Structural Changes over a Short Period Are Associated with Functional Assessments in Rheumatoid Arthritis.

OBJECTIVE: To investigate the correlation between changes in radiological quantitative assessment with changes in clinical and functional assessment from baseline to 3 months in patients with rheumatoid arthritis (RA). METHODS: Twenty-eight patients with RA [methotrexate (MTX) and anti-tumor necrosis factor-α (TNF-α) group with high disease activity (n = 18); and MTX group with low disease activity (n = 10)] underwent assessments at baseline and 3 months: clinical [28-joint count Disease Activity Score (DAS28)], functional [Health Assessment Questionnaire (HAQ) and Michigan Hand Outcome Questionnaire (MHQ)], and imaging-based [3 Tesla magnetic resonance imaging (MRI) and high-resolution peripheral quantitative computed tomography (HR-pQCT)]. MR images were evaluated semiquantitatively [RA MRI scoring (RAMRIS)] and quantitatively for the volume of synovitis and bone marrow edema (BME) lesions. Erosion volumes were measured using HR-pQCT. RESULTS: After 3 months, the anti-TNF-α group demonstrated an improvement in disease activity through DAS28, HAQ, and MHQ. MRI showed significant decreases in synovitis and BME volume for the anti-TNF-α group, and significant increases in the MTX group. HR-pQCT showed significant decreases in bone erosion volume for the anti-TNF-α group, and significant increases in the MTX group. No significance was observed using RAMRIS. Changes in synovitis, BME, and erosion volumes, but not RAMRIS, were significantly correlated with changes in DAS28, HAQ, and MHQ. CONCLUSION: Quantitative measures were more sensitive than semiquantitative grading when evaluating structural and inflammatory changes with treatment, and were associated with patient clinical and functional outcomes. Multimodality imaging with 3T MRI and HR-pQCT may provide promising biomarkers that help determine disease progression and therapy response.

Vasculitis and peripheral neuropathy.

PURPOSE OF REVIEW: Vasculitis of medium-sized and small vessels commonly affects peripheral nerves and can occur in context of a systemic vasculitis with multiorgan involvement or a nonsystemic vasculitis limited to the peripheral nervous system. This review summarizes the clinical and pathological features of systemic and nonsystemic vasculitis of the peripheral nervous system. RECENT FINDINGS: Vasculitis of peripheral nerves is a diffuse process that affects the vasa nervorum along the entire length of affected nerves but appears to cause injury primarily in a zone in the proximal-middle of the nerve that is particularly susceptible to ischemic injury. Nerve biopsy can help establish the diagnosis of a systemic vasculitis, particularly when other organ involvement is not clinically apparent, and is required for diagnosis of nonsystemic vasculitic neuropathy. Observational studies suggest that nonsystemic vasculitic neuropathy responds to immunosuppressive therapy but conclusive data are lacking. SUMMARY: The current review summarizes the clinical and pathological features of both systemic and nonsystemic vasculitis of the peripheral nervous system so that clinicians can better recognize, make a more timely diagnosis, and thus treat this condition more effectively in their patients.

Smoking Is Associated with Higher Disease Activity in Rheumatoid Arthritis: A Longitudinal Study Controlling for Time-varying Covariates.

OBJECTIVE: Prior studies around the relationship between smoking and rheumatoid arthritis (RA) disease activity have reported inconsistent findings, which may be ascribed to heterogeneous study designs or biases in statistical analyses. We examined the association between smoking and RA outcomes using statistical methods that account for time-varying confounding and loss to followup. METHODS: We included 282 individuals with an RA diagnosis using electronic health record data collected at a public hospital between 2013 and 2017. Current smoking status and disease activity were assessed at each visit; covariates included sex, race/ethnicity, age, obesity, and medication use. We used longitudinal targeted maximum likelihood estimation to estimate the causal effect of smoking on disease activity measures at 27 months, and compared results to conventional longitudinal methods. RESULTS: Smoking was associated with an increase of 0.64 units in the patient global score compared to nonsmoking (p = 0.01), and with 2.58 more swollen joints (p < 0.001). While smoking was associated with a higher clinical disease activity score (2.11), the difference was not statistically significant (p = 0.22). We found no association between smoking and physician global score, or C-reactive protein levels, and an inverse association between smoking and tender joint count (p = 0.05). Analyses using conventional methods showed a null relationship for all outcomes. CONCLUSION: Smoking is associated with higher levels of disease activity in RA. Causal methods may be useful for investigations of additional exposures on longitudinal outcome measures in rheumatologic disease.

