Rheumatology Commons^™

Bone Marrow Transplant For Macrophage Activation Syndrome In Systemic Juvenile Idiopathic Arthritis, Shailly Gaur, Michael J. Holland, J Allyson Hays, Ibrahim A. Ahmed

Research Days

Background

The recognition of macrophage-activation-syndrome (MAS) in the setting of systemic-juvenileidiopathic-arthritis (sJIA) is complex, but a necessary distinction given emerging treatment options. With overlapping clinical manifestations including fever, end-organ involvement and lymphadenopathy, there is a focus on laboratory values to differentiate MAS from a sJIA flare. Once parameters are met, multiple treatment modalities can be considered, as monotherapy or in combination, including steroids, immunosuppression, chemotherapy, intravenous immunoglobulin, and cytokine-directed biologics. Given the long-term morbidity and mortality associated with progressive inflammation and immune dysregulation due to MAS with sJIA, it is imperative to regain control over this complication. However, these treatments …

Maackia Amurensis Seed Lectin (Masl) Increases Movement Velocity Of Mice With Tnfα Induced Rheumatoid Arthritis, Amanda A. Greenspan, Kelly L. Hamilton, Alan J. Shienbaum, Bradford Fischer, Andrea Bottaro, Gary S. Goldberg

Rowan-Virtua Research Day

Up to 70 million people around the world suffer from rheumatoid arthritis. Current treatment options have varied efficacy and can cause unwanted side effects. New approaches are needed to treat this condition. Sialic acid modifications on chondrocyte receptors have been associated with arthritic inflammation and joint destruction. The transmembrane mucin receptor protein podoplanin (PDPN) has been identified as a functionally relevant receptor that presents extracellular sialic acid motifs. PDPN signaling promotes inflammation and invasion associated with arthritis and, therefore, has emerged as a target that can be used to inhibit arthritic inflammation. Maackia amurensis seed lectin (MASL) can target PDPN …

A Case Of Double-Positive Anti-Gbm And Mpo-Anca Vasculitis With No Pulmonary Involvement, Deonnie W. Huang, Patrick May, Thanh Nguyen

Research Day

Introduction

Anti-glomerular basement membrane (anti-GBM) disease is a small vessel vasculitis caused by autoantibodies directed at the glomerular and alveolar basement membranes. Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis is pauci-immune with no immune deposits. Both vasculitides can lead to precipitation of rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage. We report a case of a 58 year-old male who presented with acute renal failure with double positive anti-GBM and myeloperoxidase-anti neutrophil cytoplasmic antibodies (MPO-ANCA) but no pulmonary involvement.

Case Presentation

Patient is a 58-year-old male with a past medical history of nicotine dependence who presented to the hospital with abnormal blood work. …

Bone Marrow Transplant For Macrophage Activation Syndrome In Systemic Juvenile Idiopathic Arthritis​, Shailly Gaur, Michael J. Holland, J Allyson Hays, Ibrahim A. Ahmed

Posters

7yo w/ systemic juvenile idiopathic arthritis who developed macrophage activation syndrome and interstitial lung disease non-responsive to steroids, immunosuppression, and directed biologics with significant adverse reactions who required chemotherapy and eventual bone marrow transplant leading to complete resolution of symptoms.

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing

Dissertations and Theses (Open Access)

Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …

Quantitative Proteomic Screening Uncovers Candidate Diagnostic And Monitoring Serum Biomarkers Of Ankylosing Spondylitis, Mark Hwang, Shervin Assassi, Jim Zheng, Jessica Castillo, Reyna Chavez, Kamala Vanarsa, Chandra Mohan, John Reveille

Faculty, Staff and Student Publications

BACKGROUND: We sought to discover serum biomarkers of ankylosing spondylitis (AS) for diagnosis and monitoring disease activity.

METHODS: We studied biologic-treatment-naïve AS and healthy control (HC) patients' sera. Eighty samples matched by age, gender, and race (1:1:1 ratio) for AS patients with active disease, inactive disease, and HC were analyzed with SOMAscan™, an aptamer-based discovery platform. T-tests tests were performed for high/low-disease activity AS patients versus HCs (diagnosis) and high versus low disease activity (Monitoring) in a 2:1 and 1:1 ratio, respectively, to identify differentially expressed proteins (DEPs). We used the Cytoscape Molecular Complex Detection (MCODE) plugin to find clusters …

Treatment Outcomes For Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Real-World, Multisite Study Of The Impact Of Immunosuppression On Pulmonary Function Trajectory, Scott M Matson, Misbah Baqir, Teng Moua, Michael Marll, Jessica Kent, Nicholas S Iannazzo, Ryan D Boente, John M Donatelli, Junqiang Dai, Francisco J Diaz, M Kristen Demoruelle, Mark B Hamblin, Susan K Mathai, Jay H Ryu, Kristen Pope, Christopher M Walker, Joyce S Lee

Faculty, Staff and Student Publications

BACKGROUND: Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) is common in patients with RA and leads to significant morbidity and mortality. No randomized, placebo-controlled data are available that support the role of immunosuppression to treat RA-associated ILD, despite being widely used in clinical practice.

