Autoimmune Rheumatologic Diseases Research Articles

The development of anticyclic citrullinated peptide (anti-CCP) antibody following severe COVID-19.

The dysregulated immune response is one of the cardinal features of severe coronavirus disease 2019 (COVID-19). This study was conducted to clarify the occurrence of autoantibodies (AABs) associated with systemic autoimmune rheumatic diseases (SARDs) in hospitalized patients with a moderate, severe, and critical form of COVID-19. The serum samples obtained from 176 hospitalized COVID-19 patients were investigated in this study, including patients with moderate (N = 90), severe (N = 50), and critical (N = 36) forms of COVID-19. Also, the serum samples collected from healthy subjects before the COVID-19 pandemic were used as controls (N = 176). The antinuclear antibodies (ANAs), antidouble-stranded DNA (anti-dsDNA), cytoplasmic-anti neutrophil cytoplasmic antibody (c-ANCA), perinuclear ANCA (p-ANCA), antiphospholipid antibodies (aPLs), and anticyclic citrullinated peptide (anti-CCP) occurrence was evaluated using a solid-phase enzyme-linked immunosorbent assay (ELISA). The results showed that the occurrence of ANAs, anti-dsDNA, anti-CCP, c-ANCA, and p-ANCA was significantly higher in the COVID-19 patients compared to serum obtained from healthy subjects (p < .0001, p < .0001, p < .0001, p < .05, and p < .001, respectively). The positive number of anti-CCP tests increased significantly in severe COVID-19 compared to the moderate group (p < .01). Our study further supports the development of autoantibodies related to systemic autoimmune rheumatologic diseases. To the best of our knowledge, this is the first study with a large sample size that reported the occurrence of anti-CCP in a severe form of COVID-19.

High Prevalence of IDH Mutation in Myeloid Neoplasm with Concomitant Autoimmune Rheumatic Disorders

BACKGROUND: The association between myeloid neoplasm (MN) and autoimmune rheumatological diseases (AIRD) is increasingly recognized. Furthermore, prolonged cytotoxic disease modifying anti-rheumatological drugs (DMARD) for AIRD may potentially induce therapy-related MN (t-MN), a lethal haematological malignancy with dismal outcomes. However, the genetic association and mechanism underpinning immune dysfunction in patients with between MN and AIRD is not fully elucidated. METHODS: In this collaborative study across the two disciplines and continents (Australia and USA), we assessed the burden of well-defined AIRD in a large cohort of MN (n=1702) that included myelodysplastic syndrome (MDS; n=861), acute myeloid leukaemia (AML; n=640), myeloproliferative neoplasm (MPN; n=89) and MDS/MPN overlap (n=112). We characterized the cytogenetic and mutational landscape of MN with AIRD (MN-AIRD) and without AIRD. In order to assess the mechanistic link between AIRD and MN, we investigated the bone marrow microenvironment in MN-AIRD vs. well-curated age matched controls. RESULTS: 132 (7.75%) of MN (n=1702) had concomitant AIRD. Although association of AIRD was observed across all subtypes of MN, enrichment of AIRD was observed in patients with MDS, MDS/MPN and MPN compared to AML (9.5% vs. 9.8% vs 10.1% vs. 4.67%; P &amp;lt;0.001). Inflammatory arthritis (n=65; 49.24%) followed by inflammatory connective tissue diseases (CTD, n=23; 17.42%), polymyalgia rheumatica (PMR, n=18; 13.63%) and vasculitis (n=16; 12.12%) were the most prevalent AIRD in the MN cohort. Notably, 87.7% of inflammatory arthritis were rheumatoid arthritis (RA; n=57). Striking survival differences were observed between t-MN without AIRD and MN-AIRD (14.0 vs. 33.7 months; P &amp;lt;0.0001) and t-MDS no-AIRD and MDS-AIRD (16.1 vs. 33.4 months, P =0.001). Chromosomal abnormalities including complex karyotype, monosomal karyotype, del 5q, del 7q, marker chromosome and TP53 mutations were enriched in t-MN following independent primary cancer (t-MN without AIRD). However striking enrichment of IDH1 and IDH2 (henceforth referred as IDH) mutations in MN with AIRD compared to MN without AIRD (20% vs. 11%, P =0.02), particularly in MDS-AIRD compared to MDS without AIRD (21% vs. 7%; P =0.001). The enrichment of IDH mutations were particularly prevalent in in MN cases with RA compared to other AIRD (34% vs. 11%; P =0.005). While IDH mutations were observed in only 8% and 6% of PMR and inflammatory CTD patients, respectively. Surprisingly higher frequency of IDH mutations was observed in evaluable seronegative compared to seropositive RA patients (62% vs. 0%; P =0.006). We also observed that majority of IDH mutations in seronegative RA were IDH1 (6/8; 75%) while IDH2 mutations were common other AIRD (6/6; 100%) ( P =0.009). We also assessed the impact of DMARDs on genomics of myeloid neoplasm. The majority of MN-AIRD patients treated with methotrexate did not harbor poor risk cytogenetic and mutation features such as complex karyotype, monosomal karyotype, del 5q, del 7q and/or TP53 mutation. In contrast, the majority of patients who had cyclophosphamide harbored high risk cytogenetic and molecular features. To assess pathogenic mechanisms linking MN and AIRD, we evaluated bone marrow microenvironment in myeloid neoplasm patients with and without AIRD. Bone marrow mesenchymal stromal cells (MSC) isolated from MN-AIRD were highly senescent compared to age matched healthy controls, MN without AIRD, with defective proliferating and differentiation capacity of MN-AIRD and secretion of highly proinflammatory cytokines and chemokines. CONCLUSIONS: In summary, our key findings include: 7.8% of MN were associated with AIRD with stronger association of AIRD with MDS and MDS/MPN compared to AML and striking enrichment of IDH mutations in MN with inflammatory arthritis compared to MN with other AIRD (29% vs 11%; P =0.02), especially in seronegative RA compared to seropositive RA (62% vs. 0%; P =0.006). In contrast to cyclophosphamide and azathioprine, majority of cases treated with methotrexate did not harbor poor risk cytogenetic and/or TP53 mutation. As methotrexate is widely used as an anchor drug in many rheumatology treatment regimens, this is a highly significant finding of clinical relevance.

