Immune Checkpoint Inhibitor-Associated Remitting Seronegative Symmetrical Synovitis With Pitting Edema: Description of a New Entity by CanRIO.

OBJECTIVE: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is characterized by symmetrical synovitis with pitting edema and negative rheumatoid factor (RF). It has been described in a setting of malignancy, suggesting a paraneoplastic association. With the increasing use of immune checkpoint inhibitors (ICIs) for the treatment of cancers and emergence of immune-related adverse events (irAEs), our objective was to identify and describe cases of ICI-associated RS3PE (ICI-RS3PE) and compare them to non-ICI-RS3PE. METHODS: The Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO) network is a collaboration of Canadian rheumatologists with experience in the management of patients with rheumatic irAEs (Rh-irAEs). Standardized data on adult patients with Rh-irAE have been collected as part of retrospective and prospective cohorts. In this study, detailed information on all cases of ICI-RS3PE from both cohorts were extracted and analyzed. RESULTS: We identified 11 cases of ICI-RS3PE. The most frequently observed malignancy was nonsmall cell lung cancer (4 of 11), followed by malignant melanoma (2 of 11) and cutaneous squamous cell carcinoma (2 of 11). The median time to onset of ICI-RS3PE was 26 weeks from ICI start and 52 weeks from diagnosis of malignancy. Seven patients had stable cancer prior to onset of ICI-RS3PE, 3 had partial response, and 1 had complete response. All patients received glucocorticoids. Conventional synthetic disease-modifying antirheumatic drugs (csDMARD) were needed in 10 patients. CONCLUSION: ICI-RS3PE may be an independent Rh-irAE, separate from paraneoplastic RS3PE. The symptoms of ICI-RS3PE responded well to glucocorticoids, but concomitant treatment with csDMARDs may be necessary.

Systemic lupus erythematosus presenting with atypical hemolytic uremic syndrome: a case report and review of the literature.

Systemic lupus erythematosus (SLE) can present with a diverse array of hematologic manifestations, among which atypical hemolytic uremic syndrome (aHUS) is a rare entity. SLE-triggered aHUS has significant morbidity and mortality without timely intervention, yet its frequency remains uncertain and optimal strategies for complement-directed therapies are largely expert-driven. We performed a comprehensive literature review and present a case of a 23-year-old female newly diagnosed with SLE/class IV lupus nephritis who developed aHUS that rapidly responded to the C5 antagonist, eculizumab. Review of the current literature identified forty-nine published cases of SLE with concurrent aHUS and revealed a predilection for aHUS in younger SLE patients, concurrent presentation with lupus nephritis, anti-dsDNA positivity, and complement system abnormalities. Over seventy percent of cases used eculizumab as complement-directed therapy with a trend towards faster time to improvement in laboratory parameters, though reported outcomes were highly variable. Early recognition of aHUS in SLE is pivotal in guiding appropriate therapeutic interventions, and prompt initiation of eculizumab may reduce the potential morbidity associated with plasmapheresis and additional immunosuppression. While eculizumab showcases promising results, its optimal timing and duration remain elusive. An understanding of a patients' complement genetics could aid management strategies, and ongoing research into complement-targeted therapies offers promising avenues for both SLE and aHUS treatment.

Identification of validated case definitions for medical conditions used in primary care electronic medical record databases: a systematic review.

Objectives: Data derived from primary care electronic medical records (EMRs) are being used for research and surveillance. Case definitions are required to identify patients with specific conditions in EMR data with a degree of accuracy. The purpose of this study is to identify and provide a summary of case definitions that have been validated in primary care EMR data. Materials and Methods: We searched MEDLINE and Embase (from inception to June 2016) to identify studies that describe case definitions for clinical conditions in EMR data and report on the performance metrics of these definitions. Results: We identified 40 studies reporting on case definitions for 47 unique clinical conditions. The studies used combinations of International Classification of Disease version 9 (ICD-9) codes, Read codes, laboratory values, and medications in their algorithms. The most common validation metric reported was positive predictive value, with inconsistent reporting of sensitivity and specificity. Discussion: This review describes validated case definitions derived in primary care EMR data, which can be used to understand disease patterns and prevalence among primary care populations. Limitations include incomplete reporting of performance metrics and uncertainty regarding performance of case definitions across different EMR databases and countries. Conclusion: Our review found a significant number of validated case definitions with good performance for use in primary care EMR data. These could be applied to other EMR databases in similar contexts and may enable better disease surveillance when using clinical EMR data. Consistent reporting across validation studies using EMR data would facilitate comparison across studies. Systematic review registration: PROSPERO CRD42016040020 (submitted June 8, 2016, and last revised June 14, 2016).

A Systematic Review of Quality Measures for Inflammatory Arthritis.

