Performance of Anti-Carbamylated Protein Antibody Testing in the Routine Evaluation of Rheumatoid Arthritis from a Single Center.

BACKGROUND: Detection of anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factors (RF) in sera support the diagnosis of rheumatoid arthritis (RA); however, these markers are not detected in about 20% of RA patients. More recently, antibodies against carbamylated proteins (anti-CarP) have emerged with implications for preclinical RA diagnosis. The objective of this study was to assess the clinical performance of anti-CarP and correlate with disease severity in routine clinical practice. METHODS: Retrospective chart review of 331 subjects submitted for RA panel serology: 136 clinically defined RA-positive and 195 RA-negative patients. Fifty additional individuals were recruited for healthy controls. Patients' sera were tested for anti-CCP, anti-CarP, and RF antibodies. Clinical performance characteristics were evaluated for anti-CarP individually and in combination with anti-CCP and RF. Documented erosions and synovitis were correlated with anti-CarP positivity. RESULTS: Anti-CarP had a clinical sensitivity and specificity of 27% and 94%, respectively, for established RA. This sensitivity was lower than anti-CCP (79%) and RF (85%). The specificity of anti-CarP was similar to anti-CCP (93%) and higher than RF (69%). Anti-CarP in combination with anti-CCP and RF increased specificity (100%) but decreased sensitivity (21%). There was no correlation of anti-CarP positivity with presence of bone erosions; however, there was an increase in anti-CarP positivity among patients with synovitis. CONCLUSIONS: Anti-CarP demonstrates high specificity in diagnosis of established RA but lacks clinical sensitivity. In combination, anti-CarP does not improve clinical performance of anti-CCP and RF but may be useful in anti-CCP negative patients and in identifying patients with more active disease.

Neurologic involvement in seronegative primary Sjögren's syndrome with positive minor salivary gland biopsy: a single-center experience.

Objective: To assess the demographics, neurologic manifestations, comorbidities, and treatment of patients with seronegative primary Sjögren's syndrome (pSS). Patients and methods: We conducted a retrospective chart review on patients with seronegative pSS evaluated by a neurologist at the University of Utah Health between January 2010 and October 2018. The diagnosis was based on characteristic symptoms, positive minor salivary gland biopsy according to the American-European Consensus Group 2002 criteria, and seronegative antibody status. Results: Of 45 patients who met the study criteria, 42 (93.3%) were Caucasian, and 38 (84.4%) were female. The patients' mean age at diagnosis was 47.8 ± 12.6 (range 13-71) years. Paresthesia, numbness and dizziness, and headache were noted in 40 (88.9%), 39 (86.7%), and 36 patients (80.0%), respectively. Thirty-four patients underwent brain magnetic resonance imaging. Of these, 18 (52.9%) showed scattered nonspecific periventricular and subcortical cerebral white matter T2/fluid-attenuated inversion recovery hyperintense foci. Twenty-nine patients (64.4%) presented to the neurology clinic prior to pSS diagnosis, and the median delay in diagnosis from the first neurology clinic visit was 5 (interquartile ranges 2.0-20.5) months. Migraine and depression were the most common comorbidities in 31 patients (68.9%). Thirty-six patients received at least one immunotherapy, and 39 were on at least one medication for neuropathic pain. Conclusion: Patients often display various nonspecific neurological symptoms. Clinicians should express a high degree of skepticism regarding seronegative pSS and consider minor salivary gland biopsy to avoid delaying diagnosis, as undertreatment can affect patients' quality of life.

CONQUER Scleroderma: association of gastrointestinal tract symptoms in early disease with resource utilization.

OBJECTIVES: SSc is associated with increased health-care resource utilization and economic burden. The Collaborative National Quality and Efficacy Registry (CONQUER) is a US-based collaborative that collects longitudinal follow-up data on SSc patients with <5 years of disease duration enrolled at scleroderma centres in the USA. The objective of this study was to investigate the relationship between gastrointestinal tract symptoms and self-reported resource utilization in CONQUER participants. METHODS: CONQUER participants who had completed a baseline and 12-month Gastrointestinal Tract Questionnaire (GIT 2.0) and a Resource Utilization Questionnaire (RUQ) were included in this analysis. Patients were categorized by total GIT 2.0 severity: none-to-mild (0-0.49); moderate (0.50-1.00), and severe-to-very severe (1.01-3.00). Clinical features and medication exposures were examined in each of these categories. The 12-month RUQ responses were summarized by GIT 2.0 score categories at 12 months. RESULTS: Among the 211 CONQUER participants who met the inclusion criteria, most (64%) had mild GIT symptoms, 26% had moderate symptoms, and 10% severe GIT symptoms at 12 months. The categorization of GIT total severity score by RUQ showed that more upper endoscopy procedures and inpatient hospitalization occurred in the CONQUER participants with severe GIT symptoms. These patients with severe GIT symptoms also reported the use of more adaptive equipment. CONCLUSION: This report from the CONQUER cohort suggests that severe GIT symptoms result in more resource utilization. It is especially important to understand resource utilization in early disease cohorts when disease activity, rather than damage, primarily contributes to health-related costs of SSc.