Increased Prevalence of Autoimmune Rheumatologic Diseases in Patients With Primary Hyperparathyroidism.

Background Parathyroid hormone (PTH) and Dickkopf-related protein 1 (DKK-1) have been mentioned together at the intersection of autoimmune rheumatologic diseases (ARDs) and osteoimmunology. However, few studies have evaluated the association between primary hyperparathyroidism (PHPT) and ARDs. Methodology This retrospective study included 225 PHPT patients and 386 patients with thyroid nodules as a control group. The electronic hospital records of all patients were screened going back nine years for the presence of ARDs. Patients who were diagnosed at least three months ago, had complete serologic tests, and were continuing with rheumatologic follow-up were included. Results The prevalence of ARDs in the PHPT group was 9.77% (22/225), while the prevalence of ARDs in the CG was 1.04% (4/386, p < 0.001). The prevalence of rheumatoid arthritis in the PHPT group was 4.4% (10/225), ankylosing spondylitis 3.1% (7/225), systemic lupus erythematosus 0.88% (2/225), Behçet's disease 0.88% (2/225), and mixed connective tissue disease 0.44% (1/225). Of the 22 patients with ARDs, 21 (95.45%) were diagnosed before they were diagnosed with PHPT, and the median time from diagnosis with ARD to the onset of PHPT was 36 months (interquartile range = 61.5). Logistic regression analysis showed a positive correlation between the duration of PHPT and ARDs (odds ratio (OR) = 1.06; 95% confidence interval (CI) = 1.02-1.09, p < 0.001) and a negative correlation between ARDs and calcium levels (OR = 0.26; 95% CI = 0.09-0.79, p = 0.018). Conclusions The prevalence of ARDs increased in PHPT patients and PHPT accompanying ARDs developed after rheumatologic disease. ARDs with PHPT are cases with a prolonged duration of PHPT and mildly elevated calcium, probably preceded by parathyroid hyperplasia. Therefore, the factors that cause ARDs may trigger a process that leads to mild PHPT.

OA21 Are novel anti-IL5 biologics triggering rheumatoid arthritis?

Abstract Introduction Biologics are being increasingly used for the treatment of inflammatory diseases across a wide range of specialties. Of particular interest, it is well established that monoclonal therapy for one inflammatory disease may paradoxically trigger another inflammatory disease, for example TNF therapy triggering multiple sclerosis, and IL-17 therapy for psoriasis linked to inflammatory bowel disease. Here we report the case of a patient who developed anti-CCP positive rheumatoid arthritis soon after starting a novel anti-IL-5 biologic used to treat his severe eosinophilic asthma. Case description This 77-year-old gentleman with a background of severe eosinophilic asthma presented to our early arthritis clinic 18 months after having been started on either mepolizumab or a long-acting IL-5 blocker as part of a clinical trial. Prior to starting biologics, his asthma had been poorly controlled with salbutamol, Fostair, tiotropium inhalers and low-dose corticosteroids. Within weeks, he developed symmetrical arthralgias involving small joints, particularly his wrists and knuckles, as well as significant early morning stiffness lasting more than one hour. On examination, he had clinical synovitis in the wrists and metacarpophalangeal joints bilaterally, as well as right shoulder capsulitis with limiting range of motion. Blood tests revealed a raised CRP of 24mg/L, WCC 8.77 10*9/L, rheumatoid factor of 263.2 iu/mL and anti-CCP antibody of &amp;gt; 300 U/mL. Ultrasound imaging of the hands and wrists bilaterally showed grade II grey scale with grade II power Doppler, and some erosions in the wrists bilaterally. There was hypoechogenicity of the left extensor carpi ulnaris tendon with some associated grey scale and power Doppler. He was diagnosed with rheumatoid arthritis as per the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) diagnostic criteria and started on prednisolone 10mg daily as a rescue therapy to reduce the inflammation, followed by sulfasalazine one month later as the disease modifying agent. He was followed-up in rheumatology clinic two months later and showed significant improvements: the pains and swellings of his joints had settled, and whilst he still gets early morning stiffness this is not so debilitating. His inflammatory markers had also resolved with CRP &amp;lt;5.0mg/L and WCC 9.31 10*9/L. Discussion We report a case of new onset rheumatoid arthritis associated with the commencement of an anti-IL-5 biologics for severe asthma. To our knowledge, this has only been reported in the literature on a handful of occasions and in each case the patients were on oral corticosteroids with the majority being weaned off in parallel to developing the new symptoms [1,2]. As such there has been a challenge in associating the development of arthritis with the initiation of the anti-IL-5 biologic, as opposed to the withdrawal of steroids unmasking a pre-existing disease. Emerging evidence has implicated a core role for regulatory eosinophils (rEos) in the resolution of rheumatoid arthritis (RA) [3]. In murine models of RA, an expansion of rEos in the synovium was sufficient to bring about remission of arthritis. Inhibiting the IL-5 pathway would subsequently induce relapse of the arthritis [3]. Further studies are required to characterise the significance of these findings in clinical cohorts and to identify whether there is an actual association between novel anti-IL-5 biologics and rheumatoid arthritis. Key learning points Our improved understanding of the mechanisms underlying inflammatory diseases has led to the increased use of biological therapies in treating these conditions. However, these therapies may be paradoxically triggering other inflammatory diseases, particularly autoimmune rheumatological diseases. Here we have identified a patient who developed anti-CCP positive rheumatoid arthritis soon after commencing a novel anti-IL5 for severe asthma. Mechanistically, this may be related to the depletion of regulatory eosinophils tipping the balance towards pro-inflammatory pathways in the synovial joints. More work is required to identify whether this phenomenon is being more widely observed in clinical practice, and if so how we can best manage it going forwards.

