Joint Clinical Consensus Statement of the American College of Foot and Ankle Surgeons® and the American Association of Nurse Practitioners®: Etiology, Diagnosis, and Treatment Consensus for Gouty Arthritis of the Foot and Ankle.

Gout is a condition that commonly affects the foot and ankle, and practitioners who treat these structures should be aware of the methods to diagnose and treat this form of arthritis. Practitioners also need to recognize extra-articular manifestations of the disease. Although the acutely red, hot, swollen joint is a common presentation, chronic tophaceous gout can be associated with pain, nodule formation, and cutaneous compromise. Since the underlying causes that lead to excessive monosodium urate deposition may be treatable, early and accurate diagnosis can be very beneficial and may even prevent articular degeneration.

Ultrasound-guided synovial Tru-cut biopsy: indications, technique, and outcome in 111 cases.

OBJECTIVE: To investigate the diagnostic performance of ultrasound-guided synovial biopsy. METHODS: Clinical notes, pathology and microbiology reports, ultrasound and other imaging studies of 100 patients who underwent 111 ultrasound-guided synovial biopsies were reviewed. Biopsies were compared with the final clinical diagnosis established after synovectomy (n = 43) or clinical/imaging follow-up (n = 57) (mean 30 months). RESULTS: Other than a single vasovagal episode, no complication of synovial biopsy was encountered. One hundred and seven (96 %) of the 111 biopsies yielded synovium histologically. Pathology ± microbiology findings for these 107 conclusive biopsies comprised synovial tumour (n = 30, 28 %), synovial infection (n = 18, 17 %), synovial inflammation (n = 45, 42 %), including gouty arthritis (n = 3), and no abnormality (n = 14, 13 %). The accuracy, sensitivity, and specificity of synovial biopsy was 99 %, 97 %, and 100 % for synovial tumour; 100 %, 100 %, and 100 % for native joint infection; and 78 %, 45 %, and 100 % for prosthetic joint infection. False-negative synovial biopsy did not seem to be related to antibiotic therapy. CONCLUSION: Ultrasound-guided Tru-cut synovial biopsy is a safe and reliable technique with a high diagnostic yield for diagnosing synovial tumour and also, most likely, for joint infection. Regarding joint infection, synovial biopsy of native joints seems to have a higher diagnostic yield than that for infected prosthetic joints. KEY POINTS: • Ultrasound-guided Tru-cut synovial biopsy has high accuracy (99 %) for diagnosing synovial tumour. • It has good accuracy, sensitivity, and high specificity for diagnosis of joint infection. • Synovial biopsy of native joints works better than biopsy of prosthetic joints. • A negative synovial biopsy culture from a native joint largely excludes septic arthritis. • Ultrasound-guided Tru-cut synovial biopsy is a safe and well-tolerated procedure.

[Evidence-based recommendations for diagnostics and treatment of gouty arthritis in the specialist sector : S2e guidelines of the German Society of Rheumatology in cooperation with the AWMF]. / Evidenzbasierte Empfehlung zur Diagnostik und Therapie der Gichtarthritis im fachärztlichen Sektor : S2e-Leitlinie der Deutschen Gesellschaft für Rheumatologie (DGRh) in Kooperation mit der AWMF.

Due to the increasing prevalence of gout, particularly in old age, the disease is becoming of increasing importance in Germany. Gout is one of the most common forms of recurrent inflammatory arthritis and is induced by the deposition of monosodium urate crystals in synovial fluid and other tissues. The principal goals of therapy in chronic gout are the symptomatic treatment of the acute joint inflammation and the causal treatment of the underlying metabolic cause, the hyperuricemia. Only a consistent and permanent reduction of the serum uric acid level ultimately results in an efficient avoidance of further gout attacks and therefore the prevention of structural damage. Due to an often inadequate treatment of gout, the target of healing the disease is often not achieved. A correct and timely diagnosis and adequate assessment of comorbidities associated with gout are, however, of substantial importance for patient and physician to achieve remission of the disease. In order to create a solid basis for a timely and effective treatment of affected patients, in 2016 the German Society of Rheumatology (DGRh) initiated the development of S2e guidelines on gouty arthritis for specialists. This article summarizes these S2e guidelines on the management of gouty arthritis in the specialist sector.

