RF Titer Research Articles

The Role of Interleukin-22 in The Diagnosis and Evaluation of Disease Activity in Rheumatoid Arthritis

Background: Rheumatoid Arthritis (RA) is a chronic autoimmune disease that primarily affects small joints, resulting in joint inflammation, pain, and limited mobility. The identification of novel biomarkers specific to RA could enhance early diagnosis and treatment and also improve the monitoring of the disease activity and treatment response. In this study, the levels of IL-22 were measured in 133 patients with inflammatory arthritis using the ELISA method with the aim of assessing the diagnostic value of IL-22 in the diagnosis of RA and evaluating the disease activity. The findings revealed that serum IL-22 levels were significantly higher in RA patients compared to patients with other types of inflammatory arthritis. Additionally, positive correlations were observed between IL-22 and disease activity scores as determined by CDAI, DAS-28 ESR, and DAS-28 CRP. Notably, when IL-22 was used as a diagnostic tool, with a cut-off value of ≥ 26.9 pg/ml, it exhibited a sensitivity of 83%, specificity of 75%, and an AUC of 0.838. Furthermore, significant associations were found between IL-22 levels and the age of RA patients, while no significant correlations were observed with gender, BMI, and smoking index. It is noteworthy that IL-22 levels were significantly correlated with ESR, RF titer, and ACPA levels. Consequently, IL-22 can be regarded as a valuable biomarker for diagnosing RA and evaluating disease activity. Subjects and method: This cross-sectional study was conducted from September 2022 to January 2023, involving 133 patients with inflammatory arthritis, including RA and other forms of inflammatory arthritis. All patients were recruited from As-Sader Teaching Hospital in Najaf. The ages of the patients included in the present study range from 20 to 70 years, with a sample comprising 116 females and 17 males. Results: The higher median (IQR) value of IL-22 was observed among the RA patients [36.9 (28.6-63.7) pg/ml] compared to that of the other patients with inflammatory arthritis [23.6 (19.8-26.8) pg/ml]. The difference between the two groups of patients was highly significant (P < 0.0001). Among the RA patients, a highly significant difference in the median (IQR) level of IL-22 was observed among the disease activity groups according to CDAI, DAS-28 ESR, and DAS-28 CRP (P < 0.0001). Conclusion: Interleukin-22 can be regarded as a reliable biomarker for the diagnosis of RA and holds potential for assessing disease activity.

NLRP3 Gene Polymorphisms in Rheumatoid Arthritis and Primary Sjogren's Syndrome Patients.

Aim: The activation of NLRP3 inflammasome leads to the stimulation of cytokines and is significantly involved in the pathogenesis and progression of autoimmune diseases. The purpose of this study is to examine the associations of NLRP3 gene polymorphisms with rheumatoid arthritis (RA) and primary Sjogren's syndrome (SS) patients. Methods: A total of 239 patients with RA, 285 patients with primary SS, and 170 healthy controls were enrolled. Genomic DNA was extracted from peripheral blood mononuclear cells, and gene polymorphisms were genotyped through the TaqMan assay. Antinuclear antibody (ANA), anti-Ro, and anti-CCP antibodies were detected using immunofluorescence immunoassay. Results: The T allele of rs4612666 CT elevated the susceptibility to RA disease. The RF titer during diagnosis of RA was significantly high in RA patients with the A allele of rs12079994 G/A polymorphism. The titer of anti-CCP during diagnosis of RA was high in the absence of the C allele of rs10754558 C/G polymorphisms in RA patients. Antinuclear antibody and anti-CCP were positively associated with the A allele of rs12079994 G/A polymorphism in primary SS. The C allele of rs4612666 C/T was negatively associated with ANA in primary SS. Conclusions: The results have shown that NLRP3 gene polymorphisms may play a role in the pathogenesis of RA and primary SS.

Development of a scoring model for the Sharp/van der Heijde score using convolutional neural networks and its clinical application.

To construct a predictive model for the Sharp/van der Heijde score (SHS) and assess its applicability in clinical research settings. A prediction model for SHS was constructed in three steps using convolutional neural networks (CNN) and an in-house RA image database: orientation, detection and damage prediction. A predictive model for radiographic progression (ΔSHS >3/year) was developed using a graph convolutional network (GCN). A multiple regression model was used to assess the association between predicted SHS using the CNN model and clinical features. In the orientation and detection phases, 100% accuracy was achieved in the image orientation correction, and all predicted joint coordinates were within 10 pixels of the correct coordinates. In the damage prediction phase, the κ values between the model and expert 1 were 0.879 and 0.865 for erosion and joint space narrowing, respectively. Using a dataset scored by experts 1 and 2, a minimal overfitting was determined to the scoring by expert 1. High-titre RF was an independent risk factor of ΔSHS per year, as predicted by the CNN model in biologics users. The AUCs of the GCN model for predicting ΔSHS >3/year in patients with and without biologics at baseline were 0.753 and 0.734, respectively, superior to those of the other models. The RF titre was the most important feature in predicting ΔSHS >3/year in biologics users in the GCN model. A high-performance scoring model for SHS that is applicable to clinical research was constructed.

