Hyperuricemia and intravenous fat emulsion are risk factors for gout flares during active gastrointestinal bleeding: a case control study.

OBJECTIVE: It is well-established that patients with a history of gout are more susceptible to experiencing gastrointestinal bleeding. Gout flare during active gastrointestinal bleeding poses a significant challenge due to the gastrointestinal side effects of anti-inflammatory therapy. This study sought to investigate the risk factors associated with gout flares during episodes of gastrointestinal bleeding. METHODS: We conducted a retrospective observational study involving 94 patients who experienced active gastrointestinal bleeding and had a history of gout. This study was conducted at Jinhua Municipal Central Hospital from January 2019 to October 2022. We collected and recorded demographic information and clinical characteristics. RESULTS: Among the gout flare patients, hyperuricemia and intravenous fat emulsion therapy were more prevalent compared to those who remained stable (81.6% vs. 57.8% and 46.9% vs. 24.4%, p < 0.05). Multivariate logistic regression analysis revealed that both hyperuricemia (odds ratio 2.741, 95% CI 1.014-7.413, p = 0.047) and intravenous fat emulsion therapy (odds ratio 2.645, 95% CI 1.046-6.686, p = 0.040) were independent predictors of gout flares. Furthermore, gout attacks occurred sooner in patients receiving intravenous fat emulsion therapy compared to those not receiving it (median: 4 days (interquartile range: 2) vs. median: 5 days (interquartile range: 2.25), p = 0.049). CONCLUSION: Our study revealed a high incidence of gout flares during episodes of active gastrointestinal bleeding, with patients undergoing intravenous fat emulsion therapy and those with hyperuricemia being at increased risk.

Pathogenesis of gout: Exploring more therapeutic target.

Gout is a chronic metabolic and immune disease, and its specific pathogenesis is still unclear. When the serum uric acid exceeds its saturation in the blood or tissue fluid, it is converted to monosodium urate crystals, which lead to acute arthritis of varying degrees, urinary stones, or irreversible peripheral joint damage, and in severe cases, impairment of vital organ function. Gout flare is a clinically significant state of acute inflammation in gout. The current treatment is mostly anti-inflammatory analgesics, which have numerous side effects with limited treatment methods. Gout pathogenesis involves many aspects. Therefore, exploring gout pathogenesis from multiple perspectives is conducive to identifying more therapeutic targets and providing safer and more effective alternative treatment options for patients with gout flare. Thus, this article is of great significance for further exploring the pathogenesis of gout. The author summarizes the pathogenesis of gout from four aspects: signaling pathways, inflammatory factors, intestinal flora, and programmed cell death, focusing on exploring more new therapeutic targets.

Efficacy and safety of orlistat in male patients with overweight/obesity and hyperuricemia: results of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Obesity is associated with elevated serum uric acid (SUA) levels and frequent gout flares. Losing weight can reduce the SUA level and gout flares. The effect of orlistat on SUA levels and gout flares in patients with overweight/obesity and hyperuricemia (HUA) has not been extensively studied. This study investigated the effects of orlistat on SUA levels and gout flares compared to placebo in overweight and obese patients with HUA. METHODS: A total of 72 Chinese patients with overweight/obesity and HUA were randomly divided into a placebo group (35, 48.6%) and an orlistat group (37, 51.4%); the trial lasted 12 weeks. The primary endpoints were the relative changes in body weight, the SUA level, and gout flares in the per-protocol population. RESULTS: Orlistat reduced the proportion of patients with gout flares (log-rank P = 0.023, hazard ratio = 0.31, 95% confidence interval 0.11-0.85). There was no significant difference in SUA level between the two groups. The average weight loss of the orlistat group was 2.85 kg, and the average weight loss of the placebo group was 0.76 kg. The weight loss in the orlistat group was significantly greater than that in the control group (P < 0.05). CONCLUSIONS: This study is the first to demonstrate that orlistat has no significant effect on SUA levels in patients with overweight/obesity and HUA. The utility of orlistat as an adjunct therapy to prevent gout flares during weight loss in patients with HUA was emphasized. TRIAL REGISTRATION: Clinicaltrials.gov NCT05496075.

Risk of gout flare after medication: prescription symmetry sequence analysis.

