Presence Of Monosodium Urate Crystals Research Articles

Birefringent crystals deposition and inflammasome expression in human atheroma plaques by levels of uricemia

To verify the monosodium urate (MSU) crystal deposition in artery walls following a structure assessment and to assess NLRP3 inflammasome expression in human atheroma plaques by levels of uricemia. Patients with peripheral arterial disease who were candidates for amputation were recruited and classified as normouricemic or hyperuricemic. During surgery, an artery segment from the amputated limb was sampled, divided and fixed separately by cryo-embedding, 100% ethanol or Glyo-fixx. Samples were assessed by compensated polarized-light microscopy to identify MSU crystals on the artery walls. Afterwards, macrophages, neutrophils and NLRP3 inflammasome components at the plaque were categorized by immunostaining and compared between normouricemics and hyperuricemics. Thirty artery samples from 27 patients were studied; 10 (37.0%) participants were hyperuricemic. Birefringent needle-shaped crystals were found in three samples (10.0%), all processed by frozen sectioning. Other methods showed no crystals. No accompanying inflammatory process was noted, and the presence of crystals was equally distributed across ranges of uricemia, making it unlikely they were MSU crystals. Regarding immunostaining, 28 artery samples were available for analysis, with similar infiltration of macrophages and neutrophils. NLRP3 and gasdermin-D expression were significantly greater in hyperuricemics compared to normouricemics (P=0.044 and P=0.017, respectively). ASC content was numerically larger in hyperuricemics as well, while caspase-1 and IL-1beta expression were similar between groups. The presence of MSU crystals on artery walls was not confirmed. Hyperuricemia was associated with greater NLRP3 and gasdermin-D expression on human atheroma plaques in patients with peripheral artery disease.

Recent Insights Into the Role of Macrophages in Acute Gout.

Gout is a common type of inflammatory arthritis characterized by the presence of monosodium urate crystals (MSU) in the joints. Macrophages are believed to be involved in gout flares. It has long been recognized that resident macrophage and monocyte derived macrophages are distinct subsets and there have been attempts to investigate their roles in acute gout, respectively. Previous studies revealed that resident macrophages initiate and drive the inflammation, while monocyte derived macrophages differentiated into M1-like macrophages in response to MSU crystals. With the advancement of technologies, subpopulations of synovial resident macrophages have been defined with the characteristics more accurately described. Resident macrophages in the synovial lining layer showed an anti-inflammatory effect in rheumatoid arthritis, but specific Trpv4 depletion of them reduced MSU crystals induced murine arthritis. CD14+ monocytes in the synovial fluid from patients with gout exhibit phenotypes of anti-inflammatory as well as pro-inflammatory characteristics. Here, we review the main aspects of macrophages in the initiation and resolution of acute gout and try to clarify the specific role of each subpopulation. Building a reliable diagram of the effect of monocytes and macrophages during MSU crystals induced arthritis will bring us closer to targeting macrophages for improving the management of gout.

Entheseal Involvement in Spondyloarthritis (SpA) and Gout: An Ultrasound Comparative Study.

ObjectiveTo compare the assessment of entheses in subjects with spondyloarthritis (SpA) with patients with gout by the Madrid Sonographic Enthesis Index (MASEI).MethodThis cross-sectional study includes videos of entheses evaluated by ultrasound (US) of 30 patients with SpA diagnosed according to the ASAS criteria and 30 patients with gout established by the presence of monosodium urate crystals. Entheses were evaluated for MASEI in 2 Institutes located in two different countries. Demographic and clinical data were registered. Total MASEI score, MASEI-inflammatory, and MASEI-chronic damage were analyzed. Comparisons between groups were obtained by chi-square test and Student's t-test. An inter-reading US reliability was realized.ResultsPatients with gout were older and had significantly more comorbidities than those with SpA. The total MASEI score was not significantly different among diseases (p = 0.07). MASEI-inflammatory was significantly more prevalent at the Achilles tendon in SpA, while the proximal patellar tendon was in gout. Power Doppler was higher in SpA compared to gout (p = 0.005). MASEI-chronic damage related to calcification/enthesophytes predominated in gout (p = 0.043), while calcaneal erosions did in SpA (p = 0.008). The inter-reader concordance was excellent (0.93, CI 95% 0.87–0.96, p = 0.001).ConclusionsSpA and gout similarly involve entheses according to MASE, however, some inflammatory and chronic lesions differ significantly depending on the underlying disease and tendon scanned.