Hypomethylation of CYP2E1 and DUSP22 Promoters Associated With Disease Activity and Erosive Disease Among Rheumatoid Arthritis Patients.

OBJECTIVE: Epigenetic modifications have previously been associated with rheumatoid arthritis (RA). In this study, we aimed to determine whether differential DNA methylation in peripheral blood cell subpopulations is associated with any of 4 clinical outcomes among RA patients. METHODS: Peripheral blood samples were obtained from 63 patients in the University of California, San Francisco RA cohort (all satisfied the American College of Rheumatology classification criteria; 57 were seropositive for rheumatoid factor and/or anti-cyclic citrullinated protein). Fluorescence-activated cell sorting was used to separate the cells into 4 immune cell subpopulations (CD14+ monocytes, CD19+ B cells, CD4+ naive T cells, and CD4+ memory T cells) per individual, and 229 epigenome-wide DNA methylation profiles were generated using Illumina HumanMethylation450 BeadChips. Differentially methylated positions and regions associated with the Clinical Disease Activity Index score, erosive disease, RA Articular Damage score, Sharp score, medication at time of blood draw, smoking status, and disease duration were identified using robust regression models and empirical Bayes variance estimators. RESULTS: Differential methylation of CpG sites associated with clinical outcomes was observed in all 4 cell types. Hypomethylated regions in the CYP2E1 and DUSP22 gene promoters were associated with active and erosive disease, respectively. Pathway analyses suggested that the biologic mechanisms underlying each clinical outcome are cell type-specific. Evidence of independent effects on DNA methylation from smoking, medication use, and disease duration were also identified. CONCLUSION: Methylation signatures specific to RA clinical outcomes may have utility as biomarkers or predictors of exposure, disease progression, and disease severity.

Association of High Anti-Cyclic Citrullinated Peptide Seropositivity and Lean Mass Index With Low Bone Mineral Density in Rheumatoid Arthritis.

OBJECTIVE: Osteoporotic fractures are associated with high morbidity and mortality. Persons with rheumatoid arthritis (RA) have twice the risk of osteoporosis-related fracture than age-matched controls, the causes for which remain unknown. We investigated contributions of RA characteristics, medication use, and body composition to low bone mineral density (BMD) in patients with RA. METHODS: Data were from the Arthritis, Body Composition, and Disability Study (n = 138; 82 women, 56 men). Demographic, clinical, laboratory, and functional variables were collected at study visits. Body composition (fat, lean muscle, and BMD) was measured by dual x-ray absorptiometry. Linear regression analyses evaluated the association between predictors and femoral neck BMD. RESULTS: Average disease duration was 19 years, 70% of patients were rheumatoid factor positive, and 55% were high-positive anti-cyclic citrullinated peptide (anti-CCP). Age and high anti-CCP positivity were negatively associated with BMD after controlling for other variables (ß = -0.003 and -0.055, respectively, P < 0.05). Appendicular lean mass index (ALMI) was positively associated with BMD (ß = 0.053, P < 0.0001). In high anti-CCP positivity participants, increasing anti-CCP levels were associated with a negative linear trend in BMD (ß = -0.011, P = 0.026). CONCLUSION: High anti-CCP positivity and ALMI were strongly associated with BMD in patients with RA. The linear relationship of anti-CCP levels with lower BMD supports the hypothesis that processes specific to RA negatively impact BMD. In contrast, ALMI was positively associated with BMD, emphasizing the importance of this potentially modifiable risk factor. Our findings highlight the complicated interplay of RA disease-specific and functional factors and their impact on bone mass.

Assessment of 3-month changes in bone microstructure under anti-TNFα therapy in patients with rheumatoid arthritis using high-resolution peripheral quantitative computed tomography (HR-pQCT).

