Outcome measures for acute and chronic gout

Gout provides some unique challenges in classification and measurement of outcomes. Our aim was to evaluate criteria for classification and to develop and validate optimal instruments to measure outcomes for acute and chronic gout. A planning committee and interested attendees met to propose classification criteria and domains for outcomes. Seven of the current American Rheumatism Association preliminary criteria for classification were proposed as the best current criteria for acute gouty arthritis, pending further studies. The presence of gout is best established by crystal identification, although this technique has limitations. Five domains for acute gout outcomes and 9 for chronic gout were identified along with proposed instruments for testing and validation. The unique problems of gout evaluation can and will be addressed.     

Establishing outcome domains for evaluating treatment of acute and chronic gout

PURPOSE OF REVIEW: Novel therapies for gout have recently been developed which has prompted considerable efforts in defining the relevant outcomes for measurement in intervention trials of gout. This review summarizes the consensus exercises refining domains for measurement and the work of individual groups in assessment of the validity of measurement tools for these domains. RECENT FINDINGS: Recent publications have focused on the consensus exercises and validation studies of measurement tools, particularly in relation to tophus size and imaging. SUMMARY: Consensus on potential outcome domains has been achieved, but measuring these domains requires further validation in observational studies and confirmation of relevance from people with gout. Further work is also required in refining measurements of tophus size and imaging scores. The role of a response criteria measure is also yet to be defined, especially in relation to reduction in flare frequency, or whether composite criteria are necessary.     

Outcome reporting in randomized trials in gout: A systematic scoping review from the OMERACT gout working group assessing the uptake of the core outcome set

ObjectiveThe selection and reporting of core outcome measures in clinical trials is essential for patients, researchers, and healthcare providers for clinical research to have an impact on healthcare. In this systematic scoping review, we aimed to quantify the extent to which gout clinical trials are collecting and reporting data in accordance with the core outcome domains from Outcome Measures in Rheumatology (OMERACT) published in 2009 applicable for both acute and chronic trials and evaluate the reporting according to the core domains before and after the 2009 OMERACT endorsement.MethodsWe searched multiple databases PubMed, EMBASE, the Cochrane Library including the Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews (CDSR) and www.clinicaltrials.gov for randomized controlled trials (RCTs) allocating people with gout versus an active pharmacological gout treatment or a control comparator (no date limitation). We extracted the data in accordance with the core outcome sets, focusing individually on core outcome domains and the core outcome measurements for acute and chronic trials, respectively. In this study ‘Acute trials’ reflect studies that describe interventions for short term management of gout flares, and ‘chronic trials’ describe interventions for long-term urate lowering therapy in the management of gout.ResultsFrom 8,522 records identified in the database search, 134 full text papers were reviewed, and 71 trials were included, of which 36 were acute and 35 were chronic. Only 3 of 36 (8%) acute trials reported all five core domains and none of the 35 included chronic trials reported all 7 core domains. In the acute trials, twenty-seven unique measurement instruments across the 5 core domains were identified. For chronic trials there were 31 unique measurement instruments used across the 7 core domains. Serum urate was reported in 100% of the chronic trials and gout flares in 80%. However, other core domains were reported in <30% of chronic trials. In particular the patient-important domains such as HR-QOL, patient global assessment and activity limitations were rarely reported. A broad variety of different measurement instruments were used to assess each endorsed core domain, a minority of trials used the OMERACT endorsed instruments. For acute trials, the number reporting on all core domains was consistently low and no change was detected before and after the endorsement of the core domains in 2009. None of the included chronic trials reported on all 7 endorsed core domains at any time.ConclusionIn this study we found a low adherence with the intended endorsed (i.e., core) outcome domains for acute and chronic gout studies which represents a poor uptake of the global OMERACT efforts for the minimum of what should be measured in clinical trials. In addition, there is a significant variation in how the OMERACT endorsed outcome domains have been measured. This systematic review demonstrates the need for continuous encouragement among gout researchers to adhere to OMERACT core domains as well as further guidance on outcome measurements reporting.RegistrationProspero: CRD42019151316     

