Acute Gout Flare Research Articles

Transfusion‐associated graft‐versus‐host disease in a liver transplant recipient: an unusual presentation and review of the literature

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare, nearly universally fatal complication from transfusion of nonirradiated cellular blood components, occurring when a recipient's immune system is unable to recognize and destroy transfused T lymphocytes. Irradiation of cellular components eliminates this risk. We present an unusual case of a liver transplant recipient developing TA-GVHD 13 weeks after transfusion of a random unit of nonirradiated red blood cells (RBCs) that happened to be from a donor homozygous for an HLA haplotype shared by the patient. This study was a single case review of a liver transplant recipient who developed skin GVHD and marrow aplasia. Clinical course and the chimerism studies involving the patient, the liver donor, and the blood donor are detailed. The patient presented 3 months posttransplant with GVHD of his skin and marrow aplasia. In addition to standard antigraft immunosuppression, this patient had started the interleukin-1 receptor antagonist anakinra on Posttransplant Day 13 for an acute gout flare. Chimerism studies on the patient's peripheral blood identified a population of CD3 cells that did not originate with either the patient or his liver donor. HLA studies and microsatellite profiling of the unknown CD3 population identified the source of the patient's TA-GVHD, a unit of nonirradiated, nonleukoreduced apheresis RBCs. Use of an immunomodulating agent may have contributed to the development of TA-GVHD in a liver transplant patient who received a random unit of nonirradiated RBCs by chance from an unrelated haploidentical donor.

Foot pain, impairment, and disability in patients with acute gout flares: A prospective observational study

To evaluate the impact of acute gout on foot pain, impairment, and disability. This prospective observational study recruited 20 patients with acute gout flares. Patients were recruited from emergency departments, hospital wards, and rheumatology outpatient clinics throughout Auckland, New Zealand. Patients were recruited at the time of the flare (baseline visit) and then reassessed at a followup visit once the acute flare had resolved 6-8 weeks after the initial assessment. Swollen and tender joint counts, C-reactive protein levels, and serum urate levels were recorded at both visits. General and foot-specific outcome measures were also recorded at each visit, including pain visual analog scale, Health Assessment Questionnaire II, Lower Limb Tasks Questionnaire, and Leeds Foot Impact Scale. The foot was affected by acute gout in 17 patients (85%). Objective measures of joint inflammation, including swollen and tender joint counts and C-reactive protein levels, significantly improved at the followup visit compared with the baseline visit. At baseline, high levels of foot pain, impairment, and disability were reported. All patient-reported outcome measures of general and foot-specific musculoskeletal function improved at the followup visit compared with the baseline visit. However, pain, impairment, and disability scores did not entirely normalize after resolution of the acute gout flare. Patients with acute gout flares experience severe foot pain, impairment, and disability. These data provide further support for improved management of gout to prevent the consequences of poorly controlled disease.

Rilonacept (Interleukin‐1 Trap) in the prevention of acute gout flares during initiation of urate‐lowering therapy: Results of a phase II randomized, double‐blind, placebo‐controlled trial

To evaluate the interleukin-1 inhibitor rilonacept (Interleukin-1 Trap) for prevention of gout flares occurring in the first few months following initiation of urate-lowering therapy. In this double-blind study, adult patients with hyperuricemia and gout were randomized to receive rilonacept administered subcutaneously once per week (loading dose 320 mg followed by 160 mg weekly) or placebo, and started on allopurinol (300 mg/day, titrated to serum urate <6 mg/dl). At study visits, physical and laboratory assessments were performed and information on any adverse events was ascertained. Baseline characteristics were similar between the rilonacept and placebo groups (n = 41 and n = 42, respectively). The mean number of gout flares per patient through week 12 (primary efficacy end point) was markedly lower in the rilonacept group than in the placebo group (0.15 [6 flares] versus 0.79 [33 flares]; P = 0.0011). Fewer flares were observed with rilonacept as early as 4 weeks after initiation of treatment (P = 0.007). The proportion of patients experiencing a flare during the 12 weeks was lower in the rilonacept group than in the placebo group (14.6% versus 45.2%; P = 0.0037). No rebound in the flare rate was observed for 6 weeks after discontinuation of rilonacept or placebo at week 16. Adverse events were similar between groups, and no deaths or serious infectious adverse events were reported; the most common adverse events were infections (14.6% and 26.2% of rilonacept- and placebo-treated patients, respectively) and musculoskeletal disorders (14.6% and 21.4%, respectively). A higher percentage of rilonacept-treated patients (98%) compared with placebo-treated patients (79%) completed the primary 12-week evaluation period (P = 0.015). The current findings indicate that rilonacept significantly reduces the frequency of gout flares during the initial period of treatment with urate-lowering therapy, with a favorable safety profile.