Cubital tunnel syndrome secondary to gouty tophi: A case report.

Gout is a chronic rheumatic disease resulting from accumulation of monosodium urate crystals in tissues. The most important risk factor for the disease is hyperuricaemia. Precipitation of uric acid in the joint in the form of monosodium urate crystals is the main factor responsible for triggering attacks of arthritis. Tophi occur as a result of urate crystals that precipitate into joints and surrounding tissues. Tophi can erode the bone where they are located and cause compression in soft tissue due to a mass effect. The following case report describes a case of cubital tunnel syndrome developed in association with tophaceous compression and resolved with surgical decompression in a patient with chronic gouty arthritis.

Value and Progress of Ultrasound in Diagnosis and Treatment of Hyperuricemia.

Uric acid is the final end-product of purine metabolism and 70% of it is excreted through the kidneys. Chronic hyperuricemia can easily cause gout and meanwhile may affect the kidneys and cardiovascular system. In recent years,the incidences of hyperuricemia and gout have gradually increased. This article summarizes the correlation of hyperuricemia with hyperuricemic nephropathy,gouty arthritis,non-alcoholic fatty liver disease,and carotid atherosclerosis and the role of color Doppler ultrasound in the diagnosis of these lesions.

Pathogenesis and Clinical Management of Gouty Arthritis.

Gout, the most common of the crystal arthritides is a result of disturbed uric acid metabolism and precipitation of urate crystals in extra cellular space of joints, periarticular tissue, bones and other organs. In the West, gout affects around 1% of adult men over 45 years of age. The estimated incidence being 0.6 to 2.1 per 1000 per year, with a prevalence of 9.5 to 13.5 per 1000 persons of all ages.1 The incidence of gout has been on rise globally; potentially attributable to recent shifts in diet, lifestyle, medical care, and increased longevity.2 Gout is three to four times more common in males than in pre-menopausal females; incidence in women increases after menopause and after the age of 60, approaches that in men.3 This update aims to highlight recent developments in understanding pathogenesis of gout along with current management strategies.

[Rheumatology emergencies in general practice]. / Rheumatologische Notfälle im Alltag des Hausarztes.

In rheumatology there may occur emergencies especially in the field of inflammable diseases, the sudden occlusion of the central retinal artery in temporal arteritis as an example. Such incidents are rare. The general practitioner is more often confronted with not necessarily threatening, but very painful and function obstructing acute cases. In this paper four typical problems are represented which can be seen in everyday practice, sometimes misleading to wrong actions and therefore needing to be recognized in time and treated correctly: acute low back pain, periarthropathy of the shoulder joint, crystal arthritis and ruptured Baker's cyst.

An appraisal of the 2012 American College of Rheumatology Guidelines for the Management of Gout.

PURPOSE OF REVIEW: Appraisal of the 2012 American College of Rheumatology (ACR) Guidelines for the Management of Gout. RECENT FINDINGS: The ACRs first clinical practice guidelines for the management of gout focus on recommendations for nonpharmacologic and pharmacologic approaches to hyperuricaemia and the treatment and prophylaxis of acute gouty arthritis. The RAND/UCLA appropriateness methodology employed assessed risks and benefits of alternative treatments for efficacy, safety and quality but not for cost-effectiveness. Novel recommendations include the use of either allopurinol or febuxostat for first-line urate-lowering drug therapy (ULT), screening for HLA-B*5801 prior to initiation of allopurinol in Asians at relatively high risk for allopurinol hypersensitivity, and the use of pegloticase for patients with severe, symptomatic, tophaceous gout refractory to, or intolerant of, appropriately dosed ULTs. Appraisal and comparison with other guidelines using Guidelines International Network and Appraisal of Guidelines, Research and Evaluation (AGREE II) criteria showed good scores for scope and purpose, stakeholder involvement, rigour of development, clarity of presentation, editorial independence and, overall quality, but not for applicability. SUMMARY: The ACR guidelines provide comprehensive, up-to-date, good-quality, evidence-based, expert consensus recommendations for the management of gout in clinical practice but score poorly for applicability. To improve the management of gout in the community a summary of key recommendations, criteria for audit and standards of care are now required.