Imaging modalities and monitoring measures of gout

PURPOSE OF REVIEW: Imaging modalities for gout have been mostly restrained to radiographs. Ultrasonography, computed tomography and magnetic resonance imaging are emerging techniques that could be used for diagnosis, evaluation, and monitoring acute and chronic gout. RECENT FINDINGS: Diagnosis of gout is based on urate crystal observation with microscopy. Recently, crystal deposition in the hyaline cartilage has been described to be different in gout from that of calcium pyrophosphate, but validation of the findings is pending. Severity of gout with simple radiographs may not disclose periarticular or intra-articular urate deposition. Ultrasonography, computed tomography and magnetic resonance imaging may improve the evaluation of tophi not apparent in clinical examination or simple radiographs. Monitoring urate deposition may be accomplished with imaging techniques. This would be of outstanding interest for clinical trials, but also for evaluating clinical response to urate-lowering therapy. Although preliminary results evaluating for validity and reliability have been very recently reported for magnetic resonance imaging, computed tomography and ultrasonography, sensitivity to change studies are still pending. Also, monitoring of chronic inflammation with imaging techniques, such as power-Doppler, deserve further studies. SUMMARY: Evidence exists regarding the usefulness of imaging techniques for diagnosis, evaluation of severity, and monitoring of gout, but further investigation is needed.     

Gout: can management be improved?

Ongoing reviews of Cochrane collaboration show that there is still very little reliable information based on randomized controlled trials on which to base treatment decisions in acute and chronic gout. Recent studies have stressed that avoidance of factors contributing to development of gouty attacks such as diuretic therapy, weight gain, and alcohol consumption may lead to a decrease in gouty arthritis. Attention to minidose aspirin and its effect on serum uric acid levels was addressed. A low carbohydrate, high protein and unsaturated fat diet was recommended for gouty patients since they all enhance insulin sensitivity and therefore may promote a reduction in serum uric acid levels. Treatment of gout in transplant recipients brings into focus some of the issues regarding management of gout, because gout is a common problem among transplant patients.     

Gout

PURPOSE OF THE REVIEW: We have reviewed the latest publications on epidemiology of gout; also there have been new insights into the regulation of the inflammation resulting from the regular interaction occurring between MSU crystals and cells in both asymptomatic and symptomatic gouty joints. Finally we review different publications of clinical interest. RECENT FINDINGS: The incidence of gout has been found to be increasing, and the disease starts at an earlier age; this likely relates to changes in dietary habits that lead to the development of the insulin resistance syndrome to which hyperuricemia, and thus gout, relates. Dietary modifications to correct the insulin resistance syndrome and reduce uricemia by increasing renal clearance of urate have heath consequences that go far beyond their beneficial effect on gout. Monosodium urate crystals and cells interact in the asymptomatic joints of gouty patients. The mechanisms that trigger a gouty attack with this background and those responsible for the self-limitation of gouty attacks are not understood. The degree of maturation of the monocytes-macrophages present in the fluid appears to modulate the consequences of the crystal-cell interaction and gives a hint of how from the crystal-cell interaction may result in such divergent consequences as intense inflammation or the absence of symptoms. Interest in gout treatment continues, as shown by the number of papers on the subject reviewed. In most cases, gout is an easy disease to treat, but we do not have enough information about how to handle those few patients with "difficult" disease, and what we refer colloquially to as difficult gout has not been properly defined yet. SUMMARY: Gout incidence and severity appear to be increasing likely in relation to dietary habits. Switching the pattern of secretion of inflammatory mediators with maturating macrophages which contain MSU crystals may be the key to self limitation of gouty attacks. We must define better which gout is a "difficult" one.     

Asymptomatic hyperuricemia: the case for conservative management

The management of asymptomatic hyperuricemia is controversial. Reported benefits from treatment prevention of acute gouty arthritis, chronic tophaceous gout, urolithiasis, or gouty nephropathy. A review of experimental and clinical data suggests that the risks of asymptomatic hyperuricemia are small or unknown and the efficacy of long-term treatment in preventing gout or renal disease is unproved. The costs and risks of prolonged drug administration and practical considerations such as patient compliance mitigate against long-term therapy in asymptomatic persons. We offer some recommendations for an expectant approach to the management of asymptomatic hyperuricemia.     