Pilot Studies of Cherry Juice Concentrate for Gout Flare Prophylaxis

The management of gout involves treating pain and inflammation associated with acute flares and lowering the uric acid pool. A challenge associated with the successful management of gout is an increased risk of acute flares after initiation of urate-lowering therapy (ULT). Prophylactic anti-inflammatory therapy is recommended to prevent flares and foster compliance with urate lowering therapy. The aim of our studies was to assess whether use of cherry juice concentrate is useful for gout flare prophylaxis. We report the results of three studies using cherry juice concentrate for gout prophylaxis. The first is a randomized controlled study comparing the use of cherry juice concentrate versus pomegranate juice concentrate for flare prophylaxis. The second is a retrospective study evaluating flare prophylaxis when cherry juice concentrate was taken over a 4 month period or longer. Lastly, a third study evaluating the effect of cherry juice concentrate compared with pomegranate juice concentrate on secretion of interleukins by human monocytes exposed to monosodium urate (MSU) crystals in vitro. Ingesting cherry juice concentrate reduced the incidence of flares in gout patients regardless of whether or not they were treated with ULT. The number of flares was further reduced by cherry juice ingestion in patients receiving ULT than in patients not on ULT. We did not find a significant change in serum urate levels from baseline following intake of the cherry juice concentrate for 4 months or longer. Thus, cherry juice concentrate was most likely contributing to a reduction in flares via anti-inflammatory actions. We found cherry juice concentrate to inhibit in vitro secretion of IL-1β by up to 60%. In conclusion, our studies suggest that, consumption of cherry juice concentrate for a period of 4 months or longer, reduces acute gout flares, via anti-inflammatory actions such as inhibition of IL-1β secretion. Large long-term randomized controlled trials are needed to further evaluate the usefulness of cherries and cherry juice concentrate for gout flare prophylaxis.

Giant Gouty Tophi of the Hand and Wrist

Gout is an inflammatory-rheumatic disease characterized by an elevated serum urate concentration and recurrent flares, including painful, hot, red, and swollen joints and surrounding tissue. Untreated gout often develops into a chronic disease with tophi and destruction of joint surfaces. Giant tophi are often resistant to medication and change in diet.This article presents a case of a 44-year-old man with giant gouty tophi at his hand and wrist. The last acute gout flare in his left wrist was approximately 3 years prior. For 2 years he had refused adequate nutrition, such as a low-purine diet, and had refused to take any preventive medication. Blood urate level was elevated to 8.7 mg/dL (normal range, 3.4-7.0 mg/dL). In time, the tophi led to a massive limitation of motion and use of especially the left wrist and thumb. Under the condition that the patient changed his diet and took the medication for his underlying disease, we surgically removed the almost skin-perforating tophi. Surgical debulking significantly improved joint function and cosmetic appearance.The best treatment for gouty tophi is prevention by ensuring adequate nutrition, treating the underlying causes, and taking effective medication. In the case of massive limitation of joint motion, skin breakdown with risk of infection, and compression of neurovascular structures, surgical debulking of the tophi should be considered.

Erratum: Novel evidence‐based colchicine dose‐reduction algorithm to predict and prevent colchicine toxicity in the presence of cytochrome P450 3A4/P‐glycoprotein inhibitors; Association of PPP2CA Polymorphisms With Systemic Lupus Erythematosus Susceptibility in Multiple Ethnic Groups

In Table 4 of the article by Terkeltaub et al in the August 2011 issue of Arthritis & Rheumatism (pages 2226–2237), the colchicine dosing recommendation for acute gout flare with concomitant clarithromycin, ketoconazole, ritonavir (strong CYP34A inhibitor) therapy was incorrectly stated. The dosing recommendation should have read “0.6 mg (1 tablet), 1 dose; followed by 0.3 mg (one-half tablet) 1 hour later; dose to be repeated no earlier than 3 days.” In the article by Tan et al in the September 2011 issue of Arthritis & Rheumatism (pages 2755–2763), the name of an author was omitted: Graciela S. Alarcón, MD, MPH (University of Alabama at Birmingham) should have been listed as an author. Dr. Alarcón participated in acquisition of data for the study, was involved in drafting the article or revising it critically for important intellectual content, and approved the final version to be published. We regret the errors.