Clinical implications of autoantibodies to extractable nuclear antigens in rheumatoid arthritis patients in tertiary care hospital in Riyadh, Saudi Arabia

The purpose of this study was to assess the prevalence of autoantibodies against extractable nuclear antigens (ENAs), anti-Ro/SSA, anti La/SSB, anti Jo-1, ribo-nucleoproteins (anti UI-RNP) and antibodies to Smith (anti-Sm) in rheumatoid arthritis (RA) patients and to detect the relationship between the existence of these autoantibodies and clinical presentation, radiological damage, and disease activity markers. The study, included 57 RA patients and 35 normal controls, was conducted in Al-Quwayiya General Hospital. Sera were obtained from patients and controls to carry out Hs-CRP, ESR, RF factors, ANA and ACPA IgG. Anti-Sm, anti-U1-RNP, anti-Ro/SSA, anti-La/SSB, and anti-Jo-1 were measured using the Alegria® assay. ESR was 23.8±6.5, while CRP was 16.19±7.15 in RA patients. RF was detected in 23 (40.35%) patients and ACPA in 54 (94.73%), while ANA was positive in 14 (24.56%) cases. Anti-Ro/SSA was detected in 8 (14.03%) patients, anti-La/SSB in 3 (5.26%), anti-Jo-1 was found in 2 cases (3.50%), and anti-RNP in 1 (1.75%). Anti-Ro/SSA had a significant negative relationship with sex (r=-0.220, P=0.001), but a positive correlation was observed with sicca symptoms (r=0.149, P=0.02). Anti-La/SSB antibodies correlated positively with swollen joint count (r=0. 0.225, P=0.001), tender joint count (r=0.219, P=0.001) and ANA (r=0.367, P < 0.001). Anti-Jo-1 antibodies showed a significant positive correlation with interstitial lung disease (r=-0.429, P≤0.001). Anti-Ro/SSA had a significant positive correlation with RF titer (r=0.259, P < 0.001) and ANA (r=0.498, P < 0.001). Anti-La/SSB had significant positive correlation with ANA (r=0.372, P < 0.001). Anti-Jo-1 showed a significant positive correlation with RF titer (r=0.141, P < 0.040) and ANA (r=0.249, P < 0.001). Anti-RNP showed a significant positive correlation with ACPA titre (r=0.288, P < 0.001) and ANA (r=0.159, P < 0.018). We conclude that ENA autoantibodies are crucial and need to be correlated with clinical diagnosis and other serological testing for early diagnosis and intervention of the RA.

The Clinical and Immunological Activity Depending on the Presence of Interferon γ in Primary Sjögren's Syndrome-A Pilot Study.

The upregulation of IFN pathways and their stimulated genes is associated with primary Sjögren’s syndrome (pSS). The recent studies also indicate the involvement of interferon γ (IFNγ) in the pathogenesis of pSS. The study aimed to assess the clinical and immunological activity depending on the concentration of IFNγ in the peripheral blood in pSS patients. Methods: The study group consisted of patients over 18 years of age with a confirmed diagnosis of pSS. Based on the collected data, disease activity was assessed using the EULAR Sjögren’s syndrome disease activity index (ESSDAI) and the EULAR Sjögren’s syndrome patient reported index (ESSPRI). Results: Among 40 pSS patients, 33 (82%) showed increased levels of IFNγ. The group with positive IFNγ was younger (43 years) than the group with negative IFNγ (57 years) (p < 0.05). In the positive IFNγ group, the time to diagnosis was shorter (p < 0.05). There was a difference in ESSDAI among patients with and without IFNγ (p < 0.05). There were no differences between the groups in ESSPRI and the presence of cryoglobulins, specific anti-SSA, and anti-SSB antibodies and in C3 and C4 hypocomplementemia. RF occurred in both groups with a similar frequency (p = 0.6), but in patients with IFNγ presence, significantly higher RF titers were observed (34.9 vs. 10.5; p < 0.05). Conclusion: In the group of patients with positive IFNγ, the mean value of RF and ESSDAI was higher. This group was also younger than patients with pSS without IFNγ.

