The 2023 ACR/EULAR Classification Criteria for Calcium Pyrophosphate Deposition Disease.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease. METHODS: Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. RESULTS: Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score >56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). CONCLUSION: The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.

The 2023 ACR/EULAR classification criteria for calcium pyrophosphate deposition disease.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease. METHODS: Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. RESULTS: Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score>56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). CONCLUSION: The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Biomarkers in Axial Spondyloarthritis: Observational Studies From the Program to Understand the Longterm Outcomes in Spondyloarthritis Registry.

OBJECTIVES: This study was conducted to assess the utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting radiographic sacroiliitis and active disease in axial spondyloarthritis (SpA) and to explore the association between use of a tumor necrosis factor inhibitor (TNFi) and these laboratory values compared with traditional inflammatory markers. METHODS: Observational data from the Program to Understand the Longterm Outcomes in Spondyloarthritis (PULSAR) registry were analyzed. We generated receiver operating characteristic curves to calculate laboratory cutoff values; we used these values in multivariable logistic regression models to identify associations with radiographically confirmed sacroiliitis and active disease. We also used logistic regression to determine the likelihood of elevated laboratory values after initiation of TNFi. RESULTS: Most study participants (n = 354) were White, male, and HLA-B27 positive. NLR (odds ratio [OR] 1.459, P = 0.034), PLR (OR 4.842, P < 0.001), erythrocyte sedimentation rate (OR 4.397, P < 0.001), and C-reactive protein (CRP) level (OR 2.911, P = 0.001) were independent predictors of radiographic sacroiliitis. Models that included PLR with traditional biomarkers performed better than those with traditional biomarkers alone. NLR (OR 6.931, P = 0.002) and CRP (OR 2.678, P = 0.004) were predictors of active disease, but the model that included both NLR and CRP performed better than CRP alone. TNFi use reduced the odds of elevated NLR (OR 0.172, P < 0.001), PLR (OR 0.073, P < 0.001), erythrocyte sedimentation rate (OR 0.319, P < 0.001), and CRP (OR 0.407, P < 0.001), but models that included NLR or PLR and traditional biomarkers performed best. CONCLUSIONS: These findings demonstrate an association between NLR and PLR and sacroiliitis and disease activity, with NLR and PLR showing response after TNFi treatment and adding useful clinical information to established biomarkers, thus perhaps assisting in management of axial SpA.

Caring for older veterans with chronic low back pain using a geriatric syndrome approach: Rationale and methods for the aging back clinics (ABC) trial.

The purpose of the ongoing trial is to improve care of older Veterans with chronic low back pain (CLBP, i.e., low back pain for ≥6 months on ≥ half the days). Current CLBP care is limited by being either overly spine-focused or non-specifically prescribed and both approaches frequently lead to suboptimal reduction in pain and improvement in function. Through prior studies we have laid the foundation for a patient-centered approach to care for older Veterans with CLBP in which the spine is a source of vulnerability but not the sole treatment target. The approach considers CLBP a geriatric syndrome, a final common pathway for the expression of multiple contributors rather than a disease of the spine. We describe here the rationale and design of a randomized controlled trial to test the efficacy of an older Veteran-centered approach to CLBP care in "Aging Back Clinics (ABCs)" compared with Usual Care (UC). Three hundred thirty Veterans age 65-89 with CLBP will be randomized to ABCs or UC and followed for 12 months after randomization. We will assess the impact of ABCs on our primary outcome of pain-associated disability with the Oswestry Disability Index at 6 and 12 months, and secondary outcomes of pain intensity, health-related quality of life, balance confidence, mobility and healthcare utilization. If shown efficacious, the approach tested in ABCs has the potential to transform the care of older adults with CLBP by improving the quality of life for millions, reducing morbidity and saving substantial healthcare costs.

2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.