Automatic Classification of Antinuclear Antibody Patterns With Machine Learning.

Antinuclear antibodies (ANA) are important diagnostic markers in many autoimmune rheumatological diseases. The indirect immunofluorescence assay applied on human epithelial cells generates images that are used in the detection of ANA. The classification of these images for different ANA patterns requires human experts. It is time-consuming and subjective as different experts may label the same image differently. Therefore, there is an interest in machine learning-based automatic classification of ANA patterns. In our study, to build an application for the automatic classification of ANA patterns, we construct a dataset and learn a deep neural network with a transfer learning approach.We show that even in the existence of a limited number of labeled data, high accuracies can be achieved on the unseen test samples. Our study shows that deep learning-based software can be built for this task to save expert time.

Síndrome metabólico en autoinmunidad. Análisis transversal epidemiológico de una interacción compleja en una población latinoamericana

The link between metabolic syndrome and autoimmune disorders leads to increased cardiovascular morbidity and mortality. A cross-sectional study was conducted in 2018 with a sample of 253 patients: 140 with rheumatoid arthritis, 68 with lupus, and 45 with psoriasis. Their variables were compared to controls with similar characteristics (n = 123). ANOVA was used for quantitative variables, and chi-square for qualitative ones. The mean age found was 43.69±9.0; 280 (74.5%) were female patients. Metabolic syndrome was found in 55.5% of patients with psoriatic arthritis, 48.5% of lupus patients, 31.4% in rheumatoid arthritis, and 34.9% in controls (p = 0.007). The components of metabolic syndrome showed a larger waist circumference in lupus patients (p = 0.001) and hypertension in psoriasis patients (p = 0.001). It is concluded that the presence of metabolic syndrome should be investigated in patients with autoimmune diseases, as there is a significant association between it and autoimmune rheumatologic diseases.

Dermatomyositis: A Case Report and Review of a Rare Autoimmune Inflammatory Disease

Dermatomyositis is a chronic progressive autoimmune disease of unknown etiology and rare occurrence worldwide. It is an immunologically mediated idiopathic inflammatory disease in which damage to small blood vessels contributes to injury and inflammation of muscle and skin. Dermatomyositis belongs to a heterogeneous group of three autoimmune rheumatological diseases termed idiopathic inflammatory non-suppurative myopathies, with polymyositis and inclusion body myositis as other component diseases.&#x0D; Dermatomyositis and polymyositis typically show characteristic clinical features of autoimmune inflammatory diseases and association with autoantibodies, HLA-DR genotype, and other autoimmune diseases. While it is known that inflammation plays a significant role in the pathogenesis of these diseases, its role in inclusion body myositis remains unclear. Overlapping forms of inflammatory myopathies that are poorly differentiated and defy a precise classification have also been identified. However, the clinical response to steroids and other immunosuppressive agents may help distinguish the subtypes of inflammatory myopathies from one another.&#x0D; Dermatomyositis is further described as a multisystemic rheumatologic disease presenting with muscular and cutaneous symptoms. It is associated with malignancy in 20 – 25% of patients. Dermatomyositis occurs in children and adults, with a higher incidence observed in women. Diagnosis is usually made from clinical manifestations, elevated blood enzymes, autoantibody testing, electromyography (EMG), and muscle biopsy. The diagnosis, however, remains challenging in third-world countries. There is no known cure for dermatomyositis. However, corticosteroids and other immunosuppressive agents, and intravenous immunoglobins are routinely used for treatment.&#x0D; The index patient in this review is a 22-year-old Afro-Caribbean woman whose presentation met the probable-to-definite criteria for diagnosis based on the Bohan and Peter Classification Criteria. This article is a case report and a detailed review of the autoimmune inflammatory disease known as dermatomyositis that can be used to teach about the disease condition.

Aetiologies of Acute Complications in Autoimmune Rheumatologic Diseases: A Hospital-Based Cross-Sectional Study.

