Publications by authors named "Lisa Christopher-Stine"

117 Publications

RISK FACTORS FOR INFECTION AND HEALTH IMPACTS OF THE COVID-19 PANDEMIC IN PEOPLE WITH AUTOIMMUNE DISEASES.

medRxiv 2021 Feb 5. Epub 2021 Feb 5.

Background: People with autoimmune or inflammatory conditions who take immunomodulatory/suppressive medications may have a higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences.

Objective: Assess whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterize pandemic-associated changes to care.

Design: Longitudinal registry study.

Participants: 4666 individuals with autoimmune or inflammatory conditions followed by specialists in neurology, rheumatology, cardiology, pulmonology or gastroenterology at Johns Hopkins.

Measurements: Periodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcare.

Results: A total of 265 (5.6%) developed COVID-19 over 9 months of follow-up (April-December 2020). Patient characteristics (age, race, comorbidity, medication exposure) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in multivariable models incorporating behavior and other potential confounders (OR: 1.43; 95%CI: 1.08, 1.89). Other medication classes were not associated with COVID-19 risk. Diabetes (OR: 1.72; 95%CI: 1.08, 2.73), cardiovascular disease (OR: 1.68; 95%CI: 1.24, 2.28), and chronic kidney disease (OR: 1.76; 95%CI: 1.04, 2.97) were each associated with higher odds of COVID-19. Pandemic-related disruption to care was common. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions. Individuals experiencing changes to employment or income were at highest odds of care disruption.

Limitations: Results may not be generalizable to all patients with autoimmune or inflammatory conditions. Information was self-reported.

Conclusions: Exposure to glucocorticoids may increase risk of COVID-19 in people with autoimmune or inflammatory conditions. Disruption to healthcare and related services was common. Those with pandemic-related reduced income may be most vulnerable to care disruptions.
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http://dx.doi.org/10.1101/2021.02.03.21251069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872366PMC
February 2021

Dancing muscles: the value of real-time ultrasound evaluation of muscle in myositis and mimics.

Rheumatology (Oxford) 2021 Jan 27. Epub 2021 Jan 27.

Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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http://dx.doi.org/10.1093/rheumatology/keab088DOI Listing
January 2021

The aetiopathogenic significance, clinical relevance and therapeutic implications of vasculopathy in idiopathic inflammatory myopathy.

Rheumatology (Oxford) 2021 Jan 17. Epub 2021 Jan 17.

Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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 therapeutic significance of vasculopathy in IIM. We describe the prevalence and clinical relevance of vasculopathy in IIM, and consider how vasculopathy may be better utilized to support improved IIM diagnosis and disease classification. Areas of unmet research need are highlighted where relevant.
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http://dx.doi.org/10.1093/rheumatology/keaa816DOI Listing
January 2021

Study of Tofacitinib In Refractory Dermatomyositis (STIR): An open label pilot study of 10 patients.

Arthritis Rheumatol 2020 Dec 1. Epub 2020 Dec 1.

Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Objectives: This open-label 12-week study was conducted to evaluate the efficacy and safety of tofacitinib, a JAK inhibitor, in active, treatment-refractory dermatomyositis.

Methods: Tofacitinib was given as 11 mg XR daily to 10 subjects. All subjects underwent complete washout of all steroid sparing agents. The primary outcome measure was the IMACS definition of improvement. The response rate was measured by the 2016 ACR/EULAR Myositis Response Criteria using the total improvement score (TIS). The Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), chemokine levels, skin STAT 1 expression by immunohistochemistry, RNA sequencing analysis, and safety were secondary outcome measures.

Results: All 10 subjects met the primary outcome at 12 weeks. 5 of 10 (50%) had moderate improvement and the other half had minimal improvement on the TIS. The secondary outcome of the mean change in the CDASI activity score from baseline to 12 weeks was statistically significant (28 ± 15.4 vs. 9.5 ± 8.5, p=0.0005). Serum chemokine data (CXCL 9/10) showed a statistically significant change from baseline. Three of the 9 subjects who had a skin biopsy demonstrated a marked decrease in STAT1 signaling in association with suppression of IFN target gene expression. The mean creatine kinase was 82 ± 34.8 highlighting that those treated had skin predominant disease.

Conclusions: This is the first prospective, open-label clinical trial of tofacitinib in dermatomyositis that demonstrates strong clinical efficacy for a pan JAK inhibitor as measured by validated myositis response criteria. Future randomized controlled trials using JAK-inhibitors should be considered for treating dermatomyositis.
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http://dx.doi.org/10.1002/art.41602DOI Listing
December 2020

Patient-reported dermatomyositis and polymyositis flare symptoms are associated with disability, productivity loss, and health care resource use.

J Manag Care Spec Pharm 2020 Nov;26(11):1424-1433

Vedanta Research, Chapel Hill, NC.