Clinical Significance of Anti-U1 Ribonucleoprotein Antibody Is Analyte Dependent: Implications for Laboratory Reporting, Interpretation, and Interassay Correlations.

CONTEXT.­: Antibodies to U1 ribonucleoprotein (U1RNP) were first described more than 50 years ago, and although clinically relevant for antinuclear antibody-associated connective tissue disease (ANA-CTD), test results are challenging to interpret. OBJECTIVE.­: To evaluate the impact of anti-U1RNP analyte diversity in the assessment of patients at risk for ANA-CTD. DESIGN.­: Two multiplex assays for U1RNP (Smith [Sm]/RNP and RNP68/A) were used to test serum specimens from consecutive patients (n = 498) under evaluation for CTD in a single academic center. Discrepant specimens were further tested for Sm/RNP antibody by enzyme-linked immunosorbent assay and the BioPlex multiplex assay. Data were evaluated for antibody positivity per analyte and their method of detection, correlations between analytes, and impact on clinical diagnoses through retrospective chart review. RESULTS.­: Of the 498 patients tested, 47 (9.4%) were positive in the RNP68/A (BioPlex) and 15 (3.0%) were positive in the Sm/RNP (Theradiag) immunoassays. U1RNP-CTD, other ANA-CTD, and no ANA-CTD were diagnosed in 34% (16 of 47), 12.8% (6 of 47), and 53.2% (25 of 47) of the cases, respectively. The prevalence of antibody by method in patients with U1RNP-CTD was 100.0% (16 of 16), 85.7% (12 of 14), 81.5% (13 of 16), and 87.5% (14 of 16) for RNP68/A, Sm/RNP BioPlex, Sm/RNP Theradiag, and Sm/RNP Inova, respectively. For other ANA-CTD and no ANA-CTD, the highest prevalence was observed with RNP68/A; all others had comparable performance. CONCLUSIONS.­: In this study, the overall performance characteristics of Sm/RNP antibody assays were comparable; however, the RNP68/A immunoassay was very sensitive but less specific. In the absence of harmonization, reporting the type of U1RNP analyte in clinical testing may be useful in guiding interpretation and interassay correlations.

Assessment of a Line Immunoassay for the Detection of Mi-2 Antibodies: Results From a Single Academic Center Investigation.

OBJECTIVES: To evaluate the performance characteristics of a line immunoassay (LIA) for the detection of Mi-2 antibodies associated with dermatomyositis (DM). METHODS: In total, 432 consecutive patient specimens were tested for Mi-2 antibodies concurrently by LIA (Mi-2α or Mi-2ß) or immunoprecipitation (IP) test and antinuclear antibody by indirect immunofluorescence assay using HEp-2 substrate. Following antibody evaluation, results for patients positive in any of the assays for Mi-2 antibody had a retrospective chart review for diagnostic categorization. The performance of all tests was evaluated based on the extracted clinical data. RESULTS: Forty patients were positive in at least one of the Mi-2 assays. The frequency of Mi-2ß antibody by LIA was highest (75.0%), followed by Mi-2 by IP (35.0%) and Mi-2α by LIA (20.0%), respectively. Mi-2 by IP had the best total percent agreement for DM (95.0%) compared with 70.0% and 25.0% for the LIA Mi-2α and Mi-2ß, respectively. Positivity of the Mi-2ß antibody was significantly associated with non-DM diagnosis. CONCLUSIONS: Agreement for DM with assays for detecting Mi-2 is variable. Additional studies are required to validate Mi-2 immunoassays for routine patient evaluation.

The effect of an electronic medical record intervention on hydroxychloroquine prescribing habits and surveyed providers' opinions of the 2016 American Academy of Ophthalmology guidelines in the rheumatology and dermatology practices of an academic institutionle.