OBJECTIVES: The research aimed to study the following questions: (1) five well-known gout-related medications were selected to test the validity of the prescription symmetry sequence analysis in Taiwan; (2) four exploratory medications were selected to test their relation to gout flares. METHODS: We utilized the 2003-2017 dataset of the Taiwan National Health Insurance Program containing all claims data with 2 million beneficiaries as a data source. In order to explore the temporal association, we designed a scenario of medication-induced gout flares. Nine medications were selected as the index agent, including aspirin (low-dose), thiazide diuretics, loop diuretics, ethambutol, pyrazinamide, metformin, pioglitazone, fenofibrate, and losartan. The gout flare was defined as subjects with use of the marker agent for treatment of gout flares. The observation-window period between initiation of the index agent and initiation of the marker agent was 1 year. Subjects who used an index agent and a marker agent on the same day were excluded. The prescription symmetry sequence analysis was carried out to compare the observed number of persons who took an index agent prior to starting a marker agent with the observed number of persons who took a marker agent before starting an index agent. The adjusted sequence ratio (adjusted SR) with 95% confidence interval was applied to estimate the relation between an index agent and the marker agent. RESULTS: Among five medications including aspirin (low-dose), thiazide diuretics, loop diuretics, ethambutol, and pyrazinamide, the adjusted sequence ratio ranged from 1.15 to 3.35 and all reached statistical significance. Fenofibrate use and losartan use were associated with a lower probability of gout flares, with reaching statistical significance (adjusted SR = 0.60 for fenofibrate and adjusted SR = 0.92 for losartan). Metformin use was associated with a greater probability of gout flares, with reaching statistical significance (adjusted SR = 1.14). Pioglitazone use did not reach statistical significance. CONCLUSION: Based on the confirmatory analysis including five well-known gout-related medications, this study supports that the prescription symmetry sequence analysis can be used to detect an adverse drug event associated with one potential offending agent. The exposure to fenofibrate or losartan might be a protective factor against gout flares. Metformin use could be associated with a greater probability of gout flares, but this finding should be validated by other studies. KEY POINTS: • What is already known about this subject? 1. The prescription symmetry sequence analysis is a useful method for detecting an adverse drug reaction associated with one potential offending drug. 2. Numerous medications are found to induce gout flares. • What does this study add? 1. The prescription symmetry sequence analysis supports the evidence that aspirin (low-dose), thiazide diuretics, loop diuretics, ethambutol and pyrazinamide are associated with a greater probability of gout flares. 2. The exposure to fenofibrate or losartan might be a protective factor against gout flares. 3. Metformin use could be associated with a greater probability of gout flares. • How might this impact on clinical practice or future developments? 1. Clinicians should always consider the possibility of medication-induced gout flares. If gout flares develop, discontinuation of risky medications is the first step. Then prescribing cascades can be eliminated.

Rare Case of Gout Leading to Septic Arthritis, Osteomyelitis, and Septic Shock in an Elderly Patient.

Gout is a common, chronic inflammatory arthritis that oftentimes accompanies an initial acute and painful attack characterized by intense pain and swelling. Although it may present in different sites such as the ankles, wrists, knees, elbows, and fingers, the lower extremities are the most common site of involvement. The pathophysiology of gout is complex, but typically, the deposition of monosodium urate crystals within the joint space and the subsequent acute inflammatory response play an important role. Following an acute attack, chronic gout can present with tophi or nests of monosodium urate crystals surrounded by macrophages and multinucleated giant cells that trigger granulomatous inflammation. Progressively, chronic gout can lead to several other complications including joint destruction, gout nephropathy, spinal compression, and secondary infections. In this case report, we present an elderly female patient with chronic gout and multiple tophi formations in all digits of both of her hands. The tophi led to an ulceration and secondary septic arthritis and osteomyelitis of the right second digit. By the time the patient presented and was admitted to the hospital, she was in septic shock. We will review the pathogenesis of gout and other cases of concomitant septic arthritis and gout, as well as medical management and necessary surgical intervention as a means of treatment.

An Atypical Presentation of a Polyarticular Gout Flare: Case Report.