Acute gouty arthritis complicated with acute ST elevation myocardial infarction is independently associated with short- and long-term adverse non-fatal cardiac events

Large epidemiologic studies have associated gouty arthritis with the risk of coronary heart disease. However, there has been a lack of information regarding the outcomes for patients who have gout attacks during hospitalization for acute myocardial infarction. We reviewed the data of 444 consecutive patients who were admitted to our hospital between 2005 and 2008 due to acute ST elevation myocardial infarction (STEMI). The clinical outcomes were compared between patients with gout attack and those without. Of the 444, 48 patients with acute STEMI developed acute gouty arthritis during hospitalization. The multivariate analysis identified prior history of gout and estimated glomerular filtration rate as independent risk factors of gout attack for patients with acute STEMI (odds ratio (OR) 21.02, 95 % CI 2.96–149.26, p?=?0.002; OR 0.92, 95 % CI 0.86–0.99, p?=?0.035, respectively). The in-hospital mortality and duration of hospital stay did not differ significantly between the gouty group and the non-gouty group (controls). During a mean follow-up of 49?±?28 months, all-cause mortality and stroke were similar for both groups. Multivariate Cox regression showed that gout attack was independently associated with short- and long-term adverse non-fatal cardiac events (hazard ratio (HR) 1.88, 95 % CI 1.09–3.24, p?=?0.024; HR 1.82, 95 % CI 1.09–3.03, p?=?0.022, respectively). Gout attack among patients hospitalized due to acute STEMI was independently associated with short-term and long-term rates of adverse non-fatal cardiac events.     

Treatment of hyperuricemia, gout and other crystalline arthritidies

Gout is a very common joint disease which is due to chronic hyperuricemia and its related articular involvements. Yet it can be cured when appropriately managed. Comprehensive management of gout involves correct identification and addressing all causes of hyperuricemia, treating and preventing attacks of gouty inflammation (using colchicine NSAIDs, and/or steroids), and lowering serum urate (SUA) to an appropriate target level indefinitely. The ideal SUA target is, at a minimum, less than 6 mg/dL (60 mg/L or 360 μmol/L), or even less than 5 mg/dL in patients with tophi. The SUA target should remain at less than 6 mg/dL for long in all gout patients, especially until tophi have resolved. Patient education and adherence to therapy are key point to the optimal management of gout, aspects which are often neglected. Adherence can be monitored in part by continuing, regular assessment of the SUA level. More difficult cases of gout often need a combination of urate lowering therapy (ULT) for both refractory hyperuricemia and chronic tophaceous arthritis. Chronic tophaceous gouty arthropathy which do not respond adequately to optimized oral ULT might benefit from the use of pegloticase, when this is available in, for example, Italy and other European countries. By contrast, in calcium pyrophosphate (CPP) crystal deposition disease (CPPD), as evidenced by pseudo gout attacks or chronic polyarthritis, similar anti-inflammatory strategies have been recommended, but there have as yet been no controlled trials. Of note, there is no treatment for the underlying metabolic disorders able to control the CPPD. Management of crystal-induced arthropathies (CIA) depends not only on clinical expression, namely acute attacks or chronic arthropathy, but also on the underlying metabolic disorder. We will mainly focus on gout as an archetype of CIA.     

Acute gouty arthritis during pyrazinamide treatment: a case report

Gout is a disease caused by an inflammatory response to an aggregation of monosodium urate crystals that develop secondary to hyperuricemia. Throughout its natural history it has four stages: asymptomatic hyperuricemia, acute gouty arthritis, intercritical gout, and chronic tophaceous gout. In this article, we report the case of a patient who had asymptomatic hyperuricemia secondary to pyrazinamide, which was prescribed for pulmonary tuberculosis, and had developed an acute gouty arthritis immediately after the “Feast of Sacrifice” due to a dietary excess of purine.     

Gout in the heart transplant recipient: physiologic puzzle and therapeutic challenge

