Gouty Arthritis

Sigal LH. · Pharmaceutical Research Institute, Bristol-Myers Squibb, Princeton, New Jersey 08543-4000, USA. · J Clin Rheumatol. · Pubmed #17762462 No free full text.

Abstract: I have often said "blessed be the splitters, for they shall inherit the earth." By that I mean that it is only by studying carefully culled populations, approaching, but never quite reaching, homogeneity that we can ever gain real insights into rheumatologic diseases. Differentiating tuberculous from gouty from rheumatoid arthritis was a good start, and when Moll and Wright identified the seronegative spondyloarthropathies, we were on our way to establishing "splitters" as leaders. Predictably, once T cells were identified as different from B cells, the floodgates opened. Subsets galore were described, with more isolated populations in the T-cell family, but we are now finding heterogeneity in B-cell populations, as well, which has been discussed in a previous article in this series. But as for T cells... well, it has not been smooth sailing. I initially trained in a laboratory that was firmly committed to the proposition that there were within the CD8 population not only cytotoxic cells but also "suppressor cells." Problem is, no one could ever isolate the little buggers, and so the idea of a suppressor or regulatory subpopulation of CD8+ T cells went the way of the Edsel. As noted in a previous article in this series, T regulatory cells were finally identified but not within the CD8+ population. And there are other regulatory subsets within both CD4+ and CD8+ T-cells populations and even new effector and memory populations that can be identified by their surface markers and functions. It is high time to review some of them; some of these populations may be involved in the immunopathogenesis of our diseases and undoubtedly will shortly be targets of immunotherapeutics. Although previous articles in this series discussed some of these subsets, I thought expanding on what is known about another recently described subset and putting them all together in one review might be helpful.

Baraf HS. · The Center for Rheumatology & Bone Research, Wheaton, MD 20902 USA. · Curr Pharm Des. · Pubmed #17691996 No free full text.

Abstract: Non-steroidal antiinflammatory drugs (NSAIDs) are standard treatment for the pain and inflammation associated with arthritis. Traditional NSAIDs and cyclooxygenase-2 (COX-2) selective inhibitors exhibit comparable efficacy, with different safety profiles. Traditional NSAIDs are associated with an increased risk of serious gastrointestinal (GI) adverse events versus COX-2 selective inhibitors, and chronic use frequently necessitates adjunctive therapy with gastroprotective agents. COX-2 selective inhibitors are often used in preference to avoid these GI adverse events. Recent studies have raised the concern that COX-2 selective inhibitors and traditional NSAIDs appear to be associated with a higher incidence of thrombotic cardiovascular events versus placebo. The key in prescribing these agents is for the physician to take a proactive approach to patient management and evaluation of GI and cardiovascular risk factors. This review examines the role of the newest COX-2 selective inhibitors, etoricoxib and lumiracoxib, in treating rheumatic disease.

Taylor WJ, Schumacher HR, Singh JA, Grainger R, Dalbeth N. · Department of Medicine, Wellington School of Medicine and Health Sciences, University of Otago, PO Box 7343, Wellington 6242, New Zealand. · Rheumatology (Oxford). · Pubmed #17650521 No free full text.

Abstract: There has been renewed interest in the treatment of gout with recent reported intervention studies of new agents such as etoricoxib, febuxostat and pegylated-uricase. However, these studies have highlighted the relative paucity of validated outcome measures with which to judge efficacy. This review outlines the published information regarding which endpoints have been measured in randomized clinical trials, what should be measured, what tools or instruments are available for this and the technical properties of such instruments. It highlights recent work that validates measures of tophi, radiographic damage and patient-reported outcomes. The absence of a valid definition of gout-flare or how flare reduction defines response is problematic; this forms the basis for a current ACR-EULAR sponsored project.

Wise CM. · Internal Medicine, Division of Rheumatology, Allergy, and Immunology, Medical College of Virginia, Virginia Commonwealth University Health System, 417 North 11th Street, Box 980647, Richmond, VA 23298, USA. · Rheum Dis Clin North Am. · Pubmed #17367691 No free full text.

Abstract: Since the original recognition of these conditions in 1961, a great deal has been learned about the pathogenesis, clinical manifestations, and appropriate treatment of gout and pseudogout, and the role of crystals in osteoarthritis has been further defined. The variable manifestations of crystal-induced arthritis in elderly populations has led to a greater need for proper diagnosis and treatment strategies for these increasingly common forms of arthritis.