RESEARCH QUESTION: How does immunosuppression impact pulmonary function trajectory in a multisite retrospective cohort of patients with RA-associated ILD?

STUDY DESIGN AND METHODS: Patients with RA who started treatment for ILD with mycophenolate, azathioprine, or rituximab were identified retrospectively from five ILD centers. Change in lung function before and after treatment was analyzed using a linear …

Antibodies For Β2-Microglobulin And The Heavy Chains Of Hla-E, Hla-F, And Hla-G Reflect The Hla-Variants On Activated Immune Cells And Phases Of Disease Progression In Rheumatoid Arthritis Patients Under Treatment, Mepur H. Ravindranath, Narendranath M. Ravindranath, Carly J. Amato-Menker, Fatiha El Hilali, Senthamil R. Selvan, Edward J Filippone, Luis Eduardo Morales-Buenrostro

Department of Medicine Faculty Papers

Rheumatoid arthritis (RA) is a progressive, inflammatory, autoimmune, symmetrical polyarticular arthritis. It is characterized by synovial infiltration and activation of several types of immune cells, culminating in their apoptosis and antibody generation against "altered" autoantigens. β2-microglobulin (β2m)-associated heavy chains (HCs) of HLA antigens, also known as closed conformers (Face-1), undergo "alteration" during activation of immune cells, resulting in β2m-free structural variants, including monomeric open conformers (Face-2) that are capable of dimerizing as either homodimers (Face-3) or as heterodimers (Face-4). β2m-free HCs uncover the cryptic epitopes that can elicit antibodies (Abs). We report here the levels of IgM and IgG Abs …

Graves' Disease And Major Histocompatibility Complex Class Ii: A Meta-Analysis Of Hla-Dq And Hla-Drb1, Dylan Thibaut, Connor Sweeney, Shannon South, Mohamed Hussein

Advances in Clinical Medical Research and Healthcare Delivery

Background: Human leukocyte antigen (HLA) class II has shown potential in determining prognosis, understanding medication reactions, and predicting onset of Graves’ disease. The aim of this study is to further investigate the association between Graves’ disease and HLA class II, specifically HLA-DQ and HLA-DR, via meta-analysis to find HLAs that can be further examined for prognostic reasons.

Methods: Statistical analysis was performed to determine if variants of HLA-DQA1, HLA-DQB1, or HLA-DRB1 were associated with significantly altered odds of Graves’ disease. A minimum of three studies pertaining to a particular HLA was required for inclusion. Studies were excluded if …

Rheumatoid Vasculitis Presenting With Incidental Renal Infarcts: Case Report And Literature Review, Fatima Halilu, Howard Hauptman

Journal of Community Hospital Internal Medicine Perspectives

Rheumatoid vasculitis is a rare and late complication of rheumatoid arthritis, affecting small to medium sized vessels. Inflammation in the vessel wall produces an occlusive vasculopathy with downstream infarction. We present the case of a 70-year-old female with long standing stable RA status post recent COVID-19 vaccination admitted with community acquired Legionnaires disease found to have an incidental renal infarct on chest imaging without a clear etiology. She improved from a respiratory standpoint but then had a fever spike with repeat imaging showing a second renal infarct and CT angiography showing extensive beading with aneurysmal dilation in the bilateral hepatic …

Blood Neutrophil Count And Neutrophil-To-Lymphocyte Ratio For Prediction Of Disease Progression And Mortality In Two Independent Systemic Sclerosis Cohorts, Nancy Wareing, Vishnu Mohan, Rana Taherian, Elizabeth R Volkmann, Marka A Lyons, Holly Wilhalme, Michael D Roth, Rosa M Estrada-Y-Martin, Brian Skaug, Maureen D Mayes, Donald P Tashkin, Shervin Assassi

Faculty, Staff and Student Publications

OBJECTIVE: To assess the predictive significance of blood neutrophil count and the ratio between neutrophil and lymphocyte count (neutrophil-to-lymphocyte ratio [NLR]) for disease severity and mortality in systemic sclerosis (SSc).