BACKGROUND: Although one study showed minimal progression of erosions in patients with rheumatoid arthritis (RA) one year after TNFα inhibition therapy, no studies have investigated very early bone changes after initiation of anti-TNFα treatment. We investigated the effects of 3-month anti-TNFα treatment on bone erosion progression and bone microarchitecture in RA patients using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Patients with RA (n = 27) (17 in the anti-TNFα and 10 in the MTX-only group) underwent assessment of disease activity score in 28 joints (DAS-28), radiographs, 3-T magnetic resonance imaging (MRI) and HR-pQCT of metacarpophalangeal and wrist joints at baseline and 3 months. HR-pQCT-derived erosion volume, joint volume/width and bone microarchitecture were computed and joint destruction was assessed using Sharp and RAMRIS scorings on radiographs and MRI, respectively. RESULTS: Overall, 73 erosions were identified by HR-pQCT at baseline. Over 3 months, the anti-TNFα group had decreased mean erosion volume; increased erosion volume was observed in one clinical non-responder. The MTX-only group in contrast, trended toward increasing erosion volume despite low disease activity. In the anti-TNFα group, joint-space width and volume of MCP joints decreased significantly and was positively correlated with erosion volume changes (R 2 = 0.311, p = 0.013; R 2 = 0.527, p = 0.003, respectively). In addition, erosion volume changes were significantly negatively correlated with changes in trabecular bone mineral density (R 2 = 0.353, p = 0.020) in this group. We observed significant correlation between percentage change in erosion volume and change in DAS-28 erythrocyte sedimentation rate and C-reactive protein CRP scores (R 2 = 0.558, p < 0.001; R 2 = 0.745, p < 0.001, respectively) in all patients. CONCLUSIONS: Using HR-pQCT, our data suggest that anti-TNFα treatment prevents erosion progression and deterioration of bone microarchitecture within the first 3 months of treatment, one patient not responding to treatment, had significant progression of bone erosions within this short time period. Patients with low disease activity scores (<3.2) can have continuous HR-pQCT-detectable progression of erosive disease with MTX treatment only. HR-pQCT can be a sensitive, powerful tool to quantify bone changes and monitor RA treatment short term (such as 3 months).

Neurologic Manifestations of Rheumatoid Arthritis.

Neurologic manifestations of rheumatoid arthritis (RA) range in severity from mild paresthesias in the hand from carpal tunnel syndrome to sudden death due to impingement of the medulla by an eroded, vertically subluxed dens. Most neurologic complications are a consequence of articular inflammation and damage that leads to compression of adjacent structures of the central or peripheral nervous systems. Rare but serious extra-articular manifestations include inflammation of the meninges and ischemic neuropathies due to necrotizing arteritis of the vasa vasorum. Medical therapy with synthetic disease-modifying antirheumatic drugs and biological agents has diminished the incidence of serious neurologic manifestations in RA.

Involvement of the Peripheral Nervous System in Polyarteritis Nodosa and Antineutrophil Cytoplasmic Antibodies-Associated Vasculitis.

Peripheral nerve involvement is common in polyarteritis nodosa and the antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides. The underlying mechanism is arteritis of the vasa nervorum, leading to ischemic neuropathy. The classic presentation is stepwise involvement of peripheral nerves with ongoing antecedent constitutional symptoms. This article reviews the pathologic findings, clinical syndromes, diagnosis, and treatment of ANCA-associated vasculitides.

Current Assays to Determine Free 25-Hydroxyvitamin D in Serum.

The 25-hydroxylated metabolite of vitamin D is the best clinical indicator of vitamin D status. For many years, emphasis has been on measuring total levels of 25-hydroxyvitamin D [25(OH)D], but recently, interest in measuring free 25(OH)D as a potentially better marker of vitamin D status has arisen. Since the 1980s when the first measurements of free 25(OH)D were made, little progress has been made in the development of rapid, reliable methods to determine the levels of free 25(OH)D. For many years, assessment of free 25(OH)D relied on calculations using levels of total 25(OH)D, albumin, and vitamin D binding protein (VDBP), for which many assays exist. However, because of vagaries in the measurement of VDBP in particular and the assumption of a constant affinity of VDBP for the vitamin D metabolites (which has been shown to be problematic), calculated values have proved suspect. This changed a few years ago when a new immunoassay was developed to measure free 25(OH)D directly. This review examines methods for determining free 25(OH)D, the different methods used in clinical studies, and the relationships between free 25(OH)D and other vitamin D metabolites and the physiologic functions affected by vitamin D metabolites, such as bone cell activity and turnover. The review also comments on the value of assessing free 25(OH)D and the efforts to standardize the assays.

