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Refractory gout and Lyme disease are distinct conditions that, when coexisting, pose significant diagnostic and therapeutic challenges, particularly in regions endemic for Lyme disease. This case report presents a 49-year-old male with a three-year history of gout, presenting with acute arthritis of the first metatarsophalangeal joint, unresponsive to standard urate-lowering therapy. Despite treatment with colchicine and prednisone, the patient’s symptoms persisted, and inflammatory markers remained elevated. Imaging revealed findings consistent with gouty arthritis, but due to the atypical treatment response, further testing was conducted. Serological analysis confirmed infection with Borrelia burgdorferi, establishing the diagnosis of concurrent Lyme disease. The addition of doxycycline to the treatment regimen resulted in significant clinical improvement within days. This case highlights the importance of considering Lyme disease in patients with refractory gout in areas endemic for Lyme disease. While rare cases of Lyme disease mimicking gout have been reported, this is among the first documented instances of their coexistence. Early recognition and appropriate antibiotic treatment are critical in preventing complications and ensuring optimal management of both conditions.

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Abstract Objective We investigated the different life styles among the diet structures and exercise patterns of 100 patients with refractory gout and 79 healthy volunteers; of these, we selected 39 patients and 20 healthy volunteers for serum proton magnetic resonance (1H-NMR) metabolic network detection. We determined the potential biomarkers of refractory gout and attempted to explore the relation between potential biomarkers and diet structures and exercise patterns. Methods The study employed a questionnaire survey to analyze diet structures and exercise patterns from 100 patients of refractory gout and 79 healthy volunteers. At the same time, using 1H-NMR metabolic technology to analyze the metabolites present in the serum samples obtained from 39 patients of refractory gout (group B) and 20 healthy subjects (group A). Employing MestReNova (Version 8.0.1) to analyze the metabolites maps, collecting the NMR results, further importing into SIMCA-P+ 14.0 software (Umetrics, Sweden) for principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) statistical analysis. Combining patterns recognition and multivariate statistics, potential biomarkers were searched. Other experimental data, including creatinine and adiponectin, were counted by the SPSS21.0. The measurement data were expressed by X ± S and t test. The counting data were expressed in percent and performed by X 2 test. Results Our results revealed that patients with gout tended to be obese, and there were differences in their lifestyle with exercise, sleep, and smoking, as well as in their preference for fructose drinks, alcohol, and total and structural distribution of meat, milk, eggs, and so on when compared with the healthy volunteers. Importantly, we found the adiponectin in the gout group was lower as compared to the healthy group. Further, metabolomics in combination with KEGG analysis revealed that the biosynthesis of aminoacyl tRNA, biosynthesis of valine, leucine, and isoleucine, metabolism of alanine, aspartic, and glutamate, metabolism of glycine, serine, and threonine, phenylalanine, glycolysis/gluconeogenesis, ketone body synthesis and degradation, metabolism of d‐glutamine, citric acid cycle (TCA cycle), triglyceride metabolism, and others could be used as specific biomarkers of this disease. Conclusion Recurrent refractory gout and formation of tophus may be related to the diet structures and lifestyles between the patients and the healthy people, and their abnormal metabolic network may be related to the disorder of mitochondrial energy metabolism, which further results in abnormal metabolism of glucose, lipids, amino acids, and deposition of uric acid in joints, peripheral connective tissue, and kidney, inducing an inflammatory response.

Objective: We investigated the different life styles among the diet structures and exercise patterns of 100 patients with refractory gout and 79 healthy volunteers; of these, we selected 39 patients and 20 healthy volunteers for serum proton magnetic resonance (1H-NMR) metabolic network detection. We determined the potential biomarkers of refractory gout and attempted to explore the relation between potential biomarkers and diet structures and exercise patterns. Methods: The study employed a questionnaire survey to analyze diet structures and exercise patterns from 100 patients of refractory gout and 79 healthy volunteers. At the same time, using 1H-NMR metabolic technology to analyze the metabolites present in the serum samples obtained from 39 patients of refractory gout (group B) and 20 healthy subjects (group A). Employing MestReNova (Version 8.0.1) to analyze the metabolites maps, collecting the NMR results, further importing into SIMCA-P+ 14.0 software (Umetrics, Sweden) for principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) statistical analysis. Combining patterns recognition and multivariate statistics, potential biomarkers were searched. Other experimental data, including creatinine and adiponectin, were counted by the SPSS21.0. The measurement data were expressed by X ± S and t test. The counting data were expressed in percent and performed by X2 test. Results: Our results revealed that patients with gout tended to be obese, and there were differences in their lifestyle with exercise, sleep, and smoking, as well as in their preference for fructose drinks, alcohol, and total and structural distribution of meat, milk, eggs, and so on when compared with the healthy volunteers. Importantly, we found the adiponectin in the gout group was lower as compared to the healthy group. Further, metabolomics in combination with KEGG analysis revealed that the biosynthesis of aminoacyl tRNA, biosynthesis of valine, leucine, and isoleucine, metabolism of alanine, aspartic, and glutamate, metabolism of glycine, serine, and threonine, phenylalanine, glycolysis/gluconeogenesis, ketone body synthesis and degradation, metabolism of d‐glutamine, citric acid cycle (TCA cycle), triglyceride metabolism, and others could be used as specific biomarkers of this disease. Conclusion: Recurrent refractory gout and formation of tophus may be related to the diet structures and lifestyles between the patients and the healthy people, and their abnormal metabolic network may be related to the disorder of mitochondrial energy metabolism, which further results in abnormal metabolism of glucose, lipids, amino acids, and deposition of uric acid in joints, peripheral connective tissue, and kidney, inducing an inflammatory response. [ABSTRACT FROM AUTHOR]

