Research In Rheumatic Diseases Research Articles

International exchange on the clinical practice and research of rheumatic skin diseases: A report of the 5th International Conference of Cutaneous Lupus Erythematosus.

The 5th International Conference of Cutaneous Lupus Erythematosus was held in Tokyo, Japan on May 9 and 10, 2023. The latest topics on the pathogenesis, diagnosis, assessment, and treatment of cutaneous lupus erythematosus, dermatomyositis, and scleroderma (systemic sclerosis, morphea) were presented by experts in each field and new developments discussed. In these rheumatic skin diseases, many clinical trials of novel therapies targeting cytokines, signaling molecules, plasmacytoid dendritic cells, B cells, and other molecules are currently underway, and standardization of outcome assessment was discussed. In addition, the selection of the therapeutic agents available for the diversity of each case is becoming more important, together with the ongoing pathophysiological analysis of the diseases. The achievements of this conference will further promote the development of clinical practice and research in rheumatic skin diseases through international exchange among researchers. We hope that by reporting a summary of the conference in this manuscript, we can share its contents with readers.

Cardiovascular comorbidities in spondyloarthritis.

In recent years, many researchers have focused on the development of comorbidities associated with axial spondyloarthritis. Hypertension, smoking, dyslipidemia, diabetes mellitus, obesity, and the presence of inflammation, which is a well-known risk factor, increase cardiovascular comorbidities. Previous studies reported that HLA-B27 might be a genetic risk factor for various cardiac conditions. In the treatment and follow-up, raising the awareness of cardiovascular risk and guiding clinical practice and future research in rheumatic and musculoskeletal diseases should be aimed. There is consensus that cardiovascular risks should be evaluated periodically in these patients, particularly during the course of treatment. A decision regarding the selection and follow-up protocols of the drugs should be made considering all the risks and benefits in spondyloarthropathies. In this review, we discussed the recommendations and practices for the management of cardiovascular comorbidities in axial spondyloarthritis. Key Points •The risk of cardiovascular morbidity and mortality is increased in axial spondyloarthritis. •Higher disease activity increases cardiovascular risk factors. •Axial spondyloarthritis patients should be carefully monitored for signs of cardiovascular events as this is necessary to ensure that patients are treated appropriately and awareness should be raised in all patients. •Reducing the activity of the underlying disease with an appropriate and early treatment will also reduce the risk of cardiovascular events.

Gender-Diverse Inclusion in Immunological Research: Benefits to Science and Health.

The differences between male and female immune systems are an under-researched field, ripe for discovery. This is evidenced by the stark sex biases seen in autoimmunity and infectious disease. Both the sex hormones (oestrogen and testosterone), as well as the sex chromosomes have been demonstrated to impact immune responses, in multiple ways. Historical shortcomings in reporting basic and clinical scientific findings in a sex-disaggregated manner have led not only to limited discovery of disease aetiology, but to potential inaccuracies in the estimation of the effects of diseases or interventions on females and gender-diverse groups. Here we propose not only that research subjects should include both cis-gender men and cis-gender women, but also transgender and gender-diverse people alongside them. The known interaction between the hormonal milieu and the sex chromosomes is inseparable in cis-gender human research, without the confounders of puberty and age. By inclusion of those pursuing hormonal affirmation of their gender identity- the individual and interactive investigation of hormones and chromosomes is permitted. Not only does this allow for a fine-tuned dissection of these individual effects, but it allows for discovery that is both pertinent and relevant to a far wider portion of the population. There is an unmet need for detailed treatment follow-up of the transgender community- little is known of the potential benefits and risks of hormonal supplementation on the immune system, nor indeed on many other health and disease outcomes. Our research team has pioneered the inclusion of gender-diverse persons in our basic research in adolescent autoimmune rheumatic diseases. We review here the many avenues that remain unexplored, and suggest ways in which other groups and teams can broaden their horizons and invest in a future for medicine that is both fruitful and inclusive.

Research priority setting for paediatric rheumatology in the UK.