Keith MP, Gilliland WR. · Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA. · Am J Med. · Pubmed #17349440 No free full text.

Abstract: The majority of patients with gout are cared for by primary care physicians. Although both the physician and patient may easily recognize the acute arthritis of gout, errors in selecting the most appropriate medication and proper dose are common. The clinical stages of gout include asymptomatic hyperuricemia, intermittent gouty arthritis, and chronic tophaceous gout. Treatment of gout is usually considered after the first attack of arthritis, typically podagra. The aims of treatment are to alleviate the pain and inflammation associated with acute attacks, prevent future attacks, and decrease uric acid levels. Confusion frequently arises because certain medications such as colchicine may have dual purposes: to treat an acute attack and to suppress future attacks. The purpose of this management update is to provide practical advice about prescribing the proper medication considering both treatment goals and patient comorbidities.

Lillicrap M. · Department of Rheumatology, Hinchingbrooke Hospital NHS Trust, Huntingdon. · Clin Med. · Pubmed #17348578 No free full text.

This publication has no abstract.

Reginato AM, Olsen BR. · Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA. · Curr Opin Rheumatol. · Pubmed #17278928 No free full text.

Abstract: PURPOSE OF REVIEW: We examine the major genes in mice and humans involved in the pathogenesis of monosodium urate, calcium pyrophosphate dihydrate and hydroxyapatite crystal-induced arthritis. RECENT FINDINGS: Several genetic causes of renal disease associated with hyperuricemia and gout provide insight into genes involved in renal urate handling. Mutations or polymorphisms in exons 4 and 5 and intron 4 of urate transporter 1 may be independent genetic markers of hyperuricemia and gout. Genetic analysis supports the role of ANKH mutations in calcium pyrophosphate dihydrate-induced arthritis. ANKH gain-of-function mutations were confirmed by functional studies; however, the crystals formed in ATD5 cells were basic calcium phosphate, not calcium pyrophosphate dihydrate, underlying the significance of chondrocyte differentiation state and the factors regulating normal and pathological mineralization. Animal models have implicated a general model of crystal-induced inflammation involving innate immunity through the NALP3 (Natch domain, leucine-rich repeat, and PYD-containing protein 3) inflammasome signaling through the interleukin-1 receptor and its signaling protein myeloid differentiation primary response protein 88. SUMMARY: Genetic analysis has elucidated genes responsible for crystal formation and animal models have unveiled mechanisms in the development of crystal-induced arthritis. Future studies will hasten understanding of the pathology of crystal-induced arthritis and provide new therapies.

Schlesinger N, Schumacher R, Catton M, Maxwell L. · UMDNJ/Robert Wood Medical School, Department of Medicine, MEB 474, PO Box 19, New Brunswick, New Jersey 08903-0019, USA. · Cochrane Database Syst Rev. · Pubmed #17054279 No free full text.

Abstract: BACKGROUND: Gout is one of the most common rheumatic diseases worldwide. Colchicine is regarded as beneficial in the treatment of acute gout, but has a high frequency of gastrointestinal adverse events. OBJECTIVES: To evaluate the efficacy and safety of colchicine for relief of the signs and symptoms of acute gouty arthritis, compared to placebo and other treatment interventions. SEARCH STRATEGY: We searched the following electronic databases to March 2006: Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, 2006), MEDLINE (from 1966), EMBASE (from 1980), CINAHL (from 1982), AMED (from 1985), Web of Science (from 1945) and Current Controlled Trials. SELECTION CRITERIA: Published randomised controlled trials (RCTs) and controlled clinical trials evaluating symptom relief and adverse outcomes of colchicine therapy in acute gout were considered for this review. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened search results for inclusion, collected the data in a standardized form and assessed the methodological quality of the trial using validated criteria. Results for continuous outcome measures were expressed as weighted mean differences. Dichotomous outcome measures were pooled using relative risk. The number needed to treat was calculated for significant outcomes. MAIN RESULTS: One RCT (N=43) comparing colchicine to placebo for the treatment of acute gout was included in this review. The results favour the use of colchicine over placebo with an absolute reduction of 34% for pain and a 30% reduction in clinical symptoms such as tenderness on palpation, swelling, redness, and pain. The number needed to treat (NNT) with colchicine versus placebo to reduce pain was 3 and the NNT to reduce clinical symptoms was 2. All participants treated with colchicine experienced gastrointestinal side effects (diarrhea and/or vomiting) and the number needed to harm (NNH) with colchicine versus placebo was 1. No studies comparing colchicine to NSAIDs or other treatments such as corticosteroids or ACTH were identified. AUTHORS' CONCLUSIONS: Colchicine is an effective treatment for the reduction of pain and clinical symptoms in patients experiencing acute attacks of gout, although in the regimen studied its low benefit to toxicity ratio limits its usefulness. It should be used as a second line therapy when NSAIDs or corticosteroids are contraindicated or ineffective. More evidence is needed to compare the efficacy of colchicine to that of NSAIDs or corticosteroids, the current first line therapy for acute gout.