Quantitative characterization of metacarpal and radial bone in rheumatoid arthritis using high resolution- peripheral quantitative computed tomography.

AIM: The objectives of this study were: (i) to develop a standardized method of quantifying bone mineral density (BMD) and microarchitecture in the hand and wrist bones of patients with rheumatoid arthritis (RA) using high resolution- peripheral quantitative computed tomography (HR-pQCT); (ii) to compare quantitative bone parameters between RA and post-menopausal osteopenic (PM-OP) subjects; and (iii) to correlate quantitative bone parameters at the distal radius with those at the metacarpal heads in RA subjects. METHODS: HR-pQCT imaging of the dominant hand and wrist was performed in 12 female RA patients. BMD and trabecular parameters for the 2-12% head region of the second and third metacarpals were calculated and compared between RA patients and healthy controls. Bone parameters were also calculated for 110 slices of the distal radius in RA patients and compared to data from controls and PM-OP women from a previous study. RESULTS: Compared to controls, RA patients had significantly decreased BMD, trabecular volume and number, and increased trabecular heterogeneity in the third metacarpal and distal radius. Significantly lower trabecular number and significantly higher ratio of outer annular trabecular BMD to inner trabecular BMD were observed in patients with RA, compared to patients with osteopenia (P < 0.05). Trabecular BMD in the third metacarpal and in the distal radius were significantly correlated (ρ = 0.918, P < 0.0001) in RA patients. CONCLUSION: This study established a standardized method for quantifying bone density and trabecular properties in the hand and wrist bones of RA patients using HR-pQCT. Deterioration of bone structure in RA patients was found comparable to that in osteopenic women, and trabecular bone loss near affected joints was found to be correlated with bone loss away from joints.

Evaluating radiocarpal cartilage matrix changes 3-months after anti-TNF treatment for rheumatoid arthritis using MR T1ρ imaging.

PURPOSE: To evaluate the feasibility of MR T1ρ in assessing radiocarpal cartilage matrix changes following rheumatoid arthritis (RA) treatment. MATERIALS AND METHODS: Five healthy controls and nine RA patients were studied: three RA patients with low disease activity that were treated with methotrexate (MTX) alone and six with active disease despite MTX treatment who were additionally treated with certolizumab pegol, an anti-tumor necrosis factor biologic. Wrist 3 Tesla MRI were acquired at baseline and 3-month follow-up. T1ρ were quantified for lunar, radius, and scaphoid cartilage. Reproducibility was evaluated using coefficients of variation (CV). Longitudinal changes were evaluated with t-test and relationships between T1ρ with clinical, MRI, and patient-reported outcomes were evaluated with Spearman's rho. RESULTS: Scan/re-scan CVs of T1ρ values were all <5%, and intra- and inter-reader CVs were all < 2.0%. Baseline scaphoid T1ρ values were significantly higher in RA patients compared with healthy controls (P = 0.032). Changes in T1ρ (baseline, 3-month) were correlated with EULAR treatment response criteria: -2.26 ± 0.75 ms, 1.08 ± 0.52 ms, and 2.18 ± 0.45 ms for good, moderate, and nonresponders, respectively. Significant correlations were found between changes in global T1ρ values and changes in DAS28-CRP (rs = 0.683; P = 0.042), MHQ (rs = -0.783; P = 0.013), and HAQ (rs = 0.833; P = 0.010). CONCLUSION: Despite the limited sample size and follow-up time points, there were significant correlations between changes in radiocarpal T1ρ and changes in disease activity as assessed by clinical and patient-reported outcomes. Our findings encourage further research into MR T1ρ assessment of RA disease activity and treatment response. LEVEL OF EVIDENCE: 1 J. MAGN. RESON. IMAGING 2017;45:1514-1522.