A 54-year-old man with a history of hypertension, atrial fibrillation, chronic kidney disease, nonischemic cardiomyopathy, osteoarthritis, and gout presented to the emergency department (ED) with dysuria, painful scrotal swelling, severe bilateral flank pain, back pain, atraumatic right arm (elbow and distally) pain and swelling, and bilateral knee pain. His physical exam was notable for fever, tachycardia, bilateral costovertebral angle (CVA) tenderness, exquisite pain, erythema, and swelling of bilateral knees and the right arm (elbow and distally). He met Systemic Inflammatory Response Syndrome (SIRS) criteria, was placed on Ceftriaxone for presumed septic pyelonephritis, and was admitted to the medicine team. With initially unremarkable imaging studies, the differential diagnosis was broadened, and subsequent infectious workups yielded grossly normal results. At the end of hospital day one, the patient remained febrile and without symptomatic improvement. Rheumatology was consulted and empirically treated; the patient with a dose of Anakinra due to concerns about a polyarticular flare of crystalline arthropathy. Subsequent arthrocentesis confirmed a final diagnosis of a polyarticular gout flare. This case highlights the diagnostic challenges a polyarticular gout flare poses and the importance of early involvement of specialists for prompt recognition, treatment, and avoidance of unnecessary interventions.

A 55-Year-Old Male With Systemic Gout Complicated by Septic Shock.

Tophaceous gout is the systemic deposition of uric acid which can induce cutaneous ulceration. We present the case of a 55-year-old male with chronic tophaceous gout whose initial presentation was complicated by septic shock due to methicillin-sensitive Streptococcus aureus bacteremia and superinfection of many of his affected joints. The case and discussion will focus on the extent of his infections and approaches to preventative care.

Interleukin-1ß inhibitors for the management of acute gout flares: a systematic literature review.

OBJECTIVES: The objective of this systematic review was to assess the effects of interleukin-1ß (IL-1ß) inhibitors on gout flares. METHODS: Studies published between 2011 and 2022 that evaluated the effects of IL-1ß inhibitors in adult patients experiencing gout flares were eligible for inclusion. Outcomes including pain, frequency and intensity of gout flares, inflammation, and safety were assessed. Five electronic databases (Pubmed/Medline, Embase, Biosis/Ovid, Web of Science and Cochrane Library) were searched. Two independent reviewers performed study screening, data extraction and risk of bias assessments (Cochrane Risk of Bias Tool 2 for randomised controlled trials [RCTs] and Downs and Black for non-RCTs). Data are reported as a narrative synthesis. RESULTS: Fourteen studies (10 RCTs) met the inclusion criteria, with canakinumab, anakinra, and rilonacept being the three included IL-1ß inhibitors. A total of 4367 patients with a history of gout were included from the 14 studies (N = 3446, RCTs; N = 159, retrospective studies [with a history of gout]; N = 762, post hoc analysis [with a history of gout]). In the RCTs, canakinumab and rilonacept were reported to have a better response compared to an active comparator for resolving pain, while anakinra appeared to be not inferior to an active comparator for resolving pain. Furthermore, canakinumab and rilonacept reduced the frequency of gout flares compared to the comparators. All three medications were mostly well-tolerated compared to their comparators. CONCLUSION: IL-1ß inhibitors may be a beneficial and safe medication for patients experiencing gout flares for whom current standard therapies are unsuitable. REVIEW PROTOCOL REGISTRATION: PROSPERO ID: CRD42021267670.

Gout in an Obese Patient with Nonalcoholic Steatohepatitis on a Thiazide Diuretic and Association Between Hyperuricemia and Nonalcoholic Steatohepatitis: A Case Report.

Gout is a common inflammatory arthritis caused by increased uric acid crystals in and around various joints, mainly the big toe in adults. It happens due to the increase of urate or uric acid levels either because of increased production or decreased excretion from the body. Uric acid is the final product of purine metabolism, and many patients with hyperuricemia may remain asymptomatic. We present a case of a 46-year-old male who presented to the ambulatory care unit with the clinical features of acute pharyngitis and left toe pain for the past three days. On further questioning, he added that he had pain in the left lumber region and left side of the toe for the past few months. He also had a known case of type 2 diabetes mellitus, hypertension, and gastritis, for which he has been taking the thiazide diuretic, angiotensin-converting enzyme (ACE) inhibitors, metformin, sitagliptin, aspirin, and atorvastatin. Laboratory tests showed elevated uric acid along with raised inflammatory markers. As a result, he was referred to the specialist for arthrocentesis in order to confirm the diagnosis, and the thiazide diuretic was replaced with calcium channel blockers. He also suffered from nonalcoholic steatohepatitis (NASH) based on his ultrasound abdomen. On the follow-up visit, his symptoms had resolved, and his uric acid level had normalized.