Monosodium urate crystals in inflammation and immunity.

Uric acid crystals [monosodium urate (MSU)] have emerged as an important factor for both gouty arthritis and immune regulation. This simple crystalline structure appears to activate innate host defense mechanisms in multiple ways and triggers robust inflammation and immune activation. The recognition mechanisms of MSU following its phase change from soluble uric acid are diverse, involving both protein receptors and non-specific plasma membrane attachment. Upon contact with host cells, MSU induces a set of membrane events that trigger Syk and PI3K activation, phagocytosis, and cytokine production. Having entered the cell, MSU further triggers NALP3 inflammasome activation and induces the production of IL-1 beta, likely inducing a full spectrum of inflammation. This review describes the recognition mechanisms and activation pathways involved in MSU-mediated inflammation and adjuvanticity and hypothesizes that direct membrane binding by solid surfaces, such as MSU, may function as a generic mechanism in tissue responses to particulate and crystalline structures.

Mechanisms of uric acid crystal-mediated autoinflammation.

Gout is an arthritis characterized by elevated uric acid in the bloodstream. In this condition, crystals of uric acid are formed and accumulate in the synovial fluids. Crystal deposition leads to acute inflammation, which is associated with the spontaneous resolution of the disease. Recent studies have led to significant advances in the understanding of the basic biology of crystal-mediated inflammation. Uric acid has been identified as a danger signal that triggers a cytosolic sensor, the inflammasome. This signaling platform is required for the activation of interleukin-1, a cytokine that is critical to the initiation of acute inflammation in gout. Importantly, both molecular and pathological evidence support the notion that gout is a prototypical member of the growing family of autoinflammatory diseases. This review discusses the role of the inflammasome in gout and the emerging new therapeutic strategies aimed at controlling inflammation in crystal arthritis.

[The effects of electro-acupuncture on the signaling pathway of TLR/MYD88 in ankle joint synovial tissue of acute gouty arthritis rats].

OBJECTIVE: To investigate the effects of electro-acupuncture ( EA) on the related protein expression of the signaling pathway of the toll-like receptor2 (TLR2)/myeloid differentiation factor (MYD) 88 in ankle joint synovial tissue of acute gouty arthritis (AGA) rats. METHODS: Fifty male SD rats were randomly divided into 5 groups: normal group, SMD group, AGA model group, medication group and EA group, 10 rats in each group. SMD group established model by inducing SMD, other groups established AGA model by inducing monosodium urate, except the normal group. Two days before model was established, normal and SMD and AGA model groups were lavaged with normal saline (20 mL/kg), medication group was lavaged with colchicine solution (1 mg/kg), EA (1. 5-2 Hz, D.-D. wave, 9 V, 1-3 mA) was applied to"Sanyinjiao" (SP6),"Jiexi"(ST41) and "kunlun" (BL60) for 20 min, once daily, continuously for 9 days. Then the join sewlling index was observed periodically, the protein expression of TLR2 and MYD88 was determined by immunohistochemistry. RESULTS: Compared to the normal group, the join sewlling of the SMD group in test join increased significantly (P<0. 05) and the protein expression of TLR2 and MYD88 in synovial tissue has not statistically significant (P>0.05), the oin sewlling and protein expression of TLR2 and MYD88 in synovial tissue of model group increased significantly P<0. 05); The medication and EA group compared to the model group, the protein expression of TLR2 and MYD88 in synovial tissue decreased significantly (P <0. 05), the join sewlling in test join decreased significantly P<1. 05); There were not statistically significant between the EA group and the medication group (P>0.05). CONCLUSION: EA can alleviate the symptoms of AGA, which may be related to regulation of the protein expression Y TRI and MYD88 in the TLR/MYD88 signaling pathway.