METHODS: Neutrophil and lymphocyte counts were prospectively measured in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) and the Scleroderma Lung Study II (SLS II). Forced vital capacity percent predicted (FVC%) and modified Rodnan skin thickness score (MRSS) were used as surrogate measures for disease severity. Longitudinal analyses were performed using generalized linear mixed models. Cox proportional hazards models evaluated the predictive significance of these cell counts for mortality. …

It Is Not Pneumocystis Jiroveci (Pcp), It Is Cyclophosphamide-Induced Pneumonitis, Mery Bartl, Yilen Karen Ng-Wong, Blesset Alexander, Jose Gomez Casanovas, Josenny L. Rodriguez-Paez, Andres Suarez, Christine Loftis

School of Medicine Publications

Cyclophosphamide (CYC) is an immunosuppressive medication used to treat life-threatening complications of various rheumatic diseases like vasculitis and systemic lupus erythematosus. A rare side effect of this medication is pneumonitis, which occurs in less than 1% of patients. We describe a case of an 83-year-old woman with a past medical history of microscopic polyangiitis, who presented with progressive dyspnea at rest, exacerbated on exertion, and associated with orthopnea that was attributed to CYC-induced pneumonitis. Three months before this presentation, the patient was diagnosed with antineutrophil cytoplasmic antibodies (ANCA)-positive pauci-immune crescentic and necrotizing glomerulonephritis and started on CYC. On admission, a …

Curq+, A Next-Generation Formulation Of Curcumin, Ameliorates Growth Plate Chondrocyte Stress And Increases Limb Growth In A Mouse Model Of Pseudoachondroplasia, Jacqueline T Hecht, Alka C Veerisetty, Mohammad G Hossain, Frankie Chiu, Karen L Posey

Faculty, Staff and Student Publications

Mutations in cartilage oligomeric matrix protein (COMP) causes protein misfolding and accumulation in chondrocytes that compromises skeletal growth and joint health in pseudoachondroplasia (PSACH), a severe dwarfing condition. Using the MT-COMP mice, a murine model of PSACH, we showed that pathological autophagy blockage was key to the intracellular accumulation of mutant-COMP. Autophagy is blocked by elevated mTORC1 signaling, preventing ER clearance and ensuring chondrocyte death. We demonstrated that resveratrol reduces the growth plate pathology by relieving the autophagy blockage allowing the ER clearance of mutant-COMP, which partially rescues limb length. To expand potential PSACH treatment options, CurQ+, a uniquely absorbable …

Effect Of Nintedanib In Patients With Systemic Sclerosis-Associated Interstitial Lung Disease And Risk Factors For Rapid Progression, Dinesh Khanna, Toby M Maher, Elizabeth R Volkmann, Yannick Allanore, Vanessa Smith, Shervin Assassi, Michael Kreuter, Anna-Maria Hoffmann-Vold, Masataka Kuwana, Christian Stock, Margarida Alves, Steven Sambevski, Christopher P Denton

Faculty, Staff and Student Publications

Objective: To investigate the rate of decline in forced vital capacity (FVC), and the effect of nintedanib on the rate of decline in FVC, in subjects with systemic sclerosis-associated interstitial lung disease (SSc-ILD) who had risk factors for rapid decline in FVC.

Methods: The SENSCIS trial enrolled subjects with SSc and fibrotic ILD of ≥10% extent on high-resolution CT. The rate of decline in FVC over 52 weeks was analysed in all subjects and in those with early SSc (< 18 months since first non-Raynaud symptom), elevated inflammatory markers (C reactive protein ≥6 mg/L and/or platelets ≥330×109/L) or significant skin fibrosis (modified Rodnan skin score (mRSS) 15-40 or mRSS ≥18) at baseline.

Results: In the placebo group, the rate of decline in FVC was numerically greater in subjects with < 18 months since first non-Raynaud symptom (-167.8 mL/year), elevated inflammatory markers (-100.7 mL/year), mRSS 15-40 (-121.7 mL/year) or mRSS ≥18 (-131.7 mL/year) than in all subjects (-93.3 mL/year). Nintedanib reduced the rate of FVC decline across subgroups, with a numerically greater effect in patients with these risk factors for rapid FVC decline.