Abstract Background Uncontrolled/refractory gout patients are recalcitrant/intolerant to oral urate-lowering therapies (ULTs), experiencing frequent gout flares, functionally limiting tophi, and low quality of life. Pegloticase lowers urate, but anti-pegloticase antibodies limit urate-lowering efficacy and increase infusion reaction (IR) risk. Immunomodulator + pegloticase co-administration may improve treatment response rates, with 79% of MIRROR open-label trial (MIRROR-OL, pegloticase + oral methotrexate) participants meeting 6-month response criteria. Exploratory outcomes from MIRROR-OL are described here. Methods Adults with uncontrolled gout (serum urate [SU] ≥ 6 mg/dL and ULT-intolerance/recalcitrance or functionally limiting tophi) were included. Oral methotrexate (15 mg/week) was administered 4 weeks before and during pegloticase treatment (biweekly 8 mg infusion, ≤ 52 weeks). Exploratory outcomes included change from baseline (CFB) in number of affected joints, Health Assessment Questionnaires (HAQs), and Gout Global Assessments. Results Fourteen patients received ≥ 1 pegloticase infusion, with 13 included in 52-week analyses (1 enrolled before treatment-extension amendment, exited at 24 weeks). Three patients prematurely exited due to SU rise; 10 completed 52-week evaluations (8 completed 52 weeks of co-therapy, 2 completed 24 weeks [met treatment goals]). At 52 weeks, SU averaged 1.1 ± 2.5 mg/dL, with improvements in HAQ pain and health (CFB: − 33.6 and − 0.7, respectively), Patient and Physician Global Assessments (CFB: − 4.6 and − 5.7, respectively), and joint involvement (CFB: − 5.6, − 8.4, − 6.0 tender, swollen, tophi-affected joints, respectively). Two patients underwent dual-energy computed tomography, showing concomitant monosodium urate volume reductions. All patients had ≥ 1 AE, with 92.9% experiencing acute flare. One mild IR (“cough”) occurred and no new safety signals were identified. Conclusion Pegloticase + methotrexate co-therapy resulted in sustained SU-lowering with meaningful improvements in clinical measures, urate burden, and patient-reported outcomes. Trial registration ClinicalTrials.gov (NCT03635957)

Although gout is a common intermittent crystalline arthropathy, tophaceous gout is a rare condition. Flares of this disease are usually treated with anti-inflammatory drugs followed by control of serum uric acid levels. We present a refractory, severe, tophaceous gout overlapping with psoriatic arthritis, presenting with a hyper-inflamed phenotype resistant to conventional anti-inflammatory and hypouricemic agents. Control of the disease was only achieved after the introduction of IL-1-blocking therapy. This case highlights the need to control inflammation as the first step in gout treatment and underscores the increasing need for personalized therapies in more complex patients., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Coelho et al.)

Background: Pegloticase, a PEGylated uricase for uncontrolled gout, rapidly lowers serum urate (SU). Not all patients complete a full-therapy course because anti-pegloticase antibodies can develop, causing efficacy loss and infusion reactions. The literature and clinical trial data indicate that methotrexate co-administration markedly improves pegloticase response rates from the established monotherapy response rate of 42%. Unfortunately, methotrexate use is restricted by kidney disease, which is often present in uncontrolled gout patients. Leflunomide is less restricted in patients with renal dysfunction. This study examined the treatment response rate of pegloticase co-administered with leflunomide. Methods: Patients co-treated with pegloticase (8 mg biweekly infusion) and oral leflunomide (20 mg/day) were included. Patient/treatment characteristics and safety parameters (adverse events [AEs], laboratory parameters) were examined. Pre-infusion prophylaxis was administered (day of infusion: IV solumedrol, night before and morning of infusion: oral fexofenadine or diphenhydramine). Patients were considered treatment responders if ≥ 12 pegloticase infusions were administered and pre-infusion SU < 6 mg/dl at infusion-12. Results: Ten patients (five male, 72.7 ± 12.5 years) were included. The most common comorbidities were chronic kidney disease (90%), hypertension (70%), diabetes mellitus (60%), obesity (60%), and congestive heart failure (50%). Baseline SU was 7.1 ± 2.4 mg/dl and nine patients (90%) had subcutaneous tophi noted. Seven patients (70%) met responder criteria, receiving 26.6 ± 14.0 infusions (range 13–55) with a pre-infusion-12 SU of 0.9 ± 1.5 mg/dl. The three non-responders received < 12 infusions because of unrelated AEs or loss of follow-up. Three patients (30%) experienced AEs. One had unrelated cardiac disease worsening and three gout flares, one had a pre-infusion solumedrol reaction (wooziness/loss of consciousness), and one had two mild, transient increases in liver enzymes. Conclusions: This study supports leflunomide as co-therapy to pegloticase in uncontrolled gout patients. Heterogeneity and high comorbidity burden in uncontrolled gout patients makes having a variety of immunomodulators options important. [ABSTRACT FROM AUTHOR]