[Metabolic bone and joint diseases].

Metabolic bone and joint diseases in adults include osteomalacia, rheumatoid arthritis, gouty arthritis. Recently, the newest molecular biology procedures and the clinical observation studies can produce good results for understanding of these diseases. From this perspective, the author introduced updated information of the pathophysiology, the latest diagnostic criteria and the therapy of these diseases.

Acupuncture for gouty arthritis: a concise report of a systematic and meta-analysis approach.

OBJECTIVE: To assess the effectiveness of acupuncture as complementary therapy for gouty arthritis from randomized controlled trials (RCTs). METHODS: Five electronic databases, including English and Chinese, were systematically searched until August 2012. All RCTs involving acupuncture in combination with conventional therapy for gouty arthritis were included. RESULTS: Ten RCTs involving 852 gouty arthritis patients were systematically reviewed. Among them six studies of 512 patients reported a significant decrease in uric acid in the treatment group compared with a control group, while two studies of 120 patients reported no significant decrease in uric acid in the treatment group compared with the control group. The remaining four studies of 380 patients reported a significant decrease in visual analogue scale score in the treatment group. CONCLUSION: The results of the studies included here suggest that acupuncture is efficacious as complementary therapy for gouty arthritis patients. More research and well-designed, rigorous and large clinical trials are necessary to address these issues.

Hypothermia induced by adenosine 5'-monophosphate attenuates early stage injury in an acute gouty arthritis rat model.

To investigate whether the hypothermia induced by Adenosine 5'-Monophosphate (5'-AMP) could attenuate early stage injury in a rat acute gouty arthritis model. Ankle joint injection with monosodium urate monohydrate crystals (MSU crystals) in hypothermia rat model which was induced by 5'-AMP and then observe whether hypothermia induced by 5'-AMP could be effectively inhibit the inflammation on acute gouty arthritis in rats. AMP-induced hypothermia has protective effects on our acute gouty arthritis, which was demonstrated by the following criteria: (1) a significant reduction in the ankle swelling (p < 0.001); (2) a significant decrease in the occurrence of leukocyte infiltration and mild hemorrhage; (3) a significant reduction in the presence of serum Interleukin-1ß (IL-1ß, p < 0.001) and metalloproteinase-9 (MMP-9, p < 0.001); and (4) a significant inhibition in the Nuclear Factor -κappaB (NF-κB) activity (p < 0.001). AMP-induced hypothermia could inhibit acute inflammation reaction and protect the synovial tissue against acute injury in a rat acute gouty arthritis model.

Articular mobilization promotes improvement in functional and inflammatory parameters in a gouty arthritis model.

OBJECTIVE: Gouty arthritis is characterized by painful inflammation due to the deposition of monosodium urate crystals in joint tissues. Despite available treatments, many patients experience ineffective management and adverse effects. This study evaluated a manual therapy protocol involving passive joint mobilization at the peak of inflammation in a gouty arthritis model using functional and inflammatory parameters. METHODS: Twenty male Wistar rats, 12 weeks old, were divided into two groups (n=10 each): Gouty Arthritis and Control Groups, which were further subdivided into treated and untreated groups (n=5 each). The Gouty Arthritis Group received intraarticular knee injection of 50µL of monosodium urate crystals, while the Control Group received 50µL of phosphate buffered saline. The treatment involved a 9-minutes session of grade III joint mobilization (according to Maitland). Nociception, grip strength, and edema were evaluated before induction (EV0), 7 hours after assessment (EV1), immediately after treatment (EV2), and 1 hour after treatment (EV3). The animals were euthanized, and synovial fluid was collected to analyze leukocyte migration. RESULTS: The model mimicked the signs of the Gouty Arthritis Group, with a decrease in the threshold of nociception and strength and an increase in edema and leukocyte count. The mobilization protocol significantly increased the nociceptive threshold and grip strength and reduced edema; however, it did not reverse the increase in leukocyte count. CONCLUSION: Our results suggest that mobilization promotes analgesia and may modulate the inflammatory process owing to reduced edema and subtle attenuation of cell migration, which contributes to strength gain.