The evidence base that underlies the management of children and young people with paediatric rheumatic diseases is deficient. In this field, there are many crucial unanswered questions. The UK Paediatric Rheumatology Clinical Studies Group, supported by UK National Institute for Health Research Clinical Research Network: children and Versus Arthritis, elicited ideas for research priorities from paediatric rheumatologists, trainees, allied health-care professionals, nurse specialists, patients, parents of patients, carers, and charities. These ideas were collected through online surveys and face-to-face meetings. A modified Delphi process was used, which included online research priority ranking surveys and a consensus workshop. A longlist of 55 disease-specific research priorities and 37 general research priorities were voted on in the first survey. A list of 11 top general research priorities was produced. The top ten disease-specific research priorities were discussed in depth at a Delphi workshop to determine their final ranking. This Health Policy paper will help to guide clinicians, academics, and funding bodies to prioritise research in paediatric rheumatic diseases, specifically in areas of unmet patient needs.

A Legacy of Excellence in Research and Service

In 1961, Dr. Lourdes Manahan, a young internist at the Philippine General Hospital, presented her paper entitled “Rheumatic disease in the Philippines” at the Australian Rheumatism Congress in Sydney.1 This was the first time an article on the Philippine rheumatology experience was presented at an international convention. It was, however, not Dr. Manahan’s first foray into research. In 1948, she was published in this very journal – a report on familial non-hemolytic jaundice, a syndrome which would later bear her name, the Rotor-Manahan-Florentin syndrome.2 Her interest soon shifted towards a new field of study centered on diseases referred to then as “rheumatism.” After training in the United States for a year, she established an arthritis clinic to serve Filipino rheumatic patients in the PGH dispensary. For over a decade, she cared for patients alone, painstakingly documenting her findings in pages of handwritten notes and tables. These pages turned into scientific publications, and Dr. Manahan became a pioneer in research in rheumatology in the region. She was the first to describe gout in the Philippines.3, 4 She authored the COPCORD (Community Oriented Program for Control of Rheumatic Diseases) studies, a joint effort by the World Health Organization and International League Against Rheumatism to measure the burden of arthritis and disability in the community.5,6
 The Division of Rheumatology continues this legacy. Research in rheumatic diseases has been one of the core disciplines of the division over its now 50 years of existence. In celebration of our founder’s 100th birth anniversary, this special issue of ACTA MEDICA PHILIPPINA republishes three of Dr. Manahan’s earlier works. The first is a report of a family with Rotor-Manahan-Florentin syndrome. 7 While not a rheumatic disease, her encounter with this condition sparked her interest in scientific inquiry. Dr. Manahan also co-authored the first clinical and laboratory description of Chikungunya in the Philippines.8 She also was one of the first to investigate HLA antigens in Ankylosing Spondylitis in Filipinos.9
 This special issue in rheumatology also presents interesting cases in rheumatic diseases and original studies by the faculty of the division and its graduates. The gout registry feasibility study emphasizes the importance of databases in collecting data over time to describe the clinical profiles and outcomes of Filipino patients with gout. Penserga and Penserga’s paper shines a spotlight on the unmet need to manage rheumatoid arthritis in the Philippines, where most patients do not have access to biological treatments. Finally, Villanueva-Misa et al. demonstrate the Knee Injury and Osteoarthritis Outcome Score (KOOS) to be a valuable tool for measuring disability in Filipino patients with osteoarthritis in clinical practice and research.
 As we honor the legacy of the first among us, we are reminded that the central focus of our work, both in research and clinical practice, is always in the service of the Filipino patient
 
 Anna Kristina Gutierrez-Rubio, MD Division of Rheumatology Department of Medicine Philippine General Hospital University of the Philippines Manila
 