Flare activity or worsening symptoms are not well defined for myositis. To (a) characterize dermatomyositis (DM) and polymyositis (PM) flares from the patient perspective and (b) report the corresponding disability and rate of unplanned medical encounters. Online survey data were collected from volunteer patients from The Myositis Association and Johns Hopkins Myositis Center. Flare frequency; Health Assessment Questionnaire Disability Index (HAQ-DI), HAQ-Pain Index, Work Productivity and Activity Impairment (WPAI) scales; emergency department/urgent care (ED/UC) visits; and hospital admissions during the past year were examined. 564 individuals with selfreported diagnoses of DM/PM were surveyed between December 2017 and May 2018. Recall of symptom flares was reported by 524 respondents (78.1% were female, mean age of 55 years). Among the respondents, 378 (72.1%) reported ≥ 1 flare in the past year. The pattern of flare frequency was similar for DM and PM respondents. The most common symptoms were muscle weakness (83%), extreme fatigue (78%), and muscle pain/discomfort (64%). Increasing flare frequency was associated with significantly ( < 0.01) greater mean HAQ-DI and HAQ-Pain scores, myositis-related ED/UC visits, hospital admissions, WPAI work productivity loss (among those employed), and WPAI nonwork activity impairment. DM/PM-related flares are common with exacerbations of muscle weakness and fatigue being the most common flare symptoms. Flare frequency was associated with greater disability, pain, work productivity loss, nonwork activity impairment, and increased ED/UC utilization. Higher frequency of patient-reported flares may serve as a marker of worsening physical functioning and intensifying health care needs and, therefore, suggests their importance in the clinical assessment of patients with DM/PM. This study was supported by Mallinckrodt Pharmaceuticals (Bedminster, NJ) via grants to Vedanta Research and The Myositis Association. Christopher-Stine has received compensation from previous Mallinckrodt Advisory Board meetings, unrelated to this subject matter. Wan is an employee of Mallinckrodt Pharmaceuticals and is a stockholder of the company. Reed and Bostic received grant support from Mallinckrodt Pharmaceuticals for data collection and analysis. McGowan is an employee of The Myositis Foundation, which received grant funding to support study data collection. Kelly has no conflicts to disclose. This study was presented, in part or full, at the 2019 Annual American College of Rheumatology and Association of Rheumatology Professional Meeting (November 8-13, 2018; Atlanta, GA) and at the Third Global Conference on Myositis (March 27, 2019; Berlin, Germany).
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http://dx.doi.org/10.18553/jmcp.2020.26.11.1424DOI Listing
November 2020

IgM autoantibodies recognizing ACE2 are associated with severe COVID-19.

medRxiv 2020 Oct 15. Epub 2020 Oct 15.

SARS-CoV-2 infection induces severe disease in a subpopulation of patients, but the underlying mechanisms remain unclear. We demonstrate robust IgM autoantibodies that recognize angiotensin converting enzyme-2 (ACE2) in 18/66 (27%) patients with severe COVID-19, which are rare (2/52; 3.8%) in hospitalized patients who are not ventilated. The antibodies do not undergo class-switching to IgG, suggesting a T-independent antibody response. Purified IgM from anti-ACE2 patients activates complement. Pathological analysis of lung obtained at autopsy shows endothelial cell staining for IgM in blood vessels in some patients. We propose that vascular endothelial ACE2 expression focuses the pathogenic effects of these autoantibodies on blood vessels, and contributes to the angiocentric pathology observed in some severe COVID-19 patients. These findings may have predictive and therapeutic implications.
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http://dx.doi.org/10.1101/2020.10.13.20211664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574257PMC
October 2020

Assessing the content validity of patient-reported outcome measures in adult myositis: A report from the OMERACT myositis working group.

Semin Arthritis Rheum 2020 10 17;50(5):943-948. Epub 2020 Jun 17.

Division of Rheumatology, Department of Medicine, Johns Hopkins University, 5200 Eastern Ave, MFL Bldg, Center Tower, Suite 4100, Baltimore 21224, MD, USA. Electronic address:

Objective: To investigate the content validity of several patient-reported outcome measures (PROMs) in patients with idiopathic inflammatory myopathies (IIM).

Methods: Seven individual PROM instruments were selected by the Outcome Measures in Rheumatology (OMERACT) Myositis Working Group relating to the following domains: pain, fatigue, physical function and physical activity. Twenty patients from the Johns Hopkins Myositis Center were selected for one-on-one face-to-face or phone interviews for cognitive interviewing of individual PROMs to assess comprehension and content validity. Additionally, patients were asked if they thought muscle symptoms, an area originally identified in qualitative studies, were encapsulated by the other four domains.

Results: The majority of patients (>70%) felt that each of the instruments was clear, easy to read and understand, and could be used for assessment of its domain. Two-thirds (66%) of patients felt that 'muscle symptoms' were captured by the other domains.

Conclusions: We provided evidence to support adequate content validity for several PROMs. Further research is needed to determine whether 'muscle symptoms' warrant a separate domain.
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http://dx.doi.org/10.1016/j.semarthrit.2020.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646936PMC
October 2020

Accumulation of autophagosome cargo protein p62 is common in idiopathic inflammatory myopathies.

Clin Exp Rheumatol 2020 Sep 1. Epub 2020 Sep 1.

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objectives: The subsarcolemmal accumulation of p62 aggregates in myofibres has been proposed to be characteristic of sporadic inclusion body myositis (sIBM). The objective of this study was to analyse the patterns and prevalence of p62 immunostaining and to quantitate p62 gene expression in muscle biopsies from a large number of patients with different types of myopathic and neurogenic disorders.

Methods: For the p62 immunostaining analysis, all patients with a muscle biopsy immunostained for p62 at the Johns Hopkins Neuromuscular Pathology Laboratory from 2013 to 2017 were included (n=303). The prevalence and pattern of p62 immunostaining were compared between patients with histologically normal muscle (n=29), inflammatory myopathies (n=136), non-inflammatory myopathies (n=53), and neurogenic disorders (n=85). p62 expression levels were analysed using an existing RNAseq dataset including data from dermatomyositis (DM; n=39), immune-mediated necrotising myopathy (IMNM; n=49), antisynthetase syndrome (AS; n=18), and sIBM (n=23) patients as well as 20 histologically normal muscle biopsies.

