current studies have shown that inflammation, oxidative stress, cell necrosis, and pathological signs of GA in GA joint tissues can be effectively suppressed by modulating ROS network-related targets. In this article, on the one hand, we investigated the generative mechanism of ROS network generation and its association with GA. On the other hand, we explored the potential of related targets for the treatment of gout and the prevention of tophus formation, which can provide effective reference ideas for the development of highly effective drugs for the treatment of GA.

Mechanism of neutrophil extracellular traps in the pathogenesis of gout.

Gout is a self-limited inflammatory disease caused by the deposition of monosodium urate (MSU) crystals in joints and surrounding tissues due to abnormal purine metabolism. Neutrophil extracellular traps (NETs) are formed by neutrophils in response to pathogen attack. During gout, NETs induced by MSU crystals exacerbate inflammation, and aggregated NETs (aggNETs) promote the resolution of gout-associated inflammation by encapsulating MSU crystals, degrading cytokines and chemokines, and blocking the recruitment and activation of neutrophils. With disease progression, NETs participate in the formation of tophi. Therefore, aggNETs are a possible mechanism of spontaneous gout regression. Studying the specific mechanism by which NETs affect inflammatory bursts and spontaneous regression in gout patients is important. This review summarises the role of NETs in different stages of gout and the specific pathogenesis of NETs in gout to provide new ideas for the diagnosis and treatment of gout.

Complex Case: Acute-on-Chronic Gouty Arthritis, Septic Arthritis, and Severe Joint Deformities in a Young Adult Patient

Background: Gout is the most prevalent type of inflammatory arthritis, which can lead to inflammation in the joints. However, septic arthritis is unusual in gout.
 Case presentation: A 34-year-old male presented with lumps on the right ankle with cloudy white fluid discharge for 5 days prior to admission. The patient also has lumps observed on the left pedis, and manus bilateral. The patient regularly takes Allopurinol daily and Piroxicam prior to admission. The physical examination had a limited range of movement. Laboratory examinations found elevated uric acid, impaired renal function, elevated white blood cells, and elevated erythrocyte sedimentation rate. The patient was then referred for surgical debridement.
 Conclusion: Chronic gout marked by persistent polyarticular engagement and the formation of tophi. In individuals left untreated, septic arthritis and gout may manifest, followed by deformities of joints, which need further diagnosis and management.

Chronic tophaceous gout – A case report

Gout is an inflammatory arthritis associated with functional impairment and impact on quality of life. It arises when the tissues are supersaturated with urate leading to the formation of mono sodium urate crystals in and around the joints. This causes an inflammatory cascade resulting in secretion of several proinflammatory cytokines and neutrophil recruitment into the joint.A 60 years old male patient presented with complaints of swelling in the posterior aspect of left elbow since 2 years and pain since 15 days. Examination revealed soft tissue swellings in multiple joints including metatarsophalangeal joint. Renal function tests show increased Uric acid (8.6mg/dl). On Gross examination, we received fibrofatty mass measuring 3.5x1.5x1 cm. Cut-section showed white flakes ? Calcifications. On microscopy, sections studied show fibrocollagenous tissue with several tophi made up of pink eosinophilic material surrounded by foreign body giant cell reaction and lymphocytes. There are several cystic spaces filled with calcareous debris.Hyperuricemia is the key risk factor for gout and is considered prerequisite for mono sodium urate crystal formation. Urate under excretion through kidney is the major mechanism for hyperuricemia. Tophus formation is the cardinal feature of advanced gout.

New animal model of chronic gout reproduces pathological features of the disease in humans

ObjectivesGout, as the most prevalent form of inflammatory arthritis, necessitates the use of animal models to investigate the molecular mechanisms involved in its development. Therefore, our objective was to develop...

The Stiff Joint: Comparative Evaluation of Monotherapy and Combination Therapy With Urate Lowering Agents in Managing Acute Gout.

