LONG-TERM AND BOOSTER VACCINATION RESPONSES IN PATIENTS WITH GIANT CELL ARTERITIS AND POLYMYALGIA RHEUMATICA

BackgroundVaccination remains essential in preventing morbidity of SARS-CoV-2 infections. We previously showed that >10mg/day prednisolone and methotrexate use were associated with reduced antibody concentrations four weeks after primary vaccination in patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) [1].ObjectivesHere, we performed a follow-up study to measure the decay of antibody concentrations over time and the immunogenicity of SARS-CoV-2 booster vaccination.MethodsGCA/PMR patients included in the primary vaccination (BNT162b2 or ChAdOx1) study were asked again to donate blood samples six months after primary vaccination (n=24) and one month after booster vaccination (n=46, BNT162b2 or mRNA1273). Data were compared to that of age-, sex-, and vaccine-matched controls (n=58 and n=42, respectively).ResultsAntibody concentrations decreased faster over time in GCA/PMR patients than in controls, but this decrease was not associated with treatment during primary vaccination. Post-booster antibody concentrations were comparable between patients and controls. Antibody concentrations post booster vaccination associated strongly with antibody concentrations post primary vaccination, but not with treatment during booster vaccination. However, the fold-change of post-booster vaccination showed a slight negative correlation with the post-primary vaccine antibodies.ConclusionThese results indicate that patients with impaired vaccine responses after primary vaccination, have slightly stronger increases in humoral immunity after booster vaccination, but this is not enough to reach a similar protection. The decrease in humoral immunity, and subsequent increase after booster vaccination, is likely not impacted by prednisolone or methotrexate treatment. Rather, these treatments put the patients at an immunogenic disadvantage during primary SARS-CoV-2 vaccination, which is not fully repaired by a single booster vaccination. This longitudinal study in GCA/PMR patients stresses the importance of repeat booster vaccination for patients that used >10mg/day prednisolone or methotrexate during primary vaccination.Reference[1]van Sleen Y, van der Geest, Kornelis SM, Reitsema RD, Esen I, Terpstra JH, Raveling-Eelsing E, et al. Humoral and cellular SARS-CoV-2 vaccine responses in patients with giant cell arteritis and polymyalgia rheumatica. RMD open 2022;8(2):e002479.Figure 1.Acknowledgements:NIL.Disclosure of InterestsYannick van Sleen: None declared, Kornelis van der Geest Speakers bureau: Speaker fees from Roche, Grant/research support from: Grant support from Abbvie, Annemarie Buisman: None declared, Maria Sandovici: None declared, Debbie van Baarle: None declared, Elisabeth Brouwer: None declared.

