Faculty Bibliography

PURPOSE OF REVIEW/OBJECTIVE:Calcium pyrophosphate deposition disease (CPPD) arises from calcium pyrophosphate deposition throughout the body, leading to different clinical syndromes that may be diagnosed using various imaging modalities. The purpose of this review is to highlight recent updates in the imaging of CPPD. RECENT FINDINGS/RESULTS:Conventional radiography remains the initial test when imaging CPPD; but musculoskeletal ultrasound and conventional computed tomography (CT) may also assist in diagnosing and characterizing CPP deposits, with increased sensitivity. Dual-energy CT is also being used to differentiate CPP crystals from other crystal deposition diseases. CPP discitis has been diagnosed with MRI, but MRI has lower sensitivity and specificity than the aforementioned imaging studies in CPPD diagnosis. Assorted imaging modalities are increasingly used to diagnose CPPD involving atypical joints, avoiding invasive procedures. Each modality has its advantages and disadvantages. Future imaging may be able to provide more utility than what is currently available.

Background/Purpose: Axial gout involvement was first reported in 1950 (1). Over 100 cases have subsequently been published. Reported cases have presented as acute back pain, cord compression, and/or neurologic symptoms, with diagnosis made by invasive procedure (surgical excision or biopsy). However, the true extent of MSU deposition in the spine of gout patients, including asymptomatic patients or those with non-specific symptoms, is unknown and likely higher. We used DECT to determine the extent of MSU deposition in the lumbosacral spines of patients with gout, with and without tophi, compared to controls without gout.
Method(s): We recruited controls, nontophaceous, and tophaceous gout patients, age 45-80. Individuals with CPPD disease, RA, spondyloarthropathy, active spinal malignancy, or on urate lowering treatment (ULT) >= 6 months were excluded. Gout subjects met 2015 ACR gout classification criteria, with entry serum urate (sU) of >6.8 mg/dL ( >6.0 mg/dL if on ULT for < 6 months). Demographics, gout history, Aberdeen back pain scale, sU, ESR, and CRP were collected. Subjects underwent DECT of the lumbosacral spine (LS) to assess for MSU deposition.
Result(s): 75 subjects were enrolled, and 72 completed the study (1 nontophaceous gout patient lost to follow-up prior to DECT, 2 tophaceous excluded after sU at time of DECT found to be < 6.0mg/dL). All groups were similar in age in years (controls 61.8+/-3.8, nontophaceous 64.0+/-6.1, tophaceous 60.4+/-11.0, p=0.81) but differed in BMI (controls 28.3+/-6.5 kg/m², nontophaceous 34.1+/-7.2 kg/m², tophaceous 29.5+/-4.5 kg/m², p=0.03) and creatinine (controls 1.0+/-0.2 mg/dL, nontophaceous 1.4+/-0.7 mg/dL, tophaceous 1.4+/-0.6 mg/dL, p< 0.05). Mean sU and ESR were higher in gout subjects (sU-controls 5.3+/-1 mg/dL, nontophaceous 8.5+/-1.7 mg/dL, tophaceous 8.5+/-1.6 mg/dL, p< 0.05; ESR-controls 13.7+/-13.8 mm/h, nontophaceous 26.5+/-19.4 mm/h, tophaceous 25.1+/-15.7 mm/h, p< 0.05). Using standard DECT settings for MSU visualization, gout patients had larger MSU volumes than controls (controls 2.2+/-1.2 cm3, all gout 5.23+/-6.9 cm3; p =0.03). Tophaceous patients had numerically greater MSU deposition compared with nontophaceous (6.0+/-8.9 cm3, vs 4.4+/-4.3 cm3, ns). Reanalysis of a subset of scans using highly specific settings to eliminate artifact reduced the number of subjects with MSU signal but confirmed greater prevalence of deposition among gout patients (n=29; controls with deposition 0/9, nontophaceous with deposition 1/11, tophaceous with deposition 2/9). Back pain was also more common among gout patients. No subject had frank tophi on spinal DECT.
Conclusion(s): Gout patients have significantly greater intercritical inflammation and LS MSU deposition than controls, and trend toward greater deposition among patients with tophi. Preliminary results using the most stringent DECT threshold settings suggests MSU differences are not artifact. The complete data set is currently undergoing evaluation and the full results will be presented

