The role of albumin-to-globulin ratio in undifferentiated arthritis: Rheumatoid arthritis versus primary Sjögren syndrome

Objectives: This study aims to compare initial albumin-to-globulin ratio (AGR) in patients with rheumatoid arthritis (RA) and primary Sjögren syndrome (pSS) presenting with undifferentiated arthritis (UA) and to investigate whether there was a difference in terms of AGR between the two patient groups and healthy controls. Patients and methods: Between January 2019 and December 2019, a total of 177 patients including 96 RA (10 males, 86 females; mean age: 53.6±10.8 years; range, 21 to 74 years) and 81 pSS (5 males, 76 females; mean age: 53.2±14.1 years; range, 23 to 79 years) and 82 healthy controls (20 males, 62 females; mean age: 50.5±13.6 years; range, 20 to 79 years) were included in this case-control study. Demographic characteristics, albumin, and globulin levels of all participants were recorded. The AGR, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-nuclear antibody (ANA), and anti-citrullinated protein antibodies (ACPA) were assessed. Results: The mean AGR was 1.50±0.16 in the control group, 1.48±0.24 in the RA group, and 1.30±0.23 in the pSS group, indicating a significant difference between the pSS and the other two groups (p<0.001). The receiver operating characteristic analysis revealed that the cut-off value for AGR was 1.39 (area under the curve=0.736) with a sensitivity of 0.642 and a specificity of 0.646 (p<0.001). The ESR and CRP values were higher (p<0.001), and ANA (p<0.001) and RF (p=0.003) positivity were lower in the RA group, compared to the pSS group. Conclusion: This study findings indicate that AGR is a helpful tool in the differential diagnosis of RA and pSS presenting with UA at the time of admission, and Sjögren syndrome should be considered in case of AGR ≤1.39.

Impact of a new coronavirus infection on the clinical course of immunoinflammatory rheumatic diseases

BACKGROUND: The COVID-19 pandemic poses a particular threat to patients suffering from immunoinflammatory rheumatic diseases. New coronavirus infection has been found to be accompanied by the development of a wide range of extrapulmonary clinical and laboratory manifestations, which are characteristic of a number of immunoinflammatory rheumatic diseases. AIM: To evaluate the features of the clinical course of immunoinflammatory rheumatic diseases in patients who underwent new coronavirus infection. MATERIALS AND METHODS: The clinical course of immunoinflammatory rheumatic diseases was analyzed in 324 patients who underwent new coronavirus infection from March 2020 to February 2021 and were treated at the Clinical Rheumatology Hospital No. 25, Saint Petersburg, for exacerbation of the underlying disease. RESULTS: Analysis showed that the risk factors for severe new coronavirus infection in patients with immunoinflammatory rheumatic diseases were: age over 60, comorbidities, use of prednisolone in a dose greater than 12,5 mg, and ESR values 40 mm/hour before the development of new coronavirus infection. There was no effect of immunosuppressive and biological therapy on the severity of the course of viral infection. There was no effect of immunosuppressive therapy and biological therapy on the severity of the course of viral infection in patients with immunoinflammatory rheumatic diseases. The development of the postinfectious syndrome was observed in 1/4 of patients, which was characterized by the formation of postinfectious arthritis in 3,6% of patients, transformation of undifferentiated arthritis into various rheumatic diseases in 49% of patients (more often into early rheumatoid arthritis), as well as exacerbation of the underlying disease in 83,4% of patients with an advanced stage of rheumatoid arthritis. In patients with mixed connective tissue disease, there was a significant increase in immunologic activity due to antinuclear factor (up to a maximum of 1:163 840). Clinical cases of the development of arthritis associated with viral infection and the debut of rheumatoid arthritis after an new coronavirus infection are presented. CONCLUSIONS: New coronavirus infection in the cohort of patients with immunoinflammatory rheumatic diseases observed in the Clinical Rheumatology Hospital No. 25, Saint Petersburg, proceeded in the variant of medium severity in half of patients, initiated the development of lung lesions in 68,6% of patients, arthritis associated with viral infection in 3,6% of patients, immunoinflammatory rheumatic diseases which transformed from undifferentiated arthritis in 49% of cases and exacerbation of the main disease in an overwhelming number of patients. Patients with immunoinflammatory rheumatic diseases have a high risk of adverse outcome of new coronavirus infection, especially in cases of unstable course of the disease or exacerbation of this group of diseases.