Gout, an extremely painful form of arthritis, is triggered by the innate immune system's response to the accumulation of monosodium urate crystals in specific joints and surrounding tissues. This condition is characterized by recurring episodes of excruciating arthritis flares, interspersed with periods of disease quiescence. Over time, gout can result in disability, tophi formation, and severe pain. The treatment of gout is centered around two main objectives: alleviating inflammation and pain during acute gout attacksand long-term management to reduce serum urate levels and mitigate the risk of future attacks. Addressing inflammation and pain during acute attacks is often complicated by various factors, including underlying health conditions commonly associated with gout, such as hypertension, chronic kidney disease, cardiovascular disease, and diabetes mellitus. Moreover, gout patients are frequently older and have multiple coexisting health issues, necessitating complex medication regimens. Given the rising prevalence of gout and its associated comorbidities, there's a growing demand for improved treatment options. While existing treatments effectively manage gout in some patients, a significant portion, particularly those with comorbidities, face contraindications to these treatments and require alternative approaches. Innovative medications are required to enhance gout treatment, especially for individuals with concurrent health conditions. These considerations underscore the importance of reviewing both monotherapy and combination therapy approaches for acute gout treatment.

Uricase-Deficient Larval Zebrafish with Elevated Urate Levels Demonstrate Suppressed Acute Inflammatory Response to Monosodium Urate Crystals and Prolonged Crystal Persistence.

Gout is caused by elevated serum urate leading to the deposition of monosodium urate (MSU) crystals that can trigger episodes of acute inflammation. Humans are sensitive to developing gout because they lack a functional urate-metabolizing enzyme called uricase/urate oxidase (encoded by the UOX gene). A hallmark of long-standing disease is tophaceous gout, characterized by the formation of tissue-damaging granuloma-like structures ('tophi') composed of densely packed MSU crystals and immune cells. Little is known about how tophi form, largely due to the lack of suitable animal models in which the host response to MSU crystals can be studied in vivo long-term. We have previously described a larval zebrafish model of acute gouty inflammation where the host response to microinjected MSU crystals can be live imaged within an intact animal. Although useful for modeling acute inflammation, crystals are rapidly cleared following a robust innate immune response, precluding analysis at later stages. Here we describe a zebrafish uox null mutant that possesses elevated urate levels at larval stages. Uricase-deficient 'hyperuricemic' larvae exhibit a suppressed acute inflammatory response to MSU crystals and prolonged in vivo crystal persistence. Imaging of crystals at later stages reveals that they form granuloma-like structures dominated by macrophages. We believe that uox-/- larvae will provide a useful tool to explore the transition from acute gouty inflammation to tophus formation, one of the remaining mysteries of gout pathogenesis.

S1369 Outcomes of Gout in Patients With Cirrhosis - A NIS-Based Study

Introduction: Hyperuricemia is a prerequisite for the development of gout. Elevated serum uric acid (UA) levels result from either overproduction or decreased excretion (whether by the kidneys or bowel). Some literary works denote a positive correlation between serum UA levels, cirrhosis-related complications and the incidence of non-alcoholic fatty liver disease. The exact relationship, whether hyperuricemia results in worsening cirrhosis outcomes or vice versa, is unknown. Despite these correlations, few studies explore the relationship between cirrhosis and gout. We aim to explore a possible link between them. Methods: The National Inpatient Sample (NIS) was used to identify patients hospitalized with gout, stratified based on a history of cirrhosis, from 2001 to 2013 via the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9 CM) codes. Primary outcomes consisted of mortality, gout complications (rates of flare, tophi formation, nephrolithiasis, nephropathy, and septic arthritis), and joint interventions (arthrocentesis and joint injection). Chi-squared and independent t-tests were done to assess categorical and continuous data, respectively. Multiple logistic regression was used to control for confounders, including age, sex at birth, race, cardiac arrhythmias, chronic pulmonary disease, heart failure, diabetes, HIV, HTN, peripheral vascular disease, alcohol use disorder and renal failure. Results: Patients without cirrhosis were older (70.37±13.53 years versus 66.21±12.325 years; p< 0.05). The majority of both groups were male, but cirrhotic patients had more males versus females (74.63% versus 66.83%; adjusted p=0.121). Cirrhotic patients had higher rates of mortality (5.49% versus 2.03%; adjusted p< 0.05), gout flare (2.89% versus 2.77%; adjusted p< 0.05) and tophi (0.97% versus 0.75%; adjusted p=0.677). Non-cirrhotic patients had higher rates of arthrocentesis (2.45% versus 2.21%; adjusted p< 0.05) and joint injections (0.72% versus 0.52%; adjusted p< 0.05). Rates of septic arthritis, nephropathy and uric acid nephrolithiasis did not differ significantly among both groups. Conclusion: Cirrhotics had greater incidence of gout-related complications, representing a possible link between cirrhosis and elevated average serum UA levels. Non-cirrhotics had higher rates of more invasive interventions, which could be due to clinician hesitancy with performing these interventions given increased bleeding risk in the setting of cirrhosis-related coagulopathy. (Table) Table 1. - Patient Characteristics and Differences in Inpatient Gout Outcomes in Individuals With and Without Cirrhosis Non-Cirrhotics Cirrhotics OR CI p-value AOR ACI Adjusted p-value Percentage n Percentage n Sex at birth Female 33.17 494,890 25.37 9,372 0.685 0.669-0.701 < 0.05 0.979 0.953-1.006 0.121 Male 66.83 996,939 74.63 27,576 Mortality 2.03 30,286 5.49 2,029 2.804 2.678-2.937 < 0.05 3.092 2.939-3.252 < 0.05 Gout Flare 2.77 41,282 2.89 1,066 1.044 0.982-1.11 0.171 0.816 0.765-0.871 < 0.05 Tophi 0.75 11,202 0.97 358 1.293 1.164-1.438 < 0.05 1.025 0.914-1.149 0.677 Uric Acid Nephrolithiasis 0.02 374 0.02 9 0.972 0.502-1.882 0.932 1.037 0.53-2.03 0.915 Nephropathy 0.02 283 0.01 5 0.713 0.295-1.727 0.452 0.548 0.223-1.346 0.19 Arthrocentesis 2.45 36,611 2.21 818 0.9 0.839-0.965 < 0.05 0.741 0.686-0.8 < 0.05 Joint Injection 0.72 10,673 0.52 192 0.725 0.628-0.837 < 0.05 0.713 0.61-0.833 < 0.05 Septic Arthritis 0.31 4,637 0.31 114 0.993 0.824-1.196 0.939 0.997 0.821-1.211 0.977 Mean SD SE Mean Mean SD SE Mean Mean difference CI p-value Age at admission (years) 70.37 13.53 0.011 66.21 12.325 0.064 4.167±0.071 4.027-4.306 < 0.05 n: sample size; OR: odds ratio; CI: 95% confidence interval; AOR: adjusted odds ratio; ACI: adjusted 95% confidence interval; SD: standard deviation; SE: standard error.

