Lisa Christopher—Stine | Johns Hopkins University (original) (raw)

Papers by Lisa Christopher—Stine

Frontiers in Medicine

The aim of this review is to examine and evaluate published literature associated with idiopathic... more The aim of this review is to examine and evaluate published literature associated with idiopathic inflammatory myopathies (IIM) and interstitial lung disease (ILD) based on myositis specific autoantibodies (MSA) and the potential clinical significance of each autoantibody subtype for the practicing clinician. The review is a comprehensive search of literature published in PubMed from the year 2005 and onward coinciding with the surge in the discovery of new MSAs. Additionally, we comment on recommended multidisciplinary longitudinal care practices for patients with IIM-ILD with regard to imaging and other testing. Treatment is not covered in this review.

Annals of the Rheumatic Diseases, 2021

Acta Neuropathologica, 2021

Myositis comprises a heterogeneous group of skeletal muscle disorders which converge on chronic m... more Myositis comprises a heterogeneous group of skeletal muscle disorders which converge on chronic muscle inflammation and weakness. Our understanding of myositis pathogenesis is limited, and many myositis patients lack effective therapies. Using muscle biopsy transcriptome profiles from *

Rheumatology, 2021

It is 120 years since ‘angiomyositis’ was included alongside ‘polymyositis’ and ‘dermatomyositis’... more It is 120 years since ‘angiomyositis’ was included alongside ‘polymyositis’ and ‘dermatomyositis’ in an attempt to propose a taxonomy that reflected the major clinical characteristics of idiopathic inflammatory myopathy (IIM). Endothelial injury, perivascular inflammation and capillary loss are important histological findings in affected tissues in IIM. Overt vascular clinical features including RP and abnormal nailfold capillaroscopy (NC) are also common in IIM. Despite the presence of endothelial injury, perivascular inflammation and capillary loss in affected tissues in IIM, and the presence of clinical features such as RP and NC abnormalities, the pathogenic and therapeutic implications of vasculopathy in IIM have been somewhat overlooked. RP and NC abnormalities are not always present, providing a valuable opportunity to explore aetiopathogenic factors driving vasculopathy within autoimmune rheumatic disease. The present review examines the aetiopathogenic, prognostic and thera...

Neuromuscular Disorders, 2019

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Highlights  Dermatomyositis-specific autoantibodies define unique clinical phenotypes.  Standardized autoantibody detection methods are needed.  Patients with antisynthetase autoantibodies do not have dermatomyositis.  A new dermatomyositis classification scheme was proposed.

Respiratory Medicine, 2019

Purpose: Myositis-associated interstitial lung disease (MA-ILD) is associated with increased mort... more Purpose: Myositis-associated interstitial lung disease (MA-ILD) is associated with increased mortality, but no prognostic model exists in this population. The ILD-GAP index was developed to predict mortality risk across all subtypes of chronic ILD. The purpose of this study was to validate the ILD-GAP risk prediction model in patients with MA-ILD. Procedures: We completed a retrospective cross-sectional study of patients enrolled in the Johns Hopkins Myositis Center database between 2006 and 2017. Cumulative mortality rates were estimated using the Kaplan-Meier test. Model calibration was determined by using standardized mortality ratios of observed versus expected deaths. Main Findings: 179 participants with MA-ILD were included. The mean baseline percent predicted forced vital capacity was 65.2 ± 20.6%, forced expiratory volume in the first second 65.4 ± 20.4%, and carbon monoxide diffusing capacity 61.6 ± 20.0%. Thirty-two participants died (17.9%). The ILD-GAP model had poor discriminative performance and calibration. Conclusions: The ILD-GAP risk prediction model is a poor predictor of mortality among individuals with MA-ILD. The identification of a better predictive model for MA-ILD is needed to help guide care in this patient population.

The Journal of Rheumatology, 2019

Objective.To present and vote on a myositis modified patient-reported outcome core domain set in ... more Objective.To present and vote on a myositis modified patient-reported outcome core domain set in the life impact area at the Outcome Measures in Rheumatology (OMERACT) 2018.Methods.Based on results from international focus groups and Delphi surveys, a draft core set was developed.Results.Domains muscle symptoms, fatigue, level of physical activity, and pain reached ≥ 70% consensus and were mandatory to assess in all trials. Domains lung, joint, and skin symptoms were mandatory in specific circumstances. This core set was endorsed by > 85% at OMERACT 2018.Conclusion.We propose a life impact core set for patients with idiopathic inflammatory myopathies and will proceed with instrument selections.