Autoimmune rheumaticdiseases (ARD) present unique challenges in clinical practice. Many of them present in medical emergencies in an unstable state and need immediate evaluation for further plans of action. The clinical conundrum is to distinguish between sepsis, disease flare, or Addisonian crisis (AC) (secondary to steroid withdrawal). This may be further complicated by overlapping clinical features like shock/fever and the coexistence of a combination of the above pathophysiologic mechanisms (e.g. AC with sepsis or AC with disease flare). The known biomarkers may not perform optimally to distinguish them and additional supportive investigations like imaging, cultures, autoimmune serological markers, etc. are needed. Ultimately the boundaries between "the art of medicine" and "the science of medicine" may get blurred, as the established literature evidence falls short and the expert opinion is needed in a time-sensitive manner. In this pragmatic study, researchers have attempted to explore the presentation of rheumatologic emergencies on the above three differentials (sepsis, disease flare, and AC). In this hospital-based cross-sectional study, adult patients(age >18 years) with ARDwhohad unplanned hospital admission due to acute worseningwere enrolled. This study was conducted over one year, after getting the Institutional Human Ethics Committee's approval. All relevant hematological, immunological, and hormonal parameters(specifically morning cortisol) were collected and analyzed. The aim was to find the individual and combined prevalence of sepsis, disease flare, or AC in this study group. Forty-onepatients were analyzed, with females in the majority (95%) and the dominant age group being 26-49 years (56.1%). A majority had a diagnosis of rheumatoid arthritis (RA) (56.1%) or systemic lupus erythematosus (SLE) (31.7%); the rest were other connective tissue diseases (12.2%). High-risk Quick Sequential Organ Failure Assessment score (qSOFA) score 2-3 was present in 29.3% while the rest had low-risk scores (qSOFA score 0-1). Thirty-two percenthad severe disease activity, 46% had mild to moderate disease activity, and 22% of patients had no disease activity. While 78% of patients had low procalcitonin (PCT) values <0.5 microgm/L (low risk of sepsis), 15% had <20 microgm/L, and 7% percentage of patients had serum levels >20 microgm/L (high risk of sepsis). A total of 73.2% of patients had no evidence of infection while 26.8% had either microbiological/radiological evidence of infection. Only 7% of all patients had the presence of an AC. qSOFA scores didn't statistically correlate with a diagnosis of infection or AC but positively correlated with PCT and C-reactive protein (CRP) values. Serum PCT didn't correlate with the presence of infection with statistically significance (p-value 0.217). Infections and sepsis are the most important considerations in the emergency presentations of ARDs. Disease flare and AC are also important differentials. Current inflammatory biomarkers like serum CRP and PCT may be less valuable for discriminating between infectious and non-infectious sepsis, especially in chronic inflammatory diseases like ARDs. qSOFA scores may have a prognostic role with less discriminant value. Management of ARD emergencies needs better biomarkers and more research is warranted.

Role of vitamin D in autoimmune rheumatological diseases

Introduction: Vitamin D is a hormone synthesized in the skin, by the presence of the "precursor molecule 7-dehicrocholesterol" whose action depends directly on the stimulus of ultraviolet rays for the production of cholecalciferol. It has several functions including a fundamental role in mediating the response of the immune system, plays modulatory actions, counteracts inflammatory, oxidative and fibrotic activity, and consequently regulates autoimmune tissue lesions. As it possesses an immunomodulatory property, is related to the appearance and progression of autoimmune disorders. Objective: To describe the role of vitamin D in autoimmune rheumatologic diseases. Methods: A narrative review was performed, collecting information from January 2019 to January 2023 in scientific databases such as: Pubmed, Scopus, Web of Science, and Google Scholar, using keywords. Results: Vitamin D in autoimmune rheumatic diseases influences the control and decrease of inflammatory activity, slows its speed of progression and improves clinical manifestations, although there is no total consensus on the mode of use, however, its supplementation has a great benefit. Conclusions: The role of Vitamin D in autoimmune rheumatic diseases varies according to the underlying pathology, in combination with bisphosphonates it can improve bone mineral density in spondyloarthropathies, prevent osteoporosis, improve the clinical picture of SLE and Systemic Sclerosis, but it can increase antibody levels in Connective Tissue Diseases.

The diagnostic trajectories of Danish patients with autoimmune rheumatologic disease associated interstitial lung disease: an interview-based study

ABSTRACT Background Autoimmune rheumatologic disease associated interstitial lung diseases (ARD-ILD) are rare conditions and the association between ARDs and respiratory symptoms often goes unrecognised by ARD patients and general practitioners (GPs). The diagnostic trajectory from the first respiratory symptoms to an ARD-ILD diagnosis is often delayed and may increase the burden of symptoms and allow further disease progression.The aim of this study was to 1) characterise the diagnostic trajectories of ARD-ILD patients and to 2) identify barriers for obtaining a timely ILD diagnosis based on the experiences and perceptions of both patients and healthcare professionals. Method Semi-structured qualitative interviews were conducted with Danish ARD-ILD patients, rheumatologists, pulmonologists and ILD nurses. Results Sixteen patients, six rheumatologists, three ILD nurses and three pulmonologists participated. Five characteristics of diagnostic trajectories were identified in the patient interviews: 1) early referral to lung specialists; 2) early delay; 3) delay or shortcut depending on specific circumstances; 4) parallel diagnostic trajectories connected late in the process; 5) early identification of lung involvement without proper interpretation. With the exception of early referral to lung specialists, all of the diagnostic trajectory characteristics identified led to delayed diagnosis. Delayed diagnostic trajectories resulted in patients experiencing increased uncertainty. Inconsistent disease terminology, insufficient knowledge and lack of awareness of ARD-ILD among central healthcare professionals and delayed referral to ILD specialists were main contributors to the diagnostic delay identified by the informants. Conclusion Five characteristics of the diagnostic trajectories were identified, four of which led to diagnostic delay of ARD-ILD. Improved diagnostic trajectories can shorten the diagnostic trajectory and increase early access to appropriate specialist medical care. Improved awareness and expertise in ARD-ILD across different medical specialties, especially among GPs, may contribute to more efficient and timely diagnostic trajectories and improved patient experiences.