Results: p62 staining was absent in normal biopsies, but present in biopsies from those with polymyositis (29%), non-inflammatory myopathies (all <31%), neurogenic disorders (31%), dermatomyositis (57%), sIBM (92%) and IMNM (87%). In all diseases studied, p62 accumulation was more prevalent in biopsies with more severe muscle damage. sIBM biopsies had decreased p62 expression levels compared to the other groups (corrected p<0.04).

Conclusions: p62 accumulation is a general response to muscle injury and not a specific marker for sIBM. Also, in sIBM, p62 RNA levels are decreased, suggesting that, in this disease, p62 aggregation is not due to overexpression.
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September 2020

The indirect immunofluorescence assay autoantibody profiles of myositis patients without known myositis-specific autoantibodies.

Clin Exp Rheumatol 2020 Sep 3. Epub 2020 Sep 3.

National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, and Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objectives: The indirect immunofluorescence assay (IIFA) is used to screen for the presence of autoantibodies. Our objective was to determine the prevalence and clinical features of IIFA positive myositis patients without known myositis-specific autoantibodies (MSA).

Methods: Sera from healthy comparators (HC) and patients with dermatomyositis (DM), inclusion body myositis (IBM), and polymyositis (PM) with no detectable MSA were tested by IIFA on HEp-2 cells. The pattern of positivity was classified according to the International Consensus on Antinuclear Antibody Patterns. The prevalence and frequency of each IIFA pattern were compared between the different groups.

Results: Sera from 100 HC, 71 DM, 53 IBM, and 69 PM subjects were included in the study. The IIFA was positive in 35% HC compared to 66% DM (p<0.001), 49% IBM, and 64% (p<0.001) PM sera. Among IIFA positive sera, the staining was moderate or intense in 43% HC compared to 79% DM (p<0.001) but just 54% IBM, and 52% PM sera. IIFA positivity was predominantly nuclear in all groups (all >69%). The most common pattern in myositis patients was fine speckled with no differences between groups. In general, IIFA positive and negative DM patients showed similar clinical features and disease activity.

Conclusions: Half of MSA-negative DM patients have moderate/strong IIFA positivity, predominantly with a fine speckled pattern. In contrast, MSA-negative PM, IBM, and healthy comparators are more often weakly positive for IIFA. These findings suggest that unidentified autoantibodies are more likely to exist in DM patients than in the other myositis groups.
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September 2020

Ultra-efficient sequencing of T Cell receptor repertoires reveals shared responses in muscle from patients with Myositis.

EBioMedicine 2020 Sep 3;59:102972. Epub 2020 Sep 3.

Division of Immunology, Pathology Department, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

Background: Myositis, or idiopathic inflammatory myopathy (IIM), is a group disorders of unknown etiology characterized by the inflammation of skeletal muscle. The role of T cells and their antigenic targets in IIM initiation and progression is poorly understood. T cell receptor (TCR) repertoire sequencing is a powerful approach for characterizing complex T cell responses. However, current TCR sequencing methodologies are complex, expensive, or both, greatly limiting the scale of feasible studies.

Methods: Here we present Framework Region 3 AmplifiKation sequencing ("FR3AK-seq"), a simplified multiplex PCR-based approach for the ultra-efficient and quantitative analysis of TCR complementarity determining region 3 (CDR3) repertoires. By using minimal primer sets targeting a conserved region immediately upstream of CDR3, undistorted amplicons are analyzed via short read, single-end sequencing. We also introduce the novel algorithm Inferring Sequences via Efficiency Projection and Primer Incorporation ("ISEPPI") for linking CDR3s to their associated variable genes.

Findings: We find that FR3AK-seq is sensitive and quantitative, performing comparably to two different industry standards. FR3AK-seq and ISEPPI were used to efficiently and inexpensively characterize the T cell infiltrates of surgical muscle biopsies obtained from 145 patients with IIM and controls. A cluster of closely related TCRs was identified in samples from patients with sporadic inclusion body myositis (IBM).

Interpretation: The ease and minimal cost of FR3AK-seq removes critical barriers to routine, large-scale TCR CDR3 repertoire analyses, thereby democratizing the quantitative assessment of human TCR repertoires in disease-relevant target tissues. Importantly, discovery of closely related TCRs in muscle from patients with IBM provides evidence for a shared antigen-driven T cell response in this disease of unknown pathogenesis.

Funding: This work was supported by NIH grant U24AI118633 and a Prostate Cancer Foundation Young Investigator Award.
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http://dx.doi.org/10.1016/j.ebiom.2020.102972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484536PMC
September 2020

Potential implications of six American Indian patients with myopathy, statin exposure and anti-HMGCR antibodies.

Rheumatology (Oxford) 2021 Feb;60(2):692-698

Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objectives: Statin-associated autoimmune myopathy is a rare condition associated with the formation of autoantibodies to 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Underlying environmental and genetic risk factors remain poorly understood. American Indians have high rates of cardiovascular disease and associated co-morbidities that require lipid-lowering therapies. We observed this autoimmune myopathy in a series of American Indian statin users in rural Arizona.