Risk Factors for Developing Rheumatoid Arthritis in Patients With Undifferentiated Arthritis and Inflammatory Arthralgia

Currently, there is an increasing interest in treating patients at risk of rheumatoid arthritis (RA) to prevent the development of this chronic disease. In this sense, research has focused attention on the early identification of predictive factors of this disease. Autoantibodies and markers of systemic inflammation can be present before clinical arthritis and RA development. So, the phase of inflammatory arthralgia preceding clinical arthritis is an important part of the window of opportunity and, starting treatment might prevent progression to chronic arthritis. Additionally, the early diagnosis and treatment initiation, in patients with inflammatory arthritis at risk of persistence and/or erosive progression, are fundamental because may allow optimal clinical responses, better chances of achieving sustained remission, preventing irreversible organ damage and optimizing long-term outcomes. This review aims to give an overview of clinical risk factors for developing RA, both in suspected arthralgia and in undifferentiated arthritis. Besides taking into consideration the role of serological markers (immunological and acute phase reactants) and clinical features assessed at consultation such as: articular affection and patient's clinical perception. Other features as sociodemographic and environmental factors (lifestyle habits, microbiota, periodontal disease among others), have been included in this revision to give an insight on strategies to prevent development of RA and/or to treat it in early stages.

AB0780 GENDER FEATURES OF VERIFICATION OF DIAGNOSIS UNDIFFERENTIATED ARTHRITIS

Background:Undifferentiated arthritis (UDA) is an inflammatory arthritis that does not meet the criteria for any rheumatologic disease. Early verification of UDA is currently one of the main goals of modern rheumatology, since a diagnosis established at an early date allows determining a therapeutic strategy. The high social significance of arthritis lies in the predominant lesion of people of working age, the steady progression of the disease, early disability and a reduction in life expectancy.Objectives:To study the gender characteristics of verification of the diagnosis of undifferentiated arthritis.Methods:A retrospective analysis of 74 case histories of patients diagnosed with UDA was carried out. The study group consisted of 26 men and 48 women, mean age 50.6 ± 4.3 years. All patients underwent a comprehensive laboratory and instrumental examination according to the standard of an articular syndrome of unclear genesis.Results:According to the data obtained, the duration of the articular syndrome averaged 2.53 ± 1.2 years. In 29 patients (21.6% of women and 17.6% of men), on average, after 1.72 ± 0.9 years, the diagnosis of NDA was clarified. Taking into account modern diagnostic criteria, the following diseases were verified: rheumatoid arthritis in 13.5% (12.2% in women and 1.3% in men), ankylosing spondylitis in 10.8% (2.7% in women and 8.1% in men). Osteoarthritis, psoriatic arthritis and APS were diagnosed in 5.4%, 1.4% and 1.4% of women, and gouty arthritis, bone tuberculosis and HIV in 4.1%, 1.4% and 1.4% of men respectively. In 60.8% (43.2% in women and 17.6% in men), the etiology of arthritis was not verified.Conclusion:In a third of patients with UDA, diagnosis verification takes about 2 years on average. In more than half of patients, the diagnosis remains the same. According to the data obtained, rheumatoid arthritis was more often verified in women, while ankylosing spondylitis in men, which is consistent with statistical data.Disclosure of Interests:None declared