OBJECTIVE: To update evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). METHODS: We conducted updated systematic literature reviews for 20 clinical questions on pharmacologic treatment addressed in the 2015 guidelines, and for 26 new questions on pharmacologic treatment, treat-to-target strategy, and use of imaging. New questions addressed the use of secukinumab, ixekizumab, tofacitinib, tumor necrosis factor inhibitor (TNFi) biosimilars, and biologic tapering/discontinuation, among others. We used the Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations and required at least 70% agreement among the voting panel. RESULTS: Recommendations for AS and nonradiographic axial SpA are similar. TNFi are recommended over secukinumab or ixekizumab as the first biologic to be used. Secukinumab or ixekizumab is recommended over the use of a second TNFi in patients with primary nonresponse to the first TNFi. TNFi, secukinumab, and ixekizumab are favored over tofacitinib. Co-administration of low-dose methotrexate with TNFi is not recommended, nor is a strict treat-to-target strategy or discontinuation or tapering of biologics in patients with stable disease. Sulfasalazine is recommended only for persistent peripheral arthritis when TNFi are contraindicated. For patients with unclear disease activity, spine or pelvis magnetic resonance imaging could aid assessment. Routine monitoring of radiographic changes with serial spine radiographs is not recommended. CONCLUSION: These recommendations provide updated guidance regarding use of new medications and imaging of the axial skeleton in the management of AS and nonradiographic axial SpA.

2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.

OBJECTIVE: To update evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). METHODS: We conducted updated systematic literature reviews for 20 clinical questions on pharmacologic treatment addressed in the 2015 guidelines, and for 26 new questions on pharmacologic treatment, treat-to-target strategy, and use of imaging. New questions addressed the use of secukinumab, ixekizumab, tofacitinib, tumor necrosis factor inhibitor (TNFi) biosimilars, and biologic tapering/discontinuation, among others. We used the Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the quality of evidence and formulate recommendations and required at least 70% agreement among the voting panel. RESULTS: Recommendations for AS and nonradiographic axial SpA are similar. TNFi are recommended over secukinumab or ixekizumab as the first biologic to be used. Secukinumab or ixekizumab is recommended over the use of a second TNFi in patients with primary nonresponse to the first TNFi. TNFi, secukinumab, and ixekizumab are favored over tofacitinib. Co-administration of low-dose methotrexate with TNFi is not recommended, nor is a strict treat-to-target strategy or discontinuation or tapering of biologics in patients with stable disease. Sulfasalazine is recommended only for persistent peripheral arthritis when TNFi are contraindicated. For patients with unclear disease activity, spine or pelvis magnetic resonance imaging could aid assessment. Routine monitoring of radiographic changes with serial spine radiographs is not recommended. CONCLUSION: These recommendations provide updated guidance regarding use of new medications and imaging of the axial skeleton in the management of AS and nonradiographic axial SpA.

Musculoskeletal manifestations of alkaptonuria: A case report and literature review.

Alkaptonuria (AKU) is a rare autosomal recessive disorder that results from the deficient activity of homogentisate 1,2-dioxygenase and leads to increased levels of homogentisic acid (HGA) and its oxidized product benzoquinone acetic acid (BQA). Both HGA and BQA form polymerized deposits that lead to a bluish-black discoloration of the cartilage as well as degeneration, inflammation, and calcification of the tendons, ligaments, intervertebral discs, and large joints and increased bone resorption. A brittle and fragmented cartilage forms and leads to aberrant loading of the subchondral bone. These fragments then adhere to the synovial membrane and cause fibrosis or chondromatosis, leading to ochronotic arthropathy. Ochronotic tendinopathy most commonly affects the patellar or Achilles tendon and can lead to enthesopathy or spontaneous tendon ruptures. Ochronotic pigments deposited in the bone impair the bone mineralization process and lead to osteopenia or osteoporosis. Here, we report a case of a patient with several musculoskeletal manifestations of AKU and reviewed the literature to summarize the pathophysiology, clinical characteristics, and radiologic findings of the rheumatic features of AKU. Though medical treatment options are limited, early identification of AKU can facilitate prompt surgical intervention.