Immune-related adverse events after immune checkpoint inhibitor exposure in adult cancer patients with pre-existing autoimmune diseases.

Immune checkpoint inhibitor (ICI) therapy can predispose patients to immune-related adverse events (irAEs) and autoimmune disease (AD) flare-ups, but the characteristics of irAEs among patients with pre-existing ADs are largely unknown. We conducted this study to determine the clinical courses, irAEs, AD flares, treatment, and outcomes of patients with AD on ICIs. This was a retrospective study of adult cancer patients at a large cancer center who were diagnosed with ADs before undergoing ICI therapy. Patients' clinical courses, complications, treatments, and outcomes related to both ADs flares and irAEs were collected and analyzed. The study included 197 patients. Most (55.4%) were women. Melanoma comprised the highest proportion (28.4%) of malignancies, and most (83.8%) patients received PD-1/PD-L1 inhibitors. Fifty (25.3%) patients developed a new irAE after starting ICI therapy, while 29 (14.7%) patients had an AD flare-up. Patients with inflammatory bowel disease had the highest incidence of AD flare-ups (31.7%), while patients with Hashimoto hypothyroidism had the highest incidence of new irAEs (39.2%). Patients with inflammatory bowel disease had more severe adverse events. In our cohort, patients with a new diagnosis of irAE were treated with immunosuppressive therapy. AD flares were managed similarly. With regard to irAE manifestations, the most common presentations were colitis (24 [12.1%] patients), hepatic transaminase elevations (8 [4%] patients), and pneumonitis (7 [3.5%] patients). Our findings suggest that patients with gastrointestinal and rheumatologic ADs had a higher incidence of AD flare-ups, while patients with Hashimoto hypothyroidism and neurologic ADs had a higher incidence of new irAEs. Patients with prior ADs experiencing flare-ups or new irAEs after ICI therapy tend to require aggressive immunosuppressive treatment. Thorough evaluation of baseline disease status, appropriate medical management before ICI therapy, and early recognition of inflammatory exacerbation may help ensure long-term success in treating and improving outcomes in these patients.

Cardiovascular health worsening in patients with autoimmune rheumatological diseases during the COVID-19 pandemic.

Rheumatic autoimmune diseases are associated with a myriad of comorbidities. Of particular importance due to their morbimortality are cardiovascular diseases. COVID-19 greatly impacted the world population in many different areas. Patients with rheumatic diseases had to face changes in their healthcare, in addition to unemployment, a decrease in physical activity, social isolation, and lack of access to certain medications. This review summarizes the impact of COVID-19 pandemic on cardiovascular risk factors, comorbidities, and unhealthy behaviors in patients with rheumatic inflammatory autoimmune diseases, particularly focused on rheumatoid arthritis and systemic lupus erythematosus. Searches were carried out in MEDLINE/PubMed and Scopus from August to December 2022. Four reviewers screened the title and abstract of retrieved records. Potentially eligible reports were then reviewed in full text. Differences were reconciled by either consensus or discussion with an external reviewer. During the COVID-19 pandemic, patients with rheumatic diseases showed an increase in the prevalence of mental health disorders (43.2-57.7%), reduced physical activity (56.8%), and a worsening in eating behaviors. Alcohol intake increased (18.2%), especially in early phases of the pandemic. Smoking prevalence decreased (28.2%). Dyslipidemia and hypertension showed no changes. The pandemic and lockdown affected rheumatic patients not only in disease-related characteristics but in the prevalence of their cardiovascular comorbidities and risk factors. Lifestyle changes, such as healthy eating, physical activity, and optimal management of their rheumatic diseases and comorbidities, are essential to manage the long-lasting consequences of the COVID-19 outbreak. Key Points • During the COVID-19 pandemic, anxiety, depression, sedentarism, obesity, and a worsening in eating behaviors increased. •Patients with rheumatic diseases and comorbidities have worse clinical outcomes and a higher cardiovascular disease burden than those without them. •Comparative studies are necessary to precisely elucidate the pandemic's impact on the prevalence of cardiovascular disease, risk factors, and comorbidities in patients with rheumatoid arthritis and systemic lupus erythematosus.