Evaluating Intratester Reliability of Manual Masking of Plantar Pressure Measurements Associated with Chronic Gout

Plantar pressure measurements are commonly used to evaluate foot function in chronic musculoskeletal conditions. However, manually identifying anatomical landmarks is a source of measurement error and can produce unreliable data. The aim of this study was to evaluate intratester reliability associated with manual masking of plantar pressure measurements in patients with gout. Twenty-five patients with chronic gout (mean disease duration, 22 years) were recruited from rheumatology outpatient clinics. Patients were excluded if they were experiencing an acute gout flare at the time of assessment, had lower-limb amputation, or had diabetes mellitus. Manual masking of peak plantar pressures and pressure-time integrals under ten regions of the foot were undertaken on two occasions on the same day using an in-shoe pressure measurement system. Test-retest reliability was assessed by using intraclass correlation coefficients, SEM, 95% limits of agreement, and minimal detectable change. Mean peak pressure intraclass correlation coefficients ranged from 0.92 to 0.97, with SEM of 8% to 14%. The 95% limits of agreement ranged from-150.3 to 133.5 kPa, and the minimal detectable change ranged from 30.8 to 80.6 kPa. For pressure-time integrals, intraclass correlation coefficients were 0.86 to 0.94, and SEM were 5% to 29%, with the greater errors observed under the toes. The 95% limits of agreement ranged from -48.5 to 48.8 kPa/sec, and the minimal detectable change ranged from 6.8 to 21.0 kPa/sec. These findings provide clinicians with information confirming the errors associated with manual masking of plantar pressure measurements in patients with gout.

Gout Deserves Tender Treatment in Elderly

Gout Deserves Tender Treatment in Elderly

Nanocavity Effect On Photophysical Properties Of Colchicine: A Proof by Circular Dichroism Study and Picosecond Time-Resolved Analysis in Various Reverse Micellar Assemblies

In August 2009, colchicine won Food and Drug Administration (FDA) approval in the United States as a stand-alone drug for the treatment of acute flares of gout and familial Mediterranean fever. Recently, it is now the center of attraction in medicinal research. In this present paper, we have employed two other analogues of colchicine for exploring the photophysical properties inside nanocavity environment in details. Here we have a series of interesting results that have interesting similarity with the colchinoid-tubulin interaction. To monitor fluorescence properties of colchinoids, we have used absorption, emission, and time-resolved spectroscopy and to monitor structural properties we have measured circular dichroism. Steady-state anisotropy and dynamic light scattering results give an idea about the microenvironment sensed by the colchinoids molecules. A sharp increment for colchicine, very small increment for isocolchicine and no increment for colcemid in fluorescence and different circular dichroism (CD) spectra of all of these colchinoids upon embedment inside nanocavity of reverse micelle made a supposition that all these changes of fluorescence properties and CD results of colchinoids is not solely due to viscosity effect but also the constraint, that is, very narrow space to spread over, given by the nanocavity of reverse micelle. Moreover, we have noticed that the B ring of the colchinoids also have a pronounced effect on the interaction nature as well as on conformational change of these compounds after entrapment.

A new perspective on the pharmacoeconomics of colchicine

Background:Gout is a common inflammatory arthritis that affects ∼4% of the US population. Most patients with gout are >50 years of age and have multiple comorbidities. Gout is caused by the deposition of monosodium urate crystals in joints secondary to hyperuricemia. Gout typically presents as an acute painful inflammation (flare) involving one or more joint. Left untreated it can progress into a more chronic polyarthritis. Acute gout flare treatment options include colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), and corticosteroids. The safety and efficacy of colchicine, especially in the presence of comorbidity and potential contraindications, has only recently been systematically investigated.Methods:Through the use of a systematic computer-based literature analysis, this pharmacoeconomic review evaluated costs, risks, and benefits of Colcrys (colchicine) compared with other treatments for gout in the US.Results:Both colchicine and NSAIDs are historically associated with gastrointestinal (GI) adverse events (AEs). Colchicine has very low risk for AEs, even in patients with GI disorders; whereas, NSAIDS are contraindicated in patients with GI disorders, renal insufficiency, and heart failure. The monthly cost of treating 100 patients with Colcrys was $33,100 compared with $3000 for NSAIDs. However, hospitalization for GI complications (1.8%) and heart failure (1.9%) is common with NSAIDs and can increase the monthly cost of treating 100 patients with NSAIDs to $161,000, considering $15,000–20,000 per day of hospitalization.Conclusions:Considering high costs associated with treating patients with gout, it seems prudent to choose the treatment with greatest benefit, lowest cost, and least risk. Despite higher cost per dose, colchicine appears to be more cost effective for management of gout flares than NSAIDs.