Grassi W, Meenagh G, Pascual E, Filippucci E. · Cattedra di Reumatologia, Università Politecnica delle Marche, Ancona, Italy. · Semin Arthritis Rheum. · Pubmed #17011611 No free full text.

Abstract: OBJECTIVES: To date, high-resolution ultrasound (US) has not been fully exploited in the field of crystalline arthropathy. Both gout and calcium pyrophosphate deposition (CPPD) disease are significant diseases within the purview of the rheumatologist. The aim of this pictorial review was to present the principal findings in patients with crystal deposition in gout and CPPD. METHODS: US pictures were obtained from 60 consecutive patients, 34 with CPPD disease and 26 with gout, whose diagnosis was confirmed by synovial fluid analysis. The US examinations were performed using the following US systems: Diasus (Dynamic Imaging, Livingstone, UK) and Logiq 9 (General Electric Medical Systems, Milwaukee, WI). RESULTS: Pictorial evidence of the principal US findings in gout includes monosodium urate (MSU) deposition on the surface of articular cartilage, various patterns within synovial fluid ranging from completely anechoic fluid to collections filled with aggregates of variable shape and echogenicity, microdeposition within tendons, and tophus formation. In CPPD, the hallmark US features include crystal deposition within articular cartilage, calcification of fibrocartilage, together with focal crystal deposition within tendons. CONCLUSION: US is an impressive imaging modality in crystalline arthropathy. The anatomical location of the crystal deposits, clearly depictable by US, allows differentiation between MSU and CPPD aggregates.

Zurek M. · III interní klinika Lékarské fakulty UP a FN Olomouc. · Vnitr Lek. · Pubmed #16967617 No free full text.

Abstract: 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.

Capone ML, Tacconelli S, Patrignani P. · Department of Medicine and Center of Excellence on ageing, G.d' Annunzio' University School of Medicine and Gabriele d'Annunzio University Foundation, c/o Palazzina Se.B.I., Via dei Vestini 31, 66013 Chieti, Italy. · Expert Opin Drug Metab Toxicol. · Pubmed #16922642 No free full text.

Abstract: Etoricoxib is a highly selective COX-2 inhibitor (coxib) approved in Europe for the treatment of osteoarthritis (OA), rheumatoid arthritis and acute gouty arthritis. Etoricoxib is an effective analgesic drug that has shown some improved efficacy versus traditional NSAIDs and it is the only coxib approved for the treatment of acute gouty arthritis. Moreover, recent studies evidence its efficacy in patients with ankylosing spondylitis. In the Etoricoxib Diclofenac Gastrointestinal Evaluation study performed in patients with OA, etoricoxib significantly reduced the rate of discontinuation by 50% due to gastrointestinal adverse events versus diclofenac. Comparable rates of thrombotic cardiovascular events were detected. Rates of discontinuation due to hypertension-related adverse effects were higher on etoricoxib than diclofenac. Similarly to other selective COX-2 inhibitors, etoricoxib is contraindicated in patients with ischaemic heart disease or stroke and it should be used with caution in patients with risk factors for heart disease. The European Medicines Agency has contraindicated the use of etoricoxib in patients with uncontrolled hypertension. Selective COX-2 inhibitors remain an appropriate choice in patients at low cardiovascular risk, but with increased risk of gastrointestinal complications.