Soluble programmed death molecule 1 (sPD-1) as a predictor of interstitial lung disease in rheumatoid arthritis

BackgroundPrevious studies have indicated that the programmed death molecule 1 (PD-1) signaling pathway may play a key role in rheumatoid arthritis (RA). However, the pathogenesis of rheumatoid arthritis-related interstitial lung disease (RA-ILD) is not clear. We examined the serum levels of soluble PD-1 in patients with RA and its relationship with RA-ILD.MethodsBlood samples were obtained from 87 patients with RA (58 with ILD and 29 without ILD) and 45 healthy controls. Serum sPD-1 was measured by Enzyme-Linked Immunosorbent Assay. The pulmonary interstitial disease score was completed by a pulmonary physician and a radiologist through chest high-resolution computed tomography. Patients with RA-ILD were tested for lung function [e.g., forced vital capacity (FVC%), diffusing capacity of lungs for carbon monoxide (DLCO%)]. Associations between ILD and various markers, including sPD-1 and confounding factors, were investigated by logistic regression analysis. Diagnostic values of sPD-1 for the presence of ILD were investigated using receiver operating characteristic curve analysis.ResultsSerum sPD-1 levels were higher in RA patients with ILD than in RA patients without ILD and healthy controls (185.1 ± 109.0 pg/ml vs. 119.1 ± 77.5 pg/ml vs. 52.1 ± 21.7 pg/ml, P < 0.05). Serum sPD-1 levels were positively correlated with RF titer (P = 0.02, r = 0.249), anti-cyclic citrullinated peptide antibody status (P = 0.02, r = 0.243), and serum IgG levels (P < 0.001, r = 0.368), negatively associated with FVC% (P = 0.02, r = − 0.344), forced expiratory volume (FEV1%) (P = 0.01, r = − 0.354), total lung capacity (TLC%) (P = 0.046, r = − 0.302), and was independently associated with the presence of ILD in RA patients by multivariate logistic regression analysis. The sensitivity and specificity of sPD-1 levels for the detection of ILD in RA patients were 58.6% and 75.9%, respectively. The area under the curve was 0.689.ConclusionSerum sPD-1 levels were increased in RA patients with ILD. Increased sPD-1 may be a valuable biomarker to predict the presence of ILD in patients with RA.

Autoantibodies to extractable nuclear antigens (ENAs) pattern in rheumatoid arthritis patients: Relevance and clinical implications

ObjectivesTo study the frequency of different autoantibodies to extractable nuclear antigens (ENAs) in rheumatoid arthritis (RA) patients and to correlate findings with clinical manifestations, disease activity and radiological damage. MethodsA total of 230 RA patients were included and 75 healthy controls. In all patients rheumatological assessment was done and routine laboratory investigations and immune profile were performed in both patients and controls, including: RF, ACPA, ANA and anti-ENAs (Ro/SSA, La/SSB, U1-RNP, anti-Jo-1 and anti-Sm). Radiological damage was scored using Sharp/van der Heijde, and disease activity was evaluated by DAS28-ESR and DAS28-CRP. ResultsRF was positive in 101 (43.9%), ACPA in 220 (95.7%), ANA in 58 (25.2%), anti Ro in 31 (13.5%), anti-La in 10 (4.3%), anti-Jo1 in 5 (2.2%) and anti-RNP in 2 (0.9%). Anti-Ro/SSA positively correlated with sicca symptoms (p=.02), RF titer (p<.001), ANA (p<.001), DAS28-ESR (p=.026), and DAS28-CRP (p=.003). Anti-La antibodies correlated positively with SJC (p=.001), TJC (p=.001), ANA (p<.001), DAS-28 ESR (p=.007). Anti-Jo-1 correlated positively with interstitial lung disease (ILD) (p≤.001), RF titer (p=.037) and ANA (p≤.001). Anti-RNP antibodies correlated positively with disease duration (p≤.001), ACPA titer (p≤.001) and ANA (p=.014). In the controls ANA was positive in two (2.7%), anti-Ro in three (4%), and none of the controls tested positive for other autoantibodies. ConclusionsIn RA patients, positive ANA is frequent and positively associated with anti-Ro, anti-La and anti-Jo1 autoantibodies. Screening for autoantibodies against other anti-ENAs seems mandatory in RA patients especially when ANA is positive. RA cases with positive Anti-Jo-1 may develop anti synthetase syndrome and ILD.

Risk of progression of idiopathic pulmonary fibrosis to connective tissue disease: a long-term observational study in 527 patients.

