New onset rheumatoid arthritis with refractory hyper-eosinophilia associated with inactivated COVID-19 vaccine

COVID-19 vaccines are considered one of the primary strategies for countering the pandemic. While mRNA based and viral vector-based vaccines have been predominantly used, inactivated SARS-CoV-2 vaccines are being manufactured in countries such as China and India. Post approval, rare but serious adverse events such as myocarditis and stroke have been observed with mRNA based and viral vectored COVID-19 vaccines. Inactivated vaccines in general have shown better tolerability in clinical trials. Here we report the first case of new-onset seropositive rheumatoid arthritis (RA) with rheumatoid nodules and refractory reactive eosinophilia within two weeks of receiving an inactivated COVID-19 vaccine (COVAXIN).

Simultaneous occurrence of accelerated nodulosis in lungs, liver, and kidneys, and acute exacerbation of interstitial pneumonia in a patient with rheumatoid arthritis: an autopsy case report

Background Accelerated nodulosis (ARN) is a rare variant of rheumatoid nodules (RNs) that is characterized by a rapid onset or the worsening of RNs. It generally develops at the fingers in patients with rheumatoid arthritis (RA) receiving methotrexate (MTX). Few case reports have described ARN at an extracutaneous location. Case presentation An elderly patient with long-standing RA was admitted to our hospital with acute respiratory failure. Computed tomography upon admission showed diffuse ground-glass opacities superimposed with subpleural reticular shadowing and honeycombing and multiple nodules in the lungs and liver. Despite the discontinuation of MTX and introduction of an immunosuppressive regimen with pulse methylprednisolone followed by a tapering dose of prednisolone and intravenous cyclophosphamide, the patient died due to the acute exacerbation (AE) of RA-related interstitial lung disease (ILD) following the parallel waxing and waning of a diffuse interstitial shadow and pulmonary and liver nodules. At autopsy, RNs were scattered throughout both lung fields in addition to extensive interstitial changes. RNs were also detected in the liver and kidneys. The foci of cryptococcosis were mainly identified in alveolar spaces. Based on the clinical and pathological findings, these nodules were most consistent with ARN because of acute increases in the size and number of previously detected pulmonary nodules. Conclusion The present case is noteworthy because ARN was concurrently detected in multiple internal organs and may be associated with the AE of RA-related ILD.

In Rheumatoid Arthritis Patients, HLA-DRB1*04:01 and Rheumatoid Nodules Are Associated With ACPA to a Particular Fibrin Epitope

ObjectivesRheumatoid arthritis (RA) is associated with HLA-DRB1 genes encoding the shared epitope (SE), a 5-amino acid motive. RA is usually preceded by the emergence of anti-citrullinated protein/peptide antibodies (ACPAs). Citrulline is a neutral amino acid resulting from post-translational modification of arginine involved in peptidic bounds (arginyl residue) by PeptidylArginine Deiminases (PADs). ACPAs recognize epitopes from citrullinated human fibrin(ogen) (hFib) and can be specifically detected by the AhFibA assay. Five citrullinated peptides derived from hFib together represent almost all of the epitopes recognized by patients with ACPA-positive RA, namely: α36–50cit, α171–185cit, α501–515cit, α621–635cit, and β60–74cit. The use of antibody fine specificities as markers of clinical phenotypes has become a major challenge. Our objective was to study whether RA clinical characteristics and HLA-DRB1 genetic background were associated with a specific reactivity against the epitopes borne by the five peptides.Methods184 ACPA-positive RA patients fulfilling the 2010 ACR/EULAR criteria were studied. Patient characteristics including HLA-DRB1 genotype, were collected from their medical files. Anti-CCP2 antibodies, AhFibA, and antibodies against the five citrullinated hFib (hFib-cit) peptides were analyzed by ELISA.ResultsAnti-α505-515cit antibodies were associated with HLA-DRB1*04:01 (OR = 5.52 [2.00 – 13.64]; p = 0.0003). High level anti-α505-515cit antibodies were associated with rheumatoid nodules (OR = 2.71 [1.00 – 7.16], p= 0.044).ConclusionImmune complexes containing anti-α501-515cit antibodies and rheumatoid factors might be involved in the development of rheumatoid nodules on the HLA-DRB1*04:01 background. Apheresis of these epitope-specific antibodies might be a new therapeutic opportunity for patients with rheumatoid nodules.