Immune receptor repertoire (IRR) sequencing is increasingly employed to characterize adaptive imm... more Immune receptor repertoire (IRR) sequencing is increasingly employed to characterize adaptive immune responses. However, current IRR sequencing methodologies are complex, expensive, or both, thereby limiting routine utilization. Here we present Framework Region 3 AmplifiKation sequencing ("FR3AK-seq"), a simplified multiplex PCR-based approach for the ultra-efficient analysis of IRRs. By using minimal primer sets that target a conserved region adjacent to the hypervariable VDJ sequence, undistorted amplicon can be analyzed via short read, single-end sequencing. We find that FR3AK-seq is sensitive and quantitative, with a per sample cost of ~50fold below the current industry standard. Inference of V-allele usage from FR3AK-seq data is demonstrated using a novel algorithm: Inferring Sequences via Efficiency Projection and Primer Incorporation ("ISEPPI"). FR3AK-seq and ISEPPI were utilized to quickly and inexpensively characterize the T cell infiltrates of 146 muscle biopsies obtained from patients with idiopathic inflammatory myopathies (IIMs) and controls. A cluster of related T cell receptors were identified in samples from patients with sporadic inclusion body myositis, suggesting the presence of an .

The Journal of rheumatology, Jan 15, 2018

Patient-reported outcome measures (PROM) that incorporate the patient perspective have not been w... more Patient-reported outcome measures (PROM) that incorporate the patient perspective have not been well established in idiopathic inflammatory myopathies (IIM). As part of our goal to develop IIM-specific PROM, the Outcome Measures in Rheumatology (OMERACT) Myositis special interest group sought to determine which aspects of disease and its effects are important to patients and healthcare providers (HCP). Based on a prior qualitative content analysis of focus groups, an initial list of 24 candidate domains was constructed. We subsequently conducted an international survey to identify the importance of each of the 24 domains to be assessed in clinical research. Patients with IIM, their caregivers, and HCP treating IIM completed the survey. In this survey, a total of 638 respondents completed the survey, consisting of 510 patients, 101 HCP, and 27 caregivers from 48 countries. Overall, patients were more likely to rank "fatigue," "cognitive impact," and "difficul...

Seminars in Arthritis and Rheumatism, 2017

Objective: In the context of clinical evaluations performed on our prospective myositis cohort, w... more Objective: In the context of clinical evaluations performed on our prospective myositis cohort, we noted a striking association of severe cardiac disease in myositis patients with antimitochondrial antibodies. We sought to review all cases of anti-mitochondrial antibody (AMA) associated myositis in our cohort to describe the clinical features of this disease subset. Methods: We identified 7 patients with confirmed anti-mitochondrial antibodies who presented as an inflammatory myopathy. A retrospective chart review was completed to assess their clinical presentation, laboratory, imaging, electrophysiologic and histopathologic features. Results: One patient presented with dermatomyositis and six were classified as polymyositis using Bohan and Peter criteria. In all but one patient, a chronic course of muscle involvement was appreciated with an average of 6.5 years of weakness prior to presentation. Muscle atrophy was often noted, as well as atypical findings of scapular winging in 2 of the patients. Muscle biopsies were consistent with immune-mediated necrotizing myopathy in four patients, dermatomyositis in one, polymyositis in one and non-specific or granulomatous myositis in one patient. Changes pointing to mitochondrial alterations were seen in 2 of the 7 patients. Cardiac involvement (including myocarditis, atrial and ventricular arrhythmias and cardiomyopathy), was seen in 5 out of 7 (71%) of the patients, and usually preceded the muscle involvement. Coexisting autoimmune conditions were seen in 3/7of the patients and included primary biliary cirrhosis, autoimmune hepatitis, psoriasis, and Hashimoto's thyroiditis. Conclusions: Anti-mitochondrial antibodies identify a distinct inflammatory myopathy phenotype that is frequently associated with chronic skeletal muscle disease and severe cardiac involvement. Early recognition of this rare entity as an immune-mediated process is important due to implications for treatment. We propose that anti-mitochondrial antibody status should be determined in patients with a compatible clinical picture.

International Journal of Clinical Rheumatology, 2012

There was a time that clinicians believed that, while we did not understand the mechanism by whic... more There was a time that clinicians believed that, while we did not understand the mechanism by which statins caused myotoxicity, statins were direct myotoxins that only caused a self-limited myopathy.