PURPOSE: Hyperuricemia and gouty arthritis have been associated with cyclosporine use in renal transplant recipients. Patients requiring heart or heart-lung transplantation may have additional risk factors for the development of gout, yet it has not previously been described in this population. We share herein our clinical experience with gouty arthritis in six heart transplant recipients. PATIENTS AND METHODS: During a one-year period, six hospitalized male heart transplant patients were seen in consultation for gouty arthritis. Five were subsequently followed for gout as outpatients; the sixth died within six months. Management included trials of nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, allopurinol, and intra-articular steroid injections, as well as attempts to minimize cyclosporine nephrotoxicity. RESULTS: Three patients had gout in remission at time of transplant surgery, and three others developed gout for the first time two to 45 months after transplantation. Following transplant surgery, both pre-existing and new-onset gout appeared to exhibit an accelerated course, with unusually rapid development of chronic polyarticular disease and tophi in four of the five patients followed for more than six months. Peak serum uric acid levels ranged from 11.0 mg/dL to 16.5 mg/dL. NSAIDs produced reversible renal insufficiency in four patients. Gout-related infections occurred in three patients, one of whom died. CONCLUSION: Acute gouty arthritis may occur in the heart transplant recipient despite concomitant use of immunosuppressive drugs. Cyclosporine, with its attendant hypertension and nephrotoxicity, appears to be the major risk factor for hyperuricemia in this setting, leading to the accelerated development of tophi and chronic polyarthritis. Management is complicated by the patients' renal insufficiency and propensity to infection, as well as by interaction with transplant-related medications. Prevention of hyperuricemia by minimizing cyclosporine nephrotoxicity appears to be the best management strategy, with judicious use of allopurinol for those patients in whom this preventive approach fails.     

Acute gouty arthritis in 4 patients with systemic sclerosis

Gout with rheumatoid arthritis or systemic lupus erythematosus is rarely reported. There has been only one previous case report of gout with systemic sclerosis. We report 4 patients with chronic systemic sclerosis who developed acute gouty arthritis. Gout does occur in systemic sclerosis although the incidence is unknown. Synovial fluid analysis may be necessary to differentiate gout from the arthropathy of systemic sclerosis.     

Acute gouty arthritis during pyrazinamide treatment: a case report

Abstract

Gout is a disease caused by an inflammatory response to an aggregation of monosodium urate crystals that develop secondary to hyperuricemia. Throughout its natural history it has four stages: asymptomatic hyperuricemia, acute gouty arthritis, intercritical gout, and chronic tophaceous gout. In this article, we report the case of a patient who had asymptomatic hyperuricemia secondary to pyrazinamide, which was prescribed for pulmonary tuberculosis, and had developed an acute gouty arthritis immediately after the “Feast of Sacrifice” due to a dietary excess of purine.     

Pathogenesis, diagnostics and therapy of gout

Gout refers to heterogeneous group of metabolic diseases characterized by production of deposits of sodium urate crystals in tissues. Gout manifests as acute gouty arthritis with classic clinical picture, or as chronic gouty arthropathy with periarticular and subcutaneous deposits of sodium urate crystals, i.e. tophi. As for kidney, gout is manifested as acute or chronic gouty nephropathy and urolithiasis. These manifestations occur separately or they are combined. Hyperuricemia of primary gout is caused rather by impaired renal secretion than overproduction of uric acid. Secondary hyperuricemia is associated with many pathological conditions; it is also connected with the use of various medicaments. Pathogenesis of gouty arthritis is critically influenced by sodium urate crystals and inflammatory processes they induce. Hyperuricemia is part of metabolic syndrome X which is associated with unanswered question of the relationship between uric acid and atherosclerosis. Although gouty arthritis is the most frequent inflammatory disease of joints in men over 50 years of age, it is often diagnosed and treated inadequately. On that account, the indication of long-term hypouricemic therapy should be always based on the following criteria: secondary causes of hyperuricemia have to be excluded first; frequency of gout attacks and the risk of their recurrence should be taken into consideration; then it is necessary to search for renal manifestations of gout; and last but not least, we should check whether there are any associated diseases classified in metabolic syndrome X.     

Development of composite measures for psoriatic arthritis: a report from the GRAPPA 2010 annual meeting

Composite disease outcome measures have been used in rheumatology for some time, but a disease-specific composite measure for psoriatic arthritis (PsA) has not yet been validated. Currently, instruments developed for use in rheumatoid arthritis are employed in PsA and include the American College of Rheumatology response criteria (ACR20, 50, and 70) and the Disease Activity Score for 28 and 44 joints (DAS28 and DAS44); however, these instruments do not cover the full spectrum of psoriatic disease. A composite measure is one way of incorporating an assessment of all relevant clinical outcomes into one single measure. By definition, it incorporates several dimensions of disease status, often by combining these different domains into a single score, which in the case of PsA includes joints, skin, entheses, dactylitis, and axial disease. New indices that combine these diverse clinical manifestations of PsA are under development and, in some cases, in the validation phase. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) established the GRAPPA Composite Exercise (GRACE) project to compare existing and emerging composite measures and to develop a new index. At the GRAPPA 2010 meeting, initial results from this project were presented, and existing and new candidate measures were compared.     

