Development and Validation of an Emergency Department Electronic Medical Record Gout Flare Alert.

OBJECTIVE: Patients with acute gout are frequently treated in the emergency department (ED) and represent a typically underresourced and understudied population. A key limitation for gout research in the ED is the timely ability to identify acute gout patients. Our goal was to refine a multicriteria, electronic medical record alert for gout flares and to determine its diagnostic characteristics in the ED. METHODS: The gout flare alert used electronic medical record data from ED nursing notes and was triggered by the term 'gout' preceding past medical history in the chief complaint, the term 'gout' and a musculoskeletal problem in the chief complaint, or the term 'gout' in the problem list and a musculoskeletal chief complaint. We validated its diagnostic properties to assess presence/absence of gout through manual medical record review using adjudicated expert consensus as the gold standard. RESULTS: In January 2020, we analyzed 202 patient records from 2 university-based EDs; from these records, 57 patients were identified by our gout flare alert, and 145 were identified by other means as potentially having an acute gout flare. The gout flare alert's positive predictive value was 47% (95% confidence interval [95% CI] 34-60%), negative predictive value was 94% (95% CI 90-98%), sensitivity was 75% (95% CI 61-89%), and specificity was 82% (95% CI 76-88%). The diagnostic properties were similar at both institutions. CONCLUSION: Our multicomponent gout flare alert had reasonable sensitivity and specificity, albeit a modest positive predictive value. An electronic gout flare alert may help enable the conduct of gout research in the ED setting.

Toward Individualized Prediction of Response to Methotrexate in Early Rheumatoid Arthritis: A Pharmacogenomics-Driven Machine Learning Approach.

OBJECTIVE: To test the ability of machine learning (ML) approaches with clinical and genomic biomarkers to predict methotrexate treatment response in patients with early rheumatoid arthritis (RA). METHODS: Demographic, clinical, and genomic data from 643 patients of European ancestry with early RA (mean age 54 years; 70% female) subdivided into a training (n = 336) and validation cohort (n = 307) were used. The genomic data comprised 160 single-nucleotide polymorphisms (SNPs) previously associated with RA or methotrexate metabolism. Response to methotrexate monotherapy was defined as good or moderate by the European Alliance of Associations for Rheumatology (EULAR) response criteria at the 3-month follow-up. Supervised ML methods were trained with 5 repeats and 10-fold cross-validation using the training cohort. Prediction performance was validated in the independent validation cohort. RESULTS: Supervised ML methods combining age, sex, smoking, rheumatoid factor, baseline Disease Activity Score in 28 joints (DAS28) scores and 160 SNPs predicted EULAR response at 3 months with the area under the receiver operating curve of 0.84 (P = 0.05) in the training cohort and achieved a prediction accuracy of 76% (P = 0.05) in the validation cohort (sensitivity 72%, specificity 77%). Intergenic SNPs rs12446816, rs13385025, rs113798271, and ATIC (rs2372536) had variable importance above 60.0 and along with baseline DAS28 scores were among the top predictors of methotrexate response. CONCLUSION: Pharmacogenomic biomarkers combined with baseline DAS28 scores can be useful in predicting response to methotrexate in patients with early RA. Applying ML to predict treatment response holds promise for guiding effective RA treatment choices, including timely escalation of RA therapies.

Changes in the Presentation of Incident Gout and the Risk of Subsequent Flares: A Population-based Study over 20 Years.

