Annals of the Rheumatic Diseases




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Glucocorticoids: surprising new findings on their mechanisms of actions

Frank Buttgereit

doi : 10.1136/annrheumdis-2020-218798

Annals of the Rheumatic Diseases 2021;80:137-139.

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Johann Lucas Schoenlein (1793–1864): impact without publications 

Bernhard Manger, Georg Schett, Gerd R Burmester

doi : 10.1136/annrheumdis-2020-219205

Annals of the Rheumatic Diseases 2021;80:140-142.

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Mechanisms of progressive fibrosis in connective tissue disease (CTD)-associated interstitial lung diseases (ILDs)

Paolo Spagnolo, Oliver Distler, Christopher J Ryerson, Argyris Tzouvelekis, Joyce S Lee, Francesco Bonella, Demosthenes Bouros, Anna-Maria Hoffmann-Vold, Bruno Crestani, Eric L Matteson

doi : 10.1136/annrheumdis-2020-217230

Annals of the Rheumatic Diseases 2021;80:143-150.

Interstitial lung diseases (ILDs), which can arise from a broad spectrum of distinct aetiologies, can manifest as a pulmonary complication of an underlying autoimmune and connective tissue disease (CTD-ILD), such as rheumatoid arthritis-ILD and systemic sclerosis (SSc-ILD). Patients with clinically distinct ILDs, whether CTD-related or not, can exhibit a pattern of common clinical disease behaviour (declining lung function, worsening respiratory symptoms and higher mortality), attributable to progressive fibrosis in the lungs. In recent years, the tyrosine kinase inhibitor nintedanib has demonstrated efficacy and safety in idiopathic pulmonary fibrosis (IPF), SSc-ILD and a broad range of other fibrosing ILDs with a progressive phenotype, including those associated with CTDs. Data from phase II studies also suggest that pirfenidone, which has a different—yet largely unknown—mechanism of action, may also have activity in other fibrosing ILDs with a progressive phenotype, in addition to its known efficacy in IPF. Collectively, these studies add weight to the hypothesis that, irrespective of the original clinical diagnosis of ILD, a progressive fibrosing phenotype may arise from common, underlying pathophysiological mechanisms of fibrosis involving pathways associated with the targets of nintedanib and, potentially, pirfenidone. However, despite the early proof of concept provided by these clinical studies, very little is known about the mechanistic commonalities and differences between ILDs with a progressive phenotype. In this review, we explore the biological and genetic mechanisms that drive fibrosis, and identify the missing evidence needed to provide the rationale for further studies that use the progressive phenotype as a target population.

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Tackling osteoarthritis during COVID-19 pandemic 

Francisco Airton Castro da Rocha, Lucas da Ponte Melo, Francis Berenbaum

doi : 10.1136/annrheumdis-2020-218372

Annals of the Rheumatic Diseases 2021;80:151-153.

In this opinion article, we would like to draw attention to the fact that COVID-19 has a significant impact not only on immune-mediated arthritis but also on osteoarthritis (OA), the most common rheumatic disease. We suggest herein strategies for pain relief and symptom prevention in patients with OA during COVID-19 pandemic.

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Factors associated with progression to inflammatory arthritis in first-degree relatives of individuals with RA following autoantibody positive screening in a non-clinical setting 

Elizabeth A Bemis, M Kristen Demoruelle, Jennifer A Seifert, Kristen J Polinski, Michael H Weisman, Jane H Buckner, Peter K Gregersen, Ted R Mikuls, James R ODell, Richard M Keating, Kevin D Deane, V Michael Holers, Jill M Norris

doi : 10.1136/annrheumdis-2020-217066

Annals of the Rheumatic Diseases 2021;80:154-161.

Objectives Little is known about the likelihood of developing inflammatory arthritis (IA) in individuals who screen autoantibody positive (aAb+) in a non-clinical research setting.