Connective tissue disease (CTD) might occur during the course of idiopathic pulmonary fibrosis (IPF). Clinical factors associated with CTD development in IPF patients have still not been identified. We investigated which antibodies have a significant association with the development of CTD during the clinical course of IPF. We retrospectively reviewed the records of 527 patients with a first diagnosis of IPF between January 2007 and March 2014 and investigated the time to CTD development after IPF diagnosis in these patients. CTD developed in 15 patients at a median of 2.1 years (range 1.2-4.8) after IPF diagnosis. All patients had anti-neutrophil cytoplasmic antibodies (ANCA) or autoantibodies that met the serology criteria for interstitial pneumonia with autoimmune features (IPAF). Survival duration for IPF patients with progression to CTD was 5.3 (3.8, 6.7) years, which was significantly longer than for IPF patients without progression to CTD [2.9 (1.7, 4.8), p = 0.001]. Independent risk factors for CTD development in IPF patients included female gender [adjusted hazard ratio (HR) 5.319, p = 0.0082], titer of rheumatoid factor (RF; adjusted HR, 1.006; p = 0.022), titer of anti-citrullinated protein antibody (ACPA; adjusted HR, 1.009; p = 0.0011), and titer of myeloperoxidase (MPO)-ANCA (adjusted HR, 1.02; p < 0.0001). Progression to CTD is uncommon in IPF patients. However, a significant number of IPF patients with high titers of RF, ACPA, or MPO-ANCA progressed to CTD. RF, ACPA, and MPO-ANCA might be significantly associated with CTD development in IPF patients. Key Points • A significant number of IPF patients with high titers of RF, ACPA, or MPO-ANCA progressed to CTD. • IPF/UIP with high titers of RF, ACPA, or MPO-ANCA might be the initial clinical manifestation of CTD. • RF, ACPA, and MPO-ANCA may be significantly associated with the development of pulmonary fibrosis in patients with CTD.

High serum IgA and activated Th17 and Treg predict the efficacy of abatacept in patients with early, seropositive rheumatoid arthritis

To identify the predictive biomarkers for achieving remission with abatacept in patients with seropositive rheumatoid arthritis (RA). We enrolled patients with RA who were treated with abatacept. We compared the baseline laboratory results and longitudinal immune-phenotyping data between patients who achieved remission and those who did not achieve remission at 6months according to the clinical disease activity index. One hundred and twenty RA patients were enrolled. In the seropositive patients with early RA (n = 24), high serum IgA levels, anti-citrullinated peptide (CCP) titers, and neutrophil counts before treatment were predictors of remission (area under the curve [AUC], 0.659, 0.741, and 0.704, respectively). Additionally, activated Th17 (aTh17) cells and activated Treg (aTreg) cells before treatment were found to be significantly higher in patients with remission compared to those without remission (2.9% vs 1.1%, P = 0.02; 34.3% vs 17%, P = 0.03, respectively). The measurement of longitudinal cell subpopulation revealed a decrease in the effector CD4 T cell population after abatacept treatment, which correlated with anti-CCP titers and neutrophil counts, and was associated with remission achievement. In seropositive patients with established RA (n = 79), high RF titers and low IFN-γ levels were associated with the good response to abatacept. Our study has shown that serum IgA levels, anti-CCP titer, and neutrophil counts are predictive biomarkers for predicting the response to abatacept in patients with seropositive and early RA and may reflect the inhibition of effector CD4 T cell subpopulations by abatacept. Key Points • Serum IgA levels and neutrophil counts are novel biomarkers for predicting the efficacy of abatacept. • Those may reflect the inhibition of effector CD4 T cell subpopulations by abatacept.

Correlation With Disease Activity Score 28 (Das28) With Pulmonary Function Test In Rheumatoid Arthritis Patients

Rheumatoid Arthritis (RA) is a chronic inflammatory disease of unknown etiology involving both small and large joints with many extra-articular manifestations. There may be a variety of pulmonary complications associated with RA based on its disease activity and levels of RF and anti-CCP titers. Pulmonary involvement may be seen at different levels of the respiratory system, with infection being the most common cause of mortality. Our study shows the association and degree of pulmonary involvement in patients with RA based on the pulmonary function test and its correlation with the DAS 28 score. The aim of our study was to assess the prevalence of pulmonary involvement in patients with Rheumatoid Arthritis. The study population was 100 patients with RA diagnosed based on the 2010 ACR/EULAR criteria following all the exclusion. The patients were subjected to a PFT on diagnosis and repeated at 6 and 18 months following treatment. In our study, there is a higher prevalence of pulmonary involvement seen in doing PFT, even in asymptomatic patients with RA when compared to other studies. Pulmonary complications occurring in patients with Rheumatoid Arthritis may be identified on doing a PFT or HRCT thorax. Pulmonary involvement carries significant mortality and morbidity. Disease duration and disease activity score 28 were found to have a significant association with pulmonary complications. Although our study brings out the incidence of higher risk of pulmonary involvement in patients with RA, more studies meta-analysis are required.