Dual-Energy Computed Tomography (DECT) Resolves the Diagnostic Dilemma in an Atypically Presenting Case of Gout.

Gout is a common inflammatory arthropathy that presents as acute monoarthritis, most commonly of the first metatarsophalangeal (MTP) joint. Chronic polyarticular involvement may lead to confusion with other inflammatory arthropathies, including rheumatoid arthritis (RA). A thorough history, physical examination, synovial fluid analysis, and imaging are keys to establishing a correct diagnosis. Although a synovial fluid analysis remains the gold standard, the affected joints may be difficult to access by arthrocentesis. In cases where a large monosodium urate (MSU) crystal deposition is in the soft tissues - the ligaments, bursae, and tendons, it becomes a clinical impossibility. In such cases, dual-energy computed tomography (DECT) can assist in differentiating gout from other inflammatory arthropathies, including RA. Additionally, DECT can perform quantitative analysis of tophaceous deposits and, therefore, assess response to treatment.

Elevated serum CA72-4 predicts gout flares during urate lowering therapy initiation: a prospective cohort study.

OBJECTIVE: Gout flares during urate-lowering therapy (ULT) initiation are common, but predictors of these flares are poorly understood. The aim of this study was to determine whether serum CA72-4 is an independent predictor for gout flares during ULT initiation. METHODS: A prospective cohort study was conducted between March 2021 and January 2022. Men with gout, at least one gout flare in the past year, and at least three serum CA72-4 measurements in the previous six months were enrolled. Participants were grouped according to their highest recorded serum CA72-4 levels (above or within the normal range). All participants took oral febuxostat 20 mg daily without flare prophylaxis therapy, and attended face-to-face visits every four weeks until 24 weeks. The incidence of gout flare was compared between the two groups. Backward stepwise logistic regression analyses were used to identify risk factors associated with flares. Receiver operating characteristic curve analysis was used to evaluate prediction efficacy. RESULTS: A total of 193 completed the study (79 with high CA72-4; 114 with normal CA72-4). The cumulative incidence of at least one gout flare was 48.1% (62.1% in the high CA72-4 group, 38.4% in the normal CA72-4 group, P = 0.001), and recurrent (≥2) flares was 33.0% (47.1% in the high CA72-4 group, 23.2% in the normal CA72-4, P < 0.001). High CA72-4, disease duration, intra-articular tophus size, glucose, high-density lipoprotein-cholesterol and ESR were independent risk factors for gout flares. Serum CA72-4 alone predicted recurrent flares with an area under the curve of 0.63 (95% CI = 0.54, 0.71), and 0.78 (95% CI = 0.71, 0.85) when combined with other independent variables. CONCLUSION: High serum CA72-4 predicts the risk of gout flares during ULT initiation. TRIAL REGISTRATION: ChiCTR; https://www.chictr.org.cn/; ChiCTR2100043573.

Feasibility of conducting a randomized, placebo-controlled study assessing whether omega-3 fatty acids prevent gout flares when starting urate-lowering treatment.

Objective: The aim was to test the feasibility of a randomized controlled trial exploring whether omega-3 fatty acid supplementation limits gout flares during treat-to-target urate-lowering treatment (T2T-ULT). Methods: Adults with at least one gout flare in the past 12 months and serum urate (SU) ≥360 µmol/l were recruited from general practices (primary method) and randomly assigned 1:1 to receive omega-3 fatty acid supplementation (4 g/day) or placebo for 28 weeks. At week 5, participants began T2T-ULT. The primary outcome was drop-out rate. Secondary outcomes were recruitment rate, outcome data completeness, the number, severity and duration of gout flares between weeks 5 and 28, and study drug compliance. Results: Ninety-five per cent of randomized participants (n = 60) completed all study visits. The primary method recruitment rate was 2.2%. Fifty and 42 participants achieved SU < 360 and 300 µmol/l (6 and 5 mg/dl), respectively. The number of gout flares [median (interquartile range): active 1 (0-2) and placebo 1 (0-2)], flare duration [mean (s.d.): active 7.00 (4.52) days and placebo 7.06 (8.14) days] and time to first flare [hazard ratio (95% CI) 0.97 (0.50, 1.86)] were comparable between both arms. Study drug compliance was high and comparable in both arms [median (interquartile range) returned capsule count: active 57 (26-100) and placebo 58 (27-154)]; red blood cell omega-3 fatty acid index increased twofold in the active arm and remained unchanged in the control arm. Conclusion: The study demonstrated feasibility and provided useful metrics for conducting a community-based gout flare prophylaxis trial. Study registration: ISRCTN; https://www.isrctn.com/; ISRCTN79392964.