Deconstructing chronic low back pain in the older adult--Step by step evidence and expert-based recommendations for evaluation and treatment part III: Fibromyalgia syndrome.

OBJECTIVE: To present the third in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. The series presents CLBP as a syndrome, a final common pathway for the expression of multiple contributors rather than a disease localized exclusively to the lumbosacral spine. Each article addresses one of 12 important contributors to pain and disability in older adults with CLBP. This article focuses on fibromyalgia syndrome (FMS). METHODS: A modified Delphi approach was used to create the evaluation and treatment algorithm, the table discussing the rationale behind each of the algorithm components, and the stepped-care drug recommendations. The team involved in the creation of these materials consisted of a principal investigator, a 5-member content expert panel, and a 9-member primary care panel. The evaluation and treatment recommendations were based on availability of medications and other resources within the Veterans Health Administration (VHA) facilities. However, non-VHA panelists were also involved in the development of these materials, which can be applied to both VA and civilian settings. The illustrative clinical case was taken from the clinical practice of the principal investigator. RESULTS: Following expert consultations and a review of the literature, we developed an evaluation and treatment algorithm with supporting materials to aid in the care of older adults with CLBP who have concomitant FMS. A case is presented that demonstrates the complexity of pain evaluation and management in older patients with CLBP and concomitant FMS. CONCLUSIONS: Recognition of FMS as a common contributor to CLBP in older adults and initiating treatment targeting both FMS and CLBP may lead to improved outcomes in pain and disability.

Effects of contralateral versus ipsilateral cane use on gait in people with knee osteoarthritis.

OBJECTIVE: To compare the immediate effects of contralateral versus ipsilateral cane use on spatiotemporal gait parameters and peak vertical ground force in overweight or obese adults with symptomatic knee osteoarthritis (OA). DESIGN: Prospective observational study. SETTING: An academic tertiary Veterans Affairs Healthcare Center. PARTICIPANTS: Thirty-eight overweight or obese subjects with symptomatic knee OA who had not used a cane for the past 30 days. METHODS: Spatiotemporal gait data were obtained with an optical motion capture system while subjects walked without a cane, with a cane contralateral to the more painful lower limb, or with a cane ipsilateral to the more painful lower limb at self-selected speeds. An in-shoe dynamic pressure distribution system was used to measure the vertical ground reaction force. MAIN OUTCOME MEASUREMENTS: Spatiotemporal measures of gait and peak vertical ground reaction force on both lower limbs were recorded for each walking condition: no cane, contralateral cane, and ipsilateral cane. RESULTS: Walking with a cane either contralateral or ipsilateral to the more symptomatic limb led to significant reductions in gait velocity (14%-16%), cadence (12%-14%), and peak vertical ground reaction force (normalized for body weight; 11%-12%) on the more painful lower limb compared with walking unaided (P < .05). There were no significant differences in the peak vertical ground reaction force on either lower limbs when comparing walking with a cane contralateral to the more painful limb or walking with a cane ipsilateral to the more painful limb. Subjects also experienced a significant decrease in gait velocity with contralateral or ipsilateral cane use compared with walking without a cane; the lower walking speed was due to a decrease in cadence. CONCLUSIONS: These results support the prescription of a single-point cane to offload a lower limb with painful knee OA by holding the cane either ipsilateral or contralateral to the more painful lower limb.

Evaluation of two cane instruments in older adults with knee osteoarthritis.