Abstract Introduction The aim of this work is to evaluate the impact of the timing of pre-infusion serum uric acid (sUA) test results for use in applying stopping rules for pegloticase to identify patients at risk for infusion reactions (IRs) while on therapy. Methods Data from the phase 3 clinical trials of pegloticase were reviewed and individual uric acid levels of the 85 patients who received the approved regimen of biweekly infusions were examined in relation to the occurrence of IRs. Results Of the 22 patients (26%) who experienced an IR on pegloticase therapy without uric acid stopping rules, only seven (8%) would have had IRs if pegloticase therapy had been discontinued after two consecutive pre-infusion sUA levels above 6 mg/dl. If pegloticase therapy was stopped after a single pre-infusion sUA above 6 mg/dl, only two patients (2%) would have experienced IRs during the clinical studies. Conclusions A pre-infusion sUA level functions as a highly accurate biomarker for identification of patients who are at risk of IRs while on pegloticase therapy. Stopping pegloticase in patients who have a rise in pre-infusion uric acid levels to above 6 mg/dl while on therapy would result in most IRs being avoided. Funding Horizon Pharma.

Introduction: Gout is a common, progressive, systemic inflammatory arthritis caused by hyperuricemia. Current guidelines recommend that serum uric acid (sUA) levels be maintained below 6.0 mg/dl to minimize acute gout attacks, tophi development, and long-term joint and organ damage. This study examined the influence of uncontrolled gout on post-diagnosis comorbidities and medication use. Methods: The Humana Research Database (2007–2016, commercial insurance and Medicare) was searched (PearlDiver tool) for patients who had a gout diagnosis code, claims data for at least 6 months before and after diagnosis, and at least 90 days of continuous urate-lowering therapy within 1 year of diagnosis. Patients with controlled (all sUA measurements < 6.0 mg/dl) and uncontrolled (all sUA measurements ≥ 8.0 mg/dl) gout were further examined and compared to better understand the influence of uncontrolled gout on post-diagnosis comorbidities, medication use, and reasons for seeking medical care. Results: A total of 5473 and 1358 patients met inclusion and classification criteria for the controlled and uncontrolled groups, respectively. Identified comorbidities in both groups included hypertension, hyperlipidemia, diabetes, cardiovascular disease, and chronic kidney disease (CKD). However, the uncontrolled group was more likely to have diabetes, CKD, and cardiovascular disease (including heart failure and atrial fibrillation). Additionally, CKD tended to be more advanced in the uncontrolled gout population (Stage 4–5: 34.6 vs. 22.2%). Overall opioid use was higher in uncontrolled patients. Conclusions: The current study identified differences between controlled and uncontrolled gout patients, including usage of medication, severity of CKD, and prevalence of CKD, diabetes, and heart disease. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this work is to evaluate the impact of the timing of pre-infusion serum uric acid (sUA) test results for use in applying stopping rules for pegloticase to identify patients at risk for infusion reactions (IRs) while on therapy. Methods: Data from the phase 3 clinical trials of pegloticase were reviewed and individual uric acid levels of the 85 patients who received the approved regimen of biweekly infusions were examined in relation to the occurrence of IRs. Results: Of the 22 patients (26%) who experienced an IR on pegloticase therapy without uric acid stopping rules, only seven (8%) would have had IRs if pegloticase therapy had been discontinued after two consecutive pre-infusion sUA levels above 6 mg/dl. If pegloticase therapy was stopped after a single pre-infusion sUA above 6 mg/dl, only two patients (2%) would have experienced IRs during the clinical studies. Conclusions: A pre-infusion sUA level functions as a highly accurate biomarker for identification of patients who are at risk of IRs while on pegloticase therapy. Stopping pegloticase in patients who have a rise in pre-infusion uric acid levels to above 6 mg/dl while on therapy would result in most IRs being avoided. Funding: Horizon Pharma. [ABSTRACT FROM AUTHOR]