BACKGROUND: Retinal toxicity is a rare adverse event related to the use of hydroxychloroquine (HCQ). To address this, in 2016, the American Academy of Ophthalmology (AAO) issued guidelines recommending that HCQ not exceed 5 mg/kg/day. We analyzed HCQ prescribing habits at our institution, compared to these guidelines, and used surveys to determine the opinions on these guidelines. We then introduced, in a prospective and non-controlled study, a clinical decision support (CDS) tool into the electronic medical record (EMR) to study how this intervention might affect adherence with or opinions on these guidelines. METHODS: Data were collected pre-intervention (June 2017-January 2019) and post-intervention (March 2019-April 2020). In January 2019 we released our CDS tool. Results were analyzed using descriptive statistics for demographic data and Fisher's exact tests for comparisons of proportions between groups. RESULTS: Pre-intervention, we reviewed 1128 rheumatology charts and 282 dermatology charts. 31.0 and 39.7% respectively (32.8% combined) were prescribed HCQ > 5 .0 mg/kg/day. Post-intervention, we reviewed 1161 rheumatology charts and 110 dermatology charts. 23.0 and 25.5% respectively (23.2% combined) were prescribed HCQ > 5.0 mg/kg/day. Post-intervention, 9.6% fewer patients were prescribed HCQ > 5 mg/kg/day (P < .001). Pre-intervention, we compiled 18 rheumatology surveys and 12 dermatology surveys. Post-intervention, we compiled 16 rheumatology surveys and 12 dermatology surveys. Post-intervention, fewer rheumatologists incorrectly described the AAO weight-based guidelines. Combined, there was an overall reduction but not of statistical significance (P = .47). The majority of providers surveyed believed that the CDS tool was useful (72.2%). CONCLUSIONS: At our academic institution, there remains unfamiliarity with and hesitation to comply with the 2016 AAO guidelines. Prescribed doses often exceed what is recommended in these guidelines. A CDS tool can improve adherence with these guidelines and might improve providers' familiarity with these guidelines.

Rheumatic manifestations of diabetes mellitus.

DM is associated with various musculoskeletal manifestations. The strength of this relationship varies among the various musculoskeletal disorders; the associations are based mostly on epidemiologic data. For most of these conditions, definitive pathophysiologic correlates are lacking.Hand and shoulder disorders occur more frequently than other musculoskeletal manifestations of DM. Recognition of the association between DM and shoulder adhesive capsulitis, DD, and stenosing flexor tenosynovitis facilitates their correct diagnosis in the setting of DM and prompt initiation of appropriate treatment, which may include optimizing glycemic control. Conversely, awareness and identification of the characteristic musculoskeletal manifestations of DM may facilitate earlier diagnosis of DM and initiation of glucose-lowering therapy to retard the development of diabetic complications.Much less has been published about the musculoskeletal complications of DM than about its micro- and macrovascular complications. Prospective case-control cohort studies are needed to establish the true prevalence of musculoskeletal complications of DM and the metabolic syndrome, especially in this era of tighter glycemic control.The potential relationship between DM and the development of OA needs to be clarified in large, prospective, case-control cohort studies. The effect on musculoskeletal manifestations of various therapeutic regimens to manage DM should be studied prospectively. Treatment regimens for some musculoskeletal conditions associated with DM, such as DISH, should be studied in larger prospective, randomized,controlled clinical trials.At the molecular level, further studies are warranted to clarify the potential contribution of AGEs and adipokines to the development of OA and diabetic musculoskeletal syndromes, such as shoulder adhesive capsulitis, DD, stenosing flexor tenosynovitis, and LJM. Identification of such molecular targets for therapy would promote the development of additional treatments for these and other rheumatic diseases.

Serum cardiac troponin T, but not troponin I, is elevated in idiopathic inflammatory myopathies.

OBJECTIVE: To study the association of serum cardiac troponin T (cTnT) and cardiac troponin I (cTnI) with creatine kinase (CK) in patients with idiopathic inflammatory myopathies (IIM). METHODS: We performed a retrospective study on patients with IIM followed by the rheumatology service of a county hospital from 2004 to 2008. Patients with myocardial ischemia and/or with renal failure were excluded. Clinical data including electromyogram, muscle biopsy, and CK, cTnT and cTnI were recorded. Patients who had simultaneous analysis of CK and cardiac troponin (cTnT or cTnI) levels were studied. CK levels were correlated with cTnT and cTnI by chi-square test and Spearman correlation. RESULTS: We identified 49 patients with IIM (69 observations) who satisfied our inclusion criteria. The primary diagnosis was polymyositis in 23, dermatomyositis in 16, and myositis associated with connective tissue disease in 10 patients. There were 33/49 women with average age 45.8 years. Twenty-eight patients with IIM had simultaneous CK and cTnT values assayed. Of those patients, 18/23 with elevated CK also had elevated cTnT, and 5/5 patients with normal CK levels had normal cTnT levels (p = 0.005). In 41 patients with IIM who had simultaneous CK and cTnI levels assayed, only 1/29 with elevated CK had elevated cTnI, and 12/12 patients with normal CK had normal cTnI (p = 0.5). CK correlated strongly with the cTnT (r = 0.62, p = 0.001) but did not correlate with cTnI. CONCLUSION: Elevated cTnT, but not cTnI, was highly associated with CK in patients with IIM despite the absence of myocardial ischemia.