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Dysbiosis in the oral microbiomes of anti-CCP positive individuals at risk of developing rheumatoid arthritis

Zijian Cheng, Thuy Do, Kulveer Mankia, Josephine Meade, Laura Hunt, Val Clerehugh, Alastair Speirs, Aradhna Tugnait, Paul Emery, Deirdre Devine

doi : 10.1136/annrheumdis-2020-216972

Annals of the Rheumatic Diseases 2021;80:162-168.

Objectives An increased prevalence of periodontitis and perturbation of the oral microbiome has been identified in patients with rheumatoid arthritis (RA). The periodontal pathogen Porphyromonas gingivalis may cause local citrullination of proteins, potentially triggering anti-citrullinated protein antibody production. However, it is not known if oral dysbiosis precedes the onset of clinical arthritis. This study comprehensively characterised the oral microbiome in anti-cyclic citrullinated peptide (anti-CCP) positive at-risk individuals without clinical synovitis (CCP+at?risk).

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Risk of venous thromboembolism in rheumatoid arthritis, and its association with disease activity: a nationwide cohort study from Sweden

Viktor Molander, Hannah Bower, Thomas Frisell, Johan Askling

doi : 10.1136/annrheumdis-2020-218419

Annals of the Rheumatic Diseases 2021;80:169-175.

Objective To assess the incidence of venous thromboembolism (VTE) in rheumatoid arthritis (RA) relative to individuals without RA, and to investigate the relationship between aspects of clinical disease activity in RA and the risk of VTE.

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In vitro elimination of autoreactive B cells from rheumatoid arthritis patients by universal chimeric antigen receptor T cells

Bo Zhang, Yan Wang, Yeshuang Yuan, Jiaqi Sun, Lulu Liu, Dan Huang, Jin Hu, Min Wang, Shengjie Li, Wei Song, Hua Chen, Demin Zhou, Xuan Zhang

doi : 10.1136/annrheumdis-2020-217844

Annals of the Rheumatic Diseases 2021;80:176-184

Objectives Autoreactive B cells play a crucial role in the pathogenesis of rheumatoid arthritis (RA), and B cell-depleting therapies using an antibodies, such as rituximab, have been suggested to be effective in RA treatment. However, transient B cell depletion with rituximab is associated with significant safety challenges related to global suppression of the immune system and thus increases the risks of infection and cancer development. To address selective and persistent issues associated with RA therapy, we developed a customised therapeutic strategy employing universal antifluorescein isothiocyanate (FITC) chimeric antigen receptor T cells (CAR-T cells) combined with FITC-labelled antigenic peptide epitopes to eliminate autoreactive B cell subsets recognising these antigens in RA.

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Brodalumab in psoriatic arthritis: results from the randomised phase III AMVISION-1 and AMVISION-2 trials 

Philip J Mease, Philip S Helliwell, Kasper Fjellhaugen Hjuler, Kyle Raymond, Iain McInnes

doi : 10.1136/annrheumdis-2019-216835

Annals of the Rheumatic Diseases 2021;80:185-193.

Objective To compare the efficacy and safety of brodalumab, an interleukin-17 receptor subunit A inhibitor, with placebo, in patients with psoriatic arthritis (PsA).

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Natural killer cells and type II interferon in Ro/SSA and La/SSB autoantibody-exposed newborns at risk of congenital heart block

Margarita Ivanchenko, Gudny Ella Thorlacius, Malin Hedlund, Vijole Ottosson, Lauro Meneghel, Sophia Bj?rkander, Amina Ossoinak, Joanna Tingstr?m, Katarina Bremme, Eva Sverremark-Ekstr?m, Kristina Gemzell-Danielsson, Sven-Erik Sonesson, Karine Chemin, Marie Wahren-Herlenius

doi : 10.1136/annrheumdis-2019-216786

Annals of the Rheumatic Diseases 2021;80:194-202.

Objective Congenital heart block (CHB) with immune cell infiltration develops in the fetus after exposure to maternal Ro/La autoantibodies. CHB-related serology has been extensively studied, but reports on immune-cell profiles of anti-Ro/La-exposed neonates are lacking. In the current study, we characterised circulating immune-cell populations in anti-Ro/La+mothers?and newborns, and explored potential downstream effects of skewed neonatal cell populations.