Efficacy and safety of pricking-blood therapy for acute gouty arthritis: A protocol for systematic review and meta-analysis

Background:Acute gouty arthritis is a joint inflammatory reaction that affects the daily quality of patients. Previous reviews of pricking-blood therapy for acute gouty arthritis have been growing, but a systematic review is not available. This study aimed to systematically investigate the efficacy and safety of pricking-blood therapy in treating acute gout arthritis.Methods:We will search for relevant literature through Chinese and English databases, with the retrieval deadline being December 2020. Databases include PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, Wanfang Database, and China Biomedical Literature Database. We will also manually search Chinese Acupuncture & Moxibustion, Acupuncture Research, Chinese Clinical Trial Register, and unpublished studies or references. According to the inclusion and exclusion criteria, the literature will be screened, and the data are extracted independently by the 2 researchers. The primary outcomes were the total effective rate and Visual Analogue Scale (VAS) score. RevMan 5.3.5. software will be used for statistical analysis. According to the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE), each evidence of outcome quality will be appraised.Results:This study will provide a comprehensive review of current evidence for a pricking-blood therapy treatment for acute gouty arthritis.Conclusion:The efficacy and safety of picking-blood therapy in treating acute gout arthritis will be evaluated.Unique INPLASY number:INPLASY2020100094.     

A rare and asymptomatic case of mitral valve tophus associated with severe gouty tophaceous arthritis

Gouty arthritis is characterized by the deposition of monosodium urate crystals in the joints and soft tissues. Clinical manifestations include acute and chronic arthritis and tophaceous deposits. Chronic tophaceous gout has become less common since the introduction of the pharmacological treatment. Moreover, cardiac valve gouty tophi have been very rarely reported.     

Tuberculous arthritis presenting as tophaceous gout

A 73-year-old black man with chronic gout presented with a 1 1/2 year history of a swollen painful left wrist. Two draining ulcers over the ventral aspect of his wrist and radiographic changes of the affected area suggested chronic gouty arthritis, but culture of the fluid from the wrist grew Mycobacterium tuberculosis. This case extends the list of infectious agents producing septic arthritis in patients with gout to include Mycobacterium tuberculosis. The need for culture evaluation of joint fluid in patients with chronic as well as acute gout is emphasized.     

New and Pipeline Drugs for Gout

Gout is the most common inflammatory arthropathy in the western world. Affecting millions and accounting for lost wages, increased health care costs, and significant disability, it remains a burden for those afflicted, their families, and the health care system. Despite the availability of a number of effective therapies, gout is often inadequately treated, and its impact on the patients overall health and well-being is underestimated by physicians and patients alike. For many decades, controlling acute flares was the priority in the management of gout. More recently, however, a deeper understanding of gout pathophysiology has resulted in a new appreciation that gout impacts the patient with consequences well beyond the episodes of acute inflammatory arthritis. Reflecting the chronic nature of the disease, gout treatment needs to be chronic as well, and aimed at reducing the underlying cause of gout—hyperuricemia—as well as the symptom of acute attacks. Therapy therefore requires both urate lowering and anti-inflammatory strategies. Unfortunately, the most commonly used urate lowering and anti-inflammatory treatments may be problematic in some gout patients, who often have multiple comorbidities that establish relative contraindications. Novel urate lowering therapies, and new medications to treat and prevent acute gouty flares, can not only improve care of the individual; they can also lead to a better discourse for the edification of those who manage and are managed for this underestimated disease. In this paper, we discuss new and pipeline drugs for acute gout, prophylactic anti-inflammatory therapies as well as urate lowering therapies.     

Quality of life and quality of care for patients with gout

Significant pain, activity limitation, and disability in patients with acute and chronic gouty arthritis lower health-related quality of life. Although many effective therapies are available for gouty arthritis, medication errors are common. One goal of therapy is to reduce the frequency of gout flares by lowering serum uric acid. Further, evidence suggests that the quality of care provided to patients with gout may also impact health-related quality of life. This article reviews evidence concerning quality of care and quality of life for patients with gout.