Computed tomography and magnetic resonance imaging findings in gouty arthritis involving large joints of the upper extremities

BackgroundWe aimed to analyze the computed tomography (CT) and magnetic resonance imaging (MRI) findings of gouty arthritis primarily involving the large joints of the upper limbs, signal or density characteristics of the tophi, growth patterns, involvement of the adjacent joints, and differentiation from other lesions occurring in this area and to discuss the causes of misdiagnosis.MethodsCT and MRI data were collected from 14 patients with gouty arthritis, primarily involving the shoulder and elbow joints, and their imaging features were analyzed.ResultsAll the patiens were ranged from 28-85 years old, and the tophi deposition can be observed on either CT or MRI.The tophi deposition apperas as slightly higher density nodules or masses on CT images,or nodules or masses on MRI with isosignal/hypointensity on T1WI and hyperintensity on T2WI. Five patients showed narrowing of the affected joint space, four had different degrees of bone erosion under the articular surface, eight developed joint effusion, and all showed surrounding soft tissue swelling. The tophi grew around the joint, with anterolateral and posterolateral tophi predominantly in the shoulder joint and dorsal tophi predominantly in the elbow joint on the MRI, with compression and edema of the surrounding soft tissues.ConclusionsGouty arthritis occurs in the large joints of the upper limbs and is characterized by fluid accumulation in the joint capsule and the formation of tophi. These tophi are usually large, with subcutaneous bone resorption and erosion, with or without cartilage destruction. However, extensive edema appeared in the soft tissue around the tophi, but the edema only produced pressure without any obvious signs of soft tissue infiltration, which may be distinguished from the joint tumor. In addition, the gout incidence rate is increased in young patients. Therefore, when the patient has a large joint mass, it is important to confirm whether there is a history of gout.