Performance of the 2015 American College of Rheumatology/European League against Rheumatism Classification Criteria for Gout in Korean Patients with Acute Arthritis.

BackgroundWe aimed to assess the performance of the 2015 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for gout in Korean patients with acute arthritis and to compare the performance of the ACR/EULAR criteria to that of other sets of criteria for gout classification.MethodsPatients with acute arthritis who underwent diagnostic arthrocentesis at one of the four participating rheumatology clinics were consecutively enrolled between February and December 2017. Crystal-proven gout was diagnosed upon confirming the presence of monosodium urate (MSU) crystals in patients with a clinical impression of gout as judged by the rheumatologist. The performance of the ACR/EULAR and other gout classification criteria, including the Rome, New York, American Rheumatism Association (ARA), Mexico, and Netherlands criteria, was analyzed regardless of the presence/absence of MSU crystals.ResultsThe study enrolled 118 gout patients (all crystal-proven) and 95 non-gout patients. According to the area under the curve, the diagnostic performance was the highest for the ACR/EULAR classification criteria (sensitivity, 80.5%; specificity, 95.8%; area under the curve, 0.966), followed by the Netherlands, Rome, ARA, New York, and Mexico criteria. All six sets of criteria demonstrated lower sensitivity in patients exhibiting the first episode of acute arthritis.ConclusionIn Korean patients with acute arthritis, the ACR/EULAR classification criteria outperformed other sets of gout classification criteria even in the absence of information regarding the presence of MSU crystals. However, to enhance diagnostic sensitivity, synovial fluid analysis should be considered in patients with the first episode of acute arthritis.

Sex Steroids and the Induction of Human Neutrophil Cell Death by Monosodium Urate Crystals

Gout is characterized by the presence of monosodium urate (MSU) crystals in joints and surrounding tissues. When MSU is detected by tissue, it is treated as ＂danger/ damage＂, and there is rapid recruitment of neutrophils from the circulation into the affected area. Neutrophil death induced by MSU crystals has been found to be strongly related to gout flare-ups. Clinically, males are nearly three times more likely to develop gout than females, but the incidence of gout increases with age for both sex. Sex steroids have immunological properties and are able to modulate various immune factors and are able to relieve excessive inflammation. However, the effect of sex steroids on neutrophil cell death induced by MSU crystals remains unclear. We investigated whether progesterone (P4), estradiol (E2), testosterone (T), and dihydrotestosterone (DHT) individually are able to inhibit neutrophil cell death in the presence of MSU crystals. Neutrophils were isolated from the peripheral venous blood samples of male volunteers. Neutrophil cell death was detected using propidium iodide (PI) assays. The results confirmed that treatment of neutrophils with MSU crystals (600 μg/ml) induced significant cell death within 10 min. Furthermore, when neutrophils were pretreated with various sex steroids (P4, E2, T and DHT) individually for 15 min, the neutrophil cell death induced by MSU crystals was not affected. Sex steroids do not seem to be able to inhibit neutrophil cell lysis induced by MSU crystals and this implies that the rapid responses of neutrophils to sex steroids are not seem involved in gout flare-ups.

Tophus size is associated with hallux valgus deformity in gout.

Hallux valgus (HV) and gout are common pathologies of the first metatarsophalangeal joint (MTP1) leading to pain and deformation. In this study, we aimed to determine the correlation between tophus size and characteristics of HV in gouty patients. In this case-control study, we included patients with gout (the presence of monosodium urate crystals in synovial fluid) and control patients with spondyloarthritis, without crystal disease disorders. Radiographic assessment and ultrasound (US) assessment were performed by two blinded operators. US features of gout (double contour [DC] sign and/or tophus) were collected. HV was defined by hallux abductus (HA) angle ≥20° and/or intermetatarsal angle (IM) ≥10°. Correlation between US findings and HV angles was estimated by Spearman correlation coefficient. We included 56 gouty patients (87.5% males, mean age of 63.9±12.2years) and 41 control patients (90% males, mean age of 59.0±12.8years). HV was more frequent in patients with gout than controls (62% vs 37%, P=.0007). Regardless of HV status, correlations were found between the size of US tophi and IM (r=.3381, P=.003) and HA angles (r=.2344, P=.043). Our results confirm a high prevalence of HV in gouty patients. We also observed a correlation between the size of the US tophus and the angles defining HV, which suggests a link between urate deposition load and HV. Early urate-lowering therapy for gout could limit the occurrence of HV.