 REFERENCES 
 
 Manahan L. Rheumatic Disease in the Philippines. in Australian Rheumatism Congress. 1964. Sydney.
 Rotor AB, Manahan L, Florentin A. Familial Non-hemolytic Jaundice with Direct Van Den Bergh Reaction. Acta Med Phil. 1948; 5:37.
 Manahan L. Is Gout Found in the Philippines? Acta Med Philipp. 1954; 10: 477-82
 Manahan L. Uric Acid in Diabetic Filipinos. Acta Med Philipp. 1964; 1:11-4.
 Manahan L, Caragay R, Muirden KD, Allander E, Valkenburg HA, Wigley RD. Rheumatic Pain in a Philippine Village. A WHO[1] ILAR COPCORD Study. Rheumatol Int. 1985; 5:149-53.
 Wigley RD, Manahan L, Muirden KD, Caragay R, Pinfold B, Couchman KG, et al. Rheumatic Disease in a Philippine Village. II: A WHO-ILAR-APLAR COPCORD Study, Phases II and III. Rheumatol Int. 1991; 11: 157-61.
 Poblete PF, Reyes M, Manahan L, Dalmacio-Cruz A. Rotor's Syndrome: A Family Study. Acta Med Phil. 1967; 4: 64-71.
 Reyes, MP, Caviles AP, Manahan L, Espiritu-Campos L, Campos P. Clinical and Laboratory Study of a Newly Observed Viral Infection in the Philippines: A Preliminary Report. Phil J Intern Med. 1968; 5: 74-9.
 Manahan L, Chavez C, Pascasio FM. HLA Antigens in Filipinos with Ankylosing Spondylitis. Phil J Intern Med. 1986; 24:187-90.

Joint-on-chip platforms: entering a new era of in vitro models for arthritis.

Arthritis affects millions of people worldwide. With only a few disease-modifying drugs available for treatment of rheumatoid arthritis and none for osteoarthritis, a clear need exists for new treatment options. Current disease models used for drug screening and development suffer from several disadvantages and, most importantly, do not accurately emulate all facets of human joint diseases. A humanized joint-on-chip (JoC) model or platform could revolutionize research and drug development in rheumatic diseases. A JoC model is a multi-organ-on-chip platform that incorporates a range of engineered features to emulate essential aspects and functions of the human joint and faithfully recapitulates the joint's physiological responses. In this Review, we propose an architecture for such a JoC platform, discuss the status of the engineering of individual joint tissues and the efforts to combine them in a functional JoC model and identify unresolved issues and challenges in constructing an accurate, physiologically relevant system. The goal is to ultimately obtain a reliable and ready-to-use humanized model of the joint for studying the pathophysiology of rheumatic diseases and screening drugs for treatment of these conditions.

Future Directions of Rheumatology Training According to Saudi Vision 2030: Recommendations From a Saudi Experts Meeting.

BackgroundWorldwide research anticipates that a current shortage of rheumatologists will exacerbate over the next decade, whereas the need for arthritis specialists will continue to escalate. Saudi Arabia (SA) also encounters a limited geographical distribution of rheumatologists and rheumatology fellowship training centres.ObjectiveReporting the Saudi rheumatologists’ advisory meeting conducted in Makkah, SA in January 2020 with the aim to discuss the “Saudi Vision 2030” for rheumatology training programs.Materials and MethodsA meeting of Saudi rheumatology experts and consultants was conducted to address the future directions, challenges, and recommendations of rheumatology training. The 10th Rheumatology Practice Symposium was organised by Alzaidi Chair of Research in Rheumatic Diseases (ZCRD), and conducted in Makkah Commerce Chamber, Makkah, SA on January 28, 2020. More than 30 consultants and rheumatology fellows with five Saudi experts in the field of rheumatology assembled to form 10 recommendations that tackle rheumatology training challenges in SA.ResultsThe meeting recommendations shed light on the clinical practice of rheumatology training in SA; challenges and opportunities in rheumatology fellowship programs; efforts of the Saudi Commission for Health Specialties (SCFHS) to design and implement a competent postgraduate rheumatology training; and challenges with trainers, trainee, and within training centres.ConclusionTo address rheumatology challenges in SA, rheumatology consultants and fellows assembled to form 10 recommendations. The recommendations tackled the challenges of rheumatology fellowship programs and the efforts to implement a competent postgraduate rheumatology training. These recommendations are expected to lead us successfully to fulfil our ambition in the “Saudi Vision of 2030”.

Reporting items for capillaroscopy in clinical research on musculoskeletal diseases: a systematic review and international Delphi consensus.