Disease Characteristics of Seropositive Neuromyelitis Optica Spectrum Disorder in a Turkish Cohort

Objective To determine the clinical, demographic and imaging characteristics of a Turkish cohort with aquaporin-4-antibody positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) from a single center. Background NA. Design/Methods 35 patients seen between January-2008 and December-2020 with a diagnosis of AQP4-IgG+NMOSD who could be studied in detail were included in the study. Inclusion criteria for patients with NMOSD diagnosis was defined according to International Consensus Diagnostic Criteria (Wingerchuk et al.2015) and all patients were confirmed for AQP4-IgG positive serology at least once by Euroimmune transfected cells assay (EU90). Demographic, clinical and MRI data were obtained retrospectively. Results The female-to-male ratio was 16.5: 1. The mean age of disease onset was 26,16±10,96 years for patients with optic neuritis onset (n:12), and 43.17±11,95 for the subgroup that started with transverse myelitis (TM) (n:16), confirming a significant difference of age at onset according to the first attack type (p &lt; 0.001). The mean age at onset in 5 patients with area postrema syndrome was 35,74±16,83. Half of the total attacks occurred within the first year of disease onset (98/196). The mean time to diagnosis was 2,98±5,78 years after the initial attack. Disease duration was 10,06±9,76 years. Cerebrospinal fluid oligoclonal bands were studied in 24 and were positive in 25%. An autoimmune rheumatologic disease comorbidity was present in 34.5% of the patients. In patients with MRI disclosing = 2 McDonald dissemination in space criteria (spinal included) was more common in TM group and correlated with a higher disability (EDSS) score. Conclusions Turkish AQP4-IgG+NMOSD patients whose disease start with optic neuritis have an earlier age of onset compared to the ones with TM onset. Half of the total attacks occur within the first year of disease onset. Patients with = 2 McDonald MRI dissemination in space criteria were more common in the TM group and had a higher disability (EDSS) score.

Immune-related adverse events in patients with pre-existing autoimmune rheumatologic disease on immune checkpoint inhibitor therapy

IntroductionImmune checkpoint inhibitors (ICIs) enhance the immune system’s ability to target and destroy cancer cells, but this non-specific immune overactivation can result in immune-related adverse events (irAEs). Patients with underlying autoimmune diseases were excluded from the original ICI clinical trials because of the theoretical risk of irAEs. This study aimed to evaluate the risk of irAEs in patients with pre-existing rheumatologic diseases on ICIs, impact of anti-rheumatic therapy on irAEs, and malignancy outcomes.MethodsWe performed a retrospective chart review of patients with a pre-existing rheumatologic diagnosis receiving ICIs at the University of North Carolina from 2014 to 2019. Risk differences (RD) and asymptotic 95% confidence intervals (95% CIs) using a continuity correction along with odds ratios (OR) and exact 95% CIs were produced between pre-specified risk factors and flares of the underlying rheumatologic disease and/or irAEs. Kaplan–Meier survival estimates for time to unfavorable cancer response between subsets of patients were compared using the log-rank test.ResultsWe identified 45 patients receiving an ICI with an underlying rheumatologic diagnosis, including 22 with rheumatoid arthritis (RA). Overall, 13 patients (29%) had a flare of their autoimmune disease, 20 patients (44%) had a new-onset irAE, and 27 (60%) had either a flare or new-onset irAE. Patients with RA had higher risk of flares compared to those with other rheumatologic disorders (45% vs 13%, RD 32%, 95% CI 2.0–56.8); all RA flares were ≤ grade 2 and treated in the outpatient setting. Concurrent treatment of the rheumatologic disease at the start of ICI therapy was not associated with a reduced risk of flare (OR 0.86, 95% CI 0.19–3.76) or new onset irAE (OR 3.21, 95% CI 0.83–13.6) compared to those not on anti-rheumatic medications. Anti-rheumatic therapy did not impact time to unfavorable malignancy outcome (p = 0.52).ConclusionThe majority of our study cohort experienced a flare or new onset irAE with ICI treatment. Treatment with anti-rheumatic therapy did not prevent disease flares or new onset irAEs, but did not negatively impact malignancy outcomes. Research is needed to determine safe anti-rheumatic therapy options to prevent flares and irAEs that do not interfere with malignancy outcomes.

S963 Characteristics, Treatment and Outcome of Patients With Previously Diagnosed Autoimmune Disease After Immune Checkpoint Inhibitor Exposure

