Faculty Bibliography

Background/Purpose: Spinal gout is reported as a rare event, presenting as acute back pain, neuropathy, and spinal compression. Diagnosis is commonly based on identification of a mass, followed by tissue confirmation of monosodium urate (MSU) deposition. It is likely that many more cases of gout involve the spine asymptomatically or with non-specific or under-recognized symptoms.
Method(s): Using dual-energy CT (DECT), we are determining the prevalence/extent of MSU deposition in the lumbosacral spines of patients with gout vs without gout, and with tophaceous vs non-tophaceous gout. We are recruiting 25 controls, 25 non-tophaceous and 25 tophaceous gout patients, 50-80 years old. Exclusion criteria include known CPPD disease, RA, spondyloarthropathy or active spinal malignancy. All gout subjects meet ACR classification criteria and have entry serum urate (sU) of >6.8 mg/dL, or sU >6.0 mg/dL on ULT for < 6 months. Demographics, gout history, Aberdeen back pain scale, sU, ESR, and CRP are collected. Subjects undergo DECT of the lumbosacral spine to assess for MSU deposition and osteoarthritic changes.
Result(s): 61 subjects are enrolled to date (25 control, 24 non-tophaceous and 12 tophaceous gout). Control and gout (all pooled) subjects have similar mean age in years (controls, 61.8+/-3.8 vs gout, 64.1+/-7.32, p=0.15), but differ in BMI (controls, 28.3+/-6.5 kg/m 2 vs gout, 32.35+/-6.9 kg/m 2, p=0.02) and creatinine (controls, 1.0+/-0.2 mg/dL vs gout, 1.5+/-0.7 mg/dL, p< 0.05). Mean sU and ESR are higher in gout subjects (sU-controls, 5.3+/-1 mg/dL vs gout, 8.7+/-1.7 mg/dL, p< 0.05; ESR-controls, 13.7+/-13.8 mm/h vs gout, 25.3+/-18.3 mm/h, p< 0.05). Using default threshold settings for MSU visualization, greater MSU deposition is observed in the spine of gout patients (controls, 2.2+/-1.2 cm 3 vs gout, 10.8+/-32.2 cm 3, p=0.18; Fig 1). When a single gout outlier with excessively high sU and spinal MSU is excluded, spinal MSU deposition between controls and gout patients becomes significant (controls, 2.2+/-1.2 cm 3 vs gout, 5.6+/-7.8 cm 3, p=0.04). Reanalysis of several scans using narrower threshold settings to limit possible artifact confirms increased MSU signal among gout patients. Although many subjects in each group do not have excessive MSU deposition, deposition is more common in both gout groups (Fig 2). Thus far, MSU deposition is not different between non-tophaceous and tophaceous gout patients (non-tophaceous, 12.3+/-2.92 cm 3 vs tophaceous, 7.9+/-3.2 cm 3, p = 0.7). No subject demonstrated a frank spinal tophus. Gout patients report higher back pain scores (controls, 5.7+/-8.3, vs gout, 11.8+/-14.3, p=0.06). Across all groups deposition is greater in patients with higher sU.
Conclusion(s): Based on preliminary results, gout patients have higher inflammatory markers, more spinal MSU deposition, and increased back pain versus controls. Preliminary results with more stringent DECT threshold settings suggests these differences are not artifact, but analysis is ongoing. These data suggest that non-tophaceous MSU deposition in the spine occurs in a subset of gout patients, is associated with sU level, and may be associated with low back pain

PURPOSE OF REVIEW/OBJECTIVE:Gout is the most common inflammatory arthritis in the USA, affecting about 4% of all adults. The American College of Rheumatology (ACR) released a new guideline in 2020 to help with the management of gout. This guideline serves as an update to the previous set of guidelines which the ACR published in 2012. The purpose of this review is to compare the 2012 ACR gout guidelines to the newly released 2020 ACR gout guidelines. RECENT FINDINGS/RESULTS:There are many similarities between the two guidelines, and also several key differences. The 2020 guidelines assist in the clinical management of gout by healthcare providers. Additionally, the new guidelines utilize newer literature to help create an evidence-based approach to the treatment for gout. We discuss the methodological approach to each guideline (RAND versus GRADE), as well as the final recommendations for gout flare treatment, use of imaging, urate-lowering therapy, lifestyle changes, and genetic testing prior to initiation of allopurinol in each guideline, as well as lingering issues that the 2020 guidelines have not addressed. We dissect both the 2012 and 2020 ACR gout guidelines to summarize the key similarities and differences between the two as well as discuss how the authors came to the recommendations that they did for each set of guidelines.

To assess the impact of allopurinol on diabetes in a retrospective cohort of Veterans' Affairs patients with gout.The New York Harbor VA computerized patient record system was searched to identify patients with an ICD-9 code for gout meeting at least 4 modified 1977 American Rheumatology Association gout diagnostic criteria. Patients were divided into subgroups based on >30 continuous days of allopurinol, versus no allopurinol. New diagnoses of diabetes, defined according to American Diabetes Association diagnostic criteria or clinical documentation explicitly stating a new diagnosis of diabetes, were identified during an observation period from January 1, 2000 through December 31, 2015.Six hundred six gout patients used allopurinol >30 continuous days, and 478 patients never used allopurinol. Over an average 7.9 ± 4.8 years of follow-up, there was no significant difference in diabetes incidence between the allopurinol and non-allopurinol groups (11.7/1000 person-years vs 10.0/1000 person-years, P = .27). A lower diabetes incidence in the longest versus shortest quartiles of allopurinol use (6.3 per 1000 person-years vs 19.4 per 1000 person-years, P<.0001) was attributable to longer duration of medical follow-up.In this study, allopurinol use was not associated with decreased diabetes incidence. Prospective studies may further elucidate the relationship between hyperuricemia, gout, xanthine oxidase activity, and diabetes, and the potential impact of gout treatments on diabetes incidence.