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Transcutaneous auricular vagus nerve stimulation reduces pain and fatigue in patients with systemic lupus erythematosus: a randomised, double-blind, sham-controlled pilot trial 

Cynthia Aranow, Yemil Atish-Fregoso, Martin Lesser, Meggan Mackay, Erik Anderson, Sangeeta Chavan, Theodoros P Zanos, Timir Datta-Chaudhuri, Chad Bouton, Kevin J Tracey, Betty Diamond

doi : 10.1136/annrheumdis-2020-217872

Annals of the Rheumatic Diseases 2021;80:203-208.

Objectives Musculoskeletal pain and fatigue are common features in systemic lupus erythematosus (SLE). The cholinergic anti-inflammatory pathway is a physiological mechanism diminishing inflammation, engaged by stimulating the vagus nerve. We evaluated the effects of non-invasive vagus nerve stimulation in patients with SLE and with musculoskeletal pain.

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Proteomic, biomechanical and functional analyses define neutrophil heterogeneity in systemic lupus erythematosus 

Kathleen R Bashant, Angel M Aponte, Davide Randazzo, Paniz Rezvan Sangsari, Alexander JT Wood, Jack A Bibby, Erin E West, Arlette Vassallo, Zerai G Manna, Martin P Playford, Natasha Jordan, Sarfaraz Hasni, Marjan Gucek, Claudia Kemper, Andrew Conway Morris, Nicole Y Morgan, Nicole Toepfner, Jochen Guck, Nehal N Mehta, Edwin R Chilvers, Charlotte Summers, Mariana J Kaplan

doi : 10.1136/annrheumdis-2020-218338

Annals of the Rheumatic Diseases 2021;80:209-218.

Objectives Low-density granulocytes (LDGs) are a distinct subset of proinflammatory and vasculopathic neutrophils expanded in systemic lupus erythematosus (SLE). Neutrophil trafficking and immune function are intimately linked to cellular biophysical properties. This study used proteomic, biomechanical and functional analyses to further define neutrophil heterogeneity in the context of SLE.

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Progressive interstitial lung disease in patients with systemic sclerosis-associated interstitial lung disease in the EUSTAR database

Anna-Maria Hoffmann-Vold, Yannick Allanore, Margarida Alves, Cathrine Brunborg, Paolo Air?, Lidia P Ananieva, L?szl? Czirj?k, Serena Guiducci, Eric Hachulla, Mengtao Li, Carina Mihai, Gabriela Riemekasten, Petros P Sfikakis, Otylia Kowal-Bielecka, Antonella Riccardi, Oliver Distler

doi : 10.1136/annrheumdis-2020-217455

Annals of the Rheumatic Diseases 2021;80:209-218.

Objectives To identify overall disease course, progression patterns and risk factors predictive for progressive interstitial lung disease (ILD) in patients with systemic sclerosis-associated ILD (SSc-ILD), using data from the European Scleroderma Trials And Research (EUSTAR) database over long-term follow-up.

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Machine learning integration of scleroderma histology and gene expression identifies fibroblast polarisation as a hallmark of clinical severity and improvement

Kimberly Showalter, Robert Spiera, Cynthia Magro, Phaedra Agius, Viktor Martyanov, Jennifer M Franks, Roshan Sharma, Heather Geiger, Tammara A Wood, Yaxia Zhang, Caryn R Hale, Jackie Finik, Michael L Whitfield, Dana E Orange, Jessica K Gordon

doi : 10.1136/annrheumdis-2020-217840

Annals of the Rheumatic Diseases 2021;80:219-227.

Objective We sought to determine histologic and gene expression features of clinical improvement in early diffuse cutaneous systemic sclerosis (dcSSc; scleroderma).