Gentili A. · Department of Radiology, UCSD-Thornton Hospital, 9300 Campus Point Dr, La Jolla, CA 92037, USA. · Curr Rheumatol Rep. · Pubmed #16901082 No free full text.

Abstract: Gout is a metabolic disorder in which there is hyperuricemia caused by an increase in production or a decrease in excretion of uric acid. Long-lasting hyperuricemia causes the deposition of monosodium urate crystals in the joints and soft tissues, triggering gouty arthritis and, if not properly treated, the formation of gouty tophi. The diagnosis of gout is usually based on clinical presentation and laboratory examinations, long before any abnormality can be demonstrated with imaging. Radiography is the primary imaging modality used in the initial evaluation of gouty arthritis. Ultrasonography, CT, MRI, and nuclear medicine are seldom necessary. Occasionally a tophus has an unusual presentation and simulates neoplasm or infection prompting the utilization of cross-sectional imaging for further evaluation and surgical planning. Cross-sectional imaging is also used in areas that are difficult to visualize on radiographs such as spine, sacroiliac joints, and soft tissues.

Hoskison TK, Wortmann RL. · Department of Internal Medicine, The University of Oklahoma College of Medicine-Tulsa, 4502 East 41st Street, Tulsa, OK 74135, USA. · Scand J Rheumatol. · Pubmed #16882587 No free full text.

Abstract: An acute attack of gouty arthritis is one of the most painful experiences reported throughout medical history. Therefore it is paramount to initiate appropriate therapy quickly in order to terminate the acute phase. This goal can be achieved with non-steroidal anti-inflammatory agents, colchicine, or corticosteroid-based therapies. Rarely, because of contraindications to these agents, only symptomatic treatment can be given until the attack subsides. The next step is to lower the serum urate level below the limit of solubility (i.e., below 40.8 mmol/L, or 6.8mg/dL) which reduces recurrences and begins to return the total body urate pool to normal. This equally important goal can be achieved by uricosuric agents or xanthine oxidase inhibitors, although the latter is generally favored. Allopurinol is the agent most commonly preferred because of its safety profile and ease of use, but there are known serious allergic reactions and untoward side effects that occasionally require discontinuation. Febuxostat, a xanthine oxidase inhibitor, and pegylated uricase are new agents under development and may be beneficial in these situations or when other comorbid conditions prevent the use of conventional treatments. Alcohol and dietary consumption are also related to hyperuricemia and acute gout. Recently beer, wine, and liquor were studied and the risk of gout varied according to the alcohol ingested. Furthermore, recent data sheds light on important dietary modifications that may help in the treatment of gout, and dispels certain beliefs about protein ingestion and the occurrence of acute gout. As we learn more about the associated conditions of hypertriglyceridemia, hypertension, and the metabolic syndrome, it may allow the tailoring of medical regimens that directly prevent or reduce recurrent attacks of gouty arthritis. There are specific approved treatments for these common comorbidities that have parallel effects of lowering serum urate levels. These recent findings may be especially important for treating refractory cases. While patient education remains a cornerstone to ensure compliance, other quality indicators for the management of this disease have been reported and should guide the clinician in the treatment of gout and result in improved care.

Cronstein BN, Terkeltaub R. · Department of Medicine and Division of Clinical Pharmacology, New York University School of Medicine, New York, New York, USA. · Arthritis Res Ther. · Pubmed #16820042 No free full text.

Abstract: Gouty arthritis is a characteristically intense acute inflammatory reaction that erupts in response to articular deposits of monosodium urate (MSU) crystals. Important recent molecular biologic advances in this field have given us a clear picture of the mechanistic basis of gouty inflammation. The innate immune inflammatory response is critically involved in the pathology of gout. Specifically, MSU crystals promote inflammation directly by stimulating cells via Toll-like receptor signaling and by providing a surface for cleavage of C5 and formation of complement membrane attack complex (C5b-9), culminating in secretion of cytokines, chemokines, and other inflammatory mediators with a dramatic influx of neutrophils into the joint. Despite the detailed mechanistic picture for gouty inflammation, there are no placebo-controlled, randomized clinical studies for any of the therapies commonly used, although comparative studies have demonstrated that many nonsteroidal anti-inflammatory drugs are equivalent to indomethacin with respect to controlling acute gouty attacks. In general, the first line of anti-inflammatory therapy for acute gout is nonsteroidal anti-inflammatory drugs, and the selective cyclo-oxygenase-2 inhibitor celecoxib can be used where appropriate. The second line of treatment is glucocorticosteroids, given systemically (oral, intravenous, or intramuscular) or intra-articularly. Alternatively, synthetic adrenocorticotropic hormone is effective, partly via induction of adrenal glucocorticosteroids and partly via rapid peripheral suppression of leukocyte activation by melatonin receptor 3 signaling. The third line of treatment is oral colchicine, which is highly effective when given early in an acute gouty attack, but it is poorly tolerated because of predictable gastrointestinal side effects.