The level of detail included when describing nailfold videocapillaroscopy (NVC) methods varies among research studies, making interpretation and comparison of results challenging. The overarching objective of the present study was to seek consensus on the reporting standards in NVC methodology for clinical research in rheumatic diseases and to propose a pragmatic reporting checklist. Based on the items derived from a systematic review focused on this topic, a three-step web-based Delphi consensus on minimum reporting standards in NVC was performed among members of the European League against Rheumatism (EULAR) Study Group on Microcirculation in Rheumatic Diseases and the Scleroderma Clinical Trials Consortium. A total of 319 articles were selected by the systematic review, and 46 items were proposed in the Delphi process. This Delphi exercise was completed by 80 participants from 31 countries, including Australia and countries within Asia, Europe, North America and South America. Agreement was reached on items covering three main areas: patient preparation before NVC (15 items), device description (5 items) and examination details (13 items). Based on the available evidence, the description of NVC methods was highly heterogeneous in the identified studies and differed markedly on several items. A reporting checklist of 33 items, based on practical suggestions made (using a Delphi process) by international participants, has been developed to provide guidance to improve and standardize the NVC methodology to be applied in future clinical research studies.

Relevant non-pharmacologic topics for clinical research in rheumatic musculoskeletal diseases: The patient perspective.

The research approach on rheumatic musculoskeletal diseases (RMDs) is challenging and patient involvement is an emerging issue to obtain relevant information to research. Despite growing interest in non-pharmacologic aspects of clinical research in RMDs, the patients' perspectives are currently poorly explored. A cross-sectional no-profit online survey was devised to identify and rank the priorities for clinical research in RMDs according to patients' perspectives. Patients were asked to rate the following topics: food/nutrition, air pollution, smoking, work activity, social participation, physical activity, emotional well-being/stress, alternative medicine, and patient-physician relationship. The survey was disseminated by ALOMAR (Lombard Association for Rheumatic Diseases) between June and October 2019. Two hundred RMD patients completed the survey. The topic most rated 188 (94%) was the doctor-patient relationship, considered very or extremely important. Other topics rated as follows: psychological well-being 185 (92.5%), physical activity 155 (77.5%), nutrition, eating habits 150 (75%), alternative therapies 144 (72%), work activity 144 (72%), environmental pollution 134 (67%), social life 121 (60.5%) and cigarette smoke 119 (59.5%). The topics considered relevant were perceived to be able to influence disease symptoms. Environmental pollution and smoking were considered the most important for RMD prevention in 43.3% and 48.7% respectively. This survey highlights the relevance of several unmet needs and indicates that active patient involvement is essential to design successful translational studies and improve clinical outcomes.

World Arthritis Day 2018 ‐ Perspectives on Rheumatic musculoskeletal diseases

World Arthritis Day 2018 ‐ Perspectives on Rheumatic musculoskeletal diseases

The role of neutrophil extracellular traps in rheumatic diseases.

Rheumatic diseases are a collection of disorders defined by the presence of inflammation and destruction of joints and internal organs. A common feature of these diseases is the presence of autoantibodies targeting molecules commonly expressed in neutrophils. These preformed mediators are released by neutrophils but not by other immune cells such as macrophages. Neutrophils, major players in the host innate immune response, initiate a cell death mechanism termed neutrophil extracellular trap (NET) formation as a way to ensnare pathogens. NETs are also a source of released self-molecules found in rheumatic diseases. Subsequently, research on the role of NETs in the onset, progression and resolution of inflammation in rheumatic diseases has intensified. This Review has two aims. First, it aims to highlight the mechanisms required for the generation of NETs, the research landscape of which is rapidly changing. Second, it aims to discuss the role of neutrophils and NETs in systemic lupus erythematosus, vasculitis (specifically anti-neutrophil cytoplasmic autoantibody-associated vasculitis), rheumatoid arthritis and gout. Our goal is to clarify the field of NET research in rheumatic diseases in the hope of improving the therapeutic approaches utilized for these diseases.

Recommendations for collaborative paediatric research including biobanking in Europe: a Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative

Innovative research in childhood rheumatic diseases mandates international collaborations. However, researchers struggle with significant regulatory heterogeneity; an enabling European Union (EU)-wide framework is missing. The aims of the study were...

Future Directions of Genomics Research in Rheumatic Diseases.