High-temporospatial-resolution dynamic contrast-enhanced (DCE) wrist MRI with variable-density pseudo-random circular Cartesian undersampling (CIRCUS) acquisition: evaluation of perfusion in rheumatoid arthritis patients.

This study is to evaluate highly accelerated three-dimensional (3D) dynamic contrast-enhanced (DCE) wrist MRI for assessment of perfusion in rheumatoid arthritis (RA) patients. A pseudo-random variable-density undersampling strategy, circular Cartesian undersampling (CIRCUS), was combined with k-t SPARSE-SENSE reconstruction to achieve a highly accelerated 3D DCE wrist MRI. Two healthy volunteers and 10 RA patients were studied. Two patients were on methotrexate (MTX) only (Group I) and the other eight were treated with a combination therapy of MTX and anti-tumor necrosis factor (TNF) therapy (Group II). Patients were scanned at baseline and 3 month follow-up. DCE MR images were used to evaluate perfusion in synovitis and bone marrow edema pattern in the RA wrist joints. A series of perfusion parameters was derived and compared with clinical disease activity scores of 28 joints (DAS28). 3D DCE wrist MR images were obtained with a spatial resolution of 0.3 × 0.3 × 1.5 mm(3) and temporal resolution of 5 s (with an acceleration factor of 20). The derived perfusion parameters, most notably transition time (dT) of synovitis, showed significant negative correlations with DAS28-ESR (r = -0.80, p < 0.05) and DAS28-CRP (r = -0.87, p < 0.05) at baseline and also correlated significantly with treatment responses evaluated by clinical score changes between baseline and 3 month follow-up (with DAS28-ESR r = -0.79, p < 0.05, and DAS28-CRP r = -0.82, p < 0.05). Highly accelerated 3D DCE wrist MRI with improved temporospatial resolution has been achieved in RA patients and provides accurate assessment of neovascularization and perfusion in RA joints, showing promise as a potential tool for evaluating treatment responses.

Use of Low-Literacy Decision Aid to Enhance Knowledge and Reduce Decisional Conflict Among a Diverse Population of Adults With Rheumatoid Arthritis: Results of a Pilot Study.

OBJECTIVE: Despite innovations in treatment of rheumatoid arthritis (RA), adherence is poor and disparities persist. Shared decision making (SDM) promotes patient engagement and enhances adherence; however, few tools support SDM in RA. Our objective was to pilot a low-literacy medication guide and decision aid to facilitate patient-clinician conversations about RA medications. METHODS: RA patients were consecutively enrolled into 1 of 3 arms: 1) control; patients received existing medication guide prior to clinic visit, 2) adapted guide prior to visit, and 3) adapted guide prior to plus decision aid during visit. Outcomes were collected immediately postvisit, at 1-week, and at 3- and 6-month interviews. Eligible adults had to have failed at least 1 disease-modifying antirheumatic drug and fulfill 1 of the following: age >65 years, immigrant, non-English speaker, less than high school education, limited health literacy, and racial/ethnic minority. Primary outcomes were knowledge of RA medications, decisional conflict, and acceptability of interventions. RESULTS: The majority of 166 patients were immigrants (66%), non-English speakers (54%), and had limited health literacy (71%). Adequate RA knowledge postvisit in arm 3 was higher (78%) than arm 1 (53%; adjusted odds ratio 2.7, 95% confidence interval 1.2, 6.1). Among patients with a medication change, there was lower (better) mean decisional conflict in arms 2 and 3 (P = 0.03). There were no significant differences in acceptability. CONCLUSION: A low-literacy medication guide and decision aid was acceptable, improved knowledge, and reduced decisional conflict among vulnerable RA patients. Enhancing knowledge and patient engagement with decision support tools may lead to medication choices better aligned with RA patients' values and preferences.

Efficiency Gains for Rheumatology Consultation Using a Novel Electronic Referral System in a Safety-Net Health Setting.