Background: Gout affecting the spine is reported as a rare event presenting with neuropathy, spinal compression and acute back pain (1). Cases are often diagnosed by tissue confirmation of monosodium urate (MSU) deposition. The frequency of gout involving the spine asymptomatically or with milder, non-specific symptoms is likely higher than reported.
Objective(s): Using dual-energy CT (DECT), we are determining prevalence/ extent of MSU deposition in the lumbosacral spines of patients with gout and tophaceous gout, compared to non-gout controls.
Method(s): We are recruiting 25 controls, 25 non-tophaceous and 25 tophaceous gout patients, 45-80 years old. Exclusion criteria include CPPD disease, RA, spondyloarthropathy or spinal malignancy. All gout subjects meet ACR gout classification criteria with 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. DECT of the lumbosacral spine is used to assess MSU deposition and osteoarthritic changes.
Result(s): 63 subjects are enrolled and analyzed to date (25 control, 23 non-tophaceous and 15 tophaceous gout). Control, non-tophaceous gout, and tophaceous gout subjects have similar mean age in years (controls 61.8+/-3.8, non-tophaceous 64.0+/-6.2, tophaceous 63.5+/-9.2, p=0.45), but differ in BMI (controls 28.3+/-6.5 kg/ m2, non-tophaceous 32.1+/-6.7 kg/m², tophaceous 29.1+/-4.3 kg/m², p=0.01) and creatinine (controls 1.0+/-0.2 mg/dL, non-tophaceous 1.4+/-0.6 mg/dL, tophaceous 1.7+/-0.9 mg/dL, p=0.048). Mean sU and ESR are higher in gout subjects (sU-controls 5.3+/-1 mg/dL, non-tophaceous 8.3+/-1.4 mg/dL, tophaceous 8.4+/-2.0 mg/ dL, p<0.05; ESR-controls 13.7+/-13.8 mm/h, non-tophaceous 25.2+/-18.7 mm/h, tophaceous 22.5+/-15.1 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 cm³, non-tophaceous 4.5+/-4.3 cm³, tophaceous 8.5+/-12.5 cm³, p<0.05; Table 1). 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. No subject demonstrated a frank spinal tophus.
Conclusion(s): Based on preliminary results, gout patients have higher inflammatory markers and greater spinal MSU deposition than controls. Preliminary analyes with more stringent DECT threshold settings suggests these differences are not artifact, but analysis is ongoing. These data suggest that MSU deposition in the spine occurs in a subset of gout patients

PURPOSE OF REVIEW/OBJECTIVE:Although gout is a common, well-recognized, and extensively researched rheumatologic disease, it continues to be underappreciated and undertreated. Although the prevalence of gout has been rising over the past several decades, adherence to urate lowering therapy continues to be suboptimal. Recent studies have underscored the potential success of guideline-directed therapy. RECENT FINDINGS/RESULTS:Adherence to gout treatment continues to be suboptimal according to multinational metaanalyses. Moreover, studies measuring adherence are prone to overestimation and each methodologic approach has intrinsic limitations. Adherence may be analyzed from the perspective of patient adherence to taking a medication, or provider adherence to treatment guidelines. In addition to considering traditional risk factors, adherence should be viewed through the lens of healthcare disparities. The RAmP-Up trail and Nottingham Gout Treatment trial demonstrate the success of protocolized gout treatment using existing guidelines for reference. SUMMARY/CONCLUSIONS:Standardized gout treatment protocols should be established for all primary care and specialty practices. Two successful methods of improving adherence include using nonphysician providers to coordinate urate lowering therapy titration and monitoring serum urate. Having more frequent outpatient visits to focus on direct patient care and education has also been successful.

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.

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.

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