Recent developments in human genome genotyping and sequencing technologies, such as genome-wide association studies and whole-genome sequencing analyses, have successfully identified several risk genes of rheumatic diseases. Fine-mapping studies using the HLA imputation method revealed that classical and non-classical HLA genes contribute to the risk of rheumatic diseases. Integration of human disease genomics with biological, medical, and clinical databases should contribute to the elucidation of disease pathogenicity and novel drug discovery. Disease risk genes identified by large-scale genetic studies are considered to be promising resources for novel drug discovery, including drug repositioning and biomarker microRNA screening for rheumatoid arthritis.

Participation in Clinical Research Registries: A Focus Group Study Examining Views From Patients With Arthritis and Other Chronic Illnesses.

Patient registries have contributed substantially to progress in clinical research in rheumatic diseases. However, not much is known about how to optimize the patient experience in such registries. We assessed patient views, motivations, and potential barriers towards participation in registry research to better understand how registries can be improved to maximize patient engagement. Focus groups were held with 23 patients (mean ± SD age 59 ± 13 years) from the Boston area and led by a bilingual moderator trained in focus group methodology, using a semistructured moderator guide. Three separate focus groups were conducted to thematic saturation: patients with rheumatoid arthritis (RA) who had registry experience, patients with any chronic illness, and Spanish-speaking patients with RA or osteoarthritis. Patients in the latter 2 groups had no prior registry experience. Focus groups were audiotaped and transcribed. Four researchers independently analyzed transcripts using open data coding to identify themes. A normative group process was used to consolidate and refine themes. Seven major themes were identified, including personalization/convenience of data collection, trust and confidentiality, camaraderie, learning about yourself and your disease, altruism, material motivators, and capturing mental health and other elements of the lived experience. We observed distinct differences in the discussion content of the Spanish-speaking patients compared to the English-speaking patients. This study identified patient attitudes towards registry research among those with and without prior experience in a registry. The results provide insight into strategies for registry design to maximize patient engagement, which can lead to more robust registry data.

PMS83 - Utilizing Nordic Registries To Support Health Economics Research In Rheumatic Diseases

PMS83 - Utilizing Nordic Registries To Support Health Economics Research In Rheumatic Diseases

Patient-initiated research in rheumatic diseases in Sweden--dignity, identity and quality of life in focus when patients set the research agenda.

Patients' involvement in healthcare and research has been a growing area in the last few decades. The World Health Organization (WHO) emphasizes the importance of personalized care of the chronic diseases in order to optimize care and treatment for the individual patient (WHO, 2005). In rheumatology, this has been highlighted by different organizations, such as The European League against Rheumatism (EULAR) (de Wit et al., 2013) and Outcome Measures in Rheumatology (OMERACT) (Kirwan et al., 2009), in order to increase the involvement of patients' perspective in care and research. The rheumatic diseases consist of 80–100 diagnoses, and about 1 million people in Sweden are affected. The most common rheumatic diseases are rheumatoid arthritis, ankylosing spondylitis, osteoarthritis and chronic pain/fibromyalgia. The common denominators of the rheumatic diseases are that they are usually long lasting and affect the daily life of the patient, including pain, fatigue and problems with physical activity and function. Previous research has shown that patients' perspectives of rheumatic diseases are insufficiently illuminated and that there are differences between patients' and health professionals' perspectives in relation to the rheumatic diseases and their consequences (Fair, 2003; Gorter et al., 2002; Stinson et al., 2008; Zangi et al., 2011). For example, patients focus on their illness experience and health professionals focus on the diseases in a general way. The quality of an encounter depends on the health professional's communications skills (Fair, 2003). Studies have shown that patients with rheumatic disease have needs that are not met by health services. Unmet needs are described as a lack of continuity, a lack of discussion with patients about the physical consequences of their disease and the need of patients to be treated as a person rather than as a disease (Bergsten et al., 2011; Kjeken et al., 2006; Lacaille et al., 2007; Leung et al., 2009; Sanderson et al., 2011). Patients' interests in health care and in research are highlighted as important aspects of the future of healthcare. The Swedish Rheumatism Association (the national patient organization) and the Foundation of Research and Development at Spenshult decided to carry out a joint project to develop patient-initiated research into the rheumatic diseases. The project aimed to follow the working process of involving patients in a project group and to describe the research issues that were important from the patient's point of view.