How interleukin‐1β induces gouty arthritis

with the unique role of IL-1 in the pathogenesis of autoinflammatory diseases. In this issue of Arthritis & Rheumatism, Joosten et al provide experimental data that causally explain the clinical events that consistently precede flares of gout and assess how these mechanisms are related to the production of IL-1 (3). Despite several reports indicating that the addition of MSU crystals to mononuclear phagocytes induces IL-1 secretion (4,5), the notion that MSU is a sole activator of active IL-1 is inconsistent with the clinical reality of gouty attacks. For example, why do fewer than 10% of individuals with hyperuricemia and deposits of MSU crystals in the joints develop the disease, while the remainder do not? Why do acute flares of gout often occur in the middle of the night? Why do patients receiving antitumor therapies have high uric acid levels but no clinical signs of gout? Why do individuals with hyperuricemia have attacks of gout when they diet and lose weight? Although the associations of food and alcohol consumption with attacks of gout have been known for many centuries, how such lifestyle events are related to IL-1 activity has not been explored. Therefore, those published studies that show that MSU crystals by themselves induce active IL-1 require a careful reevaluation of the evidence to be consistent with the clinical associations of gout attacks. This editorial does not attempt to review the association of gout attacks with the consumption of food and alcohol. Instead, it draws attention to the study by Joosten and coworkers (3), which goes a long way in providing the basis for the production of IL-1 induced by MSU, with the conclusion that more than MSU is needed to trigger an acute attack of gout. First, the results of the Joosten study confirm that pure MSU crystals per se could not induce IL-1 production from primary peripheral blood mononuclear cells (PBMCs) isolated from healthy donors (6), and these observations were extended to mouse peritoneal macrophages. In order to relate the association with dietary intake of fatty foods, free fatty acids (FFAs) of increasing lengths were also added to cultures of human

Oral Colchicine (Colcrys®) in the Treatment and Prophylaxis of Gout†

Gout is a disease with a descriptive history dating back to the time of Hippocrates. It is a well known type of arthritis associated with impaired metabolism of purines, resulting in hyperuricaemia and an accumulation of the metabolic end product urate, in the form of monosodium urate crystals, in joints. The build-up of these crystals induces an acute inflammatory response that involves leukocyte recruitment, in particular that of neutrophils. Hyperuricaemia is the most important risk factor in the development of gout, and is caused more commonly by decreased renal capacity to clear urate (in »90% of patients) than by over production of urate (»10%). Hyperuricaemia is physiochemically defined as urate levels >6.8mg/dL (408 mmol/L) in men and women, as urate saturation leading to crystal formation occurs at 6.8mg/dL at 37 C. Although the risk of acute gout increases with serum urate concentration, not all patients with hyperuricaemia will develop gout. Other common risk factors for gout include excessive intake of certain purine-rich foods (e.g. meat and seafood), alcohol and fructose, obesity and the use of medications that affect urate levels (such as diuretics, furosemide and ciclosporin). In addition, some common chronic disorders, such as diabetes mellitus, the metabolic syndrome, renal disease, hypertension, cardiovascular disease and hyperlipidaemia, are associated with gout. Furthermore, hyperuricaemia may increase the risk of hypertension and chronic renal disease. The prevalence of gout is difficult to quantify, but is estimated to be »1% in adults in Western countries. The incidence of gout increases with age, and is particularly high among elderly men (aged >65 years). In recent years, increases in the prevalence and incidence of gout have been reported, which are attributed in part to the aging population, who have a higher likelihood than younger individuals of co-morbidities and concurrent medication requirements that contribute to an increase in risk factors or gout-associated disorders. Although the symptoms of an acute gout flare are self limiting, they usually include extreme pain and can take ‡1 week to resolve. Aside from pain, patients are most concerned with the loss of mobility, as well as emotional stress, interrupted sleep, work and social limitations, and joint swelling and deformities. Therefore, treatment