OBJECTIVE: To examine whether a change in the presentation of incident gout happened over the last 20 years and to determine the risk of subsequent gout flares after an initial gout attack. METHODS: All incident cases of gout were identified among residents of Olmsted County, Minnesota, diagnosed in 1989-1992 and 2009-2010 according to the earliest date fulfilling the 1977 American Rheumatism Association preliminary criteria, or the New York or Rome criteria for gout. Patients in both cohorts were then followed for up to 5 years. Cumulative incidence and person-year methods were used to compare flare rates, and conditional frailty models were used to examine predictors. RESULTS: A total of 429 patients with incident gout (158 patients in 1989-1992 and 271 patients in 2009-2010) were identified and followed for a mean of 4.2 years. The majority of patients were male (73%) and the mean age (SD) at gout onset was 59.7 (17.3) years. Classic podagra decreased significantly from 74% to 59% (p < 0.001). Cumulative incidence of first flare was similar in both cohorts (62% vs 60% by 5 yrs in 1989-1992 and 2009-2010, respectively; p = 0.70), but overall flare rate was marginally higher in 2009-2010 compared to 1989-1992 (rate ratio: 1.24). Hyperuricemia (HR 1.59) and kidney disease (HR 1.34) were significant predictors of future flares. CONCLUSION: Gout flares were common in both time periods. Hyperuricemia and kidney disease were predictors of future flares in patients with gout. Podagra as a presentation of gout has become relatively less frequent in recent years.

Hospitalization Increases the Risk of Acute Arthritic Flares in Gout: A Population-based Study over 2 Decades.

OBJECTIVE: To assess in-hospital gout flares in patients with gout. METHODS: Hospitalizations were evaluated for gout flares in a cohort of Olmsted County, Minnesota, residents with incident gout in 1989-1992 or 2009-2010. RESULTS: There were 429 patients followed up to 5 years. Of these, 169 patients experienced 454 hospitalizations. Hospitalization rates increased without reaching statistical significance from 1989-1992 to 2009-2010 [rate ratio (RR) 1.19, 95% CI 0.98-1.45]. The gout flare rate increased significantly during hospitalization (RR 10.2, 95% CI 6.8-14.5). In-hospital gout flare increased the average hospital stay by 1.8 days (p < 0.001). CONCLUSION: Hospitalization increased the risk of gout flares 10-fold. In-hospital gout flares were associated with longer hospitalization.

Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients.

Methotrexate (MTX) monotherapy is a common first treatment for rheumatoid arthritis (RA), but many patients do not respond adequately. In order to identify genetic predictors of response, we have combined data from two consortia to carry out a genome-wide study of response to MTX in 1424 early RA patients of European ancestry. Clinical endpoints were change from baseline to 6 months after starting treatment in swollen 28-joint count, tender 28-joint count, C-reactive protein and the overall 3-component disease activity score (DAS28). No single nucleotide polymorphism (SNP) reached genome-wide statistical significance for any outcome measure. The strongest evidence for association was with rs168201 in NRG3 (p = 10-7 for change in DAS28). Some support was also seen for association with ZMIZ1, previously highlighted in a study of response to MTX in juvenile idiopathic arthritis. Follow-up in two smaller cohorts of 429 and 177 RA patients did not support these findings, although these cohorts were more heterogeneous.

Vitamin D Levels, Vitamin D Receptor Polymorphisms, and Inflammatory Cytokines in Aromatase Inhibitor-Induced Arthralgias: An Analysis of CCTG MA.27.

BACKGROUND: Approximately half of women taking aromatase inhibitor (AI) therapy develop AI-induced arthralgia (AIA), and many might discontinue AI therapy because of the pain. Using plasma samples from the MA.27 study, we assessed several factors potentially associated with AIA. PATIENTS AND METHODS: MA.27 is a phase III adjuvant trial comparing 2 AIs, exemestane versus anastrozole. Within an 893-participant nested case-control AIA genome-wide association study, we nested a 72 AIA case-144 control assessment of vitamin D plasma concentrations, corrected for seasonal and geographic variation. We also examined 9 baseline inflammatory cytokines: interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, interferon (IFN)γ, IL-10, IL-12p70, IL-17, IL-23, and chemokine ligand (CCL)-20. Finally, we analyzed the multivariate effects of baseline factors: vitamin D level, previously identified musculoskeletal single nucleotide polymorphisms, age, body mass index, and vitamin D receptor (VDR) Fok-I variant genotype on AIA development. RESULTS: Changes in vitamin D from baseline to 6 months were not significantly different between cases and controls. Elevated inflammatory cytokine levels were not associated with development of AIA. The multivariate model included no clinical factors associated with AIA. However, women with the VDR Fok-I variant genotype were more likely to have a lower IL-1ß level (P = .0091) and less likely to develop AIA after 6 months of AI compared with those with the wild type VDR (P < .0001). CONCLUSION: In this nested case-control correlative study, vitamin D levels were not significantly associated with development of AIA; however, patients with the Fok-I VDR variant genotype were more likely to have a significant reduction in IL-1ß level, and less likely to develop AIA.

