Tophi and carotid atherosclerosis in gout patients: Role of insulin resistance.

BACKGROUND AND AIM: Gout and cardiovascular disease are closely related, but the mechanism linking them is still unknown. Gout may affect the insulin signaling pathway inducing insulin resistance (IR). The study aims to evaluate the association between tophi and carotid atherosclerosis, considering the potential role of IR. METHODS AND RESULTS: A total of 595 patients with gout aged 18 to 80 were enrolled in this study. Carotid intima-media thickness, plaques and tophi were evaluated by B-mode ultrasonography. IR was assessed by the HOMA index (hepatic IR) and Gutt index (peripheral IR). Multivariable logistic regression and interaction analysis were used to examine the association between tophi and IR and its impact on carotid atherosclerosis. Among these participants, the average age was 55.4 (±12.54) years, and 94.6 % were male. Tophi were associated with increased odds of carotid atherosclerosis and burden after adjustment for confounders (P < 0.05). Tophi and IR synergically interacted for inducing carotid atherosclerosis. The interaction between peripheral IR with tophi was more pronounced than hepatic IR with tophi. CONCLUSIONS: Tophi were independently associated with carotid atherosclerosis risk. IR mediated a significant amount of the effect of tophi on the development of carotid atherosclerosis. Peripheral IR probably plays a more important role than hepatic IR does.

Miliarial-type gout in association with chronic use of glucocorticoids.

A 59-year-old male patient with long-standing tophaceous gout (more than 30 years) characterized by polyarticular involvement and recurrent disseminated tophi formation; his past medical history is relevant for poor adherence to urate-lowering medications, as well as persistent use of self-prescribed systemic glucocorticoids. Despite achieving therapeutic goals for serum uric acid levels, new tophi formation with an intradermal location in the form of "miliarial-type gout" was documented. Due to functional limitations, the patient underwent surgical resection of the olecranon bursa. This case illustrates a widespread and recurrent tophi formation associated with long-standing gout and regular and sustained glucocorticoid use, despite an adequate disease control based on serum urate levels and involving an intradermal location of tophi presenting as "miliarial-type" lesions. In addition, the coexistence of urate and cholesterol crystal deposition disease in olecranon gouty bursitis is presented. Finally, a sonographic extended field of view of lesions distributed along the patient's extremities is presented as a novel characterization of this condition.

Increased Metallothionein-1 Associated with Gout Activity and Tophi.

BACKGROUND AND AIMS: Gout is a chronic self-limiting inflammatory arthritis. An increase in metallothionein-1 (MT-1) has been reported in rheumatoid arthritis and osteoarthritis, and it attenuates inflammation and the pathology of diseases. This study aims to detect MT-1 levels in patients with gout and to explore its correlation with disease activity, clinical indexes, and inflammatory cytokines. METHODS: The expression of MT-1 messenger RNAs (mRNAs) and protein levels in patients with gout were measured using real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Correlations between MT-1 and clinical indexes or inflammatory mediators were analyzed using Spearman's correlation test. RESULTS: Compared with healthy controls (HCs, n = 43), patients with active gout (n = 27) showed higher levels of MT-1 mRNA in peripheral blood mononuclear cells and protein in serum, particularly those with tophi. No significant difference in serum MT-1 levels was observed among patients with inactive gout, HCs, and patients with hyperuricemia without gout. Furthermore, no significant difference was observed between patients with gout with kidney damage and HCs. In addition, serum interleukin (IL)-1ß, IL-6, and IL-8 levels were significantly increased in patients with active gout, particularly in those with tophi. The serum MT-1 level was positively correlated with C-reactive protein, as well as with IL-1ß, IL-6, and IL-18. CONCLUSION: The higher levels of MT-1 were found in patients with gout, which were correlated with disease activity and gout related pro-inflammatory cytokines. Indicating MT-1 may serve as a new marker for predicting disease activity.Abbreviations: IL-1ß: Interleukin 1ß; MT-1: Metallothionein-1; CRP: C-Reactive Protein; ROS: Reactive Oxygen Species; IL-10: Interleukin 10; TGF-ß: Transforming Growth Factor Beta.

Patient characteristics, surgical treatment, and outcomes in spinal gout: a systematic review of 315 cases.