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Impact of the COVID-19 pandemic on the disease course of patients with inflammatory rheumatic diseases: results from the Swiss Clinical Quality Management cohort 

Adrian Ciurea, Eleftherios Papagiannoulis, Kristina Bürki, Isabell von Loga, Raphael Micheroli, Burkhard M?ller, Andrea Rubbert-Roth, Michael Andor, René Br?m, Angela Müller, Diana Dan, Diego Kyburz, Oliver Distler, Almut Scherer, Axel Finckh

doi : 10.1136/annrheumdis-2020-218705

Annals of the Rheumatic Diseases 2021;80:228-237.

Objectives To investigate whether the transient reduction in rheumatology services imposed by virus containment measures during the COVID-19 pandemic was associated with disease worsening in axial spondyloarthritis (axSpA), rheumatoid arthritis (RA) or psoriatic arthritis (PsA).

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Towards consensus in defining and handling contextual factors within rheumatology trials: an initial qualitative study from an OMERACT working group 

Sabrina Mai Nielsen, Marianne Uggen Rasmussen, Maarten Boers, Danielle A van der Windt, Maarten de Wit, Thasia G Woodworth, Caroline A Flurey, Dorcas Beaton, Beverley Shea, Reuben Escorpizo, Daniel E Furst, Josef S Smolen, Karine Toupin-April, Annelies Boonen, Marieke Voshaar, Torkell Ellingsen, George A Wells, Barnaby C Reeves, Lyn March, Peter Tugwell, Robin Christensen

doi : 10.1136/annrheumdis-2020-217895

Annals of the Rheumatic Diseases 2021;80:238-241.

Objectives The Outcome Measures in Rheumatology Initiative established the Contextual Factors Working Group to guide the understanding, identification and handling of contextual factors for clinical trials. In clinical research, different uses of the term ‘contextual factors’ exist. This study explores the perspectives of researchers (including clinicians) and patients in defining 'contextual factor’ and its related terminology, identifying such factors and accounting for them in trials across rheumatology.

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Local steroid activation is a critical mediator of the anti-inflammatory actions of therapeutic glucocorticoids

Chloe Fenton, Claire Martin, Rachel Jones, Adam Croft, Joana Campos, Amy J Naylor, Angela E Taylor, Myriam Chimen, Mark Cooper, Gareth G Lavery, Karim Raza, Rowan S Hardy

doi : 10.1136/annrheumdis-2020-218493

Annals of the Rheumatic Diseases 2021;80:242-249.

Objectives The enzyme 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1) plays a well-characterised role in the metabolism and activation of endogenous glucocorticoids (GCs). However, despite its potent upregulation at sites of inflammation, its role in peripheral metabolism and action of therapeutic GCs remains poorly understood. We investigated the contribution of 11?-HSD1 to the anti-inflammatory properties of the active GC corticosterone, administered at therapeutic doses in murine models of polyarthritis.

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Criterion validity of ultrasound in the identification of calcium pyrophosphate crystal deposits at the knee: an OMERACT ultrasound study

Georgios Filippou, Anna Scanu, Antonella Adinolfi, Carmela Toscano, Dario Gambera, Raquel Largo, Esperanza Naredo, Emilio Calvo, Gabriel Herrero-Beaumont, Pascal Zufferey, Christel Madelaine Bonjour, Daryl K MacCarter, Stanley Makman, Zachary Weber, Fabiana Figus, Ingrid M?ller, Marwin Gutierrez, Carlos Pineda, Denise Clavijo Cornejo, Hector Garcia, Victor Ilizaliturri, Jaime Mendoza Torres, Raul Pichardo, Luis Carlos Rodriguez Delgado, Emilio Filippucci, Edoardo Cipolletta, Teodora Serban, Catalin Cirstoiu, Florentin Ananu Vreju, Dan Grecu, Gaël Mouterde, Marcello Govoni, Leonardo Punzi, Nemanja S Damjanov, Helen Isobel Keen, George AW Bruyn, Lene Terslev, Maria-Antonietta D'Agostino, Carlo Alberto Scirè, Annamaria Iagnocco

doi : 10.1136/annrheumdis-2020-217998

Annals of the Rheumatic Diseases 2021;80:250-260.

Objective To evaluate the discriminatory ability of ultrasound in calcium pyrophosphate deposition disease (CPPD), using microscopic analysis of menisci and knee hyaline cartilage (HC) as reference standard.