Biostatistical Analysis and Possible Forecasting of Relationship Between Uric Acid and Specific Laboratory Tests in Cases of Gouty Arthritis

Acute gouty arthritis represents an inflammatory response to microcrystals of monosodium urate that precipitate in joint tissues from supersaturated body fluids or are shed from preexisting articular deposits [1]. Gout is a metabolic disease characterized by recurrent episodes of arthritis associated with the presence of monosodium urate crystals in the tissue or synovial fluid during the attack.These forms of crystal-induced arthritis usually affect peripheral joints, including knee, ankle, wrist, and metacarpophalangeal and metatarsophalangeal joints. All of them may be associated with other inflammatory, endocrine diseases [2]. The present study was done to highlight the relationship between increased levels of uric acid and specific laboratory tests in order to possible forecast development of further disease in patients with gouty arthrithis.The present study was done on 34 patients hospitalized in Felix Hospital of Rehabilitation in 2015-2016, with age between 44 and 74, having the main diagnosis of gouty arthritis.We studied the following laboratory tests:urea and other related analysis, like uric acid, creatinine, cholesterol, glutamate pyruvate transaminase and glutamate oxalate transaminase.

Silent Monosodium Urate Crystal Deposits Are Associated With Severe Coronary Calcification in Asymptomatic Hyperuricemia: An Exploratory Study.

To evaluate the association between monosodium urate (MSU) crystal deposits in patients with asymptomatic hyperuricemia and the severity and extension of coronary artery disease (CAD). In this cross-sectional study, consecutive inpatients with a non-ST elevation acute coronary event and asymptomatic hyperuricemia (serum uric acid concentration of ≥7.0 mg/dl) or normouricemia (serum uric acid concentration of <7.0 mg/dl) were enrolled. In patients with asymptomatic hyperuricemia, the presence of MSU crystals was determined by ultrasound evaluation of both knees and first metatarsophalangeal joints and by compensated polarized light microscopy. CAD was assessed by coronary angiography, and the following variables were considered: 1) the presence of moderate-to-severe coronary artery calcification, 2) the number of significant coronary stenoses, and 3) the presence of multivessel disease. The association between variables indicating the severity of CAD and the presence of MSU crystals was analyzed by multivariate regression. One hundred forty patients were enrolled. After ultrasonography and microscopic analyses were performed, the patients were classified as having normouricemia (n = 66), asymptomatic hyperuricemia alone (n = 61), and asymptomatic hyperuricemia with MSU crystals (n = 13). The prevalence of moderate-to-severe coronary calcification was significantly higher in the patients with asymptomatic hyperuricemia with MSU crystals compared with patients with asymptomatic hyperuricemia alone and patients with normouricemia (P = 0.003). An independent association was observed between the presence of moderate-to-severe calcification and asymptomatic hyperuricemia with crystals (odds ratio 16.8, P = 0.002). No significant association was observed for the other variables. Silent deposition of MSU crystals in patients with asymptomatic hyperuricemia was associated with more severe coronary calcification, which suggests more severe CAD in relation to crystal deposition.

Successful Treatment of Refractory Gout Using Combined Therapy Consisting of Febuxostat and Allopurinol in a Patient with Chronic Renal Failure

Gouty arthritis is a metabolic disorder associated with hyperuricemia. Despite the development of novel pharmacotherapies, some hyperuricemia patients are drug refractory and develop gout. A 74-year-old man with frequent gouty attacks and chronic renal failure presented with asymmetrical polyarthritis affecting multiple joints. The diagnosis of gout was confirmed based on the presence of monosodium urate crystals in the patient's right wrist. The administration of systemic corticosteroids relieved the joint inflammation and pain; however, the urate level increased to 28 mg/dL and the gout attacks recurred. Combined allopurinol, febuxostat, and benzbromarone therapy reduced the urate level to <6 mg/dL, and the attacks gradually declined. This is the first report of two xanthine oxidase inhibitors being used to treat refractory gout.