AB0058 ASSOCIATION BETWEEN HLA-DRB1*04:01, RHEUMATOID NODULES AND PARTICULAR EPITOPES OF CITRULLINATED FIBRIN IN PATIENTS WITH RHEUMATOID ARTHRITIS

Background:Rheumatoid arthritis (RA) is associated with HLA-DRB1 genes encoding the shared epitope (SE), a 5 amino acid motive. RA is usually preceded by the emergence of anti-citrullinated protein antibodies (ACPAs) detected by anti-CCP2 tests. Citrullin is a neutral amino acid resulting from post translational modification of arginin by Peptidyl Arginyl Deiminases (PADs). ACPAs recognize epitopes from citrullinated human fibrinogen (Fib-cit) and can be specifically detected by the AhFibA assay. Five peptides derived from Fib-cit together represent almost all of the epitopes recognized by patients with ACPA-positive RA: β60–74cit, α36–50cit, α621–635cit, α501–515cit and α171–185cit. As RA is a pleiomorphic disease, whose evolution is difficult to predict, the use of antibody fine specificity as a marker of clinical phenotypes has become a major challenge.Objectives:Our objective was to study whether clinical characteristics and HLA-DRB1 genetic background were associated with a specific reactivity against these epitopes.Methods:184 ACPA positive RA patients fulfilling the 2010 ACR/EULAR criteria were studied. Patients characteristics, including HLA-DRB1 genotype, were collected from their medical files. Anti-CCP2, AhFibA, Rheumatoid Factors (RF), and antibodies against the five major Fib-cit peptides were analyzed using ELISA assays.Results:Anti-CCP2 and AhFibA titres were strongly correlated (rs: 0.7037; p = 5.69x10-29, Pearson’s). Anti-α505-515cit antibodies were associated with HLA-DRB1*04:01 (OR = 5.52 [2.00 – 13.64]; p = 0.0003). High level anti-α505-515cit antibodies were significantly associated with rheumatoid nodules (OR = 2.71 [1.00 – 7.16], p= 0.044). Anti α501–515cit antibodies were associated with RF (OR=2.31 [1.10 – 4.78], p= 0.026).Conclusion:Immune complexes containing anti-α501–515cit antibodies and rheumatoid factors might be involved in the development of rheumatoid nodules on the HLA-DRB1*04:01 background. These findings highlight the role played by the HLA-DRB1*04:01 molecule and its rapid intracellular route into the lysosomes, enabling original antigen processing. Finally, purifying these epitope specific antibodies might be a new therapeutic opportunity for rheumatoid nodules.Disclosure of Interests:None declared

POS0588 USUAL INTERSTITIAL PNEUMONIA DURING RHEUMATOID ARTHRITIS: PREVALENCE AND ASSOCIATED FACTORS

Background:Lung involvement is the second common extraarticular manifestation of rheumatoid arthritis (RA). Its prevalence varies widely according to the screening tool used and it could reach up to 80% of patients. This lung disease can affect all the lung compartments. However, interstitial lung disease during RA needs a particular attention due to the increased morbidity and usual interstitial pneumonia (UIP) pattern especially due to its higher rate of mortality.Objectives:To determine the frequency and associated factors of UIP among RA patientsMethods:This was a retrospective study conducted at the Rheumatology department of Farhat Hached University Hospital from 2005 to 2020. We included all RA patients who had undergone high-resolution computed tomography (HRCT) scans of the lung. Demographic data, disease characteristics, pulmonary function tests (PFT) and drugs intake were collected at the time of the realization of the HRCT. UIP pattern and NON-UIP patterns were based on HRCT results. Khi-2 and T-student tests were used in the univariate analysis. Binary logistic regression was used in the multivariate analysis. Statistical significance level was set at 5%.Results:Fifty-nine patients with RA patients having HRCT of the lung were identified among them 27.1% (16) were male. The mean age of the patients was 60.27± 11.3 years; the mean disease duration was 7.16 ± 2.9 years and current or previous smoking habits were recorded in 18.8% (11) of our population with a median. Secondary Sjogren’s syndrome and cutaneous rheumatoid nodules were documented in 33.9% (20) and 10.17% (6) respectively. RA was erosive in 81.5% (48) of our population. The median tender joint count and the median swollen joint count were 10 and 4 respectively. The mean erythrocyte sedimentation rate (ESR) and the mean C-reactive protein (CRP) were 49±20.31 mm and 32±14.07 mg/dl respectively. The mean disease activity score (DAS 28 ESR) was 5.49±1.66. The median rheumatoid factor and Anti-CCP levels were 260UI/ml and 68 UI/ml respectively. Exertional dyspnea (stage 2 or higher) was present in 42.37% (25) and inspiratory crackles were found in 22.4% (13) of our patients. PFT revealed a restrictive ventilatory defect, an obstructive pattern and a mixed pattern were found in 20.3% (12), 13.6 (8) and 3.4% (2) respectively. The mean DLCO value was 70±24.6%. According to HRCT results, parenchymal involvement was found in 83.1% (49) of our patients and among them, we documented UIP pattern in 18 (36.73%), Non Specific Interstitial Pneumonia (NSIP) in 14.28% (7), unclassifiable fibrosis in 14.29 (7), organizing pneumonia in 2% (1) and isolated pulmonary nodules in 32.6% (16). Pleural effusion was found in 5.1% (3) and airways disease in 15.3% (9). Mediastinal lymphadenopathy was found in 15.25% (9). Abnormalities on HRCT lead to a change in treatment in 30.5% (18) of our patients. Compared to the group with a non-UIP pattern, male sex was significantly associated with UIP pattern on HRCT (47.4% vs. 17.5%, p=0.016). UIP pattern was significantly associated with smoking (37.5% vs. 9.4% p=0.022, Unadjusted OR=5.88, 95%IC=[1.217-27.634]), with cutaneous rheumatoid nodules (31.3% vs.3.4%, p=0.017, Unadjusted OR=12.72, 95IC=[1.331-121.658]) and with the presence of lymphadenopathy on HRCT (41.2% vs. 6.5%, p=0.004, Unadjusted OR=10.15, 95%IC=[1.803-57.140]). There was no significant difference between the two groups regarding age (p=0.454), disease duration (p=0.126), DAS28 (p=0.447), anti-CCP level (p=0.454). After multivariate analysis, male sex (Adjusted OR=11.58, 95%IC=[1.622-82.67] p=0.015), Presence of lymphadenopathy on HRCT (Adjusted OR=10.53, 95%IC=[1.146-96.87], p=0.037) and exertional dyspnea (Adjusted OR=6.43, 95%IC=[1.036-40.011], p=0.046) were independently associated with UIP pattern.Conclusion:UIP was present in 36.73% and it was the most prevalent pattern of lung involvement in RA. It was associated with male sex, mediastinal lymphadenopathy and exertional dyspnea.Disclosure of Interests:None declared

