Acute gout is an intensely painful, inflammatory arthritis. Although the non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for this condition, the efficacy is based on only a few studies, particularly in China. We tried to assess the safety and efficacy of etoricoxib in the treatment of acute gouty arthritis in China.A randomized, double-blind, active comparator study was conducted at 10 sites in China. Patients (n = 178; ≥ 18 years of age) with acute gouty attack (< 48 hours) were treated for 5 days with etoricoxib (120 mg/d; n = 89) or indometacin (75 mg twice daily; n = 89). The primary efficacy end point was self-assessed pain in the affected joint (0-4 point Likert scale) from days 2 - 5. Secondary end points included investigator assessments of tenderness and swelling, patient/ investigator global assessments of response to therapy, and patients discontinuing treatment. Safety was assessed by adverse events (AEs).Etoricoxib and indometacin had comparable primary and secondary end points. Mean change difference from baseline from days 2 - 5 was 0.03 (95% confidence interval (CI) -0.19 to 0.25; P = 0.6364), which fell within the prespecified comparative bounds of -0.5 to 0.5. No severe AEs were associated with etoricoxib use. Non-severe AEs were mainly digestive and general, and most (73.7%) were mild, although they caused withdrawal of two subjects in the etoricoxib group, due to bilateral renal calculi and uronephrosis of the left kidney (unrelated to etoricoxib) and fever and chills (potentially etoricoxib-related). Overall, AEs were similar, although the absolute number of AEs in the etoricoxib group (n = 31) was less than the indometacin group (n = 34).Etoricoxib (120 mg once daily) is effective in treating acute gout, is generally safe and well-tolerated, and is comparable in efficacy to indometacin (75 mg twice daily).

OBJECTIVES:

To report our experience with the efficacy and safety of anakinra for acute gouty arthritis in medically complex hospitalized patients

METHODS:

We reviewed the hospital charts of 26 patients treated with anakinra for crystal-induced arthritis since 2007. Demographics, co-morbid conditions, reason for Anakinra use, response to treatment and any adverse outcomes were recorded

RESULTS:

Twenty-six patients received 40 courses of anakinra therapy. In 67% of patients, pain improved significantly within 24 hours and complete resolution of signs and symptoms of gout occurred by day 5 in 72.5%. Seven patients receivedmultiple courses with no decrement in response with repeated treatments. Anakinra was well tolerated and no adverse outcomes were attributed to the drug. Only one patient appeared to be refractory to this form of IL-1 inhibition.

CONCLUSIONS:

Anakinra is an effective and safe alternative treatment for acute gouty arthritis in medically complex hospitalized patients who fail or cannot undergo more conventional therapy © 2013 by the American College of Rheumatology.

Gout is a common autoinflammatory disease characterized with elevated serum urate and recurrent attacks of intra-articular crystal deposition of monosodium urate. Accumulating evidence has demonstrated that MSU crystal-induced inflammation is a paradigm of innate immunity and the TLRs, NALP3 inflammasome and IL1R pathways are involved in gout development. Innate immunity components containing TLR2, TLR4, CD14, NALP3, ASC, Caspase-1 and CARD-8 are essential in the development of gouty inflammation. Recent studies suggest that innate immunity component gene functional mutations contribute to the development of autoinflammatory diseases including hereditary periodic fever syndrome, arthritis as well as inflammatory bowel disease. Taking into account these genetic findings, we would like to propose a novel hypothesis that the gene functional mutations might make innate immunity components as attractive susceptibility candidates and genetic markers for gout. Further clinical genetic studies need to be performed to confirm the role of innate immunity in the etiology of gout.

Illicitly distilled beverages (colloquially referred to as moonshine) account for approximately one third of alcohol consumption worldwide. Moonshine is often produced in makeshift distilling units composed of old, repurposed parts, whose component elements can leach into the distillate. Consequently, the resultant beverages may inadvertently contain harmful toxins, one of which is the metal lead. One manifestation of chronic lead toxicity-from moonshine or other forms of chronic lead poisoning-is the rheumatologic entity known as saturnine gout. With the increasing prevalence of gout over the past few decades, physicians should be aware of the association of moonshine consumption or lead toxicity with gouty arthritis. In this article, we present an overview of saturnine gout, beginning with a discussion of lead poisoning in antiquity and tracing its path to modern times. The contribution of lead to human disease and the clinical features of saturnine gout are outlined. After describing the role of lead in renal insufficiency and purine metabolism, we conclude with a discussion of specific strategies to manage this clinically important form of secondary gout.

Gout is the most common type of inflammatory arthritis. This review summarizes the most recent studies on newer therapeutics, disease management strategies and treatment recommendations.There are several new therapeutic agents being investigated both for the management of the acute gout symptoms, targeting interleukin-1β, as well as urate-lowering therapies including uricase and inhibitors of renal urate transporter proteins. Interventions led by pharmacists and nurses, which include patient education, lifestyle advice, monitoring and titration of urate-lowering medications have been implemented to improve gout management. Recently, the American College of Rheumatology has published guidelines for nonpharmacologic and pharmacologic therapeutic approaches for hyperuricemia and acute gouty arthritis.New therapeutic agents targeting the mechanism of inflammation (IL-1β) are under investigation. In addition, new urate-lowering medications to be used alone or in combination with allopurinol are undergoing rigorous evaluation to use for patients not responding to or unable to take current therapies. There is also increasing interest in redesigning clinical care to improve patient education, self-management training and urate-lowering medication titration. Although we await results of these investigations, the American College of Rheumatology treatment guidelines provide a framework for clinicians in order to provide optimal gout care.