Increased serum soluble programmed death ligand 1(sPD-L1) is associated with the presence of interstitial lung disease in rheumatoid arthritis: A monocentric cross-sectional study.

This paper is to examine the relationship between serum soluble programmed death ligand 1(sPD-L1) levels and the development of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). Serum sPD-L1 were measured by enzyme-linked immunosorbent assay. sPD-L1 levels in RA with ILD, RA without ILD and healthy controls were compared. Associations between ILD and various markers including sPD-L1 and confounding factors were investigated by logistic regression analysis. Diagnostic values of sPD-L1 for the presence of ILD were investigated using receiver operating characteristics curve analysis. Serum sPD-L1 levels were higher in RA patients with ILD than RA patients without ILD and healthy controls (23.7±9.8 vs. 18.0±7.7pg/mL, P=0.01 and 23.7±9.8 vs. 2.9±1.5pg/mL, P<0.0001). sPD-L1 levels were positively correlated with RF titer (r=0.245, P=0.03), CRP (r=0.265,P=0.01), HRCT score (r=0.265, P=0.04) and Ferritin (r=0.442, P=0.01), but negatively associated with FVC% (r=-0.359, P=0.01) and DLCO% (r=-0.399, P=0.008). sPD-L1 and anti-CCP antibody status were independently associated with the presence of ILD during multivariate logistic regression analysis. Sensitivity and specificity of sPD-L1 levels for the detection of ILD in RA patients were 51.7% and 79.3%, respectively (area under the curve=0.661). Serum sPD-L1 levels were increased in RA patients with ILD. Increased sPD-L1 levels were associated with the presence of ILD.

Serum and synovial fluid levels of matrix metalloproteinase-3 as a biomarker of joint damage in patients with rheumatoid arthritis

Abstract Background Rheumatoid arthritis (RA) is one of the systemic autoimmune diseases characterized by chronic synovitis and progressive joint destruction leading to decline in functional capacity, eventual work disability, and reduced quality of life. Considering the common disease activity indicators are unspecific for arthritis, novel biomarkers have been rapidly developed for predicting structural destruction progression in RA. Matrix metalloproteinase-3 plays a special role in rheumatoid arthritis pathogenesis and has been suggested as a marker of disease activity and joint damage. Patients and Methods MMP-3 was measured by ELISA in serum samples of 40 early RA patients and compared to age and sex matched control group of 40 healthy volunteers. Synovial levels of MMP-3 were measured only in 8 RA patients, who were indicated for knee arthrocentesis. Joint damage was assessed using SENS score on plain radiography. Results Serum MMP-3 levels were significantly higher in RA patients than healthy volunteers (P-value &amp;lt;0.001). Measured synovial levels of MMP-3 were significantly correlated to the serum levels. There were statistically significant positive correlations between serum MMP-3 with RF titers, AntiCCP titres, CRP, and DAS28 -ESR activity score. There was no significant correlation to total SENS score. ROC curve was used to define the best cut off value of serum MMP3 to discriminate between RA and healthy controls, which was found to be &amp;gt;50ng/ml. Conclusion Serum levels of MMP-3 can be used as noninvasive biomarker of RA, and also indicator of disease activity in early RA patients.

Autoantibodies to extractable nuclear antigens (ENAs) pattern in rheumatoid arthritis patients: Relevance and clinical implications.

To study the frequency of different autoantibodies to extractable nuclear antigens (ENAs) in rheumatoid arthritis (RA) patients and to correlate findings with clinical manifestations, disease activity and radiological damage. A total of 230 RA patients were included and 75 healthy controls. In all patients rheumatological assessment was done and routine laboratory investigations and immune profile were performed in both patients and controls, including: RF, ACPA, ANA and anti-ENAs (Ro/SSA, La/SSB, U1-RNP, anti-Jo-1 and anti-Sm). Radiological damage was scored using Sharp/van der Heijde, and disease activity was evaluated by DAS28-ESR and DAS28-CRP. RF was positive in 101 (43.9%), ACPA in 220 (95.7%), ANA in 58 (25.2%), anti Ro in 31 (13.5%), anti-La in 10 (4.3%), anti-Jo1 in 5 (2.2%) and anti-RNP in 2 (0.9%). Anti-Ro/SSA positively correlated with sicca symptoms (p=.02), RF titer (p<.001), ANA (p<.001), DAS28-ESR (p=.026), and DAS28-CRP (p=.003). Anti-La antibodies correlated positively with SJC (p=.001), TJC (p=.001), ANA (p<.001), DAS-28 ESR (p=.007). Anti-Jo-1 correlated positively with interstitial lung disease (ILD) (p≤.001), RF titer (p=.037) and ANA (p≤.001). Anti-RNP antibodies correlated positively with disease duration (p≤.001), ACPA titer (p≤.001) and ANA (p=.014). In the controls ANA was positive in two (2.7%), anti-Ro in three (4%), and none of the controls tested positive for other autoantibodies. In RA patients, positive ANA is frequent and positively associated with anti-Ro, anti-La and anti-Jo1 autoantibodies. Screening for autoantibodies against other anti-ENAs seems mandatory in RA patients especially when ANA is positive. RA cases with positive Anti-Jo-1 may develop anti synthetase syndrome and ILD.