PURPOSE: To systematically investigate all published literature on spinal gout regarding location demographics, patient characteristics, treatment, and outcomes. METHODS: We performed a systematic literature search of Medline and EMBASE from inception until April 15, 2023. Two investigators performed data extraction and quality assessment of location demographics and patient characteristics and outcomes of all article types describing spinal gout. RESULTS: A total of 214 articles (204 case reports and 10 case series) were included, encompassing 315 subjects with spinal gout (81% male, mean age 58.1 years; range: 16-92). Most cases (36%) were between the age of 60-69 years. We observed an increase in publications and cases from 1950 to the present. Most patients were from institutions in Asia (n = 119, 37.8%) and North America (n = 96, 30.5%). Reported symptoms frequently included back pain (75%), radiating pain to extremities (27.3%), and weakness in the extremities (26.3%). The lumbar spine was most often affected. Pharmacological treatment was described for 108 (34.2%) patients. Surgery was performed for 146 (46.3%) of patients, of which 4.8% had postoperative complications. Three patients (2%) required secondary surgery for recurrence. CONCLUSION: Published cases of spinal gout have increased over the last decades. Patient characteristics of spinal gout were similar to findings in systemic gout. Trends identified in patient characteristics and treatment outcomes may help guide patient management and improve our understanding of spinal gout.

Surgical Management of Tophaceous Gout in the Upper Limb.

PURPOSE: Gouty tophi are a clinical manifestation of hyperuricemia in advanced stages. They can produce pain, functional limitation, and severe deformities. Patients with severe symptoms require short-term symptomatic solutions that standard medical management is not able to provide. The objective of this study was to present the results obtained with the surgical management of tophaceous gout in the upper limb, as well as present a detailed characterization of the disease in the upper limb. METHODS: Databases of the hand surgery service of a quaternary care hospital were reviewed to identify patients aged >18 years old undergoing tophi resection in the upper limbs between 2014 and 2020. Medical history records were reviewed retrospectively, and the relevant data were extracted to establish demographic profile, clinical presentation, anatomic distribution, postoperative outcomes, and additional procedures required. RESULTS: The most frequent symptom was pain (83%), followed by limited range of motion (56%), deformity (50%), and daily living/occupational activity limitation (28%). The main indications for surgical management were the presence of deformity, pain, and/or limited range of motion. The most frequently affected anatomic sites were the metacarpophalangeal joints, followed by the elbows, proximal interphalangeal joints, and proximal phalanges. The postoperative complication rate was 28%. The most common complications were operative site infections and wound dehiscence. Decreased pain was associated with surgical resection. Additional procedures, such as extensor tenorrhaphy and local flaps, were required in 47.2% of patients. CONCLUSION: Surgical resection of tophi can decrease pain. Although surgery is associated with a high rate of complications, most are minor. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Association between specific ultrasound features of joints and impaired kidney function among gout patients.

OBJECTIVE: To investigate the relationship between the specific ultrasonic manifestations of lower limb joints and impaired kidney function in gouty arthritis. METHODS: In this cross-sectional study, 408 patients with gouty arthritis were divided into two groups based on the status of renal function: normal group (n = 240) and renal impairment (n = 168) group. All patients underwent ultrasound examination of the bilateral knee, ankle, and first metatarsophalangeal joints to detect ultrasound features of double-contour sign (DC) and tophus. Multiple logistic regression analysis was conducted to assess the association between kidney dysfunction and ultrasound features. A number of potential clinical confounders were adjusted in the model. RESULTS: Univariable conditional logistic regression produces several significant risk factors of impaired kidney function which were the highest and current lever of serum urate acid, course of disease, frequency of attack, hyperlipidemia, hypertension, diabetes, coronary heart disease, presence of multiple tophus, and DC (P < 0.05). After correcting the course of disease and other risk factors, tophus was still an independent risk factor of impaired kidney function and the multivariable adjusted odds ratios (95% CI) was 1.789 (1.005-3.185, P = 0.05), however, the association was not significant in DC (OR = 1.098, 95% CI: 0.668-1.803, P = 0.71). CONCLUSION: The ultrasound feature of tophus was associated with kidney dysfunction in patients with gout, independent of clinical risk factors, which may be helpful in guiding clinical practice.

[Tophaceous gout as a differential diagnosis of preauricular tumor]. / Tophöse Gicht als Differenzialdiagnose eines präaurikulären Tumors.

Primary gout is a hereditary disorder in nucleotide metabolism. In addition to typical manifestations in the feet, hands, and large joints, there may be rare manifestations in the head and neck. We report a case of tophaceous gout in the temporomandibular joint in a patient who presented with preauricular swelling and progressive hearing impairment. Physical examination showed obliteration of the auditory canal and imaging revealed a destructive process involving the skull base. The diagnosis was confirmed by imaging and biopsy.

WHEN TOPHACEOUS GOUT INVOLVES MULTIPLE ORGANS: CHALLENGES AND SOLUTIONS.