Methods: We reviewed the charts of six American Indian patients with statin-associated autoimmune myopathy. We provide an illustrative case in addition to summaries of clinical presentations and treatment courses.

Results: This is the first report of statin-associated autoimmune myopathy in American Indians. These cases were all identified at the same geographically isolated hospital that exclusively serves an American Indian population with only 1800 statin users. There is relatively low migration. Each case was consistent with the previously described classical presentations for the disease. All six of our cases had diabetes and developed myopathy on high-dose atorvastatin, often with a recent change in statin type or dose.

Conclusion: Providers serving American Indians need to be aware of the possibility of statin-associated autoimmune myopathy and familiar with its presentation. Larger, inclusive, population-based investigations are needed to elucidate risk factors for this condition, in particular the potential interactions between predisposing HLA alleles, diabetes and specific statin exposures. This is necessary to identify effective and safe lipid-lowering medications.
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http://dx.doi.org/10.1093/rheumatology/keaa337DOI Listing
February 2021

Machine learning algorithms reveal unique gene expression profiles in muscle biopsies from patients with different types of myositis.

Ann Rheum Dis 2020 09 16;79(9):1234-1242. Epub 2020 Jun 16.

Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Insititutes of Health, Bethesda, Maryland, USA

Objectives: Myositis is a heterogeneous family of diseases that includes dermatomyositis (DM), antisynthetase syndrome (AS), immune-mediated necrotising myopathy (IMNM), inclusion body myositis (IBM), polymyositis and overlap myositis. Additional subtypes of myositis can be defined by the presence of myositis-specific autoantibodies (MSAs). The purpose of this study was to define unique gene expression profiles in muscle biopsies from patients with MSA-positive DM, AS and IMNM as well as IBM.

Methods: RNA-seq was performed on muscle biopsies from 119 myositis patients with IBM or defined MSAs and 20 controls. Machine learning algorithms were trained on transcriptomic data and recursive feature elimination was used to determine which genes were most useful for classifying muscle biopsies into each type and MSA-defined subtype of myositis.

Results: The support vector machine learning algorithm classified the muscle biopsies with >90% accuracy. Recursive feature elimination identified genes that are most useful to the machine learning algorithm and that are only overexpressed in one type of myositis. For example, CAMK1G (calcium/calmodulin-dependent protein kinase IG), EGR4 (early growth response protein 4) and CXCL8 (interleukin 8) are highly expressed in AS but not in DM or other types of myositis. Using the same computational approach, we also identified genes that are uniquely overexpressed in different MSA-defined subtypes. These included apolipoprotein A4 (APOA4), which is only expressed in anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) myopathy, and MADCAM1 (mucosal vascular addressin cell adhesion molecule 1), which is only expressed in anti-Mi2-positive DM.

Conclusions: Unique gene expression profiles in muscle biopsies from patients with MSA-defined subtypes of myositis and IBM suggest that different pathological mechanisms underly muscle damage in each of these diseases.
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http://dx.doi.org/10.1136/annrheumdis-2019-216599DOI Listing
September 2020

Ultrasound can differentiate inclusion body myositis from disease mimics.

Muscle Nerve 2020 06 11;61(6):783-788. Epub 2020 Apr 11.

School of Medicine, Division of Rheumatology, Johns Hopkins University, Baltimore, Maryland.

Introduction: The diagnosis of inclusion body myositis (IBM) can be challenging, and its presentation can be confused with other forms of myositis or neuromuscular disorders. In this study we evaluate the ability of quantitative muscle ultrasound to differentiate between IBM and mimicking diseases.

Methods: Patients 50 years of age and older were included from two specialty centers. Muscle echogenicity and muscle thickness of four characteristically involved muscles in IBM were measured and compared with polymyositis (PM)/dermatomyositis (DM), other neuromuscular disorders, and healthy controls.

Results: Echogenicity was higher and muscle thickness generally lower in all four muscles in IBM compared with PM/DM and normal controls. When comparing IBM with the comparator groups, the flexor digitorum profundus was the most discriminative muscle.

Discussion: Ultrasound appears to be a good test to differentiate established IBM from PM/DM and neuromuscular controls, with value as a diagnostic tool for IBM.
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http://dx.doi.org/10.1002/mus.26875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317807PMC
June 2020

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases.

Arthritis Rheumatol 2020 04 23;72(4):529-556. Epub 2020 Feb 23.

ECRI Institute, Plymouth Meeting, Pennsylvania.

Objective: To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD).

Methods: We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary.

Results: This American College of Rheumatology guideline provides 12 ungraded good practice statements and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSB antibodies. Recommendations and good practice statements support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physician-patient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD.

Conclusion: This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.
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http://dx.doi.org/10.1002/art.41191DOI Listing
April 2020

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases.

Arthritis Care Res (Hoboken) 2020 04 26;72(4):461-488. Epub 2020 Feb 26.

ECRI Institute, Plymouth Meeting, Pennsylvania.

Objective: To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD).

Methods: We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary.

Results: This American College of Rheumatology guideline provides 12 ungraded good practice statements and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSB antibodies. Recommendations and good practice statements support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physician-patient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD.

Conclusion: This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.
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http://dx.doi.org/10.1002/acr.24130DOI Listing
April 2020

Neutrophil dysregulation is pathogenic in idiopathic inflammatory myopathies.

JCI Insight 2020 02 13;5(3). Epub 2020 Feb 13.

Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, Maryland, USA.