7. Anti-MDA5 associated dermatomyositis

IntroductionThis is a complex case of a 50-year-old lady who presented with peripheral synovitis, fever and rash. She developed ulcerative skin lesions, proximal muscle weakness and pulmonary fibrosis.Case descriptionA 50-year-old woman presented with a 6-week history of joint pain and swelling, an erythematous rash and fever. No preceding illness. She had fibromyalgia and chronic low back pain. She had several courses of prednisolone 20mg for presumed reactive arthritis with no benefit. She was a non-smoker, did not drink alcohol and was unemployed. She had florid symmetrical synovitis affecting MCPs, PIPs, wrists, ankles and knees. She had an erythematous rash across her face, chest and upper arms. She was pyrexic at night when her skin became inflamed.ESR-35 and CRP-13. RF, anti-CCP, ANA, ANCA, ACE and ASOT titre were negative. U&E was normal. LFTs were elevated with GGT-113, ALP-143, AST-432 and ALT-281. CK-33, LDH-367 and ferritin-2573. CXR, urine dip and liver screen were normal. USS abdomen, ECHO, CT CAP and PFTs were normal. Skin biopsy showed features of interface dermatitis. Extended myositis panel was negative. MRI of thighs showed active myositis. Muscle biopsy was insufficient. Tumour markers, mammogram, USS of breasts, OGD and colonoscopy were normal. The working diagnosis was dermatomyositis.She was treated with hydroxychloroquine and prednisolone 60mg with little benefit. She had three pulses of IV methylprednisolone with good benefit for joints. Azathioprine was not tolerated. Skin worsened and she was treated with 5 days IV immunoglobulins. She developed ulcerating skin lesions and swabs confirmed pseudomonas which was treated with ciprofloxacin and topical steroids. Dapsone caused haemolysis. She was switched to mycophenolate. Joints flared when prednisolone was reduced below 60mg and she was treated with rituximab. She developed proximal muscle weakness. Repeat MRI of thighs showed further progression of active myositis. Extended myositis panel confirmed Anti-MDA5 myositis. HRCT showed established pulmonary fibrosis. The myositis tertiary referral centre recommended IV cyclophosphamide. She responded well with improvement in joints and skin and prednisolone was weaned.DiscussionThis was a refractory case of anti-MDA 5 myositis which failed to respond to multiple immunosuppressive treatments. The patient failed high dose oral steroids initially and therefore treatment was escalated to IV methylprednisolone. Her joint disease responded but unfortunately her skin deteriorated. We treated with IV immunoglobulins with no benefit. She was unable to tolerate azathioprine and was switched to mycophenolate as an alternative steroid sparing agent. Despite steroids, mycophenolate and immunoglobulins her disease progressed with worsening myositis, ulcerating skin lesions and pulmonary fibrosis. Rituximab is a well-recognised potential treatment option for patients with myositis resistant to conventional treatment. The extended myositis panel revealed anti-MDA5 myositis, which is associated with rapidly progressive interstitial lung disease and ulcerative skin lesions. These are case reports in Rheumatology in 2017 which describe successful treatment with rituximab for anti-MDA5 myositis. However in this particular case, our patient failed to respond to rituximab. Cyclophosphamide is reserved for severe cases of myositis with rapidly progressive lung disease. We took the opportunity to discuss this case with the tertiary myositis referral centre in Liverpool and they advised to proceed with cyclophosphamide with good benefit.This was an interesting case of anti MDA 5 myositis. The initial presentation was not classical for an inflammatory myopathy with peripheral synovitis, fever and a rash. This patient’s signs and symptom evolved with development of muscle weakness and pulmonary fibrosis. CK was normal and this highlights the importance of checking other muscle enzymes in cases of suspected myositis. An extended myositis panel is also invaluable and helped to confirm the diagnosis in this particular case.Key learning pointsIt is important to consider anti-MDA5 dermatomyositis particularly if patient presents with polyarthritis and ulcerative skin lesions. CK may be normal in myositis and it is important to check other muscle enzymes. There are five muscle enzymes to consider in cases of suspected myositis including CK, aldolase, AST, ALT and LDH. It is important to consider myositis if a patient presents with raised ALT and AST without underlying liver disease. If the Royal Free myositis panel is negative, consider sending research myositis panel to Bath.Conflicts of interestThe authors have declared no conflicts of interest.