Uncontrolled chronic gout can lead to deposition of monosodium urate crystals, better known as tophi. Such depositions can involve several organ systems, including unusual locations such as the vertebrae. Nevertheless, certain complications, such as hypercalcemia, can arise because of tophi. Despite an aggressive intervention, hypercalcemia might not resolve spontaneously, as long as an ongoing inflammatory process secondary to gouty tophi is taking place. Herein, we present the case of a 62-year-old man with a long history of gouty tophi who presented for back pain and was found to have spinal cord involvement with PTH-independent hypercalcemia which only resolved with pegloticase therapy.

Miliarial gout: Clinical case and a brief review.

Miliarial gout is a rare clinical variant of chronic tophaceous gout characterised by tiny milia-like papules containing chalky tophaceous material. In this report, we present a case of miliarial gout in a patient with known history of gouty arthritis and review the reported cases of miliarial gout in the literature to discuss its characteristics, diagnosis and treatment.

Volumetric reduction and dissolution prediction of monosodium urate crystal during urate-lowering therapy - a study using dual-energy computed tomography.

METHODS: Baseline and follow-up DECTs were performed under a standard ULT protocol. Monthly dissolution rates were calculated by simple and compound methods. Correlations with average SU were compared and analyzed. Best-fit regression model was identified. MSU dissolution times were plotted against SU at different endpoints. RESULTS: In 29 tophaceous gout patients, MSU volume reduced from baseline 10.94 ± 10.59 cm3 to 2.87 ± 5.27 cm3 on follow-up (p = .00). Dissolution rate had a stronger correlation with SU if calculated by compound method (Pearson's correlation coefficient r= -0.77, p = .00) and was independent of baseline MSU load. The ensuing dissolution model was logarithmic and explained real-life scenarios. When SU > 0.43 mmol/l, dissolution time approached infinity. It improved to 10-19 months at SU = 0.24 mmol/l. When SU approximated zero (as with pegloticase), dissolution flattened and still took 4-8 months. CONCLUSION: MSU dissolution is better described as a logarithmic function of SU, which explains, predicts, and facilitates understanding of the dissolution process.

Management of ulcerated finger pad tophi.

Finger pad tophi are an unusual but not very rare presentation of uncontrolled gout. Unlike tophaceous lesions of other locations, finger pad tophi are often difficult to diagnose at presentation due to resemblance to a variety of nodular lesions, coexistence with other connective tissue disorders and sometimes occurrence in asymptomatic hyperuricemia. They also pose a therapeutic dilemma due to a lack of clear treatment guidelines. Several case reports of finger pad tophi have been published before, focusing mainly on diagnosis and medical management. We discuss here a case of thumb pad tophi as primary presentation of undiagnosed asymptomatic hyperuricemia and treated surgically with excision and full-thickness skin graft along with urate-lowering therapy. This article highlights the diagnosis and treatment of finger pad tophi. We also discuss the surgical management of tophaceous lesions of hands and digits.

Characterization of patients with chronic refractory gout who do and do not have clinically apparent tophi and their response to pegloticase.

OBJECTIVES: To determine the characteristics and response to pegloticase of patients with chronic refractory gout with and without clinically apparent tophi. METHODS: Results from two randomized controlled trials of pegloticase in patients with chronic refractory gout with clinically apparent tophi or without tophi were used to assess baseline and on-treatment between-group differences. RESULTS: Patients with tophi were significantly older than those without tophi, had a significantly longer duration of disease, higher numbers of tender and swollen joints, higher Patient Global Assessment scores and Health Assessment Questionnaire-Disability Index scores, and lower Arthritis-Specific Health Index scores. Patients with tophaceous gout also had significantly lower scores for physical functioning, role physical, social functioning, and the physical component summary scores of the Short Form 36 vs patients without tophi. In addition, subjects with clinically apparent tophi had a significantly lower mean estimated glomerular filtration rate. Pegloticase treatment of tophaceous patients caused significant reductions in serum urate, flares, Patient Global Assessment, tender joints, swollen joints, Health Assessment Questionnaire-Disability Index, visual analogue scale pain and Short Form 36 Bodily Pain, whereas patients without tophi had significant improvement in serum urate, flares, Patient Global Assessment, tender joints, and Short Form 36 Bodily Pain, but not swollen joints, Health Assessment Questionnaire-Disability Index functional score or pain visual analogue scale. Treatment with pegloticase had no effect on estimated glomerular filtration rate despite significant lowering of the urinary uric acid: creatinine ratio. CONCLUSION: Patients with chronic refractory gout and clinically apparent tophi have more severe disease as well as reduced renal function. Both groups experienced significant clinical benefit with pegloticase treatment, although no change in renal function was noted.