Topics in Magnetic Resonance Imaging, 2011

The following article reviews the role of magnetic resonance imaging (MRI) in patients with idiop... more The following article reviews the role of magnetic resonance imaging (MRI) in patients with idiopathic inflammatory myopathies (IIMs), focusing on the 3 major types of IIM: polymyositis, dermatomyositis, and inclusion-body myositis. After a brief introduction with general information about IIM, we will discuss the reasons why MRI plays an important role in the diagnosis and management of patients with polymyositis, dermatomyositis, and inclusion-body myositis. Magnetic resonance imaging can confirm the diagnosis and can help to phenotype the disease. Moreover, the support of MRI is important in addressing the muscle biopsy site and in reducing the high false-negative rate of biopsy when performed in a blind fashion. In monitoring therapy, MRI can add important information about the activity of the muscle disease and can identify cases where continued immunosuppressive therapy is no longer warranted owing to complete fatty replacement of the muscles. Lastly, we provide an overview about some advanced MRI techniques that focus more on function than on morphology of muscle.

Rheumatology and Immunology Research

Purpose of review—To review autoantibodies associated with different subtypes of idiopathic infla... more Purpose of review—To review autoantibodies associated with different subtypes of idiopathic inflammatory myopathy (IIM) and their clinical applications. IIM are a heterogenous group of autoimmune disorders characterized by muscle weakness, cutaneous features, and internal organ involvement. The diagnosis and classification, which is often challenging, is made using a combination of clinical features, muscle enzyme levels, imaging, and biopsy. The landmark discoveries of novel autoantibodies specific to IIM subtypes have been one of the greatest advancements in the field of myositis. The specificity of these autoantibodies has simplified the diagnostic algorithm of IIM with their heterogenous presentation and outdated the earlier diagnostic criteria. Myositis-specific antibodies (MSAs) have improved diagnostics, clinical phenotyping, and prognostic stratification of the subtypes of IIMs. Furthermore, the levels of certain MSAs correlate with disease activity and muscle enzyme levels ...

Neurology, Apr 8, 2014

OBJECTIVE: To compare the results of standard patient reported outcomes measures (PROMs) obtained... more OBJECTIVE: To compare the results of standard patient reported outcomes measures (PROMs) obtained by home infusion personnel and physicians to determine the reliability of these measures in the home environment. BACKGROUND: IVIG use in the US is increasing at a rate of 8-10% per year; utilization in patients with neurological conditions comprises 25% of total use. Regular and real-time communication of patient outcomes between home infusion and physicians can aid in clinical management, research, and cost containment. DESIGN/METHODS: We developed a clinical record platform (PartnerPoint) that includes standard PROMs for approximately 4000 IVIG patients. We limited our pilot validation data set to myositis and CIDP and to patients seen by five physicians over one month. Home telephone evaluations were conducted by pharmacists and synchronized with physician visits. PROMs included the IBM-FRS, INCAT, 0-10 pain scale, and R-ODS CIDP. Clinical evaluations included the MRC sum score performed by physicians as an objective measure. RESULTS: Our preliminary data (n = 4) suggest a good correlation between PROMs obtained by infusion personnel and treating physicians. Differences in average raw scores were: IBM-FRS = 2/33, INCAT = 0/10, Pain scale = 1/10, R-ODS = 3/48. In a combined analysis considering each score as a percent of normal, combined means differed by 3.5% between MD and home evaluations. A power calculation using this data determined that a sample size of 19 is needed for each disease state to detect a 10% difference. CONCLUSIONS: The expansion of this data set will allow us to evaluate agreement between the two evaluation methods. Validity will be assessed by correlating telephone and MD scores with MRC sum scores. Analysis of this larger data set will define whether PROMs are subject to reporting differences and clarify the value of homecare PROMs for the treating clinician. Study Supported by: Walgreens IG Program Disclosure: Dr. Ayer has received personal compensation for activities with Walgreens as an employee. Dr. Christopher-Stine has received personal compensation for activities with Questcor, Novartis, and Walgreens. Dr. Christopher-Stine has received royalty or licensee fee or contractual rights payments from INOVA Diagnostics. Dr. Christopher-Stine has received research support from NUFactor, Crescent Health, and Walgreens. Dr. Ladha has received personal compensation for activities with Genzyme Corp. as a speaker. Dr. Mozaffar has received personal compensation for activities with California Stem Cell Inc., NuFactor, Crescent-Walgreens, CSL Behring, Crescent Healthcare, Genzyme Corporation, Baxter, and Grifols. Dr. Mozaffar has received clinical research support from Cytokinetics, Neuraltus, Biogen Idec, Alexion, FDA, Cytokinetics, Amicus, Genzyme Corporation and Avanir Pharmaceuticals. Dr. So has received personal compensation for activities with medical-legal cases. Dr. Hehir has nothing to disclose. Dr. Silvestri has received personal compensation for activities with Walgreens and Biogen Idec.