The Rising Incidence of Gout and the Increasing Burden of Comorbidities: A Population-based Study over 20 Years.

OBJECTIVE: To examine the incidence of gout over the last 20 years and to evaluate possible changes in associated comorbid conditions. METHODS: The medical records were reviewed of all adults with a diagnosis of incident gout in Olmsted County, Minnesota, USA, during 2 time periods (January 1, 1989-December 31, 1992, and January 1, 2009-December 31, 2010). Incident cases had to fulfill at least 1 of 3 criteria: the American Rheumatism Association 1977 preliminary criteria for gout, the Rome criteria, or the New York criteria. RESULTS: A total of 158 patients with new-onset gout were identified during 1989-1992 and 271 patients during 2009-2010, yielding age- and sex-adjusted incidence rates of 66.6/100,000 (95% CI 55.9-77.4) in 1989-1992 and 136.7/100,000 (95% CI 120.4-153.1) in 2009-2010. The incidence rate ratio was 2.62 (95% CI 1.80-3.83). At the time of their first gout flare, patients diagnosed with gout in 2009-2010 had higher prevalence of comorbid conditions compared with 1989-1992, including hypertension (69% vs 54%), diabetes mellitus (25% vs 6%), renal disease (28% vs 11%), hyperlipidemia (61% vs 21%), and morbid obesity (body mass index ≥ 35 kg/m2; 29% vs 10%). CONCLUSION: The incidence of gout has more than doubled over the recent 20 years. This increase together with the more frequent occurrence of comorbid conditions and cardiovascular risk factors represents a significant public health challenge.

Patient-provider discordance between global assessments of disease activity in rheumatoid arthritis: a comprehensive clinical evaluation.

BACKGROUND: Discordance between patients with rheumatoid arthritis (RA) and their rheumatology health care providers is a common and important problem. The objective of this study was to perform a comprehensive clinical evaluation of patient-provider discordance in RA. METHODS: A cross-sectional observational study was conducted of consecutive RA patients in a regional practice with an absolute difference of ≥ 25 points between patient and provider global assessments (possible points, 0-100). Data were collected for disease activity measures, clinical characteristics, comorbidities, and medications. In a prospective substudy, participants completed patient-reported outcome measures and underwent ultrasonographic assessment of synovial inflammation. Differences between the discordant and concordant groups were tested using χ2 and rank sum tests. Multivariable logistic regression was used to develop a clinical model of discordance. RESULTS: Patient-provider discordance affected 114 (32.5%) of 350 consecutive patients. Of the total population, 103 patients (29.5%) rated disease activity higher than their providers (i.e., 'positive' discordance); only 11 (3.1%) rated disease activity lower than their providers and were excluded from further analysis. Positive discordance correlated with negative rheumatoid factor and anticyclic citrullinated peptide antibodies, lack of joint erosions, presence of comorbid fibromyalgia or depression, and use of opioids, antidepressants, or anxiolytics, or fibromyalgia medications. In the prospective study, the group with positive discordance was distinguished by higher pain intensity, neuropathic type pain, chronic widespread pain and associated polysymptomatic distress, and limited functional health status. Depression was found to be an important mediator of positive discordance in low disease activity whereas the widespread pain index was an important mediator of positive discordance in moderate-to-high disease activity states. Ultrasonography scores did not reveal significant differences in synovial inflammation between discordant and concordant groups. CONCLUSIONS: The findings provide a deeper understanding of patient-provider discordance than previously known. New insights from this study include the evidence that positive discordance is not associated with unrecognized joint inflammation by ultrasonography and that depression and fibromyalgia appear to play distinct roles in determining positive discordance. Further work is necessary to develop a comprehensive framework for patient-centered evaluation and management of RA and associated comorbidities in patients in the scenario of patient-provider discordance.