A rare case of tophaceous gout manifesting as an osteolytic lesion of the acromioclavicular joint.

An osteolytic lesion on imaging can be considered malignancy until proven otherwise. However, advanced stages of gout have presented with sclerotic rims and lytic lesions thought to be due to overexpression of osteoclasts. Patients have been found to demonstrate osteolytic lesions in patellar regions, which are common locations for gout to manifest; however, to our knowledge, no other cases of osteolytic gout in the acromioclavicular joint have been reported at this time. We report a rare case of a 56-year-old male who presented with acute-on-chronic left upper extremity pain and was found to have an osteolytic lesion of the shoulder on imaging. This lesion was later biopsied and found to be histologically consistent with gout. This case report aims to elucidate further understanding of the various ways that gout can present, to diagnose and treat these patients more effectively.

Palpable tophi and more comorbidities associated with adherence to urate-lowering medical therapy in a Chinese gout cohort.

OBJECTIVE: Urate-lowering therapy (ULT) nonadherence is common and problematic in gout. Since, sociocultural factors affect adherence, we analyzed a Chinese cohort. METHODS: We studied 903 Chinese gout patients aged 46.4±14.7 years (mean±SD), uniquely extending to assay of 2-year medication possession ratio (MPR) ≥80% defined as high adherence. Multivariable logistic regression analyses evaluated factors linked with adherence and ULT target attainment. RESULTS: Characterization of ULT outcomes in this cohort revealed that after 2 years ULT, MPR ≥80% patients had better target serum urate (SU) achievement (from 23.3% to 71.0%, P <0.001), lower flare frequency and palpable tophi compared to MPR <80%. However, only 44.7% of cohort subjects had MPR ≥80%. Male sex (OR 3.68), gout onset age >60 years (OR 3.51), disease duration >5 years (OR 1.70), more comorbidities (OR 1.74), baseline palpable tophi (OR 1.53), SU <6mg/dL (360µmol/L) (OR 1.92) and more frequent follow-up visits (OR 1.98) were significantly associated with high adherence. Nevertheless, significant independent risk factors for failed SU target achievement included male sex (OR 0.36) and more comorbidities (OR 0.85). CONCLUSION: Despite adherence to ULT linked to better outcomes for flares and tophi, the more adherent Chinese male patients and those with more comorbidities had decreased target SU attainment. Differences in adherence of Chinese gout patients compared to several primarily Western studies emphasize the importance of not stereotyping gout patients for projected nonadherence. Results underline the dual importance of identifying gout patients more likely to be ULT-adherent and leveraging adherence to drive treatment to SU target.

Risk of gout flares after COVID-19 vaccination: A case-crossover study.

OBJECTIVE: Routine vaccinations are associated with an increased risk of gout flares. We examined the association between COVID-19 vaccination, an immunization program implemented to a large proportion of population, and the risk of gout flares. METHODS: We conducted a time-stratified case-crossover study among patients with gout who experienced gout flares between December 2020 and September 2021, using data from The Health Improvement Network. We compared the risk of gout flares on each of the seven days on and after the day of COVID-19 vaccination vs. no vaccination during that period using conditional logistic regression. In addition, we performed subgroup analyses stratified by different COVID-19 vaccines (i.e., BNT162b2, hereafter referred to as BNT, and ChAdOx1 nCov-19, hereafter referred to as ChAd). RESULTS: Among 5,904 patients with gout (mean age: 63·1 years; 85·5% male) who experienced gout flares within one month, the risk of gout flares slightly increased on the second day after COVID-19 vaccination (odds ratio: 1·44; 95% CI: 1·02 to 2·07). The risk of gout flares also slightly increased after receiving COVID-19 vaccine on other remaining days (ORs ranged from 1·03 to 1·22); however, none of them was statistically significant. An increased risk of gout flares on the second day after vaccination was mainly observed for the ChAd vaccine (odds ratio: 1·44; 95% CI: 1·00 to 2·05), but not for BNT vaccine (odds ratio: 1·18; 95% CI: 0·67 to 2·02). CONCLUSION: COVID-19 vaccination, mainly ChAd vaccination, slightly increases the risk of gout flares on the second day after vaccination. This finding reassures the safety of COVID-19 vaccination for patients with gout.