Subtypes in eosinophilic granulomatosis with polyangiitis classified according to rheumatoid factor.

To investigate the relevance of RF in patients with EGPA, we reviewed consecutive patients who were newly diagnosed with EGPA from August 1998 to February 2019 in Keio University Hospital with RF titer at diagnosis available. We divided the patients according to the median level of RF titer of 75IU/mL and compared clinical features between the two groups. Among 16 patients identified, 8 patients were in the RF high group and the other 8 patients were in the RF low group. All patients in the high RF group were negative for MPO-ANCA, whereas all in the low RF group was positive for MPO-ANCA with a mean titer of 103IU/mL. The eosinophil count at diagnosis was significantly higher in the RF high group than the RF low group (20001/μL vs 5144/μL, p < 0.01). Gastrointestinal lesion was significantly more frequent in the RF high group, and parenchymal organ lesions, such as heart and renal organ involvement, were frequent in the RF low group. With principal component analysis, RF high and low groups were clearly divided by the combination of eosinophil count, MPO-ANCA titer, gastrointestinal lesions, musculoskeletal symptoms, and disease activity score. Those results suggest EGPA can be divided into two groups in association with RF.Key Points• Our study showed that patients with EGPA can be separated into two groups according to RF titer.• The two subtypes reflect different underlying pathogenesis in EGPA, and the optimal treatment for them may be different.

Comparison of efficacy of TNF inhibitors and abatacept in patients with rheumatoid arthritis; Adjusted with propensity score matching

The aim of this study was to compare the clinical outcome of patients with rheumatoid arthritis seen in routine clinical practice treated with either TNF inhibitors or abatacept. To overcome potential bias, both propensity score matching and Inverse Probability of Treatment Weighting were used for patient selection. The propensity score matching procedure selected 315 matched pairs of patients who were treated with TNF inhibitors or abatacept. At week 52, SDAI in TNF inhibitors was lower than abatacept. In contrast, analysis of biologics-naive patients using the propensity-score matching (n = 150; in each group) showed comparable clinical efficacy. Consistent results were obtained by the use of Inverse Probability of Treatment Weighting (581 patients treated with TNF inhibitors and 353 patients treated with abatacept). The predictors of response to each treatment were different; abatacept appeared to benefit patients with high baseline RF titers while TNF inhibitors appeared to benefit patients with low baseline HAQ-DI.

How to Distinguish Patients with pSS among Individuals with Dryness without Invasive Diagnostic Studies.

In the course of pSS, inflammatory cell infiltration consists mainly of lymphocytes infiltrating exocrine glands, which leads to their impaired function. The characteristic feature is generalized dryness. The aim of this study was to attempt to answer the question whether it is possible to distinguish between patients with pSS and individuals with dryness caused by other pathologies without applying invasive studies. The study included 68 patients with pSS and 43 healthy controls with dryness. FS ≥ 1 was observed in 90% of patients with pSS (with or without dryness), and only in 23% of the control group (only with xerostomia). In the pSS group, anaemia (p = 0.0085), lymphocytopenia (p = 0.0006), elevated ERS (p = 0.001), higher RF titer, and ANA antibodies were noted. Configuration of anti-SSA + SSB + Ro52 antibodies was characteristic for the pSS group. Considering the clinical symptoms, statistically significant differences were noted between pSS patients and the control group in frequency (p = 0.02) and severity (p = 0.042) of fatigue, lymphadenopathy, major salivary gland involvement, and photosensitivity to UV light. In conclusion, invasive methods are pivotal in pSS diagnosis in this salivary gland biopsy. Chronic fatigue syndrome is more common in pSS patients and can be subjective distinguishing factor in the group of people with dryness.

Soluble glycoprotein VI, a specific marker of platelet activation is increased in the plasma of subjects with seropositive rheumatoid arthritis.