Complicated Rheumatoid Nodules in Lung

A 65-year-old nonsmoker lady carrying a diagnosis of seropositive erosive rheumatoid arthritis for nine years presented with acute shortness of breath, following a spontaneous pneumothorax while on combination therapy with methotrexate, leflunomide, and tocilizumab. Imaging studies revealed multiple cavitory lung nodules, and a transbronchial lung biopsy favoured a diagnosis of rheumatoid lung nodules. Her initial pathological samples were negative for any infectious cause. A follow-up computerized tomography scan (CT scan) confirmed enlargement of lung nodules with a positive antibody test for aspergillosis which needed antifungal therapy, and currently, her arthritis is managed well with rituximab therapy, sulfasalazine, and hydroxychloroquine.

Collision Lesions of Calcifying Pseudoneoplasm of the Neuraxis and Rheumatoid Nodules: A Case Report With New Pathogenic Insights

Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumor-like lesion with unclear pathogenesis. Collision lesions of CAPNONs with neoplasms are occasionally reported. In this article, we report the first case of collision lesions between CAPNON and rheumatoid nodules (RNs) in a patient with systemic lupus erythematosus. The patient was a 51-year-old female who presented with lower back pain and subsequently a lower back mass over 2 years. Spinal magnetic resonance imaging demonstrated a heterogeneous, partially calcified mass centered in the L3-4 paravertebral regions. A biopsy of the mass was diagnostic of CAPNON. As the mass grew over the following 5 months, it was resected en bloc. Its pathological examination revealed collision lesions of RNs at different histopathological stages and CAPNON lesions, and transitional lesions exhibiting combined RN and CAPNON features, with immune cell infiltrates. Our findings provide new evidence for an immune-mediated reactive process and insights into the pathogenies of CAPNON.

AB1048 RHUPUS SYNDROME IN A TERTIARY HOSPITAL

Background:Rhupus syndrome (RhS) is a rare combination of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Different studies describe RhS cases that begin with erosive arthritis and the presence of rheumatoid factor (RF) and/or anti CCP and then the SLE symptoms.Objectives:Despite the fact that RhS shows a low prevalence, it would be useful to know clinical characteristics of RhS patients since their therapy and outcome differ from those having RA or SLE alone.Methods:Retrospective study with systematic revision of electronic clinical records of RhS patients was performed. Demographic, clinical and immunological data were collected.Results:Eight RhS patients were included (all fulfilled SLICC 2012 criteria for SLE and ACR 2010 for RA). Mean age was 67.3 (45-84) years (7 were female).In 3 cases RA was the first diagnosis with a mean evolution of 4.5 years until SLE diagnosis. In contrast, in 5 cases SLE was the first diagnosis with a mean evolution of 7.2 years until RA diagnosis. Photosensitivity and arthritis were the predominant clinical manifestations. One patient presents pericarditis and other case showed rheumatoid nodules in elbows. Renal, pulmonary or neurological affection was no reported.4 patients were under biological/JAK inhibitors therapies (2 abatacept, 1 rituximab and 1 baricitinib) with favorable response of treatment.Conclusion:In contrast to other series, only the 37.5% of our RhS cases begins with polyarticular seropositive arthritis. The 62.5% started with SLE symptoms as haematological alterations, cutaneous and serological manifestation, and showed longer progression to have polyarticular affection. Thus, RhS diagnosis is earlier in patients that begin with RA symptoms. 4 RhS patients were refractory to DMARd treatments, where biological/JAK inhibitors therapies are needed.Disclosure of Interests:None declared