TCL1A Single-Nucleotide Polymorphisms and Estrogen-Mediated Toll-Like Receptor-MYD88-Dependent Nuclear Factor-κB Activation: Single-Nucleotide Polymorphism- and Selective Estrogen Receptor Modulator-Dependent Modification of Inflammation and Immune Response.

In a previous genome-wide association study (GWAS) for musculoskeletal adverse events during aromatase inhibitor therapy for breast cancer, we reported that single nucleotide polymorphisms (SNPs) near the TCL1A gene were associated with this adverse drug reaction. Functional genomic studies showed that TCL1A expression was induced by estradiol, but only in cells with the variant sequence for the top GWAS SNP (rs11849538), a SNP that created a functional estrogen response element. In addition, TCL1A genotype influenced the downstream expression of a series of cytokines and chemokines and had a striking effect on nuclear factor κB (NF-κB) transcriptional activity. Furthermore, this SNP-dependent regulation could be reversed by selective ER modulators (SERMs). The present study was designed to pursue mechanisms underlying TCL1A SNP-mediated, estrogen-dependent NF-κB activation. Functional genomic studies were performed using a panel of 300 lymphoblastoid cell lines for which we had generated genome-wide SNP and gene expression data. It is known that toll-like receptors (TLRs) can regulate NF-κB signaling by a process that requires the adaptor protein MYD88. We found that TLR2, TLR7, TLR9, and TLR10 expression, as well as that of MYD88, could be modulated by TCL1A in a SNP and estrogen-dependent fashion and that these effects were reversed in the presence of SERMs. Furthermore, MYD88 inhibition blocked the TCL1A SNP and estrogen-dependent NF-κB activation, as well as protein-protein interaction between TCL1A and MYD88. These observations greatly expand the range of pathways influenced by TCL1A genotype and raise the possibility that this estrogen- and SNP-dependent regulation might be altered pharmacologically by SERMs.

Estrogen, SNP-Dependent Chemokine Expression and Selective Estrogen Receptor Modulator Regulation.

We previously reported, on the basis of a genome-wide association study for aromatase inhibitor-induced musculoskeletal symptoms, that single-nucleotide polymorphisms (SNPs) near the T-cell leukemia/lymphoma 1A (TCL1A) gene were associated with aromatase inhibitor-induced musculoskeletal pain and with estradiol (E2)-induced TCL1A expression. Furthermore, variation in TCL1A expression influenced the downstream expression of proinflammatory cytokines and cytokine receptors. Specifically, the top hit genome-wide association study SNP, rs11849538, created a functional estrogen response element (ERE) that displayed estrogen receptor (ER) binding and increased E2 induction of TCL1A expression only for the variant SNP genotype. In the present study, we pursued mechanisms underlying the E2-SNP-dependent regulation of TCL1A expression and, in parallel, our subsequent observations that SNPs at a distance from EREs can regulate ERα binding and that ER antagonists can reverse phenotypes associated with those SNPs. Specifically, we performed a series of functional genomic studies using a large panel of lymphoblastoid cell lines with dense genomic data that demonstrated that TCL1A SNPs at a distance from EREs can modulate ERα binding and expression of TCL1A as well as the expression of downstream immune mediators. Furthermore, 4-hydroxytamoxifen or fulvestrant could reverse these SNP-genotype effects. Similar results were found for SNPs in the IL17A cytokine and CCR6 chemokine receptor genes. These observations greatly expand our previous results and support the existence of a novel molecular mechanism that contributes to the complex interplay between estrogens and immune systems. They also raise the possibility of the pharmacological manipulation of the expression of proinflammatory cytokines and chemokines in a SNP genotype-dependent fashion.