Diagnosis and Management of Gout in Total Knee Arthroplasty

Gout is a common arthritic condition that continues to increase in prevalence. Symptoms of gout include a rapid onset of pain, erythema, swelling, and warmth in the affected joint. These symptoms may mimic cellulitis, thrombophlebitis, and septic arthritis (); however, a definitive diagnosis can be obtained through joint aspiration and subsequent fluid analysis to assess for the presence of monosodium urate crystals. Gout can also be present after total joint replacement. Because of the similarity of symptoms to septic arthritis, the diagnosis may be missed. Gout may be present in a prosthetic knee or may coexist with septic arthritis. Therefore, analysis of knee aspirations should include cell count, gram stain, cultures, and an examination of the synovial fluid for crystals. The following case study discusses the complex issues involved in treating coexistent gout and infection in a prosthetic knee.

FRI0385 Factors associated with refractoriness to NSAIDS in GOUTY arthritis

BackgroundIn gouty arthritis, we most often start with a non-steroid anti-inflammatory drug (NSAID). Many patients with gout have comorbidities that make NSAIDs use problematic. In clinical practice, we observe more...

2011 Recommendations for the Diagnosis and Management of Gout and Hyperuricemia

Gout is a major health problem in the United States; it affects 8.3 million people, which is approximately 4% of the adult population. Gout is most often diagnosed and managed in primary care practices; thus, primary care physicians have a significant opportunity to improve patient outcomes. Following publication of the 2006 European League Against Rheumatism (EULAR) gout guidelines, significant new evidence has accumulated, and new treatments for patients with gout have become available. It is the objective of these 2011 recommendations to update the 2006 EULAR guidelines, paying special attention to the needs of primary care physicians. The revised 2011 recommendations are based on the Grading of Recommendations Assessment, Development, and Evaluation approach as an evidence-based strategy for rating quality of evidence and grading the strength of recommendation formulated for use in clinical practice. A total of 26 key recommendations, 10 for diagnosis and 16 for management, of patients with gout were evaluated, resulting in important updates for patient care. The presence of monosodium urate crystals and/or tophus and response to colchicine have the highest clinical diagnostic value. The key aspect of effective management of an acute gout attack is initiation of treatment within hours of symptom onset. Low-dose colchicine is better tolerated and is as effective as a high dose. When urate-lowering therapy (ULT) is indicated, the xanthine oxidase inhibitors allopurinol and febuxostat are the options of choice. Febuxostat can be prescribed at unchanged doses for patients with mild-to-moderate renal or hepatic impairment. The target of ULT should be a serum uric acid level that is ≤ 6 mg/dL. For patients with refractory and tophaceous gout, intravenous pegloticase is a new treatment option. This article is a summary of the 2011 clinical guidelines published in Postgraduate Medicine. This article provides a streamlined, accessible overview intended for quick review by primary care physicians, with the full guidelines being a resource for those seeking additional background information and expanded discussion.

Chronic tophaceous gout

Forty-three-year old male, consumer of 2 litres (80 ounces) of beer every day for the past 21 years. Fifteen years ago, he presented acute pain along with monoarticular inflammation of the lower limbs. At first he presented 2-3 annual episodes of monoarthritis, which improved with non-steroidal anti-inflammatory drugs. The patient did not follow the pharmaceutical treatment or the hygienic-dietetic measures recommended by his general practitioner correctly, so his monoarthritic crises became more frequent, extending to affectation of upper limb joints; the clinical picture evolved to oligoarthritis and finally to polyarthritis. He currently attended consultation due to worsening of inflammatory arthralgias in the hands and feet, along with deformity, which made daily activities difficult. Physical exploration highlighted the presence of tophi at the level of the elbows, feet, and hands, some of them complicated with fistula to the exterior (Figures 1A and 1B), where the presence of monosodium urate crystals was observed. Laboratory tests detected uricemia a level of 8.3, with the rest of basic biochemistry at normal levels. Tests for blood count, acute phase reactants, rheumatoid factor, and citrullinated antibodies were normal or negative. Bone X-rays of the hands and feet showed increased soft tissue, along with the presence of significant bone erosion with sclerotic margins, highlighting a small, thin calcified line,1 characteristic of gouty arthropathy (Figures 2A and 2B).