Risk Factors for Postsurgical Gout Flares after Thoracolumbar Spine Surgeries.

Gouty arthritis is the most common form of inflammatory arthritis and flares frequently after surgeries. Such flares impede early patient mobilization and lengthen hospital stays; however, little has been reported on gout flares after spinal procedures. This study reviewed a database of 6439 adult patients who underwent thoracolumbar spine surgery between January 2009 and June 2021, and 128 patients who had a history of gouty arthritis were included. Baseline characteristics and operative details were compared between the flare-up and no-flare groups. Multivariate logistic regression was used to analyze predictors and construct a predictive model of postoperative flares. This model was validated using a receiver operating characteristic (ROC) curve analysis. Fifty-six patients (43.8%) had postsurgical gout flares. Multivariate analysis identified gout medication use (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.14−0.75; p = 0.009), smoking (OR, 3.23; 95% CI, 1.34−7.80; p = 0.009), preoperative hemoglobin level (OR, 0.68; 95% CI, 0.53−0.87; p = 0.002), and hemoglobin drop (OR, 1.93; 95% CI, 1.25−2.96; p = 0.003) as predictors for postsurgical flare. The area under the ROC curve was 0.801 (95% CI, 0.717−0.877; p < 0.001). The optimal cut-off point of probability greater than 0.453 predicted gout flare with a sensitivity of 76.8% and specificity of 73.2%. The prediction model may help identify patients at an increased risk of gout flare.

Comparison of Benzbromarone and Allopurinol on Primary Prevention of the First Gout Flare in Asymptomatic Hyperuricemia.

Objectives. Whether uric acid-lowering agent use in asymptomatic hyperuricemia can reduce the development of the first gout flare remains unsettled. The goal of the present research was to test the efficacy of benzbromarone and allopurinol on primary prevention of the first gout flare in persons with asymptomatic hyperuricemia in Taiwan. Methods. One observational cohort study was constructed to examine the 2001−2015 dataset adapted from the National Health Insurance Program of Taiwan containing the claims data of 2 million beneficiaries. Asymptomatic hyperuricemia was considered as individuals on uric acid-lowering therapy who did not have gout flares. Individuals aged 20−84 without gout flares who had the use of benzbromarone alone were assigned into a benzbromarone group. Individuals ages 20−84 without gout flares who had the use of allopurinol alone were assigned into an allopurinol group. The final study included 6111 pairs of 1:1 propensity score-matched individuals from both benzbromarone and allopurinol groups. The end point was assigned as individuals who were newly diagnosed with their first gout flare. The incidence rate of the first gout flare was estimated between the benzbromarone and allopurinol groups. A Cox proportional hazards regression model was applied to explore the hazard ratio and 95% confidence interval of the first gout flare related to benzbromarone use and allopurinol use. Results. The incidence rate of the first gout flare was lower in the benzbromarone group compared with an allopurinol group (3.29 versus 5.46 per 1000 person-months, incidence rate ratio = 0.60 and 95% confidence interval = 0.56−0.64). After adjustment for co-variables, the adjusted hazard ratio of the first gout flare was 0.63 (95% confidence interval = 0.59−0.68, p < 0.001) for the benzbromarone group when compared with the allopurinol group. Conclusion. People with asymptomatic hyperuricemia taking benzbromarone have a lower hazard of developing their first gout flare when compared with those taking allopurinol. Based on the medication safety, the therapeutic effects and the low price, with oral administration once daily, we suggest that benzbromarone should be the first drug of choice if clinicians are treating asymptomatic hyperuricemia.