ObjectivesAnti-citrullinated protein antibodies (ACPA) have been shown to cause platelet activation in vitro, through the low-affinity immunoglobulin G (IgG) receptor (FcγRIIa) on platelets. Platelet activation via engagement of FcγRIIa results in proteolytic cleavage and shedding of platelet specific glycoprotein VI (GPVI) which can be detected in the plasma as soluble GPVI (sGPVI). We hypothesized that plasma levels of sGPVI would be increased among patients with seropositive RA as a consequence of antibody-induced platelet activation and GPVI shedding.MethodsSamples from 84 patients with RA (65 seropositive and 19 seronegative) and 67 healthy controls were collected prospectively and analysed for sGPVI using a standardised ELISA.ResultsPatients with seropositive RA had significantly higher levels of sGPVI compared to seronegative RA and controls. Median (IQR) sGPVI levels were 4.2 ng/ml (3.2, 8.0) in seropositve RA, 2.2 ng/ml (1.5, 3.5) in seronegative RA and 2.2 ng/ml (1.6, 3.4) in controls (p<0.0001). sGPVI levels correlated with ACPA titres (r = 0.32, p = 0.0026) and with RF titres (r = 0.48, p<0.0001).ConclusionPlasma sGPVI, a specific marker of platelet activation is increased among patients with seropositive RA.

Chest Pain- Volleyball

HISTORY: A 20-year-old female collegiate volleyball player presented with a 3-month history of chest pain. Pain was non-exertional, localized to the mid-chest and described as constant with rating of 8/10. She initially sought consult 3 months prior in the emergency room with EKG and labs unremarkable. The patient was diagnosed with costochondritis and managed with a steroid dose pack that provided temporary relief. Her pain then progressively increased to inability to tolerate volleyball activity. Of note, she reported mild left hip and lower back pain that started one week prior to consult. PHYSICAL EXAMINATION: Cardiac exam revealed regular rate and rhythm with no murmurs. Tenderness to palpation was significant over the sternomanubrial junction. Left hip exam revealed positive piriformis test and sacroiliac compression test. Range of motion was full throughout the bilateral upper and lower extremities. Strength, reflexes, sensation, and pulses normal throughout. DIFFERENTIAL DIAGNOSIS: 1. Costochondritis 2. Osteomyelitis of sternum 3. Seronegative spondyloarthropathy TEST AND RESULTS: Anterior-posterior and lateral chest x-rays: —Normal cardiac silhouette. No bony abnormalities. Anterior-posterior and lateral pelvis x-rays: — Normal joint space. No bony deformities. Nuclear medicine total bone scan: — Increased uptake at sternomanubrial interval concerning for inflammatory process. Further evaluation with CT scan suggested. CT scan of the sternum with IV contrast: — Increased uptake at the manubriosternal joint demonstrating subchondral sclerosis. CBC, RF, ESR, CRP, HLA-B27, ANA, Lupus panel and Lyme titers ordered. — Lab results normal with the exception of slightly elevated ESR. FINAL/WORKING DIAGNOSIS: Seronegative spondyloarthropathy TREATMENT AND OUTCOMES: 1. Patient referred to Rheumatology given concern for inflammatory arthritis. 2. Initiated NSAIDs and physical therapy for suspected piriformis syndrome. 3. MRI of bilateral SI joints performed and suggestive of sacroiliitis. 4. In preparation for TNF agent treatment, patient found to be Hep B core antibody positive and referred to Hepatology. 5. Started entacavir for Hepatitis B treatment and adalimumab. 6. After 2 months, the patient returned to full volleyball participation with complete resolution of her symptoms.

Discontinuation of tofacitinib after achieving low disease activity in patients with rheumatoid arthritis: a multicentre, observational study.

To determine whether tofacitinib can be discontinued in patients with RA who achieve low disease activity (LDA). RA patients with LDA after tofacitinib treatment in a phase III and long-term extension study were enrolled in this multicentre, non-randomized, open, prospective, observational study. The decision of discontinuation or continuation of tofacitinib was determined based on patient-physician decision making with informed consent. The primary endpoint was the proportion of patients who remained tofacitinib-free at post-treatment week 52. Clinical outcome was compared between those who continued and those who discontinued tofacitinib. The last observation carried forward method was used for patients who could not discontinue tofacitinib before week 52. Of 64 patients, 54 discontinued and 10 continued tofacitinib therapy. At post-treatment week 52, 20 of the 54 patients (37%) of the discontinuation group remained tofacitinib-free without disease flare. Disease activity at post-treatment week 52 was higher in the discontinuation group than the continuation group. Among the discontinuation group, the RF titre at baseline was significantly lower in patients who remained tofacitinib-free than those who did not (40 vs 113 U/ml). In fact, a higher proportion of patients with lower RF remained tofacitinib-free at week 52 compared with those with higher RF at baseline. In patients who could not achieve tofacitinib-free status, re-initiation of tofacitinib or other biologics improved disease activity. It is possible to discontinue tofacitinib without flare in about a third of patients with RA. A low RF predicts maintenance of LDA after discontinuation of tofacitinib.