Co-present rheumatoid arthritis and gout successfully treated with abatacept

Dear Editor, We have read with much interest the article by Kuo et al., ‘Rare co-present rheumatoid arthritis and gout: comparison with pure rheumatoid arthritis and literature review’ [1], presenting eight new cases of concomitant rheumatoid arthritis and gout and summarizing 32 reported cases. The authors noticed that over 85% of co-present patients experienced at least one acute gout attack after continuous disease modifying antirheumatic drugs (DMARDs) and nonsteroidal anti-inflammatory drugs administration, while only one patient became totally quiescent after etanercept therapy. It is similar to our observation of a 45-year-old patient with gout and rheumatoid arthritis successfully treated with abatacept. He was admitted to our department in 2001 because of a 12-year experience of recurrent arthritis, associated with erythema, warmth, and swelling. Likemost co-present patients, he had more comorbidities [1–3], i.e., hypertension, glucose intolerance, but, interestingly, no kidney dysfunction. Laboratory tests revealed erythrocyte sedimentation rate (ESR) of 37 mm/h, C-reactive protein (CRP) of 5 mg/L, uric acid (UA) of 0.49 mmol/L, and rheumatoid factor (RF) of 1:40. There were no significant changes in X-rays of his hands and feet. While the diagnosis of gout was confirmed by the presence of monosodium urate crystals on polarized light microscopy (synovial fluid aspirated from left knee), oral colchicine and allopurinol were introduced with improvement. He was readmitted to our department in 2006 due to a 6-month history of persistent pain and swelling of joints of hands and feet, exudation in left knee, and morning stiffness lasting over 2 h. In laboratory tests, ESR revealed 72 mm/h, CRP 58.7 mg/L, UA 0.2 mmol/L, RF 1:80, and anticyclic citrullinated peptide antibodies 136 IU. In synovial fluid aspirated from left knee, not only monosodium urate crystals were found but also rheumatoid factor (1:40), which was previously negative. X-rays of feet revealed symmetrical erosive changes typical for RA with no changes in X-rays of hands and narrowing of left knee joint space. DAS28 score was 6.14. Oral methylprednisolone 6 mg was administered, and the patient was introduced to the program of abatacept therapy for early RA. He had obtained several courses of abatacapt from April 2006 to March 2008. Since the abatacept administration, no further gout attacks were observed, and DAS28 score decreased to 1.86. Both, the patient described by Kuo et al. and our patient, responded very well to biologics, etanercept and abatacept, respectively, with no gout attacks after the introduction of therapy. They were both younger than ‘average’ co-present patients and did not respond well to DMARDs (in 2001, before gout was diagnosed, our patient obtained 6 months MTX therapy, but without any improvement). This might suggest that the introduction of biologics in co-present patients may not only inhibit RA activity but also decrease the frequency of gout attacks.

How PCP Education Can Impact Gout Management

Weaver, Arthur L. MD*; Cheh, Michelle A. PhD†; Kennison, Richard H. DPM, MBA‡ Author Information

Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial

Non-steroidal anti-inflammatory drugs and colchicine used to treat gout arthritis have gastrointestinal, renal, and cardiovascular adverse effects. Systemic corticosteroids might be a beneficial alternative. We investigated equivalence of naproxen and prednisolone in primary care. We did a randomised clinical trial to test equivalence of prednisolone and naproxen for the treatment of monoarticular gout. Primary-care patients with gout confirmed by presence of monosodium urate crystals were eligible. 120 patients were randomly assigned with computer-generated randomisation to receive either prednisolone (35 mg once a day; n=60) or naproxen (500 mg twice a day; n=60), for 5 days. Treatment was masked for both patients and physicians. The primary outcome was pain measured on a 100 mm visual analogue scale and the a priori margin for equivalence set at 10%. Analyses were done per protocol and by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN14648181. Data were incomplete for one patient in each treatment group, so per-protocol analyses included 59 patients in each group. After 90 h the reduction in the pain score was 44.7 mm and 46.0 mm for prednisolone and naproxen, respectively (difference 1.3 mm; 95% CI -9.8 to 7.1), suggesting equivalence. The difference in the size of change in pain was 1.57 mm (95% CI -8.65 to 11.78). Adverse effects were similar between groups, minor, and resolved by 3 week follow-up. Oral prednisolone and naproxen are equally effective in the initial treatment of gout arthritis over 4 days.

Reduced secretion of proinflammatory cytokines of monosodium urate crystal‐stimulated monocytes in chronic renal failure: an explanation for infrequent gout episodes in chronic renal failure patients?