Genetic polymorphisms and decreased protein expression of ABCG2 urate transporters are associated with susceptibility to gout, disease severity and renal-overload hyperuricemia

Gout is a common crystal induced disease of high personal and social burden, characterised by severe arthritis and comorbidity if untreated. Impaired function of ABCG2 transporter is causative in gout and may be responsible for renal-overload type hyperuricemia. Despite its importance, there is limited information on how clinical parameters correlate with protein expression and that with genetic changes. Urate and clinical parameters of 78 gouty patients and healthy controls were measured among standardised circumstances from a Hungarian population. ABCG2 membrane expression of red blood cells was determined by flow cytometry-based method and SNPs of this protein were analysed by TaqMan-based qPCR. The prevalence of ABCG2 functional polymorphisms in gouty and control patients were 32.1 and 13.7%, respectively. Most common SNP was Q141K while one sample with R236X, R383C and the lately described M71V were found in the gouty population. These polymorphisms showed strong linkage with decreased protein expression while the latter was also associated with higher fractional urate excretion (FUE) and urinary urate excretion (UUE). This study firstly evaluated ABCG2 protein expression in a clinically defined gouty population while also proving its associations between ABCG2 genetic changes and renal-overload hyperuricemia. The paper also highlighted relations between ABCG2 SNPs, gout susceptibility and disease severity characterised by an early onset disease with frequent flares and tophi formation.

Immunosuppression by piperine as a regulator of the NLRP3 inflammasome through MAPK/NF-κB in monosodium urate-induced rat gouty arthritis.

Background and Aim:Gouty arthritis is a metabolic disorder involving monosodium urate (MSU) crystal deposition as a key initiator of acute inflammation. Dysregulation of the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome is associated with the pathogenesis of gout through the maturation of interleukin-1β. Piperine (PIP) is a phytochemical with an anti-inflammatory activity that has the potential as an alternative treatment for gout. In this study, we examined the effect of PIP in immunosuppression of gout inflammation through the regulation of the NLRP3 inflammasome.Materials and Methods:An in silico study was done by pharmacodynamic modeling of PIP in suppressing MSU-induced inflammation through disruption of the NLRP3 inflammasome. In vivo tests, including inflammatory assessment, histopathology, cytology, estimation of lipid peroxidation index, and detection of systemic inflammatory reactants, were performed on two groups using preventive and curative protocols.Results:In silico studies of molecular docking demonstrated the activity of PIP as a competitive inhibitor of the mitogen-activated protein kinases/nuclear factor-kappa B axis, upstream of the NLRP3 inflammasome. Analysis of gout models with curative and preventive protocols revealed the immunosuppression activity of PIP by reducing inflammatory symptoms, inhibiting tophus formation resulting from NETosis, reducing cartilage erosion, inhibiting leukocyte exudation, suppressing lipid peroxidation index, and inhibiting the production of C-reactive protein.Conclusion:The results demonstrate the activity of PIP as an immunosuppressant in gout flare. These findings indicate the potential of PIP as a candidate for prophylactic and therapeutic agent for the treatment of gouty arthritis.

Multiple Gouty Arthritis With Tophi Formation in a Patient With End-Stage Kidney Disease Treated After Kidney Transplant

Hyperuricemia is a common condition in patients with chronic kidney disease and end-stage kidney disease. It occurs even after kidney transplant because of the use of calcineurin inhibitors and transplanted kidney failure. We describe the case of a patient with end-stage kidney disease who had multiple gouty arthritis with tophi formation despite receiving appropriate treatment but was successfully cured after kidney transplant. A 36-year-old male patient undergoing hemodialysis treatment was treated with febuxostat for multiple gouty arthritis and underwent tophi removal twice. He received a deceased donor kidney transplant 10 years after dialysis treatment. He received immunosuppressants (basiliximab, tacrolimus, mycophenolate mofetil) and steroids. Results of renal biopsy performed on days 7 and 21 postoperation showed no specific findings and normal renal function. The uric acid level before transplant was 3.1 mg/dL, and when renal function was normal, it reached 6-7 mg/dL and remained stable. Although hyperuricemia was still present, the tophi disappeared 3 months after transplant. It is presumed that the high-dose steroids interfered with the activation of inflammatory responses during tophi formation, which may have caused the tophi to disappear. It is also presumed that the patient adhered to the diet well after transplant, which suppressed tophi formation. Our findings suggest that disappearance of multiple tophi and arthritis in patients undergoing hemodialysis can be achieved with kidney transplant, especially when uric acid-lowering drugs are not effective.