Determinants of Disability in Rheumatoid Arthritis: A Community-Based Cohort Study.

Longitudinal care of a community-based cohort of patients with rheumatoid arthritis (RA) was evaluated retrospectively. Candidate determinants of disability included visual analog scales (VAS) for patient global assessment and pain, comorbidities, and medications. The outcome was the 'patient-acceptable symptom state' for disability as defined by the Health Assessment Questionnaire (HAQ) disability index, using a cutoff of <1.04. Two-sample t tests and multivariable logistic regression were used to determine odds ratios (OR) for associations between predictor variables and disability. Out of a total of 99 patients, 28 (28%) patients had HAQ ≥1.04 at their last visit. The greatest odds of not attaining the patient-acceptable symptom state in a multivariable model was associated with corticosteroids (OR: 5.1; p=0.02), antidepressants (OR: 5.3; p=0.02), and female sex (OR: 6.5; p=0.05). In the era of biologic therapy, female sex, corticosteroids, and antidepressants remain profound determinants of disability highlighting the need to understand the underlying mechanisms.

Dual-energy CT for the diagnosis of gout: an accuracy and diagnostic yield study.

OBJECTIVES: To assess the accuracy of dual-energy CT (DECT) for diagnosing gout, and to explore whether it can have any impact on clinical decision making beyond the established diagnostic approach using polarising microscopy of synovial fluid (diagnostic yield). METHODS: Diagnostic single-centre study of 40 patients with active gout, and 41 individuals with other types of joint disease. Sensitivity and specificity of DECT for diagnosing gout was calculated against a combined reference standard (polarising and electron microscopy of synovial fluid). To explore the diagnostic yield of DECT scanning, a third cohort was assembled consisting of patients with inflammatory arthritis and risk factors for gout who had negative synovial fluid polarising microscopy results. Among these patients, the proportion of subjects with DECT findings indicating a diagnosis of gout was assessed. RESULTS: The sensitivity and specificity of DECT for diagnosing gout was 0.90 (95% CI 0.76 to 0.97) and 0.83 (95% CI 0.68 to 0.93), respectively. All false negative patients were observed among patients with acute, recent-onset gout. All false positive patients had advanced knee osteoarthritis. DECT in the diagnostic yield cohort revealed evidence of uric acid deposition in 14 out of 30 patients (46.7%). CONCLUSIONS: DECT provides good diagnostic accuracy for detection of monosodium urate (MSU) deposits in patients with gout. However, sensitivity is lower in patients with recent-onset disease. DECT has a significant impact on clinical decision making when gout is suspected, but polarising microscopy of synovial fluid fails to demonstrate the presence of MSU crystals.

Incidence and mortality of obstructive lung disease in rheumatoid arthritis: a population-based study.

OBJECTIVE: Pulmonary disease represents an important extraarticular manifestation of rheumatoid arthritis (RA). While the association of RA and interstitial lung disease is widely acknowledged, obstructive lung disease (OLD) in RA is less well understood. We therefore aimed to assess the incidence, risk factors, and mortality of OLD in patients with RA. METHODS: We examined a population-based incident cohort of patients with RA and a comparison cohort of individuals without RA. OLD was defined using a strict composite criterion. Cox proportional hazards models were used to compare OLD incidence between the RA and comparator cohorts to investigate risk factors and to explore the impact of OLD on patient survival. RESULTS: A total of 594 patients with RA and 596 subjects without RA were followed for a mean of 16.3 and 19.4 years, respectively. The lifetime risk of developing OLD was 9.6% for RA patients and 6.2% for subjects without RA (hazard ratio [HR] 1.54, 95% confidence interval [95% CI] 1.01-2.34). The risk of developing OLD was higher among male patients, among current or former smokers, and for individuals with more severe RA. Survival of RA patients diagnosed with OLD was worse compared to those without OLD (HR 2.09, 95% CI 1.47-2.97). CONCLUSION: Patients with RA are at higher risk of developing OLD, which is significantly associated with premature mortality. Effective diagnostic and therapeutic strategies to detect and manage OLD in patients with RA may help to improve survival in these patients.