Unusual presentation of gouty tophus in the liver with subsequent appearance in the same site of HCC: a correlate diagnosis? Case report.

BACKGROUND: Although gout is a common disease, the presence of gouty tophi outside joints is rare and in literature, there is to date only one report of hepatic tophaceous nodule. We would like to highlight here the difficult diagnostic workup in a patient with history of cancer and the presence of a tophus inside the liver. Moreover, we address the possible etiologic role of chronic inflammation related to tophi and liver cancer. CASE PRESENTATION: We present the case of a 72-year-old man with a localization of gouty tophus in the liver, who thereafter developed a hepatocellular carcinoma (HCC) in the same site. The patient was followed up after surgery for left renal cancer from 1992 to 2011, when a hepatic nodule was discovered for the first time. After a detailed evaluation, the nodule was classified as a urate tophus of the liver. However, further follow-up showed that the nodule increased in size and changed its characteristics, bringing to the diagnosis of HCC. CONCLUSIONS: With the present case report, we would discuss the possible neoplastic degeneration of a gouty tophus and its etiologic role favouring cellular degeneration linked to chronic inflammation. We would also highlight the importance of histopathological evaluation of hepatic lesions in gouty patients at high risk of liver neoplasm, due to the difficulty in characterizing gouty tophi by imaging.

Gouty Tophi in Sinus Tarsi of Bilateral Feet Mimicking Synovial Sarcoma:A Case Report.

Chronic gout is defined as accumulation of monosodium urate crystals in joints, cartilage, tendons, bursae, bone, and soft tissue. The foot is the most common location for acute gout flares, with the first metatarsophalangeal joint being the most frequent site of tophus formation. However, few studies have reported gouty tophus formation in the subtalar joint. Gout has been termed the "great mimicker" because of its tendency to mimic other pathologic conditions, such as pigmented villonodular synovitis and synovial sarcoma. Herein, we present a rare case of chronic tophaceous gout in the sinus tarsi in both feet in a 23-year-old healthy male, with extensive bony erosions mimicking pigmented villonodular synovitis and synovial sarcoma. We discuss the clinical presentation, distinguishing radiologic characteristics, surgical procedures, and outcome regarding this unique presentation.

Risk factors for ulceration over tophi in patients with gout.

Ulceration over tophi in patients with gout usually causes a number of clinical problems. The aim of this study was to investigate the risk factors for ulceration of tophi in patients with gout. Patients with gout who had tophi with or without ulceration were prospectively recruited and underwent a comprehensive clinical assessment. Clinical factors independently associated with the presence of ulceration were analysed using logistic regression models. Of the 113 participants, 18 (13·7%) had clinically apparent ulceration over tophi. In univariate analysis, ulceration over tophi correlated with age, tophus duration, size, location and lack of protective sensation. In logistic regression analysis, age, tophus size and lack of protective sensation were associated with ulceration over tophi. These findings indicate that old age, large tophus size and lack of protective sensation were independent risk factors for ulceration over tophi.

Cytokine Profile in Gout: Inflammation Driven by IL-6 and IL-18?

INTRODUCTION: Gout is considered to be an autoinflammatory disease and the presence of monosodium urate (MSU) crystals stimulates activation of NPRL3 inflammasome and subsequently caspase-1, generating production of active IL-1ß and IL-18. However, the association between serum cytokines levels and clinical manifestations of the disease is not yet well understood. We evaluated the serum profile of proinflammatory cytokines (IL-1ß, IL-6, IL-8, IL-17A, IL-18, IL-22, and IL-23) and described their relationship with clinical and laboratory data. METHODOLOGY: Thirty-nine male patients with gout (GG) were assessed for clinical and laboratory variables and cytokine levels were measured by ELISA. For the purposes of comparison, 34 males with no previous history of arthritis were also included in the study (CG). RESULTS: Seventeen participants (43%) exhibited active arthritis on evaluation. Levels of IL-18 were significantly higher in patients in relation to the CG (p = 0.0013). No statistically significant differences were found between the GG and CG for the other measured cytokines. There was a moderate correlation between IL-18 and ESR (R = 0.43, p = 0.0073), CRP (R = 0.47, p = 0.0025), and serum levels of IL-6 (R = 0.36, p = 0.023). An association was observed between serum levels of IL-6 and the presence of tophi (p = 0.005) and deformities (p = 0.0008), as well as a correlation between this cytokine and ESR (R = 0.41, p = 0.011) and CRP (R = 0.48, p = 0.02). CONCLUSIONS: IL-18 is associated with inflammatory activity in gout, as well as with IL-6 levels, while IL-6 is associated with clinical and laboratory activity, the presence of tophi and articular deformities, and may be a prognostic marker of this pathology.