Conclusion: In the …

The Ra-Be-Real Multinational, Prospective, Observational Study In Patients With Rheumatoid Arthritis Receiving Baricitinib, Targeted Synthetic, Or Biologic Disease-Modifying Therapies: A 6-Month Interim Analysis, Rieke Alten, Gerd R Burmester, Marco Matucci-Cerinic, Jean-Hugues Salmon, Pedro Lopez-Romero, Walid Fakhouri, Inmaculada De La Torre, Liliana Zaremba-Pechmann, Thorsten Holzkämper, Bruno Fautrel

Faculty, Staff and Student Publications

INTRODUCTION: RA-BE-REAL has the overall aim of defining a profile of patients with rheumatoid arthritis (RA) starting baricitinib or any other targeted synthetic (ts) or any biologic (b) disease-modifying antirheumatic drug (DMARD) for the first time, and the primary objective of estimating time until discontinuation from any cause (excluding sustained response) of the initial treatment.

METHODS: RA-BE-REAL is an ongoing, prospective, observational, 36-month study in patients with RA initiating treatment with baricitinib (cohort A) or any other tsDMARD or any bDMARD (cohort B) for the first time. The primary objective is to assess the time until treatment discontinuation from any …

Risks Of Mortality And Severe Coronavirus Disease 19 (Covid-19) Outcomes In Patients With Or Without Systemic Lupus Erythematosus, Sebastian Bruera, Xiudong Lei, Hui Zhao, Jinoos Yazdany, Mariana Chavez-Macgregor, Sharon H Giordano, Maria E Suarez-Almazor

Faculty, Staff and Student Publications

OBJECTIVES: We compared the outcomes of patients with or without systemic lupus erythematosus (SLE) who were diagnosed with coronavirus disease 19 (COVID-19) and evaluated factors within patients with SLE associated with severe outcomes.

METHODS: This retrospective cohort study used the deidentified Optum COVID-19 electronic health record dataset to identify patients with COVID-19 from 1/1/2020 to 31/12/2020. Cases with SLE were matched with general controls at a ratio of 1:10 by age, sex, race and ethnicity and COVID-19 diagnosis date. Outcomes included 30-day mortality, mechanical ventilation, hospitalisation and intensive care unit admission. We evaluated the relationship between COVID-19-related outcomes and SLE …

Rapid Onset Hydralazine-Induced Antineutrophil Cytoplasmic Antibody (Anca) Associated Vasculitis Presenting With Hemoptysis And Kidney Failure: Case Report, Rachel E. Easter, Andinet Gizaw, Natalie Klein

Internal Medicine Publications

Hydralazine-induced vasculitis can be challenging to recognize and diagnose as presenting symptoms vary and can mimic other conditions or diseases, however, swift intervention and treatment is key in halting progression of the disease and providing patients with the best possible outcomes. A 71-year-old African American female presented to the emergency department with weakness, fatigue, anemia, blood-streaked sputum, fever, chills, and severe myalgias. Hydralazine was prescribed to treat resistant hypertension eight months prior to presentation. Hydralazine was discontinued on hospital day (HD) 4. Pertinent laboratory values showed elevated inflammatory markers, positive antinuclear antibody (ANA), negative rheumatoid factor (RF), normal complement levels, …

Metformin-Induced Giant Cell Arteritis: An Uncommon Case Of Drug-Induced Vasculitis, Christine Angeles, Wendy Lee

South Atlantic Division GME Research Day 2023

No abstract provided.

Why A High Titer Rheumatoid Factor And Joint Pain Should Not Automatically Translate Into A Diagnosis Of Rheumatoid Arthritis, Saba Ashraf, Julio Gonzalez-Paoli

West Florida Division GME Research Day 2023

No abstract provided.

An Iceberg I Can’T Handle: A Qualitative Inquiry On Perceptions Towards Paediatric Rheumatology Among Healthcare Workers In Kenya, Angela Migowa, Sasha Bernatsky, Anthony Ngugi, Helen E. Foster, Peter Muriuki, Adelaide Lusambili, Stanley Luchters

Paediatrics and Child Health, East Africa

Background: Delay in diagnosis and access to specialist care is a major problem for many children and young people with rheumatic disease in sub-Saharan Africa. Most children with symptoms of rheumatic disease present to nonspecialists for care. There is an urgent need to understand and scale-up paediatric rheumatology knowledge and skills amongst non-specialist healthcare workers to promote early diagnosis, prompt referral, and management.

Purpose: We evaluated the knowledge, attitudes and practices towards diagnosis and care of paediatric rheumatology patients among health care workers in Kenya.

Methods: We conducted 12 focus group discussions with clinical officers (third-tier community health …