Idiopathic inflammatory myopathies (IIM) are characterized by muscle inflammation and weakness, myositis-specific autoantibodies (MSAs), and extramuscular organ damage. The role of neutrophil dysregulation and neutrophil extracellular traps (NETs) in IIM is unclear. We assessed whether pathogenic neutrophil subsets (low-density granulocytes [LDGs]) and NETs were elevated in IIM, associated with clinical presentation and MSAs, and their effect on skeletal myoblasts and myotubes. Circulating NETs and LDGs were quantified and correlated with clinical measures. Specific MSAs were tested for their ability to induce NETs. NETs and neutrophil gene expression were measured in IIM biopsies. Whether NETs damage skeletal myoblasts and myotubes was tested. Circulating LDGs and NETs were increased in IIM. IIM LDGs had an enhanced ability to form NETs. LDGs and NETs correlated with IIM disease activity and muscle damage. The serum MSA anti-MDA5 correlated with circulating and tissue NETs and directly enhanced NET formation. An enhanced neutrophil gene signature was present in IIM muscle and associated with muscle injury and tissue IFN gene signatures. IIM NETs decreased the viability of myotubes in a citrullinated histone-dependent manner. Dysregulated neutrophil pathways may play pathogenic roles in IIM through their ability to directly injure muscle cells and other affected tissues.
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http://dx.doi.org/10.1172/jci.insight.134189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098779PMC
February 2020

Pregnancy in myositis and scleroderma.

Best Pract Res Clin Obstet Gynaecol 2020 Apr 18;64:59-67. Epub 2019 Oct 18.

Johns Hopkins University School of Medicine, 5200 Eastern Avenue, Mason F.Lord Center Tower, Baltimore, MD 21224, USA. Electronic address:

Myositis and scleroderma are both rare autoimmune diseases with female predominance and often occur before and during reproductive years. The rarity of diseases explains the low frequency of concurrent disease and pregnancy. Like other autoimmune diseases, myositis and scleroderma may be more active during pregnancy as well. To date, many patients with myositis and scleroderma can have favorable pregnancy outcomes with careful management. This chapter provides a current overview of pregnancy outcomes in myositis and scleroderma. A major theme that appears to have emerged across these inflammatory diseases is that active maternal disease during pregnancy is associated with adverse pregnancy outcomes, and thus, personalized management is necessary depending on the disease state and comorbidities.
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http://dx.doi.org/10.1016/j.bpobgyn.2019.10.004DOI Listing
April 2020

Dysphagia in Myositis: A Study of the Structural and Physiologic Changes Resulting in Disordered Swallowing.

Am J Phys Med Rehabil 2020 05;99(5):404-408

From the Department of Physical Medicine and Rehabilitation, Johns Hopkins University School of Medicine, Baltimore, Maryland (AA, RM, JP, THC); Department of Psychological Sciences, Case Western Reserve University, Cleveland, Ohio (RM); Rehabilitation Department, Johns Hopkins Bayview Medical Center, Baltimore, Maryland (GM); Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland (TL, THC); and Department of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland (LC-S).

Objectives: Dysphagia in patients with myositis is associated with an increased risk of aspiration pneumonia. However, the pathophysiology of dysphagia is poorly understood. The aim of this study was to understand how myositis affects swallowing physiology on videofluoroscopic swallow study.

Design: This is a retrospective review of video fluoroscopic swallowing studies on 23 myositis patients with dysphagia from 2011 to 2016. Swallow studies were analyzed by timing of swallowing events and duration of swallowing events, diameter of upper esophageal sphincter opening, Modified Barium Swallow Impairment Profile, and Penetration-Aspiration Scale. The outcome measures for patients were compared with an archived videofluoroscopic swallow study from healthy, age-matched participants by Wilcoxon rank-sum tests.

Results: Patients with myositis had a shorter duration of upper esophageal sphincter opening (P < 0.0001) and laryngeal vestibule closure (P < 0.0001) than healthy subjects. The diameter of upper esophageal sphincter opening did not differ between groups. Patients with myositis presented with higher scores on the MBSIMP than healthy subjects, indicating great impairment particularly during the pharyngeal phase of swallowing, and a higher frequency of penetration and aspiration.

Conclusions: Dysphagia in patients with myositis may be attributed to reduced endurance of swallowing musculature rather than mechanical obstruction of the upper esophageal sphincter.
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http://dx.doi.org/10.1097/PHM.0000000000001354DOI Listing
May 2020

Validation of anti-Mi2 autoantibody testing by line blot.

Autoimmun Rev 2020 Jan 14;19(1):102425. Epub 2019 Nov 14.

Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, United States of America; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2019.102425DOI Listing
January 2020

More prominent muscle involvement in patients with dermatomyositis with anti-Mi2 autoantibodies.

Neurology 2019 11 8;93(19):e1768-e1777. Epub 2019 Oct 8.

From the Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Regulation (I.P.-F., M.C.-D., K.P., Y.H., W.H., A.L.M.), National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda; Departments of Neurology (I.P.-F., M.C.-D., A.M.C., L.C.-S., A.L.M.) and Medicine (C.A.M., J.A., E.T., J.J.P., S.K.D., L.C.-S., A.L.M.), Johns Hopkins University School of Medicine, Baltimore, MD; Faculty of Health Sciences (I.P.-F.), Universitat Oberta de Catalunya, Barcelona, Spain; Department of Medicine (J.H.), Medstar Georgetown University Hospital, Washington, DC; and Department of Medicine (C.J.), Hospital of the University of Pennsylvania, Philadelphia.