The objectives of this study were to describe the psychometric properties of the Cane Cognitive Mediator Scale (CCMS) and the Psychosocial Impact of Assistive Devices Scale (PIADS) in adults with knee osteoarthritis (OA) and to determine the feasibility of applying these instruments as screening tools to identify patients with the propensity to use a cane. Data from a randomized crossover trial were analyzed for 53 older adults with knee OA. Perceptions on using a cane were measured at baseline using the CCMS and PIADS. The CCMS was repeated 1 wk later. At 6 mo, subjects rated their intention to use a cane. The findings indicated that 1 wk test-retest reliability was acceptable for the CCMS Attitudes and Subjective Norms subscales (r = 0.48 to 0.93) and low for the CCMS Perceived Behavioral Control subscale (r = 0.15). Internal consistency reliability was good for each CCMS and PIADS subscale. The CCMS Subjective Norms subscale demonstrated acceptable predictive validity across all subgroups (r = 0.53 to 0.88). The PIADS Adaptability subscale demonstrated acceptable predictive validity for the 45 to 64 yr-old age group (r = 0.54). The findings indicate that the CCMS Subjective Norms subscale exhibits good psychometric properties and has potential application as a screening tool.

Clinical and spatiotemporal gait effects of canes in hip osteoarthritis.

OBJECTIVE: To investigate the effects of cane use on spatiotemporal gait parameters, pain, and function in adults with hip osteoarthritis (OA). DESIGN: Prospective observational study. SETTING: An academic tertiary Veterans Affairs Healthcare Center. PARTICIPANTS: Thirteen adults with symptomatic hip OA and 13 healthy adults. METHODS: We undertook gait analysis in all subjects with an optoelectronic camera system. Pain, stiffness, and physical function in subjects with hip OA were assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). MAIN OUTCOME MEASUREMENTS: Baseline spatiotemporal measures of unaided gait were obtained for healthy subjects. Baseline and 4-week spatiotemporal gait parameters were assessed for hip OA subjects while they walked with and without a cane. Participants with hip OA completed the WOMAC at baseline and after 4 weeks of cane use. RESULTS: At baseline when walking unaided, the subjects with hip OA (age range 60-75 years) had a significantly slower gait velocity, shorter affected limb stride length, and longer double-stance time compared with healthy control subjects. When walking with a cane, they had a reduction in gait velocity (P < .05) caused by a decrease in cadence (P < .05) compared with walking unaided. After 4 weeks of cane use, the participants with hip OA demonstrated significant improvements in gait velocity (P < .05) and double-stance time (P < .05) when walking with a cane in comparison with baseline data. There was no improvement in pain and function after 4 weeks of cane use, a period in which only approximately 60% of the hip OA subjects used the cane 6 or more times per week. CONCLUSIONS: Initial use of a cane led to decreased gait velocity and cadence in people with hip OA compared with walking unaided. This difference in gait velocity diminished after they practiced walking with the cane. Inconsistent use of the cane may have contributed to the lack of improvement in the subjects' hip OA pain and function.

Immediate effects of contralateral and ipsilateral cane use on normal adult gait.

OBJECTIVE: To determine the effects of ipsilateral and contralateral cane use on gait kinematics and peak vertical force in young healthy adults. DESIGN: Prospective observational study. SETTING: Veterans Affairs Healthcare Center. PARTICIPANTS: Fifteen healthy adults of aged 26 to 52 years (mean age 31 years) with no gait impairment and minimal experience using single-point canes. METHODS: The Pedar-X Mobile System plantar pressure measurement system was used to collect kinematic data from subjects walking in 3 different conditions (relative to a randomly "assigned" limb): contralateral cane (C), ipsilateral cane (I), and no cane (N). MAIN OUTCOME MEASURES: Peak vertical force, cadence, percentage swing phase and double limb support, and regional plantar pressure ratios. RESULTS: Peak vertical force (normalized for body weight) was reduced during both cane use conditions on the randomly assigned limb when compared to walking unaided (P<.001). The peak vertical force was 7% to 11% lower for the assigned limb than the opposite limb when a cane was used on either side (P<.016). Mean cadence was higher when participants ambulated without a cane (113 steps/min) than with a cane used on either the contralateral (98 steps/min) or ipsilateral (98 steps/min) side (P<.0001). Mean cadence did not significantly differ between the cane use conditions (P=.93). Regional plantar pressure ratios did not significantly change on either limb in any of the tested conditions. Double limb support slightly increased with cane use (P<.016). CONCLUSION: Both ipsilateral and contralateral cane use reduced cadence and mean peak vertical plantar force on the limb advanced with the cane in healthy young adults. Double limb support increased with cane use likely due to the reduced cadence and initial unfamiliarity with using an assistive device. A clinical implication of these findings is that prescription of canes for either ipsilateral or contralateral use effectively offloads a designated lower limb.