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SARS CoV-2 infection among patients using immunomodulatory therapies

Kevin L Winthrop, Amanda E Brunton, Susan Beekmann, Philip Polgreen, John Baddley, Kenneth G Saag, Cassandra Calabrese, Leonard Calabrese, Philip C Robinson, Zachary S Wallace, Jeffrey R Curtis

doi : 10.1136/annrheumdis-2020-218580

Annals of the Rheumatic Diseases 2021;80:261-267.

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Interleukin-6 receptor blockade with subcutaneous tocilizumab in severe COVID-19 pneumonia and hyperinflammation: a case–control study 

Nicola Potere, Marcello Di Nisio, Donatella Cibelli, Rosa Scurti, Antonella Frattari, Ettore Porreca, Antonio Abbate, Giustino Parruti

doi : 10.1136/annrheumdis-2020-218243

Annals of the Rheumatic Diseases 2021;80:269-271.

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Hydroxychloroquine shortages among patients with systemic lupus erythematosus during the COVID-19 pandemic: experience of the Systemic Lupus International Collaborating Clinics 

Arielle Mendel, Sasha Bernatsky, Anca Askanase, Sang-Cheol Bae, Ann Elaine Clarke, Nathalie Costedoat-Chalumeau, Dafna D Gladman, Caroline Gordon, John Hanly, S?ren Jacobsen, Ken Kalunian, Anselm Mak, Marta Mosca, Bernardo A Pons-Estel, Guillermo Ruiz-Irastorza, Murray Urowitz, ?velyne Vinet

doi : 10.1136/annrheumdis-2020-218164

Annals of the Rheumatic Diseases 2021;80:1-2.

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The use of tocilizumab and tofacitinib in patients with resolved hepatitis B infection: a case series

Naomi Serling-Boyd, Amir M Mohareb, Arthur Y Kim, Emily P Hyle, Zachary S Wallace

doi : 10.1136/annrheumdis-2020-218289

Annals of the Rheumatic Diseases 2021;80:1-2.

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Coronavirus disease 19 (Covid-19) and non-steroidal anti-inflammatory drugs (NSAID) 

Alessandro Giollo, Giovanni Adami, Davide Gatti, Luca Idolazzi, Maurizio Rossini

doi : 10.1136/annrheumdis-2020-217598

Annals of the Rheumatic Diseases 2021;80:1-2.

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Non-steroidal anti-inflammatory treatment during covid-19: friend or foe? Response to: ‘Coronavirus disease 19 (Covid-19) and non-steroidal anti-inflammatory drugs (NSAID)’ by Giollo et al 

Sara Monti, Carlomaurizio Montecucco

doi : 10.1136/annrheumdis-2020-217638

Annals of the Rheumatic Diseases 2021;80:e13.

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COVID-19 pneumonia in a large cohort of patients treated with biological and targeted synthetic antirheumatic drugs

Edoardo Conticini, Elena Bargagli, Marco Bardelli, Giuseppe Domenico Rana, Caterina Baldi, Paolo Cameli, Stefano Gentileschi, David Bennett, Paolo Falsetti, Nicola Lanzarone, Francesca Bellisai, Cristiana Barreca, Roberto D'Alessandro, Luca Cantarini, Bruno Frediani

doi : 10.1136/annrheumdis-2020-217681

Annals of the Rheumatic Diseases 2021;80:e14.

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Prevalence of COVID-19 among patients with rheumatic diseases: the need to await results from large collaborative studies. Response to: ‘COVID-19 pneumonia in a large cohort of patients treated with biological and targeted synthetic antirheumatic drugs’ by Conticini et al 

Sara Monti, Carlomaurizio Montecucco

doi : 10.1136/annrheumdis-2020-217738

Annals of the Rheumatic Diseases 2021;80:e15.