Analysis of animal models based on pre-clinical symptoms of gout

Gout is a type of arthritis, which is a group of related disorders caused by episodes of abnormal inflammation in the joints. It is a metabolic disease characterized by high levels of uric acid in the blood. Uric acid is the end product of purine metabolism and hyperuricemia is caused by abnormalities of purine metabolism. Hyperuricemia is a risk factor for gout, heart disease, high blood pressure (hypertension), diabetes, and acute and chronic kidney disease. This research may attract widespread interest to researchers focusing on the different types of crystalline arthritis. There are over 100 types of arthritis. The most common forms are osteoarthritis (degenerative joint disease), rheumatoid arthritis, gout and pseudo-gout, septic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, still's disease etc.&#x0D; Many animal models are available to get rid of gout, mainly the hyperuricemia animal model, monosodium urate air pouch gout model, Intra-articular gout in rat, Paw edema, Gouty Arthritis Model, and Gouty nephropathy model. Various investigations have created a reliable and economical animal model for arthritis in a relatively short brief timeframe, manifested by long-term gross and behavioral abnormalities along with intra-articular monosodium urate deposition and tophi formation.&#x0D; Lately years, hyperuricemia disease has gradually increased in the world. There are many updates that can be made by taking the arthritis model. If such a situation prevails, then in a few years, the patients of gout can increase in great quantity and there is some treatment for this disease. In any case, further review is really needed to focus on its particular pathogenesis and drugs.&#x0D; Keywords: Gout, Arthritis, Gout Animal Model, Inflammation, Hyperuricemia, monosodium urate, crystalline arthritis.

Unusual Finding of Gouty Tophus in Adult Male with Acute Locked Knee: A Rare Case Report

Gout is an inflammatory disease commonly characterized by tophus deposits containing uric acid crystals in the intraarticular joints. An acute locked joint due to gouty tophus formation is a rare finding. This case describes a 36-year-old man with sudden pain and locking in the knee joint. Physical examination, plain radiography, and serum uric acid examination showed unremarkable results. Further investigation with diagnostic arthroscopy confirmed tophaceous gout as the sole cause of an acutely locked knee. The patient exhibited satisfactory clinical results following surgical intervention under arthroscopy and the administration of urate-lowering agents. This case highlights the probability of tophus deposition as the cause of an acute locked knee, despite unremarkable initial presentation. The awareness regarding this case should be raised, especially on emphasizing arthroscopy as a cost-effective diagnostic and therapeutic modality in patient management.

Taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism

ObjectiveTo evaluate the taxonomic composition of the gut microbiome in gout patients with and without tophi formation, and predict bacterial functions that might have an impact on urate metabolism.MethodsHypervariable V3–V4 regions of the bacterial 16S rRNA gene from fecal samples of gout patients with and without tophi (n = 33 and n = 25, respectively) were sequenced and compared to fecal samples from 53 healthy controls. We explored predictive functional profiles using bioinformatics in order to identify differences in taxonomy and metabolic pathways.ResultsWe identified a microbiome characterized by the lowest richness and a higher abundance of Phascolarctobacterium, Bacteroides, Akkermansia, and Ruminococcus_gnavus_group genera in patients with gout without tophi when compared to controls. The Proteobacteria phylum and the Escherichia-Shigella genus were more abundant in patients with tophaceous gout than in controls. Fold change analysis detected nine genera enriched in healthy controls compared to gout groups (Bifidobacterium, Butyricicoccus, Oscillobacter, Ruminococcaceae_UCG_010, Lachnospiraceae_ND2007_group, Haemophilus, Ruminococcus_1, Clostridium_sensu_stricto_1, and Ruminococcaceae_UGC_013). We found that the core microbiota of both gout groups shared Bacteroides caccae, Bacteroides stercoris ATCC 43183, and Bacteroides coprocola DSM 17136. These bacteria might perform functions linked to one-carbon metabolism, nucleotide binding, amino acid biosynthesis, and purine biosynthesis. Finally, we observed differences in key bacterial enzymes involved in urate synthesis, degradation, and elimination.ConclusionOur findings revealed that taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism.

Presence of tophi is associated with a rapid decline in the renal function in patients with gout

We aimed to compare clinical characteristics of patients with and without tophi at the time of the diagnosis of gout and investigate the association of tophi and renal function in gout patients. The patients who were first diagnosed with gout at the Kangwon National University Hospital 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. Of 276 patients, 66 (25.5%) initially presented with tophi. Tophi group was older, had a longer symptom duration, and a higher prevalence of multiple joint involvement than those without tophi. In multivariate logistic regression analysis, prolonged symptom duration and multiple joint involvement were significantly associated with increased risk of formation of tophi. The decline in the eGFR was more prominent in patients with tophi than in those without (− 4.8 ± 14.5 vs. − 0.7 ± 11.9 ml/min/1.73 m2/year, respectively; P = 0.039). The presence of tophi was significantly associated with a rapid decline in the eGFR (β = − 0.136; P = 0.042). In conclusion, the presence of tophi was associated with a rapid declining renal function. Therefore, an early diagnosis and closely monitoring of renal function might be important in gout patients with tophi.