Effectiveness and safety of anakinra in gouty arthritis: A case series and review of the literature.

Background: Gout is the most common type of inflammatory arthritis. Nonsteroidal anti-inflammatory drugs, corticosteroids, and colchicine are the first-line agents, although they are contraindicated in many patients. Blockade of IL-1 with anakinra can be an alternative. Objective: To present a case series of 10 difficult-to-treat gout patients treated with anakinra and perform a scoping review of the effectiveness and safety of anakinra in gout patients. Methods: A total of 1,519 citations were screened. The reviewers ran a two-stage screening process by title/abstract and full-text reading. Thirty-eight articles finally met the selection criteria and were included for data extraction and synthesis. Experience in difficult-to treat and complex clinical scenarios, such as active infection, hemodialysis, and transplantation, were specifically described. Results: The study sample comprised 551 patients, from whom 648 flares were finally analyzed. The mean age was 57.9 years, and 82.9% were men. The clinical presentation was polyarticular in 47.5% and tophaceous in 66.9%. Sixty-five patients with an active infection, 41 transplanted patients and 14 in haemodyalisis treated with anakinra are described. More than half of the patients had >1 associated comorbidity. Anakinra was effective both for flares (94%) and for long-term treatment (91%) and well tolerated. In the case of flares, 34 (6.7%) adverse effects were registered. Adverse events were more prevalent in long-term treatment. Conclusion: Anakinra was effective and safe for management of gout flares in difficult-to-treat patients. It has been used in multiple complex scenarios, such as active infections, dialysis, transplantation, chronic kidney disease, and polyarticular gout. Anakinra has also proven effective as long-term treatment, although there are more concerns about its safety.

Acute gout flare of bilateral first metatarsophalangeal joints due to ibrutinib use in chronic lymphocytic leukemia.

INTRODUCTION: Bruton tyrosine kinase inhibitors represent important tools in the therapeutic armamentarium against chronic lymphocytic leukemia (CLL) and other B-lymphoproliferative disorders. CASE REPORT: We describe herein a unique 65-year-old patient who presented with bilateral foot pain four months after starting treatment with ibrutinib for CLL. Of note, the patient had previously been diagnosed with gout, and was taking allopurinol prophylactically at the time of the event. Compliance with allopurinol was in excess of 99%. Yet, he was diagnosed with acute gout flare of bilateral first metatarsophalangeal (MTP) joints.Management & Outcome: Ibrutinib dose was reduced by one third, and the patient's gout flare up was treated with ibuprofen as needed. After symptoms abated, ibrutinib was continued at 2/3rds of the dose, with an excellent CLL control. The patient tolerated this dose without any further adverse effects.Discussion/Conclusions: We have reported a unique side effect of acute bilateral first MTP joint gout flare likely triggered by ibrutinib use for CLL while the patient was taking a xanthine oxidase inhibitor. The mechanism by which ibrutinib caused this phenomenon remains to be elucidated.

The GOUT-36 prediction rule for inpatient gout flare in people with comorbid gout: derivation and external validation.

OBJECTIVES: To develop and validate a gout flare risk stratification tool for people with gout hospitalized for non-gout conditions. METHODS: The prediction rule for inpatient gout flare was derived from a cohort of 625 hospitalized people with comorbid gout from New Zealand. The rule had four items: no pre-admission gout flare prophylaxis, no pre-admission urate-lowering therapy, tophus and pre-admission serum urate >0.36 mmol/l within the previous year (GOUT-36 rule). Two or more items are required for the classification of high risk for developing inpatient gout flares. The GOUT-36 rule was validated in a prospective cohort of 284 hospitalized people with comorbid gout from Thailand and China. RESULTS: The GOUT-36 rule had a sensitivity of 75%, specificity of 67% and area under the curve of 0.71 for classifying people at high risk for developing inpatient gout flares. Four risk groups were developed: low (no items), moderate (one item), high (two items) and very high risk (three or four items). In a population with frequent (overall 34%) in-hospital gout flares, 80% of people with very high risk developed inpatient flares while 11% with low risk had inpatient flares. CONCLUSION: The GOUT-36 rule is simple and sensitive for classifying people with high risk for inpatient gout flares. The rule may help inform clinical decisions and future research on the prevention of inpatient gout flares.