INTRODUCTION:

In phase-3 clinical trials, the interleukin (IL-1) blocker, rilonacept (IL-1 Trap), demonstrated efficacy for gout flare prevention during initiation of urate-lowering therapy. This trial evaluated rilonacept added to a standard-of-care, indomethacin, for treatment of acute gout flares.

METHODS:

Adults, aged 18-70 years, with gout presenting within 48 hours of flare onset and having at least moderate pain as well as swelling and tenderness in the index joint were randomized to subcutaneous (SC) rilonacept 320 mg at baseline plus oral indomethacin 50 mg TID for 3 days followed by 25 mg TID for up to 9 days (n = 74); SC placebo at baseline plus oral indomethacin as above (n = 76); or SC rilonacept 320 mg at baseline plus oral placebo (n = 75). The primary efficacy endpoint was change in pain in the index joint (patient-reported using a Likert scale (0 = none; 4 = extreme)) from baseline to the average of values at 24, 48 and 72 hours (composite time point) for rilonacept plus indomethacin versus indomethacin alone. Comparison of rilonacept monotherapy with indomethacin monotherapy was dependent on demonstration of significance for the primary endpoint. Safety evaluation included clinical laboratory and adverse event (AE) assessments.

RESULTS:

Patient characteristics were comparable among the groups; the population was predominantly male (94.1%), white (75.7%), with mean ± SD age of 50.3 ± 10.6 years. All treatment groups reported within-group pain reductions from baseline (P < 0.0001). Although primary endpoint pain reduction was greater with rilonacept plus indomethacin (-1.55 ± 0.92) relative to indomethacin alone (-1.40 ± 0.96), the difference was not statistically significant (P = 0.33), so formal comparison between monotherapy groups was not performed. Pain reduction over the 72-hour period with rilonacept alone (-0.69 ± 0.97) was less than that in the other groups, but pain reduction was similar among groups at 72 hours. Treatment with rilonacept was well-tolerated with no reported serious AEs related to rilonacept. Across all groups, the most frequent AEs were headache and dizziness.

CONCLUSIONS:

Although generally well-tolerated, rilonacept in combination with indomethacin and rilonacept alone did not provide additional pain relief over 72 hours relative to indomethacin alone in patients with acute gout flare.

TRIAL REGISTRATION:

ClinicalTrials.gov registration number NCT00855920.

Acute gouty arthritis is a severe but self-limiting arthritis caused by inflammatory responses to urate crystals. Oral colchicines are effective for initial stages or prophylaxis, but generally, colchicines are ineffective for established gouty arthritis. We describe an unusual case of gouty arthritis with systemic inflammatory reactions, including high fever and polymyalgia. Refractory polyarthritis and high fever were eradicated by colchicine treatment. Genetic analysis revealed a heterozygous mutation in exon 2 of the MEFV gene (E148Q). This case underscores the possibility that MEFV gene mutations may modify the phenotype of gouty arthritis.

Paracoccidioidomycosis is an endemic South American systemic mycosis caused by the dimorphic fungus Paracoccidioides brasiliensis (P. brasiliensis). The main clinical form of disease is pulmonary, but all organs may be involved. We report a case of overinfection by P. brasiliensis in chronic gouty arthritis affecting the proximal phalanx of the right hallux. The patient required proximal amputation and long-term antifungal therapy.

In the presence of sodium, uric acid from purine metabolism precipitates as monosodium urate (MSU) needles and forms renal calculi or causes gouty arthritis in kidneys and joints, respectively. The latter is characterized by red, hot, and swollen arthritic joints. Here we report the in vitro effect of MSU crystals on blood granulocytes and analyze their contribution to granuloma formation and neutrophil extracellular traps (NETs) formation (NETosis) in synovial fluid of patients with gouty arthritis in vivo. We observed that MSU crystals induce NETosis in vitro in a reactive oxygen species (ROS)-dependent manner. Indeed, blocking ROS (e.g., the oxidative burst) by various anti-oxidants partially inhibited NETosis induced by MSU crystals. Analyses of synovial fluids and of tissue sections of patients suffering from gout revealed that NETs are also formed in vivo, especially during acute gouty flares and/or granuloma formation. Since prolonged exposure to NETs carries the risk for the development of chronic inflammation we also studied the opsonization of NETs, as a prerequisite for their clearance. The established dead cells' opsonins C3b, galectin-9, and CRP decorated the residual dead cells' corpses and opsonized these for disposal. Surprisingly, all three soluble pattern recognizing molecules spared the spread NET structures. We conclude that (i) MSU crystals are strong inducers of ROS-dependent NETosis and (ii) that the prolonged presence of NET-pathogen or NET-crystal aggregates observed in patients with systemic autoimmunity, especially in those with low serum DNase-1 activity, cannot be compensated by CRP, complement, and galectin-mediated phagocytic clearance.

Despite exciting progress in the understanding and treatment of gout, management of this condition remains suboptimal. In the face of this inadequacy, new guidelines provide recommendations both for therapeutic approaches to hyperuricaemia and for the management and anti-inflammatory prophylaxis of acute gouty arthritis.