AB0037 UNDIFFERENTIATED ARTHRITIS

Background:Early recognition and treatment of inflammatory arthritis is imperative for the further course of the disease.Objectives:This study aims to determine the evolution of undifferentiated arthritis observed in rheumatology.Methods:Retrospective descriptive study which collects patients files identified as undifferentiated Arthritis and followed in the Rheumatology Department at Fattouma Bourguiba Hospital Monastir TUNISIA over a period of 15 years (2005, 2019). Epidemiological, clinical, paraclinical, and evolutionary data were collected and analyzed.Results:99 files were analyzed. The average age was 42.06±15.56; they were 42 males and 57 females with an average body mass index of 27±6.1 Kg/m2. The reason leading to consultation was, polyarthritis (37), oligoarthritis (27), mono-arthritis (21), and polyarthralgia (15). The median time to visit was 60 days [15 days, 3 months]. The median number of painful joints and swollen joints was 4 [2, 8], and 2 [1, 4] respectively. The mean duration of morning derusting was 34.8 ±24.4 minutes. Extra-articular manifestations were: a dry syndrome (22), a rheumatoid nodule (2), and serosal damage (1). Anemia (52 patients), leukopenia (6 patients), and lymphopenia (13 patients) were found in the blood cell count with a biological inflammatory syndrome in most patients (72/99). The immunology results showed: positive anti-nuclear antibodies (15/99), positive Anti-Citrullinated Protein Antibodies (9/99) and positive rheumatoid factor (8/99). 31 patients had standard radiological signs represented mainly by joint pinching and erosions. A joint puncture was done in 36/99 revealing inflammatory fluid in most cases. After an average follow-up of 1047 days [365, 1460]. undifferentiated arthritis was classified as rheumatoid arthritis (RA) (23), spondyloarthritis (SpA) (10), connective tissue disease (11), Crystalline Arthritis (5), and paraneoplastic arthritis (2). One patient had self resolution of symptoms and 38 remain undifferentiated.we found that the more the patients were seropositive, the more likely to develop Rheumatoid Arthritis (p=0.001), the more there was disorder in the blood cell count, the more the evolution was towards connective tissue disease (0.01), The more male patients were, the more likely to develop SpA (p=0.04). The patients management was mainly based on: analgesics (94), systemic corticosteroids (57) with a mean dose of 10.89± 5.8 mg/day. The use of Methotrexate and antimalarial drugs was noted in 18 and 15 patients respectively.Conclusion:Follow-up of patients with undifferentiated arthritis leads to a definite inflammatory rheumatism diagnosis in 61.6% of cases. Our data indicate that seropositive patients with chronic symptoms carry an increased risk of developing Rheumatoid Arthritis (P=0,001). Clinical, biological and genetic data can help the health care provider to predict future outcomes.References:[1]DOI: 10.1007/s00132-018-3539-2.Disclosure of Interests:None declared

AB0258 DMARD-TREATMENT OF UNDIFFERENTIATED ARTHRITIS INTENSIFIED DURING THE LAST DECENNIA, BUT DID NOT RESULT IN IMPROVED LONG TERM OUTCOMES

Background:EULAR guidelines stress timely initiation of DMARD-treatment in early arthritis patients also when classification criteria are not yet fulfilled. Consequently, undifferentiated arthritis (UA) patients may be increasingly treated with disease modifying antirheumatic drugs (DMARDs), despite inadequate placebo-controlled evidence for its effectivity. Implementation of this guideline also hampers future placebo-controlled trials in UA. However, historical data, with inclusion period as instrumental variable, can provide insight whether long term outcome is improved with increased DMARD-use, and thus serve to investigate if DMARD-treatment is effective in UA.Objectives:With 25-years of observational data of newly referred UA-patients, we studied whether enhanced treatment strategies resulted in better long term outcomes for UA.Methods:Between 1993 and 2019, 1132 consecutive UA-patients, not fulfilling the 1987/2010 criteria for RA or any other distinct diagnosis, were included in the Leiden Early Arthritis Cohort; patients were divided in 5 inclusion periods (1993-1998, 1999-2005, 2006-2010, 2011-2014, 2015-2019). Frequency of DMARD-initiation after diagnosis was compared. We studied the following outcomes: the course of disease activity scores (DAS28-CRP) and Health assessment questionnaires (HAQ), progression to RA after 1-year (according to the 1987 and/or 2010 criteria) and the frequency of prolonged DMARD-free status within 10-years of follow-up (this was defined as either spontaneous remission or sustained remission after discontinuation of DMARD-treatment).Results:The current population of UA-patients, thus not fulfilling 1987 or 2010 criteria, had rather mild disease: the median SJC was 1, the median TJC 2, 95% was autoantibody-negative and the median HAQ was 0.6. These characteristics were similar in the different inclusion periods. Initiation of DMARD-treatment in UA increased over time: 18%, 35%, 38%, 43% up to 55% in respectively 1993-1998, 1999-2005, 2006-2010, 2011-2014 and 2015-2019, in which methotrexate became more common in the last decade. Frequency of progression to RA after 1-year did not decrease and was 14%, 21%, 26%, 19% and 28% in the respective inclusion periods. Long-term DAS28CRP-scores improved from 2011 onwards (range -0.18, -0.24; p<0.05). However HAQ-score over time did not improve compared to the 1993-1998 period (range -0.00, -0.08; p>0.05). Also the percentages of patients in DMARD-free status after 10-years of follow-up did not significantly improve over time: 57%, 58%, 59% (for 1993-1998, 1999-2005, 2006-2010 respectively, p=0.59).Conclusion:Intensified DMARD-treatment of patients with UA did not result in improved outcomes. These data may indicate overtreatment of UA-patients. Yet, methods to stratify which UA-patients should be treated remains warranted.Disclosure of Interests:None declared