Nuki G, Simkin PA. · University of Edinburgh Rheumatic Diseases Unit, Scotland, UK. · Arthritis Res Ther. · Pubmed #16820040 No free full text.

Abstract: First identified by the Egyptians in 2640 BC, podagra (acute gout occurring in the first metatarsophalangeal joint) was later recognized by Hippocrates in the fifth century BC, who referred to it as 'the unwalkable disease'. The term is derived from the Latin word gutta (or 'drop'), and referred to the prevailing medieval belief that an excess of one of the four 'humors'--which in equilibrium were thought to maintain health--would, under certain circumstances, 'drop' or flow into a joint, causing pain and inflammation. Throughout history, gout has been associated with rich foods and excessive alcohol consumption. Because it is clearly associated with a lifestyle that, at least in the past, could only be afforded by the affluent, gout has been referred to as the 'disease of kings'. Although there is evidence that colchicine, an alkaloid derived from the autumn crocus (Colchicum autumnale), was used as a powerful purgative in ancient Greece more than 2000 years ago, its first use as a selective and specific treatment for gout is attributed to the Byzantine Christian physician Alexander of Tralles in the sixth century AD. Uricosuric agents were first used at the end of the 19th century. In the modern era, nonsteroidal anti-inflammatory drugs are usually the drugs of choice for treating acute gout. Perhaps the most important historical advance in the treatment of hyperuricemia was the development of xanthine oxidase inhibitors, which are effective in reducing plasma and urinary urate levels and have been shown to reverse the development of tophaceous deposits.

Bradna P. · II. interni klinika Lékarské fakulty UK a FN, Hradec Králové. · Vnitr Lek. · Pubmed #16771097 No free full text.

Abstract: Gout is the most frequent cause of acute arthritis in men over 40 years of age. In the recent years, gout incidence has been increasing in developed countries probably due to dietary changes, alcohol consumption, ageing of population and also application of high-risk medications. Hyperuricemia is one of the symptoms of hyperinsulinism and metabolic syndrome. The level of uricemia correlates with the degree of insulin resistance. Correlation of uric acid levels and the risk of coronary and cerebral accidents were reported both in diabetic and non-diabetic population. It has not been explained satisfactorily whether this is the direct result of hyperuricemia or concurrently present symptom of metabolic syndrome. The study describes symptomatology of clinical signs of gout and discusses about appropriate therapeutic approach in each stage of the disease. New therapeutic possibilities that are still in the stage of clinical studies are mentioned. Also, we focus on alternative dietary recommendations for hyperuricemia and gout patients. The reason of changes in dietary regime is the effort to alleviate the signs of metabolic syndrome. The study emphasises the practical significance of screening of metabolic syndrome signs during examination of gout patients so that appropriate targeted therapeutic intervention could be performed. On the contrary, increased risk of gout-induced movement disorders should be taken into account in patients with diagnosed insulin resistance.

Ellman MH, Becker MA. · University of Chicago, Pritzker School of Medicine, Rheumatology Section, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois 60637, USA. · Curr Opin Rheumatol. · Pubmed #16582687 No free full text.