Incidence of spondyloarthropathy in patients with Crohn's disease: a population-based study.

OBJECTIVE: Spondyloarthritis (SpA) is an extraintestinal manifestation of inflammatory bowel disease with significant clinical effects, although the frequency is uncertain. We assessed the cumulative incidence and clinical spectrum of SpA in patients with Crohn's disease (CD) in a population-based cohort. METHODS: The medical records of a population-based cohort of Olmsted County, Minnesota, residents diagnosed with CD between 1970 and 2004 were reviewed. Patients were followed longitudinally until migration, death, or December 31, 2010. We used the European Spondylarthropathy Study Group, Assessment of Spondyloarthritis international Society (ASAS) criteria and modified New York criteria to identify patients with SpA. The Kaplan-Meier method was used to estimate the cumulative incidence of SpA following diagnosis of CD. RESULTS: The cohort included 311 patients with CD (49.8% females; median age 29.9 yrs, range 8-89). Thirty-two patients developed SpA based on ASAS criteria. The cumulative incidence of SpA after CD diagnosis was 6.7% (95% CI 2.5%-6.7%) at 10 years, 13.9% (95% CI 8.7%-18.8%) at 20 years, and 18.6% (95% CI 11.0%-25.5%) at 30 years. The 10-year cumulative incidence of ankylosing spondylitis was 0, while both the 20-year and 30-year cumulative incidences were 0.5% (95% CI 0-1.6%). CONCLUSION: We have for the first time defined the actual cumulative incidence of SpA in CD using complete medical record information in a population-based cohort. The cumulative incidence of all forms of SpA increased to approximately 19% by 30 years from diagnosis of CD. Our results emphasize the importance of maintaining a high level of suspicion for SpA when following patients with CD.

Aromatase inhibitors, estrogens and musculoskeletal pain: estrogen-dependent T-cell leukemia 1A (TCL1A) gene-mediated regulation of cytokine expression.

INTRODUCTION: Arthralgias and myalgias are major side effects associated with aromatase inhibitor (AI) therapy of breast cancer. In a recent genome-wide association study, we identified SNPs - including one that created an estrogen response element near the 3' end of the T-cell leukemia 1A (TCL1A) gene - that were associated with musculoskeletal pain in women on adjuvant AI therapy for breast cancer. We also showed estrogen-dependent, SNP-modulated variation in TCL1A expression and, in preliminary experiments, showed that TCL1A could induce IL-17RA expression. In the present study, we set out to determine whether these SNPs might influence cytokine expression and effect more widely, and, if so, to explore the mechanism of TCL1A-related AI-induced side effects. METHODS: The functional genomic experiments performed included determinations of TCL1A, cytokine and cytokine receptor expression in response to estrogen treatment of U2OS cells and lymphoblastoid cell lines that had been stably transfected with estrogen receptor alpha. Changes in mRNA and protein expression after gene knockdown and overexpression were also determined, as was NF-κB transcriptional activity. RESULTS: Estradiol (E2) increased TCL1A expression and, in a TCL1A SNP-dependent fashion, also altered the expression of IL-17, IL-17RA, IL-12, IL-12RB2 and IL-1R2. TCL1A expression was higher in E2-treated lymphoblastoid cell lines with variant SNP genotypes, and induction of the expression of cytokine and cytokine receptor genes was mediated by TCL1A. Finally, estrogen receptor alpha blockade with ICI-182,780 in the presence of E2 resulted in greatly increased NF-κB transcriptional activity, but only in cells that carried variant SNP genotypes. These results linked variant TCL1A SNP sequences that are associated with AI-dependent musculoskeletal pain with increased E2-dependent TCL1A expression and with downstream alterations in cytokine and cytokine receptor expression as well as NF-κB transcriptional activity. CONCLUSIONS: SNPs near the 3' terminus of TCL1A were associated with AI-dependent musculoskeletal pain. E2 induced SNP-dependent TCL1A expression, which in turn altered IL-17, IL-17RA, IL-12, IL-12RB2, and IL-1R2 expression as well as NF-κB transcriptional activity. These results provide a pharmacogenomic explanation for a clinically important adverse drug reaction as well as insights into a novel estrogen-dependent mechanism for the modulation of cytokine and cytokine receptor expression.