POS0506 TENOSYNOVITIS HAS A HIGH SENSITIVITY FOR EARLY ACPA-POSITIVE AND ACPA-NEGATIVE RA: A LARGE CROSS-SECTIONAL MRI STUDY

Background:Clinically evident tenosynovitis can be seen in established Rheumatoid arthritis (RA). Imaging research has recently shown that tenosynovitis at small joints occurs in early RA, contributes to typical RA symptoms (including joint swelling) and is infrequent in healthy controls. Imaging-detectable tenosynovitis is often not recognizable at joint examination, hence its prevalence can therefore be underestimated.Objectives:We hypothesized that if MRI-detectable tenosynovitis is a true RA-feature, the sensitivity for RA is high, in both ACPA-positive and -negative RA, and lower in other diseases that are associated with enthesitis (such as Spondyloarthritis (SpA) and Psoriatic Arthritis (PsA)). So far, no large MRI-study addressed these questions.Methods:Consecutive early arthritis patients (n=1211) from one health-care region underwent contrast-enhanced 1.5T MRI of hand and foot at diagnosis. MRIs were scored for synovitis and tenosynovitis by two readers blinded for clinical data. All included patients with ACPA-positive RA (n=250), ACPA-negative RA (n=282), PsA (n=88), SpA with peripheral arthritis (n=24), reactive arthritis (n=30) and self-limiting undifferentiated arthritis (UA;n=76) were studied. Sensitivity was calculated.Results:The sensitivity of tenosynovitis in RA was 85%; 88% for ACPA-positive RA and 82% for and ACPA-negative RA (p=0.19). The sensitivity for RA was significantly higher than for PsA (65%;p=0.001), SpA (53%;p<0.001), reactive arthritis (36%;p<0.001) and self-limiting UA (42%;p<0.001). The observed sensitivity of MRI-synovitis was 91% in RA and ranged 83-54% in the other groups.Conclusion:MRI-detected tenosynovitis has a high sensitivity for early ACPA-positive and ACPA-negative RA. This supports both juxta-articular (tenosynovitis) and intra-articular synovial involvement is characteristic for RA.Figure 1.Presence of tenosynovitis (in black) in wrist MCPs and MTPs, in rheumatoid arthritis, stratified for ACPA-status and compared to other diseases Legend: RA: Rheumatoïd arthritis; ACPA: anti-citrullinated protein antibodies; UA: undifferentiated arthritisDisclosure of Interests:None declared

Microbiome–miRNA interactions in the progress from undifferentiated arthritis to rheumatoid arthritis: evidence, hypotheses, and opportunities

The human microbiome has attracted attention for its potential utility in precision medicine. Increasingly, more researchers are recognizing changes in intestinal microbiome can upset the balance between pro- and anti-inflammatory factors of host immune system, potentially contributing to arthritis immunopathogenesis. Patients who develop rheumatoid arthritis from undifferentiated arthritis can face multiple irreversible joint lesions and even deformities. Strategies for identifying undifferentiated arthritis patients who have a tendency to develop rheumatoid arthritis and interventions to prevent rheumatoid arthritis development are urgently needed. Intestinal microbiome dysbiosis and shifts in the miRNA profile affect undifferentiated arthritis progression, and may play an important role in rheumatoid arthritis pathophysiologic process via stimulating inflammatory cytokines and disturbing host and microbial metabolic functions. However, a causal relationship between microbiome–miRNA interactions and rheumatoid arthritis development from undifferentiated arthritis has not been uncovered yet. Changes in the intestinal microbiome and miRNA profiles of undifferentiated arthritis patients with different disease outcomes should be studied together to uncover the role of the intestinal microbiome in rheumatoid arthritis development and to identify potential prognostic indicators of rheumatoid arthritis in undifferentiated arthritis patients. Herein, we discuss the possibility of microbiome–miRNA interactions contributing to rheumatoid arthritis development and describe the gaps in knowledge regarding their influence on undifferentiated arthritis prognosis that should be addressed by future studies.