Tophi - surgical treatment.

Gout is an inflammatory joint disease associated with deposition of monosodium urate crystals in the bones forming the joints, in periarticular tissues and in other organs. The disease is one of the most frequent causes of disability. This paper presents the case of a 57-year-old male patient treated for generalised gout. A "clinical mask" suggesting another disease was the cause of making the correct diagnosis only six years after the occurrence of the first manifestations. The patient, with high values of inflammatory markers, severe pain and advanced joint destruction, was given an aggressive anti-inflammatory treatment. The unsatisfactory effect of the conservative treatment forced the authors to perform surgical resection of the gouty nodules in the hands. After several operations the function of the hand joints operated on, appearance of the hands and the quality of the patient's life improved significantly.

Bone erosions in patients with chronic gouty arthropathy are associated with tophi but not bone oedema or synovitis: new insights from a 3 T MRI study.

OBJECTIVES: Bone erosion has been linked with tophus deposition in gout but the roles of osteitis (MRI bone oedema) and synovitis remain uncertain. Our aims in this prospective 3 T MRI study were to investigate the frequency of these features in gout and determine their relation to one another. METHODS: 3 T MRI scans of the wrist were obtained in 40 gout patients. Scans were scored independently by two radiologists for bone oedema, erosions, tophi and synovitis. Dual-energy CT (DECT) scans were scored for tophi in a subgroup of 10 patients. RESULTS: Interreader reliability was high for erosions and tophi [intraclass correlation coefficients (ICCs) 0.77 (95% CI 0.71, 0.87) and 0.71 (95% CI 0.52, 0.83)] and moderate for bone oedema [ICC = 0.60 (95% CI 0.36, 0.77)]. Compared with DECT, MRI had a specificity of 0.98 (95% CI 0.93, 0.99) and sensitivity of 0.63 (95% CI 0.48, 0.76) for tophi. Erosions were detected in 63% of patients and were strongly associated with tophi [odds ratio (OR) = 13.0 (95% CI 1.5, 113)]. In contrast, no association was found between erosions and bone oedema. Using concordant data, bone oedema was scored at 6/548 (1%) sites in 5/40 patients (12.5%) and was very mild (median carpal score = 1, maximum = 45). In logistic regression analysis across all joints nested within individuals, tophus, but not synovitis, was independently associated with erosion [OR = 156.5 (21.2, >999.9), P < 0.0001]. CONCLUSION: Erosions were strongly associated with tophi but not bone oedema or synovitis. MRI bone oedema was relatively uncommon and low grade. These findings highlight the unique nature of the osteopathology of gout.

Interventions for tophi in gout: a Cochrane systematic literature review.

OBJECTIVE: To systematically review the available literature on the management of tophi in gout. This article is based on the Cochrane Review Interventions for Tophi in Gout published in the Cochrane Database of Systematic Reviews. METHODS: Medline, Embase, and The Cochrane Library were searched using a strategy developed with an experienced librarian. We also searched American College of Rheumatology and European League Against Rheumatism conference abstracts from 2010-2011. Included articles were reviewed in detail and a risk of bias (using the Cochrane tool) and quality assessment were performed. RESULTS: In total, 3206 references were recovered. Of these, 72 articles were selected based on our inclusion criteria. This included 1 report of 2 randomized controlled trials, 2 nonrandomized studies, and 69 case series and reports. The study with 2 randomized controlled trials looked at pegloticase. This showed improvement in tophi with treatment. One observational prospective trial looked at allopurinol and benzbromarone individually and in combination. It noted that achieving lower serum urate levels was associated with a faster reduction of tophi. An open-label extension trial noted that longterm maintenance of serum uric acid < 6.0 mg/dl with febuxostat led to a reduction in tophi. The case series and reports looked at surgical, pharmacological, and other interventions, as well as combination therapies. All surgical interventions reported improvement in pain and/or function. No report had objective measures of outcome. CONCLUSION: Treatment with urate-lowering therapy such as allopurinol, benzbromarone, allopurinol + benzbromarone in combination, febuxostat, or pegloticase can lead to reduction in tophi. There is some evidence that achieving a lower serum urate level leads to a faster rate of tophi reduction.

[Giant abdominal urate tumor-like mass with multiple crystalline deposits in the bowel and lung walls in a patent with terminal heart failure].

The paper describes a unique case of a large abdominal urate mass with a peculiar inflammatory process with giant cells and smaller urate deposits in the lung and small bowel without articular changes and kidney injury in a patient with terminal heart failure.