A111‐a: Setting Up of Japanese Online Registry of Pediatric Rheumatic Disease

Background/Purpose:Performing quality clinical and translational research in pediatric rheumatic diseases (eg. Juvenile Idiopathic Arthritis (JIA), Child onset Systemic Lupus Erythematosus (cSLE) and Juvenile Dermatomyositis (JDM)) had been difficult due the rarity of these diseases.Methods:Professor Takei, the former chairman of Pediatric Rheumatology Association of Japan (PRAJ), had ordered his working group to set up a new registry system in 2012. We, working group, have set up Japanese online registry for pediatric rheumatic disease in 2014 and have named it as Pediatric Rheumatology International Collaboration Unit Registry (PRICURE).Results:Under this registry, PRAJ will collect basic information (e.g. age of onset, sex, symptoms, major complication, main treatment) about these diseases (JIA, SLE, JDM, Sjogren syndrome, Mixed Connective Tissue Disease, Systemic Sclerosis, Behcet's disease, Vasculitis, Autoinflammatory syndromes, Fibromyalgia).Conclusion:We had set up new registry of pediatric rheumatic diseases. We will show initial data from this registry here.

261 : Outcome of Naïve Actemra therapy in patients with rheumatoid arthritis using multi-plex analysis

Modern research in rheumatic diseases has led to the development of anti-cytokine therapies and some treatment specific biomarkers have been discovered. Our aim in this report is to observe the changes in a set of cytokine/chemokine pre- and post Actemra anti-cytokine therapy in naive rheumatoid arthritis (RA) patients. Thirty-four naive RA patients were selected and treated with 8 mg/kg of Actemra once every 4 weeks. Before, and 16 weeks after therapy, we used Bio-plex beads based array method to measure and analyze patients’ serum cytokine/chemokine levels: IL-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, 101 IL-10, IL-12 (p70), IL-13, IL-15, IL-17, basic FGF, eotaxin, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-BB, RANTES, TNF-α, VEGF. Clinical response according to disease activity score (DAS-28) criteria was determined at week 16 of therapy and clinical efficacy was judged as remission or non-remission (further divided into high, moderate, low) depending on patients’ DAS-28 value. Fifty percent of patients (n = 17) experienced complete remission and the remaining 17 patients were classified as non-remission even though many of them displayed some improvements. A comparison of cytokine/chemokine changes before and after therapy revealed that patients with extremely high levels of inflammatory cytokines (such as IL-1b, IL-8, IL-12p40, IFN-γ) before therapy did not go into remission even though these cytokine levels decreased after treatment. Contrary to this, these cytokines significantly decreased in patients who went into complete remission. These results demonstrate that anti-IL-6 therapy affects many kinds of cytokine/chemokine systems, and suppression of the IL-6 network may lead to clinical efficacy. Further analysis is required to reveal more detailed mechanism of anti-IL-6 therapy.

AB1265 Accuracy of standardized muscuoloskeletal examination of the hand and wrist joints in detecting arthritis in comparison to ultrasound findings in patients attending rheumatology clinics

BackgroundMusculoskeletal (MSK) examination lacks standardization and appropriate validation1,2. Ultrasound (US) has the potential to facilitate early diagnosis of arthritis 3,4. There is a current trend incorporating the use of US...

Podocyte research in rheumatic diseases

Podocytes are glomerular visceral epithelial cells, which function as molecular sieve with foot process (FT) and slit diaphragm (SD) spanning FT, not to allow high molecular weight protein to be filtrated through glomerular capillary loop. Pathological proteinuria is caused by discoordinated tertiary podocyte structure such as disappearance of FT and/or SD, and irreversible glomeular sclerosis is caused by podocyte loss due to cell death and/or detachment from capillary wall. With recent advance of nephrological research technology such as podocyte cell culture system, genetically engineered transgenic mice with podocyte-specific regulation of gene expression, podocyte-associated biomarkers, the new isolation method of glomeruli, laser capture microdissection, multiphoton imaging and extracellular flux analyzer, new findings of pathogenesis of glomerular lesions will be expected, not only in primary glomerulonephritis, but also in secondary glomerulonephritis or glomerulopathy due to rheumatic diseases.