OBJECTIVE: Health information technology (HIT) holds promise in increasing access to rheumatologists by improving the quality and efficiency of referrals, but few studies have examined its use for this purpose. We evaluated the use and impact of a novel electronic referral (eReferral) system in rheumatology in a safety-net health system. METHODS: We examined eReferrals over 4 years. Our primary outcome was use of preconsultation exchange, defined as back-and-forth communication between referring and specialty care providers, facilitating triage of referrals, requests for more information, or resolution of questions without a visit. We calculated the proportion of eReferrals that underwent preconsultation exchange, time to reviewer response, and number of visits scheduled. To increase generalizability, we selected a random sample of eReferrals to undergo additional blinded, adjudicated review to assess agreement on appropriateness for preconsultation exchange. RESULTS: Between 2008 and 2012, 2,383 eReferrals were reviewed and 2,105 were eligible for analysis. One-fourth of eReferrals were resolved without a clinic visit. The proportion of eReferrals undergoing preconsultation exchange increased over time (55% in 2008 versus 74% in 2011), and the volume of referrals also steadily increased over time. Reviewer response time averaged between 1 and 4 days. In the random sample of eReferrals that underwent adjudicated review, agreement between reviewers was high (κ = 0.72). CONCLUSION: HIT-enabled preconsultation exchange was used for a majority of eReferrals and facilitated communication between referring clinicians and rheumatologists. This redesigned system of care allowed for triage of a high number of referrals, with many referrals determined to be appropriate for preconsultation exchange.

Correlation of structural abnormalities of the wrist and metacarpophalangeal joints evaluated by high-resolution peripheral quantitative computed tomography, 3 Tesla magnetic resonance imaging and conventional radiographs in rheumatoid arthritis.

AIM: In rheumatoid arthritis (RA) hands, we applied high-resolution peripheral quantitative computed tomography (HR-pQCT) and 3 Tesla (3 T) magnetic resonance imaging (MRI), which are new methods for erosion detection and bone marrow edema (BME) quantification. We compared the erosion measurements between these techniques with conventional radiographs (CR) in order to examine their significance for evaluating structural abnormalities. METHODS: In 16 RA patients, HR-pQCT of metacarpophalangeal and wrist joints, 3 T MRI of wrist joints, as well as CR in both hands and feet were performed. Ten patients had 1-year follow-up CR. CRs were graded according to the modified Sharp score (MSS). Bone erosions were evaluated in HR-pQCT and MRI. BME pattern was quantified from MRI for volume, signal change and total burden. RESULTS: The erosion detection sensitivity of MRI was 85.7% and CR was 60.9% when HR-pQCT was considered as a reference method. The smallest dimensions of erosion detected by HR-pQCT, MRI and CR were 0.09, 0.14 and 0.66 cm, respectively. Baseline total MSS was correlated with HR-pQCT erosion measures, MRI erosion measures and MRI BME volume (P < 0.05). The mean difference between baseline and 1-year follow-up MSS (delta MSS) was 1.2. A trend was observed toward a correlation between delta MSS and MRI BME volume and burden. CONCLUSION: This study demonstrates that HR-pQCT detects more and smaller bone erosions compared to MRI and CR. In addition, 3 T MRI can provide quantitative measurement of BME. Combination of HR-pQCT and MRI modalities may provide powerful tools to evaluate joint inflammation and bone damage in RA.

Computer-aided and manual quantifications of MRI synovitis, bone marrow edema-like lesions, erosion and cartilage loss in rheumatoid arthritis of the wrist.