Abstract: PURPOSE OF REVIEW: To highlight recent investigations that have stimulated renewed interest in crystal-induced arthropathies. RECENT FINDINGS: Specific diet-related and alcohol-related risks for gout have been clarified, and alternative urate-lowering treatments likely to benefit patients with difficult-to-treat gout are in development. Progress toward understanding mechanisms underlying the renal deficits defining most cases of gout includes characterization of a urate-specific renal tubule transporter explaining many aspects of renal uric acid handling and identification of mutations in the UMOD gene, resulting in altered uromodulin protein in the gout-associated disorders familial juvenile hyperuricemic nephropathy and medullary cystic kidney disease type 2. A genetic marker associated with the risk for severe allopurinol toxicity has been reported. Hyperuricemia and gout are increasing in incidence, as is complicated gout, especially among the elderly and patients with cardiovascular and renal comorbidities, organ transplants, or complex concomitant medication regimens. Asymptomatic hyperuricemia is clearly associated with hypertension, chronic kidney disease, cardiovascular disease, and the insulin resistance syndrome, and the pathogenetic significance of these associations is under intensive study. Mutation in the ANKH gene has been found among some patients with sporadic as well as familial calcium pyrophosphate deposition disease. SUMMARY: The results of these clinical, epidemiologic, experimental, and therapeutic investigations presage advances in the management of crystal-induced arthropathies.

Schumacher HR, Chen LX. · Division of Rheumatology, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA 19104, USA. · Rheum Dis Clin North Am. · Pubmed #16504833 No free full text.

Abstract: Newer approaches to the treatment of gout have included modifications and further attention to aspects of current therapies, and development of interesting new therapies. Colchicine prophylaxis appears to be needed longer than previously recognized after introduction of a urate-lowering agent. Diet has received attention, though most dietary effects are small. New agents under investigation include pegylated formulations of uricase and a new potent xanthine oxidase inhibitor, febuxostat. Some cardiovascular drugs have been shown to be uricosuric.

Getting SJ. · The William Harvey Research Institute, Charterhouse Square, London, EC1M 6BQ, United Kingdom. · Pharmacol Ther. · Pubmed #16488018 No free full text.

Abstract: Adrenocorticotrophic hormone (ACTH(1-39)) and the melanocortins (alpha, beta and gamma-melanocyte-stimulating hormone [MSH]) are derived from a larger precursor molecule known as the pro-opiomelanocortin (POMC) protein. They exert their numerous biological effects by activating 7 transmembrane G-protein coupled receptors (GPCR), leading to adenylyl cyclase activation and subsequent cAMP accumulation within the target cell. To date, 5 melanocortin receptors (MCR) have been identified and termed MC1R to MC5R, they have been shown to have a wide and varied distribution throughout the body, being found in the central nervous system (CNS), periphery and immune cells. Melanocortins have a multitude of actions including: (i) modulating disease pathologies including arthritis, asthma, obesity; (ii) affecting functions, for example erectile dysfunction, skin tanning; and (iii) organ systems, for example cardiovascular system. Recently a mechanistic approach has been identified with alpha-MSH preventing NF-kappaB activation via the preservation and expression of IkappaBalphaprotein. This leads to a reduction of pro-inflammatory mediators including cytokines and inhibition of adhesion molecule expression, with subsequent reduction in leukocyte emigration. Development of selective ligands with an appropriate pharmacokinetic profile will enable a pharmacological evaluation of the potential beneficial effects of the melanocortins. In this review I have discussed the potential mechanistic action for the melanocortins and some of the disease pathologies shown to be modulated. This review proposes targeting the MCR with the ultimate aim of controlling many of the diseases that we face today.

Schlesinger N. · Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08903-0019, USA. · Curr Pharm Des. · Pubmed #16375734 No free full text.

Abstract: The connection of gout and hyperuricaemia with gluttony, overindulgence in food and alcohol and obesity dates from ancient times. Studies from different parts of the world suggest that the incidence and severity of hyperuricaemia and gout may be increasing. Uric acid (urate) is the end product of purine degradation. Although most uric acid is derived from the metabolism of endogenous purine, eating foods rich in purines contributes to the total pool of uric acid. Sustained hyperuricaemia is a risk factor for acute gouty arthritis, chronic tophaceous gout, renal stones and possibly cardiovascular events and mortality. Before starting lifelong urate-lowering drug therapy, it is important to identify and treat underlying disorders that may be contributing to hyperuricaemia. It is relevant to recognize the strong association of the insulin resistance syndrome (IRS) (abdominal obesity, dyslipidaemia, hypertension, raised serum insulin levels and glucose intolerance) with hyperuricaemia. Consumption of meat, seafood and alcoholic beverages in moderation and attention to food portion size is important. Moderation in the consumption of not only beer but also other forms of alcohol is essential. In the obese, controlled weight management has the potential to lower serum urate in a quantitatively similar way to relatively unpalatable "low purine" diets. Non-fat milk and low-fat yogurt have a variety of health benefits and dairy products may have clinically meaningful antihyperuricaemic effects. In addition, fruits, such as cherries and high intakes of vegetable protein diet may reduce serum urate levels.