Electroacupuncture for acute gouty arthritis: a systematic review and meta-analysis of randomized controlled trials.

Acute gouty arthritis (AGA) is a metabolic disorder in which recurrent pain episodes can severely affect the quality of life of gout sufferers. Electroacupuncture (EA) is a non-pharmacologic therapy. This systematic review aimed to assess the efficacy and safety of electroacupuncture in treating acute gouty arthritis. We searched eight Chinese and English databases from inception to July 30, 2023, and 242 studies were retrieved. Finally, 15 randomized controlled trials (n=1076) were included in a meta-analysis using Review Manager V.5.4.1. meta-analysis results included efficacy rate, visual rating scale (VAS) for pain, serum uric acid level (SUA), immediate analgesic effect, and incidence of adverse events. Electroacupuncture (or combined non-pharmacologic) treatment of AGA was significantly different from treatment with conventional medications (RR = 1.14, 95% confidence interval CI = 1.10 to 1.19, P < 0.00001). The analgesic effect of the electroacupuncture group was superior to that of conventional Western drug treatment (MD = -2.26, 95% CI = -2.71 to -1.81, P < 0.00001). The electroacupuncture group was better at lowering serum uric acid than the conventional western drug group (MD =-31.60, CI -44.24 to -18.96], P < 0.00001). In addition, electroacupuncture combined with Western drugs had better immediate analgesic effects than conventional Western drug treatment (MD = -1.85, CI -2.65 to -1.05, P < 0.00001). Five studies reported adverse events in the electroacupuncture group versus the drug group, including 19 cases of gastrointestinal symptoms and 6 cases of neurological symptoms (RR = 0.20, 95% CI = 0.04 to 0.88, P = 0.03). Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=450037, identifier CRD42023450037.

MSC therapy ameliorates experimental gouty arthritis hinting an early COX-2 induction.

Objective: The specific effect of Adipose-Derived Mesenchymal Stem Cells (Ad-MSC) on acute joint inflammation, where the response mostly depends on innate immunity activation, remains elusive. The pathogenesis of gouty arthritis, characterized by the deposition of monosodium urate (MSU) crystals in the joints, associated to acute flares, has been associated to NLRP3 inflammasome activation and subsequent amplification of the inflammatory response. Our aim was to study the effect of human Ad-MSC administration in the clinical inflammatory response of rabbits after MSU injection, and the molecular mechanisms involved. Methods: Ad-MSC were administered by intraarterial route shortly after intraarticular MSU crystal injections. Joint and systemic inflammation was sequentially studied, and the mechanisms involved in NLRP3 inflammasome activation, and the synthesis of inflammatory mediators were assessed in the synovial membranes 72h after insult. Ad-MSC and THP-1-derived macrophages stimulated with MSU were co-cultured in transwell system. Results: A single systemic dose of Ad-MSC accelerated the resolution of local and systemic inflammatory response. In the synovial membrane, Ad-MSC promoted alternatively M2 macrophage presence, inhibiting NLRP3 inflammasome and inducing the production of anti-inflammatory cytokines, such as IL-10 or TGF-ß, and decreasing nuclear factor-κB activity. Ad-MSC induced a net anti-inflammatory balance in MSU-stimulated THP-1 cells, with a higher increase in IL-10 and IDO expression than that observed for IL-1ß and TNF. Conclusion: Our in vivo and in vitro results showed that a single systemic dose of Ad-MSC decrease the intensity and duration of the inflammatory response by an early local COX-2 upregulation and PGE2 release. Ad-MSCs suppressed NF-kB activity, NLRP3 inflammasome, and promoted the presence of M2 alternative macrophages in the synovium. Therefore, this therapeutic approach could be considered as a pharmacological alternative in patients with comorbidities that preclude conventional treatment.

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.