OBJECTIVE: To conduct a systematic review and quality appraisal of quality measures for inflammatory arthritis, including rheumatoid arthritis (RA), spondyloarthritis, psoriatic arthritis (PsA), and juvenile idiopathic arthritis (JIA). METHODS: Embase, MEDLINE, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched from January 1, 2000, to October 23, 2016, using Medical Subject Headings terms for inflammatory arthritis and quality measures. A "grey literature" search of international arthritis organizations and quality measure libraries was also conducted. Two reviewers independently considered the papers for inclusion, with disagreements resolved by consensus. A modified guideline appraisal tool (AGREE II) was used to appraise the measure development process, which determined final inclusion. Measures were abstracted in duplicate and categorized into themes, measure type, and domains of quality. RESULTS: Thirteen measurement sets were included from 4 countries (United States, Canada, United Kingdom, Netherlands) and 1 European consortium. They included 10 sets on RA and 1 each for PsA, inflammatory arthritis, and JIA. There were 161 unique individual measures (136 process, 20 structure, and 5 outcome). Major themes included assessment, medications, and comorbidities. Measure development methods were varied, including RAND/University of California, Los Angeles appropriateness methodology, prioritization exercises, or other modified-Delphi methods. Inclusion of patients occurred in 77% of development groups. Discussion of barriers to measurement was infrequent. CONCLUSION: Inflammatory arthritis quality measures cover a diversity of themes encompassing process, structure, and outcomes of care across the 6 domains of quality. However, between organizations, measure development is not standardized. Local assessment of measurement feasibility before use outside the original development context is recommended.

Prevalence and risk factors for liver fibrosis detected by transient elastography or shear wave elastography in inflammatory arthritis: a systematic review.

OBJECTIVES: Emerging technologies for monitoring subclinical liver fibrosis include transient elastography (TE) and shear wave elastography (SWE). A systematic review was conducted to assess the prevalence and report on predictors of liver fibrosis as detected by these technologies in inflammatory arthritis (IA) patients, including rheumatoid arthritis, spondyloarthritis and juvenile idiopathic arthritis. METHODS: MEDLINE, EMBASE and Web of Science were searched from inception to 06/27/2016 using search terms for IA or DMARDs and TE/SWE. Studies reporting on prevalence and/or risk factors for liver fibrosis as detected by TE/SWE were included. A meta-analysis was not conducted due to study heterogeneity. RESULTS: Seven cross-sectional and three case-control studies were included. The cut-off values to define liver fibrosis ranged from 5.3-8.6 kPa. The prevalence of liver fibrosis in RA detected by TE/SWE ranged from 3-23%, with higher prevalence found in studies using a 5.3kPa cut-off. In two studies fibrosis was reported in 16-17% of PsA patients with no JIA studies identified. Obesity was the most consistently reported independent predictor of fibrosis in three studies. Liver function tests (LFTs) were found to independently predict increased liver stiffness in one study, while cumulative dose of either methotrexate or leflunomide were predictors in two studies. CONCLUSIONS: Methotrexate or leflunomide cumulative dose was not consistently reported as an independent predictor of liver fibrosis; whereas, obesity was more consistently identified. Of note, LFTs did not consistently predict elevated TE/SWE measures. Further studies are needed to evaluate the prevalence and predictors of liver fibrosis and to explore the utility of using TE/SWE in IA patients.

Identification of validated case definitions for chronic disease using electronic medical records: a systematic review protocol.

BACKGROUND: Primary care electronic medical record (EMR) data are being used for research, surveillance, and clinical monitoring. To broaden the reach and usability of EMR data, case definitions must be specified to identify and characterize important chronic conditions. The purpose of this study is to identify all case definitions for a set of chronic conditions that have been tested and validated in primary care EMR and EMR-linked data. This work will provide a reference list of case definitions, together with their performance metrics, and will identify gaps where new case definitions are needed. METHODS: We will consider a set of 40 chronic conditions, previously identified as potentially important for surveillance in a review of multimorbidity measures. We will perform a systematic search of the published literature to identify studies that describe case definitions for clinical conditions in EMR data and report the performance of these definitions. We will stratify our search by studies that use EMR data alone and those that use EMR-linked data. We will compare the performance of different definitions for the same conditions and explore the influence of data source, jurisdiction, and patient population. DISCUSSION: EMR data from primary care providers can be compiled and used for benefit by the healthcare system. Not only does this work have the potential to further develop disease surveillance and health knowledge, EMR surveillance systems can provide rapid feedback to participating physicians regarding their patients. Existing case definitions will serve as a starting point for the development and validation of new case definitions and will enable better surveillance, research, and practice feedback based on detailed clinical EMR data. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016040020.