PURPOSE: To investigate the reliability and validity of computer-aided automated and manual quantification as well as semiquantitative analysis for MRI synovitis, bone marrow edema-like lesions, erosion and cartilage loss of the wrist in rheumatoid arthritis (RA) compared to the OMERACT-RAMRIS. METHODS AND MATERIALS: Wrist MRI was performed at 3 T in 16 patients with RA. Synovial volume and perfusion, bone marrow edema-like lesion (BMEL) volume, signal intensity and perfusion, and erosion dimensions were measured manually and using an in-house-developed automated software algorithm; findings were correlated with the OMERAC-RAMRIS gradings. In addition, a semiquantitative MRI cartilage loss score system was developed. Intraclass correlation coefficients (ICCs) were used to test the reproducibility of these quantitative and semiquantitative techniques. Spearman correlation coefficients were calculated between lesion quantifications and RAMRIS and between the MRI cartilage score and radiographic Sharp van der Heijde joint space narrowing scores. RESULTS: The intra- and interobserver ICCs were excellent for synovial, BMEL and erosion quantifications and cartilage loss grading (all >0.89). The synovial volume, BMEL volume and signal intensity, and erosion dimensions were significantly correlated with the corresponding RAMRIS (r = 0.727 to 0.900, p < 0.05). Synovial perfusion parameter maximum enhancement (Emax) was significantly correlated with synovitis RAMRIS (r = 0.798). BMEL perfusion parameters were not correlated with the RAMRIS BME score. Cartilage loss gradings from MRI were significantly correlated with the Sharp joint space narrowing scores (r = 0.635, p = 0.008). CONCLUSION: The computer-aided, manual and semiquantitative methods presented in this study can be used to evaluate MRI pathologies in RA with excellent reproducibility. Significant correlations with standard RAMRIS were found in the measurements using these methods.

Pauci-immune glomerulonephritis in individuals with disease associated with levamisole-adulterated cocaine: a series of 4 cases.

Exposure to levamisole-adulterated cocaine can induce a distinct clinical syndrome characterized by retiform purpura and/or agranulocytosis accompanied by an unusual constellation of serologic abnormalities including antiphospholipid antibodies, lupus anticoagulants, and very high titers of antineutrophil cytoplasmic antibodies. Two recent case reports suggest that levamisole-adulterated cocaine may also lead to renal disease in the form of pauci-immune glomerulonephritis. To explore this possibility, we reviewed cases of pauci-immune glomerulonephritis between 2010 and 2012 at an inner city safety net hospital where the prevalence of levamisole in the cocaine supply is known to be high. We identified 3 female patients and 1 male patient who had biopsy-proven pauci-immune glomerulonephritis, used cocaine, and had serologic abnormalities characteristic of levamisole-induced autoimmunity. Each also had some other form of clinical disease known to be associated with levamisole, either neutropenia or cutaneous manifestations. One patient had diffuse alveolar hemorrhage. Three of the 4 patients were treated with short courses of prednisone and cyclophosphamide, 2 of whom experienced stable long-term improvement in their renal function despite ongoing cocaine use. The remaining 2 patients developed end-stage renal disease and became dialysis-dependent. This report supports emerging concern of more wide spread organ toxicity associated with the use of levamisole-adulterated cocaine.

Depletion of B-cells with rituximab improves endothelial function and reduces inflammation among individuals with rheumatoid arthritis.

BACKGROUND: Individuals with rheumatoid arthritis (RA) are at increased risk for cardiovascular disease, partly due to systemic inflammation and endothelial dysfunction. B-cells play an important pathogenic role in the inflammatory process that drives RA disease activity. Rituximab, a chimeric murine/human monoclonal antibody that depletes B-cells, is an effective therapy for RA. The purpose of this study was to determine whether B-cell depletion with rituximab reduces systemic inflammation and improves macrovascular (brachial artery flow-mediated dilation, FMD) and microvascular (reactive hyperemia) endothelial function in RA patients. METHODS AND RESULTS: RA patients received a single course of rituximab (1000 mg IV infusion at baseline and on day 15). FMD, reactive hyperemia, inflammatory markers, and clinical assessments were performed at baseline, week 12, and week 24. Twenty patients (95% female, median age 54 years) completed the study. Following treatment, FMD improved from a baseline of 4.5±0.4% to 6.4±0.6% at 12 weeks (mean±SE; P<0.0001), followed by a decline at week 24; a similar pattern was observed for hyperemic velocity. Significant decreases in RA disease scores, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, and circulating CD19+ B-cells were sustained through week 24. Cholesterol and triglycerides became significantly although modestly elevated during the study. CONCLUSIONS: Depletion of B-cells with rituximab improved macrovascular and microvascular endothelial function and reduced systemic inflammation, despite modest elevation in lipids. Given these results, rituximab should be evaluated in the future for its possible role in reducing excess cardiovascular risk in RA. CLINICAL TRIAL REGISTRATION: URL http://ClinicalTrials.gov. Unique identifier: NCT00844714.