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Rheumatic diseases in intensive care unit patients with COVID-19

Sergey Moiseev, Sergey Avdeev, Michail Brovko, Andrey Yavorovskiy, Pavel I Novikov, Karina Umbetova, Larisa Akulkina, Natal'ya Tsareva, Victor Fomin

doi : 10.1136/annrheumdis-2020-217676

Annals of the Rheumatic Diseases 2021;80:e16.

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Comorbidities and rheumatological diseases at the time of COVID-19. Response to: ‘Rheumatic diseases in intensive care unit patients with COVID-19’ by Moiseev et al

Sara Monti, Carlomaurizio Montecucco

doi : 10.1136/annrheumdis-2020-217800

Annals of the Rheumatic Diseases 2021;80:e17.

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What is the true incidence of COVID-19 in patients with rheumatic diseases? 

Ennio Giulio Favalli, Francesca Ingegnoli, Rolando Cimaz, Roberto Caporali

doi : 10.1136/annrheumdis-2020-217615

Annals of the Rheumatic Diseases 2021;80:e18.

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Is there a future for hydroxychloroquine/chloroquine in prevention of SARS-CoV-2 infection (COVID-19)? 

Sergey Moiseev, Sergey Avdeev, Michail Brovko, Pavel Novikov, Victor Fomin

doi : 10.1136/annrheumdis-2020-217570

Annals of the Rheumatic Diseases 2021;80:e19.

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Response to ‘Is there a future for hydroxychloroquine/chloroquine in prevention of SARS-CoV-2 infection (COVID-19)?’ by Moiseev et al 

Francesca Romana Spinelli, Fulvia Ceccarelli, Manuela Di Franco, Fabrizio Conti

doi : 10.1136/annrheumdis-2020-217636

Annals of the Rheumatic Diseases 2021;80:e20.

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Patients with lupus are not protected from COVID-19 

Amr H Sawalha

doi : 10.1136/annrheumdis-2020-217656

Annals of the Rheumatic Diseases 2021;80:e21.

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No evidence so far on the protective effect of hydroxychloroquine to prevent COVID-19: comment by Joob and Wiwanitkit

Vasco C. Rom?o, Ana Rita Cruz-Machado, Jo?o Eurico Fonseca

doi : 10.1136/annrheumdis-2020-217665

Annals of the Rheumatic Diseases 2021;80:e22.

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SLE patients are not immune to covid-19: importance of sending the right message across 

Mohit Goyal

doi : 10.1136/annrheumdis-2020-217658

Annals of the Rheumatic Diseases 2021;80:e23.

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Response to: ‘Patients with lupus are not protected from COVID-19: a comment’ by Sawalha, ‘No evidence so far on the protective effect of hydroxycloroquin to prevent COVID-19: response to the Comment by Joob and Wiwanitkit’ by Rom?o et al and ‘SLE patients are not immune to COVID-19: importance of sending the right message across’ by Goyal 

Beuy Joob, Viroj Wiwanitkit

doi : 10.1136/annrheumdis-2020-217695

Annals of the Rheumatic Diseases 2021;80:e24.

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Are patients with systemic lupus erythematosus at increased risk for COVID-19? 

Ennio Giulio Favalli, Maria Gerosa, Antonella Murgo, Roberto Caporali

doi : 10.1136/annrheumdis-2020-217787

Annals of the Rheumatic Diseases 2021;80:e25.

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Response to: ‘Are patients with systemic lupus erythematosus at increased risk for COVID-19?’ by Favalli et al 

Alexis Mathian, Zahir Amoura

doi : 10.1136/annrheumdis-2020-217859

Annals of the Rheumatic Diseases 2021;80:e26.

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Correction: Knee osteoarthritis risk in non-industrial societies undergoing an energy balance transition: evidence from the indigenous Tarahumara of Mexico

doi : 10.1136/annrheumdis-2019-215886corr1

Annals of the Rheumatic Diseases 2021;80:e27.

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Correction: High prevalence of spondyloarthritis-like MRI lesions in postpartum women: a prospective analysis in relation to maternal, child and birth characteristics 

doi : 10.1136/annrheumdis-2020-217095corr1

Annals of the Rheumatic Diseases 2021;80:e28.

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