Masseoud D, Rott K, Liu-Bryan R, Agudelo C. · Division of Rheumatology, Emory University School of Medicine/The Emory Clinic, 1365A Clifton Rd NE, 4th floor, Atlanta, GA 30322, USA. · Curr Pharm Des. · Pubmed #16375732 No free full text.

Abstract: In most mammals purine degradation ultimately leads to the formation of allantoin. Humans lack the enzyme uricase, which catalyzes the conversion of uric acid to allantoin. The resulting higher level of uric acid has been hypothesized to play a role as an antioxidant. Hyperuricaemia is usually an asymptomatic condition which is hypothesized to play a role in cardiovascular disease and hypertension. Some hyperuricaemic individuals develop gout, an inflammatory arthritis caused by the deposition of monosodium urate crystals in joints. Over time, acute intermittent gouty arthritis can develop into a chronic condition with deposits of monosodium urate (MSU) crystals in joints and as tophi. The mechanisms by which MSU crystals lead to an acute inflammatory arthritis are under investigation and current knowledge is reviewed here. Treatment of gout includes management of acute flares with anti-inflammatory medications such as non-steroidal anti-inflammatory drugs or corticosteroids and long term management with urate-lowering therapy when indicated. Future directions in the treatment of gout, in part guided by a better understanding of pathophysiology, are discussed.

Schumacher HR, Edwards LN, Perez-Ruiz F, Becker M, Chen LX, Furst DE, Joseph-Ridge N, Schlesinger N, Horowitz Z, Saag K, Boice JA, Yamanaka H, Anonymous00376. · University of Florida, Gainesville, Florida, USA. · J Rheumatol. · Pubmed #16331785 No free full text.

Abstract: 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.

Schlesinger N. · No affiliation provided · Am J Manag Care. · Pubmed #16300458 links to  free full text

Abstract: Acute gouty arthritis typically presents with a sudden and severe exquisitely painful joint, most classically in the first metatarsophalangeal joint (toe). Demonstrating the presence of monosodium urate (MSU) crystals in the joint fluid or tophus has been the gold standard for the diagnosis of gout. However, many physicians do not perform synovial fluid analysis. In the absence of demonstrating the presence of MSU crystals in aspirated joint fluid or tophus, clinical, radiologic, and laboratory criteria are helpful. This article presents an overview of the various classification criteria, clinical presentations, and laboratory and radiologic studies needed to make the diagnosis of gout.

Choy G. · Division of Rheumatology, University of Toronto, Sunnybrook and Women's College Health Science Centre, M1-401, Toronto, ON, M4N 3M5, Canada. · Expert Opin Pharmacother. · Pubmed #16259576 No free full text.

Abstract: Gout and calcium pyrophosphate deposition disease are two common causes of inflammatory joint disease. Despite differences underlying their pathogenesis, their clinical presentation and treatment share some common features. Optimal treatment for both requires prompt resolution of acute synovitis, reduction of chronic joint damage and management of associated conditions. Available therapeutic interventions and future strategies are reviewed in this article.

Ene-Stroescu D, Gorbien MJ. · Internal Medicine Northwest, Tacoma, Washington, USA. · Geriatrics. · Pubmed #16026179 No free full text.

Abstract: Gouty arthritis, a common source of pain and disability, is the most common form of inflammatory arthritis affecting older people. The authors review the epidemiology and pathogenesis of hyperuricemia and gout, as well as the clinical forms of gouty arthritis. Gout is part of a clinical spectrum of conditions (obesity, diabetes mellitus, hyperlipidemia, coronary artery disease) and need for better patient education on management of these associated conditions is emphasized. The general algorithm of gout management is presented. Clinical particularities of gout presentation in older patients (increased incidence in women, polyarticular onset with hand involvement, earlier development of tophi, association with use of diuretics) are reviewed. Barriers against an optimal control of gout include lack of patient education, presence of comorbid conditions, particularly renal impairment, use of multiple drugs such as diuretics, and cognitive decline. Gout management in older adults remains unsatisfactory.