Objective: To define the clinical phenotype of dermatomyositis (DM) with anti-Mi2 autoantibodies.

Methods: In this longitudinal cohort study, the prevalence and severity of clinical features at disease onset and during follow-up in patients with anti-Mi2-positive DM were compared to patients with anti-Mi2-negative DM, antisynthetase syndrome (AS), and immune-mediated necrotizing myopathy (IMNM). Longitudinal anti-Mi2 autoantibody titers were assessed.

Results: A total of 58 patients with anti-Mi2-positive DM, 143 patients with anti-Mi2-negative DM, 162 patients with AS, and 170 patients with IMNM were included. Among patients with anti-Mi2-positive DM, muscle weakness was present in 60% at disease onset and occurred in 98% during longitudinal follow-up; fewer patients with anti-Mi2-negative DM developed weakness (85%; = 0.008). Patients with anti-Mi2-positive DM were weaker and had higher creatine kinase (CK) levels than patients with anti-Mi2-negative DM or patients with AS. Muscle biopsies from patients with anti-Mi2-positive DM had prominent necrosis. Anti-Mi2 autoantibody levels correlated with CK levels and strength ( < 0.001). With treatment, most patients with anti-Mi2-positive DM had improved strength and CK levels; among 10 with multiple serum samples collected over 4 or more years, anti-Mi2 autoantibody titers declined in all and normalized in 3, 2 of whom stopped immunosuppressant treatment and never relapsed. Patients with anti-Mi2-positive DM had less calcinosis (9% vs 28%; = 0.003), interstitial lung disease (5% vs 16%; = 0.04), and fever (7% vs 21%; = 0.02) than did patients with anti-Mi2-negative DM.

Conclusions: Patients with anti-Mi2-positive DM have more severe muscle disease than patients with anti-Mi2-negative DM or patients with AS. Anti-Mi2 autoantibody levels correlate with disease severity and may normalize in patients who enter remission.
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http://dx.doi.org/10.1212/WNL.0000000000008443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946486PMC
November 2019

Identification of distinctive interferon gene signatures in different types of myositis.

Neurology 2019 09 21;93(12):e1193-e1204. Epub 2019 Aug 21.

From the National Institute of Arthritis and Musculoskeletal and Skin Diseases (I.P.-F, M.C.-D, A.D., K.P., P.P., F.W.M., A.L.M.), NIH, Bethesda; Johns Hopkins University School of Medicine (I.P.-F., M.C.-D., J.P., J.A., L.C.-S., T.E.L., A.M.C., A.L.M.), Baltimore, MD; Clinic Hospital and the University of Barcelona (J.C.M., J.M.G.-J.); Vall d'Hebron Hospital and Autonomous University of Barcelona (A.S.-O.); and Faculty of Health Sciences (I.P.-F.), Universitat Oberta de Catalunya, Barcelona, Spain.

Objective: Activation of the type 1 interferon (IFN1) pathway is a prominent feature of dermatomyositis (DM) muscle and may play a role in the pathogenesis of this disease. However, the relevance of the IFN1 pathway in patients with other types of myositis such as the antisynthetase syndrome (AS), immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM) is largely unknown. Moreover, the activation of the type 2 interferon (IFN2) pathway has not been comprehensively explored in myositis. In this cross-sectional study, our objective was to determine whether IFN1 and IFN2 pathways are differentially activated in different types of myositis by performing RNA sequencing on muscle biopsy samples from 119 patients with DM, IMNM, AS, or IBM and on 20 normal muscle biopsies.

Methods: The expression of IFN1- and IFN2-inducible genes was compared between the different groups.

Results: The expression of IFN1-inducible genes was high in DM, moderate in AS, and low in IMNM and IBM. In contrast, the expression of IFN2-inducible genes was high in DM, IBM, and AS but low in IMNM. The expression of IFN-inducible genes correlated with the expression of genes associated with inflammation and muscle regeneration. Of note, expression levels alone performed as well as composite scores relying on multiple genes to monitor activation of the IFN1 pathway in myositis muscle biopsies.

Conclusions: IFN1 and IFN2 pathways are differentially activated in different forms of myositis. This observation may have therapeutic implications because immunosuppressive medications may preferentially target each of these pathways.
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http://dx.doi.org/10.1212/WNL.0000000000008128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808530PMC
September 2019

Long-Term Treatment With Azathioprine and Mycophenolate Mofetil for Myositis-Related Interstitial Lung Disease.

Chest 2019 11 22;156(5):896-906. Epub 2019 Jun 22.

Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address:

Background: The efficacy of azathioprine (AZA) and mycophenolate mofetil (MMF) for interstitial lung disease (ILD) has been described, but mainly in connective tissue disease-associated ILD. The objective of this study was to evaluate the effect of AZA and MMF on lung function and prednisone dose in myositis-related ILD (M-ILD).

Methods: In this retrospective study, patients with M-ILD seen at Johns Hopkins and treated with AZA or MMF and no other steroid-sparing agents were included. Linear mixed-effects models adjusted for sex, age, antisynthetase antibody, and smoking status were used to compare the change in FVC % predicted, diffusing capacity of the lungs for carbon monoxide (Dlco) % predicted, and prednisone dose.