Introduction: Immune checkpoint inhibitors (ICI) can predispose to immune related adverse events (irAEs) and autoimmune disease (AD) flare-ups. irAE characteristics among patients with previously diagnosed AD have not been well studied. We aim to describe the clinical course, complications, treatment, and outcomes of patients with AD on ICIs. Methods: This is a retrospective chart review of adult cancer patients at the MD Anderson Cancer Center diagnosed with AD (based on ICD code) prior to the first dose of ICI treatment between 01/01/2010 and 04/30/2021. Patients’ clinical course, treatment and outcomes related to both AD and irAE were collected and analyzed. Results: A total of 197 patients were included in this study. A majority of our sample were female (55.4%) most frequently having melanoma (28.4%) and receiving PD-1/L1 inhibitors (83.7%). Forty-two patients (21.3%) developed a new irAE after starting immunotherapy, while 29 had an AD flare (14.7%). Patients with inflammatory bowel disease (IBD) had the highest rate of AD flare (31.7%), while patients with hypothyroidism had the highest incidence of new irAEs at 39.2%. Patients with IBD had more severe adverse events however with a median CTCAE grade of 3.5. In our cohort, all patients that were diagnosed with a new irAE were treated with immunosuppressive therapy. AD flares were managed similarly. With regards to irAE manifestations, colitis was the most common presentation in our cohort; at least 24 patients (23.2%) excluding those patients with a diagnosis of (IBD and microscopic colitis) had this type of complication. This was followed by pneumonitis in 9 patients (4.5%) and transaminitis in 7 patients (3.5%). Conclusion: Studies on the correlation between prior AD and immunotherapy are still lacking. Our findings suggest that patients with GI and rheumatologic ADs had higher incidence of AD flare up than new irAE development, while patients with thyroid and neurologic ADs appeared to have higher incidence of new irAEs compared to AD flare. Patients with prior AD experiencing a flare or a new irAE after immunotherapy tend to require more aggressive immunosuppressive treatment for symptom control. Thorough evaluation of baseline disease status, the appropriate medical management prior to ICI, and early recognition of inflammatory exacerbation could be key factors to ensure long-term success with treating and improving outcomes of these patients. Table 1. - Summary of irAE characteristics per Autoimmune Disease system, N=197 Autoimmune Disease per system Active AD status before ICI, N (%) On medical Rx before ICI, N (%) Flare up after ICI, N (%) Type of ICI Peak CTCAE grade of flare up (median, IQR) Required IMS for flare up, N (% of those that had flare) New irAE in different organ from AD, N (%) Peak CTCAE of irAE (median, IQR) IMS required for irAE, N (% of those that had irAE) Hematological ITP (N=2) 0 (0) 0 (0) 0 (0) PD1/L1=2 (100) N/A N/A 0 (0) N/A N/A Endocrine Hypothyroidism (N=51) 0 (0) 51 (100) 2 (3.9) Combined= 9 (17.6); PD1/L1=42 (82.3) Grade 2 in 1 (50) 0 (0) 20 (39.2) 2(1-3) 20 (100) Neurological MS-TM-GBS (N=27) 27 (100) 3 (11.1) 2 (7.4) Combined= 1 (3.8); PD1/L1= 21 (77.7); CTLA-4=5 (18.5) N/A 2 (100) 5 (18.5) 1(1-1.5) 5 (100) Rheumatological Rheumatoid A (N=58) 0 (0) 58 (100) 15 (25.8) Combined= 1 (1.7); PD1/L1= 57 (98.2); N/A 15 (100) 12 (20.6) 2.5(2-3) 9 (75) Gastroenterological (N=30) 0 (0) 30 (100) 10 (33.3) Combined=3 (10); PD1/L1=27 (90) N/A 10 (100) 5 (16.6) N/A 5 (100) Microscopic Colitis (N=10) 0 (0) 3(30) 8 (80) PD1/L1=10 (100) N/A 8 (100) 1 (10) N/A 1 (100) Celiac Disease (N=1) 0 (0) 0 (0) 0 (0) PD1/L1=1 (100) N/A N/A 0 (0) N/A N/A IBD (N=19) 1 (5.2) 10 (52.6) 6 (31.7) Combined=3 (15.7); PD1/L1=16 (84.2) N/A 6 (100) 4 (21) 3.5(3-4) 4 (100) Footnote: IMS=immunosuppressant. ITP=Immune Thrombocytopenic Purpura. MS=Multiple Sclerosis. TM= Transverse Myelitis. GBS=Guillain Barre Syndrome. IBD=Inflammatory Bowel Disease.*all the patients had baseline low activity at the time of ICI initiation. Flare up occurred when the symptoms progressed from baseline activity.

Subcutaneous immunoglobulin therapy for refractory skin thickening in rapidly progressive systemic sclerosis: A case report and literature review.

The use of immunoglobulin is a therapeutic option with increasing evidence of efficacy for different rheumatologic autoimmune systemic diseases. Some studies concerning immunoglobulin use in systemic sclerosis have been published with encouraging results. We present the case of a young woman diagnosed with rapidly progressive diffuse cutaneous systemic sclerosis, refractory to therapy with methotrexate and rituximab, which presented a relevant skin improvement after one year of subcutaneous immunoglobulin (2 g/kg cumulative monthly dose, refracted in weekly administrations). Furthermore, a narrative literature review of the evidence for alternative treatments with a focus on immunoglobulin use for systemic sclerosis skin involvement was carried out.

Value of speckle tracking echocardiography for detection of clinically silent left ventricular dysfunction in patients with systemic lupus erythematosus

Background and Aims : Background: SLE is a chronic autoimmune inflammatory rheumatological disease. Characterized by autoantibodies directed against nuclear antigens. It is a disease of young women, with a peak incidence between the ages of 15 and 40 with a female: male ratio of 9:1. Cardiac involvement in patients with SLE is common. Subclinical involvement is more common than Clinically apparent cardiomyopathy or myocarditis Aim: Assess LV function in asymptomatic SLE patients by conventional, speckle tracking and tissue Doppler echocardiography.

A Safety Analysis of Programmed Death 1 Pathway Inhibitors in Patients With Solid Tumor Malignancies and Preexisting Autoimmune Disease.