Oral Colchicine (Colcrys®)

Oral colchicine (Colcrys) is approved in the US for the treatment of acute gout flares in adult patients and the prophylaxis of gout flares in patients aged >16 years. Colchicine is a tricyclic alkaloid that interrupts multiple inflammatory response pathways. Its principal mechanism of action in gout is thought to be inhibition of cytoskeletal microtubule polymerization, an important process in neutrophil functioning. In a phase III, randomized, double-blind, placebo-controlled, multicentre trial, the recommended dosage of Colcrys (1.2 mg at the first sign of the flare, followed by 0.6 mg in 1 hour) was significantly more effective than placebo in treating acute gout flare, as assessed by the proportion of patients experiencing a >or=50% reduction in pain within 24 hours of initiating treatment. In a randomized, double-blind, placebo-controlled, single-centre trial, non-approved colchicine 0.6 mg once or twice daily (up to 6 months) was more effective than placebo in preventing gout flares in patients receiving allopurinol as urate-lowering therapy. At the recommended dosage for the treatment of acute gout flares, Colcrys was as well tolerated as placebo in patients with gout. The incidence of the most common adverse events was similar between recipients of the recommended dosage of Colcrys and placebo.

Spotlight on Colchicine: The Colcrys Controversy

On April 16, 2010, we summarized an article on an industry-sponsored randomized trial of colchicine for acute gout flares (JW Gen Med Apr 16 2010). But

High versus low dosing of oral colchicine for early acute gout flare: Twenty‐four–hour outcome of the first multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group, dose‐comparison colchicine study

Despite widespread use of colchicine, the evidence basis for oral colchicine therapy and dosing in acute gout remains limited. The aim of this trial was to compare low-dose colchicine (abbreviated at 1 hour) and high-dose colchicine (prolonged over 6 hours) with placebo in gout flare, using regimens producing comparable maximum plasma concentrations in healthy volunteers. This multicenter, randomized, double-blind, placebo-controlled, parallel-group study compared self-administered low-dose colchicine (1.8 mg total over 1 hour) and high-dose colchicine (4.8 mg total over 6 hours) with placebo. The primary end point was > or = 50% pain reduction at 24 hours without rescue medication. There were 184 patients in the intent-to-treat analysis. Responders included 28 of 74 patients (37.8%) in the low-dose group, 17 of 52 patients (32.7%) in the high-dose group, and 9 of 58 patients (15.5%) in the placebo group (P = 0.005 and P = 0.034, respectively, versus placebo). Rescue medication was taken within the first 24 hours by 23 patients (31.1%) in the low-dose group (P = 0.027 versus placebo), 18 patients (34.6%) in the high-dose group (P = 0.103 versus placebo), and 29 patients (50.0%) in the placebo group. The low-dose group had an adverse event (AE) profile similar to that of the placebo group, with an odds ratio (OR) of 1.5 (95% confidence interval [95% CI] 0.7-3.2). High-dose colchicine was associated with significantly more diarrhea, vomiting, and other AEs compared with low-dose colchicine or placebo. With high-dose colchicine, 40 patients (76.9%) had diarrhea (OR 21.3 [95% CI 7.9-56.9]), 10 (19.2%) had severe diarrhea, and 9 (17.3%) had vomiting. With low-dose colchicine, 23.0% of the patients had diarrhea (OR 1.9 [95% CI 0.8-4.8]), none had severe diarrhea, and none had vomiting. Low-dose colchicine yielded both maximum plasma concentration and early gout flare efficacy comparable with that of high-dose colchicine, with a safety profile indistinguishable from that of placebo.

Progress in the pharmacotherapy of gout

To summarize new knowledge on approved and emerging drugs used to treat hyperuricemia or the clinical manifestations of gout. Results of several clinical trials provide new data on the efficacy and safety of the approved urate-lowering drugs, allopurinol and febuxostat. New recommendations have been presented on appropriate dosing of colchicine for acute gout flares and potential toxicities of combining colchicine with medications such as clarithromycin. Emerging therapies, including pegloticase, the uricosuric agent RDEA596, and the interleukin-1 inhibitors, rilonacept and canakinumab, have shown promise in early and late phase clinical trials. Recent publications demonstrate an opportunity to use existing gout therapies more effectively in order to improve both efficacy and safety. Emerging therapies for gout show promise for unmet needs in selected gout populations.