Experience of arthroscopic surgery in tophaceous gout: indications, results and complications

Background Gout, lasting 5 years or more, and high uncontrollable levels of uric acid in blood lead to the formation of tophi – gouty stones containing the UA crystals surrounded with connective tissue. As the result of tophi formation in the joint area patients felt extreme discomfort and quite often completely lose ability to work. Objectives To define indications for tophaceous gout surgery in the Chengdu Rheumatism Hospital, evaluate surgical results and complications, as well as the effectiveness of a new surgery equipment. Materials and methods The indications and results of tophaceous gout surgery were investigated in 63 male gout patients of Chengdu Rheumatism hospital in 2019-2020. A retrospective analysis was carried out on the basis of medical records for all patients who were prescribed with urate lowering therapy and underwent arthroscopic intervention or complex surgical intervention combining arthroscopic shaving with open tophectomy procedure. Results The most common lesion site was foot joints: toes (49.41 %), ankle (39.68 %) and knee (34.92 %), with restricted mobility in the mentioned joints. Among common complaints were inability to perform daily routines due to enlarged joints (inability to wear shoes), joints’ dysfunction and pain. Younger patients (aged 20–44) had significantly higher levels of uric acid in serum before treatment. In most cases, indications for surgery for this group of patients were pain and discomfort in joints, inability to perform daily work. After accessing pain levels, 38.46 % of younger patients reported pain leveled 6 or higher on VAS score, which was more often, compared to patients aged 45–55 (26.92 %) and older than 55 (10.0 %). After surgery and following urate lowering therapy all patients noted functional improvement and reduction of pain. Decrease in serum urate levels were reported in 96.83 % of patients. Conclusion The results of surgical treatment for functional impairment of the joint (inability to perform daily work due to restricted range of motions) and massive joint transformation (inability to wear shoes/clothes) in gout patients are positive, with all patients reporting functional improvement and reduction of pain, and the risk of complications is low. In addition to urate lowering therapy we cautiously recommend performing arthroscopic shaving even in younger gout patients consistent with aforementioned indications.

Gout

Gout is a metabolic process characterized by the deposition of uric acid crystals in various tissues of the body. Pathogenesis of gout is based on the accumulation of uric acid salts and its reduced renal elimination, leading to an increase in its concentration in the blood. Clinically, gout manifests itself in the form of recurrent attacks of arthritis with the formation of tophi. Development of renal pathology is also noted against the background of arthritis. The disease is more common among men, however, recently, cases of lesions of women are not rare. Prevalence of gout increases with age. Medicines that affect the pathogenetic mechanism of the disease are used for the treatment, as well as drugs for symptomatic treatment.

Risk factors of ultrasound-detected tophi in patients with gout.

Tophus is a characteristic manifestation of advanced gout, the clinical significance of which is often underestimated. This study aimed to compare the difference of clinical and ultrasound features between gout patients with and without ultrasound-detected tophus and identify risk factors associated with the presence of ultrasonographic tophus in gout patients. A total of 85 gout patients were divided into tophaceous (n = 54) and non-tophaceous group (n = 31) according to the presence of ultrasound-detected tophus. All patients underwent ultrasound examination of the bilateral knee, ankle, and first metatarsophalangeal joint (MTP1). Clinical information and ultrasound findings were compared between the groups. A multivariate logistic regression analysis to determine possible risk factors is associated with the number of ultrasound-detected tophaceous joints. Older age, longer gout duration, higher gout flare frequency, lower estimated glomerular filtration rate (eGFR), and higher prevalence of hypertension, hyperlipidemia, and ultrasound manifestations including double contour sign (DCS) and erosion were observed in tophaceous patients from the univariate analysis. Multivariable logistic regression analysis showed that eGFR and disease duration were independently associated with the number of tophaceous joints. Lower eGFR and longer course duration were associated with a higher risk of tophi (B = -0.020, 0.141; P = 0.009, 0.010, respectively). The main factors that may influence the formation of tophi are disease duration and eGFR.Key Points• Lower eGFR and longer course duration are independent risk factors of tophi formation in gout patients.• The incidence of ultrasound manifestations including double contour sign (DCS) and erosion in patients with tophi were higher than those without tophi.