In gouty arthritis, monosodium urate (MSU) crystals interact with monocytes and neutrophils to produce inflammatory reactions associated with acute synovitis. In patients with end-stage renal disease (ESRD), gouty arthritis is a rare condition despite often severe hyperuricaemia. We wondered whether differences in the secretion of proinflammatory cytokines by MSU crystal-stimulated monocytes might be one explanation for the low incidence of gouty arthritis in patients with ESRD compared with healthy controls. Thirteen patients with ESRD on intermittent haemodialysis treatment, six patients with chronic renal failure not yet on dialysis, and 15 age- and sex-matched healthy controls were examined. Monocytes, purified from peripheral blood mononuclear cells (PBMC) by immunomagnetic bead separation, were incubated for 18 h in the presence of MSU crystals, Escherichia coli lipopolysaccharide (LPS) or medium alone. The supernatants were studied for the presence of interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) using cytokine-specific enzyme-linked immunosorbent assays. Monocytes from patients with ESRD produced significantly lower amounts of IL-1beta, IL-6 and TNF-alpha after stimulation with MSU crystals or LPS than did monocytes from healthy subjects. Cytokine production was not significantly different between ESRD patients on haemodialysis and chronic renal failure patients not yet on dialysis. Artificial MSU crystals were stronger stimuli than tophus-derived 'natural' MSU crystals. We demonstrate that monocyte-associated immunosuppression in ESRD leads to reduced secretion of proinflammatory cytokines in response to stimuli such as MSU crystals. This may be one of the factors preventing many ESRD patients from the manifestation of acute gout despite often severe hyperuricaemia.

Synovial fluid analysis for diagnosis of intercritical gout.

The diagnosis of gout in the intercritical phase can be difficult. To determine whether synovial fluid analysis allows the diagnosis of intercritical gout. Cross-sectional study. Outpatient rheumatology clinics. 101 patients with gout. Arthrocentesis of 80 knees and 21 first metatarsophalangeal joints (each joint from a different patient) that had been inflamed but were currently asymptomatic. Frequency with which arthrocentesis yielded synovial fluid; presence of monosodium urate crystals in the synovial fluid sample; and, for synovial fluid with crystals, the number of microscope fields that had to be scanned before crystals were found. Synovial fluid was obtained from 91 of 101 joints. The fluid from all 43 patients not receiving hypouricemic agents contained monosodium urate crystals. These crystals were found in the synovial fluid of only 34 of 48 patients receiving hypouricemic agents. In 90% of the synovial fluid samples that contained crystals, crystals were seen in the first five microscope fields examined. Arthrocentesis of asymptomatic knees and first metatarsophalangeal joints and synovial fluid analysis are simple procedures that facilitate the diagnosis of gout during intercritical periods.

Unusual presentations of gout

In cases of unusual presentations, such as the three cases described here, gout or gouty arthritis may be misdiagnosed as rheumatoid arthritis, septic arthritis, or other rheumatic conditions and thus inappropriately treated. Microscopic analysis using compensated polarized light and culture of synovial fluid helps distinguish gouty arthritis from other arthropathies, and the presence of monosodium urate crystals establishes the diagnosis of gout. When gout is suspected, yet the initial examination does not reveal the telltale crystals, reexamination of synovial fluid is warranted. It is important for physicians to remember, though, that diagnosis of gout does not rule out the possibility of concurrent arthritic conditions.

Evaluation of allopurinol use in patients with gout

The use of long-term allopurinol therapy in patients with gout was evaluated. A pharmacy computer printout was used to identify all outpatients for whom allopurinol had been prescribed during a six-month period in 1985 at a large Veterans Administration medical center. Medical records were reviewed to (1) classify patients as either having or not having definite indications for allopurinol treatment, (2) determine whether physicians had ordered roentgenographic and laboratory tests for presence of monosodium urate crystals, uric acid excretion, and renal function, and (3) identify gout-associated risk factors and disease entities that could cause hyperuricemia. A pharmacy record of all allopurinol and probenecid prescriptions for the six-month period was obtained, along with cost data. Of the 286 patients who received allopurinol, 32 received the drug for an indication that could not definitely be established as gout. Of the 254 remaining patients, only 45 (17.7%) had a definite indication for allopurinol use as defined by the pharmacy and therapeutics committee. Although pretreatment measurement of serum creatinine was common, only a few patients underwent joint aspiration, a 24-hour urine collection, or roentgenography of affected joints. Large proportions of the patients were found to have gout-associated risk factors. If the 209 patients without definite indications for allopurinol therapy had been treated with probenecid instead of allopurinol, the annual cost savings would have been about $3700. Most of the patients receiving allopurinol for gout could reasonably have been treated with a uricosuric agent such as probenecid at a lower cost. Generally, physicians did not use diagnostic tests optimally before prescribing allopurinol and did not attempt to modify risk factors for gout.