The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented challenge and opportunity for translational investigators to rapidly develop safe and effective therapeutic interventions. Greater risk of severe disease in COVID-19 patients with comorbid diabetes mellitus, obesity, and heart disease may be attributable to synergistic activation of vascular inflammation pathways associated with both COVID-19 and cardiometabolic disease. This mechanistic link provides a scientific framework for translational studies of drugs developed for treatment of cardiometabolic disease as novel therapeutic interventions to mitigate inflammation and improve outcomes in patients with COVID-19.

BACKGROUND:Patients with gout have arterial dysfunction and systemic inflammation, even during intercritical episodes, which may be markers of future adverse cardiovascular outcomes. We conducted a prospective observational study to assess whether initiating guideline-concordant gout therapy with colchicine and a urate-lowering xanthine oxidase inhibitor (XOI) improves arterial function and reduces inflammation. METHODS:Thirty-eight untreated gout patients meeting American College of Rheumatology (ACR)/European League Against Rheumatism classification criteria for gout and ACR guidelines for initiating urate-lowering therapy (ULT) received colchicine (0.6 mg twice daily, or once daily for tolerance) and an XOI (allopurinol or febuxostat) titrated to ACR guideline-defined serum urate (sU) target. Treatment was begun during intercritical periods. The initiation of colchicine and XOI was staggered to permit assessment of a potential independent effect of colchicine. Brachial artery flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) assessed endothelium-dependent and endothelium-independent (smooth muscle) arterial responsiveness, respectively. High-sensitivity C-reactive protein (hsCRP), IL-1β, IL-6, myeloperoxidase (MPO) concentrations, and erythrocyte sedimentation rate (ESR) assessed systemic inflammation. RESULTS:Four weeks after achieving target sU concentration on colchicine plus an XOI, FMD was significantly improved (58% increase, p = 0.03). hsCRP, ESR, IL-1β, and IL-6 also all significantly improved (30%, 27%, 19.5%, and 18.8% decrease respectively; all p ≤ 0.03). Prior to addition of XOI, treatment with colchicine alone resulted in smaller numerical improvements in FMD, hsCRP, and ESR (20.7%, 8.9%, 13% reductions, respectively; all non-significant), but not IL-1β or IL-6. MPO and NMD did not change with therapy. We observed a moderate inverse correlation between hsCRP concentration and FMD responsiveness (R = - 0.41, p = 0.01). Subgroup analyses demonstrated improvement in FMD after achieving target sU concentration in patients without but not with established cardiovascular risk factors and comorbidities, particularly hypertension and hyperlipidemia. CONCLUSIONS:Initiating guideline-concordant gout treatment reduces intercritical systemic inflammation and improves endothelial-dependent arterial function, particularly in patients without established cardiovascular comorbidities.

Gout is a disease in which the metabolic condition hyperuricemia leads to the formation of monosodium urate crystals, which provoke acute and chronic inflammatory responses through activation of the innate immune system. Recent advances in our knowledge of gout pathogenesis have emphasized the role of the kidneys in urate handling, the evolutionary loss of uricase as a necessary precondition for hyperuricemia, and the central role of IL-1ß in the pathogenesis of gouty inflammation. These, and other advances, have shaped our current strategies for managing gout. Here, we review the most current, evidence-based gout management approaches, including treating acute flares, addressing gout through the long-term regulation of serum urate, and prophylaxis against gouty flares during urate lowering.

BACKGROUND:Inflammation is associated with coronary artery disease (CAD) and myocardial infarction (MI). Patients with gout are at increased risk of MI, and colchicine is associated with a reduced risk of MI. The objective of this study was to determine whether colchicine prevents incident development of CAD in patients with gout. METHODS:This retrospective study followed a cohort of male gout patients without known CAD at the time of gout diagnosis in the VA New York Harbor Healthcare System. The association between colchicine use and development of incident CAD, defined as evidence of ischemia or obstructive CAD on stress test or angiography, was determined using an inverse probability weighted (IPW) cox proportional hazard model. RESULTS:Among 178,877 patients, 1,638 met gout criteria, of whom 722 patients without known CAD at baseline (446 colchicine users and 276 non-users) were followed for a median of 96 months [57-117]. A trend toward association between colchicine use and reduced incident CAD was observed but not statistically significant (IPW HR 0.49 [0.23-1.05]). In patients without chronic kidney disease, colchicine use was associated with a lower rate of incident CAD (interaction p=0.005, IPW HR 0.31 [0.14-0.70]). Colchicine was also associated with a lower rate of the composite of incident CAD and MI (IPW HR 0.37 [0.16-0.83]). CONCLUSIONS:In male patients with gout and no known CAD, a trend of reduced incident CAD was observed with colchicine use that was not statistically significant. Larger, prospective studies will be required to definitively assess the primary prevention benefit of colchicine.