Results: Sixty-six patients with M-ILD were treated with AZA and 44 with MMF. At treatment initiation, mean FVC % predicted and Dlco % predicted were significantly lower in the AZA group than in the MMF group. In both groups, FVC % predicted improved and the prednisone dose was reduced over 2 to 5 years; however, for Dlco % predicted, only the AZA group improved. The adjusted model showed no significant difference in posttreatment FVC % predicted or Dlco % predicted between groups (mean difference of 1.9 and -8.2, respectively), but a 6.6-mg lower dose of prednisone at 36 months in the AZA group. Adverse events were more frequent with AZA than MMF (33.3% vs 13.6%; P = .04).

Conclusions: In M-ILD, AZA treatment was associated with improved FVC % predicted and Dlco % predicted, and lower prednisone dose. Patients treated with MMF had improved FVC % predicted and lower prednisone dose. After 36 months, patients treated with AZA received a lower prednisone dose than those treated with MMF.
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http://dx.doi.org/10.1016/j.chest.2019.05.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945652PMC
November 2019

Pattern of muscle involvement in inclusion body myositis: a sonographic study.

Clin Exp Rheumatol 2019 May-Jun;37(3):518. Epub 2019 May 21.

Johns Hopkins University, Applied Physics Laboratory, Laurel, MD, USA.

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May 2019

Efficacy and adverse effects of methotrexate compared with azathioprine in the antisynthetase syndrome.

Clin Exp Rheumatol 2019 Sep-Oct;37(5):858-861. Epub 2019 Apr 29.

Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objectives: To study the efficacy in terms of muscle strength, and corticosteroid tapering as well as the prevalence of adverse effects in patients with the antisynthetase syndrome (ASyS) treated with azathioprine (AZA) compared to those treated with methotrexate (MTX).

Methods: We compared the clinical outcomes in ASyS patients treated with AZA versus MTX including change in corticosteroid dose, strength, and creatine kinase (CK) as well as the prevalence of adverse effects.

Results: Among 169 patients with ASyS, 102 were treated at some point exclusively with either AZA or MTX (± corticosteroids). There were no significant differences in the rate of muscle strength recovery, CK decrease or corticosteroid tapering between those ASyS patients treated with MTX versus AZA. The prevalence of adverse events in patients treated with AZA and MTX was similar (29% vs. 25%, p>0.05); elevated liver enzymes (17% AZA vs. 12% MTX) and gastrointestinal involvement (10% AZA vs. 8% MTX) were the most common adverse events. While no patients treated with AZA developed lung complications, two of the patients treated with MTX experienced reversible pneumonitis with MTX cessation.

Conclusions: AZA and MTX showed similar efficacy and adverse events in patients with ASyS. Pneumonitis is a rare but important event in patients receiving MTX.
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October 2019

Use of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Statin-Associated Immune-Mediated Necrotizing Myopathy: A Case Series.

Arthritis Rheumatol 2019 10 6;71(10):1723-1726. Epub 2019 Aug 6.

Johns Hopkins University School of Medicine, Baltimore, Maryland.

Objective: To determine the safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in patients with statin-associated anti-3-hydroxy-3-methlyglutaryl coenzyme A reductase (anti-HMGCR)-positive immune-mediated necrotizing myopathy (IMNM).

Methods: Muscle strength was assessed in anti-HMGCR-positive patients at each visit before and after initiation of PCSK9 inhibitors. The trends in creatine kinase (CK) levels and serum anti-HMGCR antibody titers were monitored over time.

Results: Among 122 anti-HMGCR-positive patients, we identified 8 patients who were receiving PCSK9 inhibitors for hyperlipidemia. Patients were followed up for an average of 1.5 years (range 3-37 months), and none exhibited reduction in muscle strength. The mean ± SD CK level prior to the initiation of PCSK9 inhibitors was 956 ± 1,137 IU/liter, which was reduced to 419 ± 393 IU/liter at their last visit. Anti-HMGCR antibody titers followed a similar trend. Notably, in 2 patients, the initiation of the lipid-lowering medication was followed by unanticipated spontaneous clinical improvement and reduction in immunosuppression.

Conclusion: PCSK9 inhibitors are safe for long-term use as a cholesterol-lowering agent in patients with statin-associated IMNM.
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http://dx.doi.org/10.1002/art.40919DOI Listing
October 2019

The ILD-GAP risk prediction model performs poorly in myositis-associated interstitial lung disease.

Respir Med 2019 04 21;150:63-65. Epub 2019 Feb 21.

Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 500, Baltimore, MD, 21224, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.rmed.2019.02.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461370PMC
April 2019

Myositis Autoantigen Expression Correlates With Muscle Regeneration but Not Autoantibody Specificity.

Arthritis Rheumatol 2019 08 18;71(8):1371-1376. Epub 2019 Jun 18.

National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland, and Johns Hopkins University School of Medicine, Baltimore, Maryland.

Objective: Although more than a dozen myositis-specific autoantibodies (MSAs) have been identified, most patients with myositis are positive for a single MSA. The specific overexpression of a given myositis autoantigen in myositis muscle has been proposed as initiating and/or propagating autoimmunity against that particular autoantigen. The present study was undertaken to test this hypothesis.

Methods: In order to quantify autoantigen RNA expression, RNA sequencing was performed on muscle biopsy samples from control subjects, MSA-positive patients with myositis, regenerating mouse muscles, and cultured human muscle cells.