Hyperuricemia and Gout: A Review Article

Hyperuricemia and Gout: A Review Article

Febuxostat: A selective xanthine-oxidase/xanthine-dehydrogenase inhibitor for the management of hyperuricemia in adults with gout

Background: Febuxostat, a nonpurine selective inhibitor of both the oxidized and reduced forms of xanthine oxidase, was approved in February 2009 by the US Food and Drug Administration for the management of hyperuricemia in adults with gout. Objective: The purpose of this review was to summarize available information about the clinical use of febuxostat, including its chemistry, pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, and safety profile. Methods: A search of the medical literature using PubMed (1949–August 2009) and the Iowa Drug Information Service (1966–August 2009) was performed to identify all published articles about febuxostat. Key search terms included febuxostat, hyperuricemia, gout, TMX-67, and TEI-6720. Articles were limited to those published in English. Reference lists of the primary set of articles identified were reviewed for pertinent articles and scientific meeting abstracts not identified in the original search. Results: A total of 88 published articles (including 14 human studies) were identified in the original search. Review of the references of these 88 articles yielded 7 additional trials published in abstract form. Clinical trial data from this review were obtained from these 21 studies. Dose-dependent reductions from baseline in serum urate occur with febuxostat. Clinical trials found that 40 mg/d of febuxostat was noninferior to conventionally dosed allopurinol (300 mg/d) in the percentage of subjects achieving the primary end point of serum urate <6.0 mg/dL (45% for febuxostat vs 42% for allopurinol), whereas 80 mg/d of febuxostat was reported to be superior (67% vs 42%; P < 0.001). Febuxostat 40 and 80 mg/d appeared to be well tolerated in the populations studied, with adverse events mostly limited to liver enzyme elevations (6.6% and 4.6%, respectively), nausea (1.1% and 1.3%), arthralgias (1.1% and 0.7%), and rash (0.5% and 1.6%). Febuxostat does not require dosage adjustment in patients with mild to moderate renal impairment (creatinine clearance, 30–89 mL/min). Because of the risk of acute gout flares occurring when febuxostat treatment is initiated, concomitant therapy with colchicine or an NSAID for ≥8 weeks is recommended. Conclusions: Febuxostat is the first agent marketed in the United States to treat hyperuricemia of gout since allopurinol was approved in 1964. In English-language published clinical trials, it was found to be noninferior to allopurinol and generally well tolerated.

Are glucocorticoids equivalent to NSAIDs for the treatment of gout flares?

NSAIDs are the current mainstay of treatment for gout flares, despite being associated with an increased risk of gastrointestinal bleeding and cardiovascular events. Janssens et al. conducted a randomized, double-blind, equivalence clinical trial to determine whether the glucocorticoid prednisolone can be used as an alternative to NSAIDs in this setting. Patients referred from primary care community clinics with monosodium urate crystal-proven acute gout flares (n =120) underwent treatment with once-daily oral prednisolone 35 mg or twice-daily oral naproxen 500 mg for 5 days. The results revealed a nonsignificant difference between the two groups, both in the primary outcome measure of pain reduction and in the secondary outcomes of disability related to the affected joint and walking, suggesting equivalence between the two agents. This study helps to position oral glucocorticoids as effective and safe alternatives in the management of acute gout flares. Future studies should address the treatment of acute gout in elderly populations and in those with multiple comorbidities.

An Unusual Patient with Hypothyroidism, Tophaceous Gout, and Marked Joint Destruction

This report describes a 75-year-old Caucasian man with extensive urate deposits and severe gouty arthropathy that confined him to a wheelchair. Since age 50, he suffered multiple acute gout flares and progressive deformities in his hands, feet, knees, and elbows (tophi). Serum creatinine was 1.4 mg/dL and serum urate 9.4 mg/dL. Conditions known to increase uric acid production (psoriasis, chronic bronchitis) and to decrease uric acid excretion (hypothyroidism, metabolic syndrome, and nephroangiosclerosis) may operate in a single patient, illustrating the dramatic clinical course of untreated gout.