The aim of this study was to characterize the safety of programmed death 1 inhibitors in patients with preexisting autoimmune disease. A medical records review study was conducted on adults with solid tumor malignancies who received ≥1 dose of pembrolizumab or nivolumab at Emory Healthcare from September 4, 2014 until December 31, 2019. All autoimmune patients were included (n = 77), whereas the nonautoimmune patients were randomized and the first 156 patients were included in a 2:1 ratio to autoimmune patients. The primary objective was the comparison of incidence of immune-related adverse events (irAEs) between patients with preexisting autoimmune disease and those without. Secondary objectives included irAE characterization, irAE treatment, and survival analyses. Preexisting autoimmune disease was controlled in all of the autoimmune patients before immunotherapy initiation. The rate of irAE was 32.7% in the nonautoimmune group and 42.9% in the autoimmune group (odds ratio, 0.65; 95% confidence interval, 0.37-1.14; p = 0.130). In the patient population diagnosed with a rheumatologic autoimmune disease, 23.81% of irAEs were considered to be a flare of their preexisting autoimmune disease. Less patients in the autoimmune group experienced a grade ≥3 irAE (21.21% vs 37.25%, p = 0.379) and received systemic corticosteroids (54.55% vs 67.35%, p = 0.241) for the treatment of the irAE. These results suggest that pembrolizumab and nivolumab can be safely administered in patients with controlled preexisting autoimmune diseases without a significant increase in irAE compared with patients without autoimmune diseases. Inclusion of patients with preexisting autoimmune diseases in prospective clinical trials is warranted.

Dermatomyositis – A Rare Case with Excellent Outcome

Dermatomyositis and Polymyositis are autoimmune rheumatologic diseases with prominent feature of inflammatory myopathy. When the characteristic cutaneous manifestations coexist with myositis it is called dermatomyositis, otherwise it is polymyositis. There are also differences in histological findings. A 25-years-old lady presented with characteristic skin rash and progressive inflammatory proximal myopathy. The patient had difficulty in Activity of Daily Living (ADL) and ultimately she was unable to walk and became bed bound. Her muscle enzymes were very high, MRI and Electromyography (EMG) showed features of inflammatory myopathy (myositis). Muscle biopsy showed typical findings of dermatomyositis. She responded well with steroid and immunosuppressive drug along with exercise, physiotherapy and rehabilitation therapy. Now she is leading almost normal life with minimum maintenance dose of prednisolone and azathioprine. JAFMC Bangladesh. Vol 17, No 2 (December) 2021: 91-94

P263 Autoantibodies in ankylosing spondylitis: a systematic literature review

Abstract Background/Aims Ankylosing spondylitis (AS) is a chronic inflammatory arthritis leading to long term disability. It is frequently diagnosed late when irreversible damage has already occurred. Unlike most autoimmune rheumatological diseases, there are no known autoantibodies associated with AS; this can confound the diagnostic challenge as diagnosis depends not only on symptoms but on finding evidence of active inflammation at the time of assessment or damage from previously active disease. Our aim was to determine the extent to which autoantibodies may be pathognomonic of AS. Methods A systematic literature review was conducted to identify all articles reporting on autoantibodies in AS. The protocol was preregistered on PROSPERO. Articles were screened and reviewed independently by two reviewers. Disagreements were solved by consensus. Data were extracted and the MINORS (Methodological Index for Non-Randomised Studies) tool was used to assess and compare the quality of the studies. Data were pooled in a narrative synthesis. Results 743 papers were identified after removal of duplicates. Following review of abstracts, 31 full text articles were assessed for eligibility and 18 were excluded, leaving 13 studies to be included in the final systematic review. 12 articles looked at 14 biomarkers; one article looked at 2 high density nucleic acid protein arrays expressing 3,498 proteins. Samples sizes were small and the papers were found to be of modest quality. AS patients showed a wide-ranging autoantibody response across studies. One study found that 60% of autoantibodies detected were found only in the AS cohort versus the rheumatoid arthritis cohort and heathy controls. Antibodies against HLA-B27, pANCA, CD74, OmpC, collagens, PPM1A, noggin, sclerostin, Klebsiella pneumoniae and Breg cells were found more commonly in AS patients than in controls (both healthy controls and those with other autoimmune diseases). Antibodies to human tTG and anti DFS70 were not found to be associated with AS and there was conflicting evidence regarding the association of antibodies to the cell-wall mannan of Saccharomyces cerevisiae (ASCA) in AS from different papers. Conclusion Although many autoantibodies have been found among persons with AS, there is currently no evidence that any are specifically and independently associated with the disease. We therefore conclude that as yet no autoantibodies can be considered to be pathognomonic for AS. However, some autoantibodies may be clinically significant and combined with other biomarkers, such as HLA-B27, may prove fruitful in reducing the delay to diagnosis. Further work should seek to explore other avenues, in particular autoantibodies in closely related diseases, such as inflammatory bowel disease, to try to determine autoantibodies that may aid in the earlier diagnosis of this chronic disease. Disclosure E.J. Davies: None. G.T. Jones: None. R. Sengupta: Honoraria; Received grants, honoraria, and expenses for attendance at advisory board meetings or conferences and for giving lectures from AbbVie, Biogen, Celgene, Lilly, MSD, Novartis, Roche and UCB. Grants/research support; Received grants, honoraria, and expenses for attendance at advisory board meetings or conferences and for giving lectures from AbbVie, Biogen, Celgene, Lilly, MSD, Novartis, Roche and UCB.