Results: Muscle biopsy samples were available from 20 control subjects and 106 patients with autoantibodies recognizing hydroxymethylglutaryl-coenzyme A reductase (n = 40), signal recognition particles (n = 9), Jo-1 (n = 18), nuclear matrix protein 2 (n = 12), Mi-2 (n = 11), transcription intermediary factor 1γ (n = 11), or melanoma differentiation-associated protein 5 (n = 5). The increased expression of a given autoantigen in myositis muscle was not associated with autoantibodies recognizing that autoantigen (all q > 0.05). In biopsy specimens from both myositis muscle and regenerating mouse muscles, autoantigen expression correlated directly with the expression of muscle regeneration markers and correlated inversely with the expression of genes encoding mature muscle proteins. Myositis autoantigens were also expressed at high levels in cultured human muscle cells.

Conclusion: Most myositis autoantigens are highly expressed during muscle regeneration, which may relate to the propagation of autoimmunity. However, factors other than overexpression of specific autoantigens are likely to govern the development of unique autoantibodies in individual patients with myositis.
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http://dx.doi.org/10.1002/art.40883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663619PMC
August 2019

Muscular and extramuscular features of myositis patients with anti-U1-RNP autoantibodies.

Neurology 2019 03 1;92(13):e1416-e1426. Epub 2019 Mar 1.

From the Muscle Disease Unit (M.C.-D., I.P.-F., A.L.M.), Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda; Departments of Neurology (M.C.-D., I.P.-F., A.M.C., L.C.-S., A.L.M.) and Medicine (J.P., J.A., L.C.-R., C.J., S.K.D., L.C.-S., E.T., A.L.M.), Johns Hopkins University School of Medicine, Baltimore, MD; and Faculty of Health Sciences (J.P.-F.), Universitat Oberta de Catalunya, Barcelona, Spain.

Objective: To define the clinical phenotype of patients with myositis with anti-U1-ribonucleoprotein (RNP) autoantibodies.

Methods: In this longitudinal cohort study, the prevalence and severity of clinical features at disease onset and during follow-up in patients with anti-U1-RNP-positive myositis were compared to those with dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), and the antisynthetase syndrome (AS).

Results: Twenty anti-U1-RNP-positive patients, 178 patients with DM, 135 patients with IMNM, and 132 patients with AS were included. Anti-U1-RNP-positive patients were younger (∼37 years) and more likely to be black (60%) than patients with AS, DM, or IMNM. Muscle weakness was a presenting feature in 15% of anti-U1-RNP-positive patients; 80% eventually developed weakness. Four of 7 anti-U1-RNP-positive patients had necrotizing muscle biopsies. Arthritis occurred in 60% of anti-U1-RNP-positive patients; this was increased compared to DM (18%) or IMNM (6%) (all < 0.01). DM-specific skin features developed in 60% of anti-U1-RNP-positive patients. Interstitial lung disease (ILD) occurred in 45% of anti-U1-RNP-positive patients; fewer patients with DM (13%) and IMNM (6%) and more patients with AS (80%) developed ILD (all < 0.01). Glomerulonephritis and pericarditis occurred in 25% and 40% of anti-U1-RNP-positive patients, respectively, but rarely in the other groups; these features occurred only in those with coexisting anti-Ro52 autoantibodies. No anti-U1-RNP patient had cancer-associated myositis or died during the study period.

Conclusions: Patients with anti-U1-RNP myositis typically present with proximal weakness and necrotizing muscle biopsies. Arthritis, dermatitis, and ILD are the most common extramuscular clinical features. Pericarditis and glomerulonephritis are uniquely found in patients with anti-U1-RNP-positive myositis.
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http://dx.doi.org/10.1212/WNL.0000000000007188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453768PMC
March 2019

Sonographic findings from inflammatory arthritis due to antisynthetase syndrome.

Clin Rheumatol 2019 May 27;38(5):1477-1483. Epub 2019 Feb 27.

Division of Rheumatology, Johns Hopkins University School of Medicine, 5200 Eastern Ave, Mason F Lord Building Center Tower, Suite 4100, Baltimore, MD, 21224, USA.

Inflammatory arthritis is a common feature of antisynthetase syndrome. Ultrasonography is able to characterize important features of bone and tendon pathology but has not been evaluated in this setting. We review the sonographic findings in a series of patients with antisynthetase syndrome and inflammatory arthritis. A retrospective chart review was performed of patients with antisynthetase syndrome-associated inflammatory arthritis who had undergone ultrasound imaging for joint pathology. Seventeen sonographic assessments of eight patients were included. Synovial hypertrophy was seen in all eight patients, with active Doppler signal present in six patients (13 of 17 ultrasound locations). Tendon involvement was common, with tenosynovitis in seven patients (11 of 17 ultrasound locations). Erosions were present in five patients. Musculoskeletal ultrasound showed significant joint pathology including proliferative synovitis and tenosynovitis. This may be severe and associated with erosive disease. Further systematic studies are needed to better understand the articular involvement of antisynthetase syndrome. Key points • Marked inflammatory change-with proliferative synovitis, tenosynovitis, and erosions-can be seen in selected patients with antisynthetase syndrome (ASyS). • Inflammatory arthritis from ASyS can be severe and erosive in the absence of RF and ACPA and can be refractory to immunosuppressive therapy used to manage the myositis and interstitial lung disease. • Systematic sonographic evaluation of patients with ASyS is needed to further evaluate pathology and treatment response of inflammatory arthritis.
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http://dx.doi.org/10.1007/s10067-019-04471-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541484PMC
May 2019