Barriers in the management of glucocorticoid-induced osteoporosis.

OBJECTIVE: To determine present practice for the management of glucocorticoid-induced osteoporosis (GIOP) in veterans; to characterize provider knowledge, beliefs, and practice behaviors regarding management of GIOP; and to identify potential barriers and interventions in the management of GIOP. METHODS: To characterize current management of GIOP in an academic veterans administration medical center, we conducted a retrospective chart review of 100 patients who were prescribed a 90-day supply of prednisone. To assess clinicians' knowledge of GIOP clinical guidelines and perceptions of GIOP management, primary care clinicians and subspecialists completed a questionnaire and participated in focus groups. RESULTS: Chart review revealed that only 32 of 100 patients receiving long-term glucocorticoid treatment underwent bone mineral density testing, and only 32 patients were prescribed the recommended calcium supplements. Of the 23 providers who completed the questionnaire and participated in the focus groups, 4 correctly identified both the dose and duration of glucocorticoid use at which GIOP prevention measures should be instituted. Common GIOP management barriers cited by participants were lack of knowledge, having limited time during the clinic visit to address all problems, patient nonadherence, and system problems. The most commonly mentioned potential interventions were the use of computerized clinical reminders and patient education. CONCLUSION: Clinicians frequently do not follow recommended guidelines for the management of GIOP. Improving the management of GIOP will likely require a fundamental redesigning of care processes for this disorder in order to overcome provider, patient-related, and system barriers.

Effects of footwear on medial compartment knee osteoarthritis.

This pilot study investigated whether lateral-wedge insoles inserted into shock-absorbing walking shoes altered joint pain, stiffness, and physical function in patients with symptomatic medial compartment knee osteoarthritis (OA). Twenty-eight subjects wore full-length lateral-wedge insoles with an incline of 4 degrees in their walking shoes for 4 weeks. Pain, stiffness, and functional status were measured with the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index at baseline and 4 weeks postintervention. Significant improvements were observed in all three WOMAC subscales (pain, stiffness, and function). Pain scores were significantly reduced for the most challenging activity-stair climbing. Subjects wore insoles daily and tolerated them well. The results of this study indicated that lateral-wedge insoles inserted into shock-absorbing walking shoes are an effective treatment for medial compartment knee OA.

Leflunomide use during the first 33 months after food and drug administration approval: experience with a national cohort of 3,325 patients.

OBJECTIVE: To describe leflunomide (LEF) use in a national cohort of 3,325 veterans. METHODS: Prescriptions for LEF and 9 disease-modifying antirheumatic drugs written between October 1998 and June 2001 at all Veterans Affairs (VA) medical centers were obtained from VA national databases. RESULTS: LEF was initiated with a loading dose of 100 mg daily for 3 days in 61% of patients, and 42% of patients discontinued LEF. LEF was more likely to be discontinued if a 3-day 100-mg loading dose was prescribed, patients were younger than 44 years or older than 75 years, or reported an annual family income <$60,000. Review of medical records of 291 discontinuers revealed that the most common reasons for discontinuation were inefficacy (30%), gastrointestinal symptoms (29%), medication noncompliance or lost to followup (14%), and elevated liver enzymes (5%). CONCLUSION: LEF is relatively safe in clinical practice. The VA's national databases provide an excellent, inexpensive resource for postmarketing evaluation of rheumatologic medications.