Perioperative care for patients with rheumatic diseases.

The perioperative care of patients with rheumatic diseases is hampered by a lack of evidence-based recommendations. Rheumatologists are called upon to 'clear' their patients for surgery, yet the evidence upon which to base decisions is fractionated and inconsistent. We have systematically reviewed the current literature and developed suggestions for three key areas that require particular deliberations in patients with rheumatic diseases scheduled for surgery: the management of cardiovascular risk, use of immunosuppressive drugs, and states of altered coagulation. For patients with rheumatic diseases associated with increased cardiovascular risk, such as rheumatoid arthritis and systemic lupus erythematosus, we suggest following the American College of Cardiology-American Heart Association guidelines using the underlying disease as a risk modifier. Most evidence suggests a neutral effect of conventional DMARDs in the perioperative period, with no need to discontinue them prior to surgery. Conversely, we suggest minimizing perioperative steroid use and unnecessary 'steroid preps'. The potential benefits of discontinuing biologic drugs in the perioperative setting needs to be carefully balanced with the risks associated with a disease flare. We discuss the American College of Chest Physicians guidelines, which classify individuals with antiphospholipid antibody syndrome as high-risk patients for perioperative thrombosis who are likely to require bridging therapy in most perioperative settings.

Identification of intraarticular and periarticular uric acid crystals with dual-energy CT: initial evaluation.

PURPOSE: To estimate the accuracy, sensitivity, specificity, and interobserver agreement of dual-energy computed tomography (CT) in detection of uric acid crystals in joints or periarticular structures in patients with arthralgia and patients suspected of having gout, with joint aspiration results as reference standard. MATERIALS AND METHODS: With institutional review board approval, patient consent, and HIPAA compliance, 94 patients (age range, 29-89 years) underwent dual-source, dual-energy (80 and 140 kVp) CT of a painful joint. A material decomposition algorithm was used to identify uric acid. Two blinded musculoskeletal radiologists evaluated the dual-energy CT images and classified the examination findings as positive or negative for the presence of uric acid crystals. Reference standard was the result of joint aspiration. RESULTS: Forty-three of 94 patients (46%) underwent attempted joint aspiration within 1 month of dual-energy CT. Aspiration was successful in 31 of 43 patients (72%). In 12 of 31 patients (39%), uric acid crystals were identified at joint aspiration; in 19 patients, they were not. Readers 1 and 2 had no false-negative findings for uric acid at dual-energy CT. Sensitivity was 100% (12 of 12; 95% confidence interval (CI): 74%, 100%) for both readers. Specificity was 89% (17 of 19; 95% CI: 67%, 99% ) for reader 1 and 79% (15 of 19; 95% CI: 54%, 94%) for reader 2, with near-perfect agreement between the readers (κ = 0.87; range, 0.70-1.00) in the 31 patients who underwent aspiration. CONCLUSION: Initial retrospective assessment suggests that dual-energy CT is a sensitive, noninvasive, and reproducible method for identifying uric acid deposits in joints and periarticular soft tissues in patients suspected of having gout.