POSSIBLE ROLE OF PEPTIDE EPITOPES OF COVID-19 BNT-162B2 MRNA VACCINE IN FOMENTING AUTOIMMUNITY: AN IN SILICO ANALYSIS

BackgroundFollowing the launch of the global COVID-19 vaccination campaign, there have been increased reports of autoimmune diseases developing de novo following vaccination. These cases include rheumatoid arthritis, autoimmune hepatitis, immune thrombotic thrombocytopenia, and connective tissue diseases. Nevertheless, COVID-19 vaccines are considered safe for patients with autoimmune diseases and are strongly recommended.ObjectivesThe aim of this in silico analysis is to investigate the presence of protein epitopes encoded by the BNT-162b2 mRNA vaccine, one of the most commonly administered COVID-19 vaccines, that could elicit an aberrant adaptive immune response in predisposed individuals.MethodsThe FASTA sequence of the protein encoded by the BNT-162b2 vaccine was retrieved from http://genome.ucsc.edu and used as a key input to the Immune Epitope Database and Analysis Resource (www.iedb.org). Linear peptides with 90% BLAST homology were selected, and T-cell, B-cell, and MHC ligand assays without MHC restriction were searched and evaluated. HLA-disease associations were screened on the HLA-SPREAD platform (https://hla-spread.igib.res.in) by selecting only positive markers.ResultsA total of 183 epitopes were found, corresponding to 178 SARS-CoV-2 and 5 SARS-CoV spike epitopes, respectively. Results were obtained from 22 T-cell assays, 398 B-cell assays, and 2 MHC ligand assays. Complementary receptors included 1080 T-cell receptors and 0 B-cell receptors.Specifically, the IEDB_epitope:1329790 (NATNVVIKVCEFQFCNDPFLGVYY) was shown to bind to HLA-DRB1*15:02 and HLA-DRB1*15:03 alleles, whereas the IEDB_epitope:1392457 (TKCTLKSFTVEKGIYQTSNFRVQPT) was reported to bind to HLA-DRB1*07:01, HLA-DRB1*03:01, HLA-DRB3*01:01, and HLA-DRB4*01:01 alleles. The HLA alleles detected were found to be positively associated with various immunological disorders (Table 1).Table 1.MHC-restricted epitopes of the BNT-162b2 vaccine and potentially associated immunological conditionsEpitopeAssayMHC moleculeAssociated disease (population)NATNVVIKVCEFQFCNDPFLGVYY + OX(C10)cellular MHC/mass spectrometry ligand presentationHLA-DRB1*15:02Takayasu arteritis (Japanese) Arthritis (Taiwanese) Scleroderma (Japanese) Colitis (Japanese)HLA-DRB1*15:03Systemic lupus erythematosus (Mexican American)TKCTLKSFTVEKGIYQTSNFRVQPT + SCM(K2)as aboveHLA-DRB1*07:01Allergy, hypersensitivity (Caucasian)HLA-DRB1*03:01Type 1 diabetes (African) Sarcoidosis, good prognosis (Finnish)HLA-DRB3*01:01Graves' disease (Caucasian) Thymoma (Caucasian) Sarcoidosis (Scandinavian) Autoimmune hepatitis (Caucasian)HLA-DRB4*01:01Vitiligo (Saudi Arabian)ConclusionSimilar to the SARS-CoV-2 spike protein, the protein product of the BNT-162b2 mRNA vaccine contains immunogenic epitopes that may trigger autoimmune phenomena in predisposed individuals. Genotyping for HLA alleles may help identify at-risk individuals. However, further research is needed to elucidate the underlying mechanisms and potential clinical implications.References[1]Vita R, Mahajan S, Overton JA et al. The Immune Epitope Database (IEDB): 2018 update. Nucleic Acids Res. 2019 Jan 8;47(D1):D339-D343. doi: 10.1093/nar/gky1006.[2]Dholakia D, Kalra A, Misir BR et al. HLA-SPREAD: a natural language processing based resource for curating HLA association from PubMed s. BMC Genomics 23, 10 (2022). https://doi.org/10.1186/s12864-021-08239-0[3]Parker R, Partridge T, Wormald C et al. Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells. Cell Rep. 2021 May 25;35(8):109179. doi: 10.1016/j.celrep.2021.109179.[4]Knierman MD, Lannan MB, Spindler LJ et al. The Human Leukocyte Antigen Class II Immunopeptidome of the SARS-CoV-2 Spike Glycoprotein. Cell Rep. 2020 Dec 1;33(9):108454. doi: 10.1016/j.celrep.2020.108454.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BURDEN OF COVID-19 IN PATIENTS WITH INFLAMMATORY RHEUMATIC DISEASES: INSIGHTS FROM A SWISS APP-BASED SURVEY

BackgroundCOVID-19 comes with a significant medical risk for patients with inflammatory rheumatic diseases, with an increased risk of infection and severe outcomes[1]. The vulnerability of rheumatologic patients might also affect their quality of life[2], for example by keeping up protective measures (masking, restriction of social contacts, etc.) while the general Swiss public no longer does so.ObjectivesThe aim of this study was to better understand the health-related burden of COVID-19 among patients with inflammatory rheumatic diseases and to investigate factors contributing to a different perception of the burden of COVID-19.MethodsWe included all patients registered in the Swiss Clinical Quality Management (SCQM) registry with rheumatoid arthritis (RA), axial spondylarthritis (axSpA), psoriatic arthritis (PsA), undifferentiated arthritis, polymyalgia rheumatica or giant cell arteritis who answered the questionnaire in the mobile My-SCQM app between the 4.11 and 11.12.2022. The questionnaire contained questions about the extent to which the pandemic is affecting patients' personal and social lives. We performed descriptive analysis on the whole population and also in subgroups according to 5 treatment groups, assigned in the following order: rituximab > JAK-inhibitors > other b/tsDMARDs > csDMARDs > none of these treatments. This means that someone taking e.g., both a JAKi and a csDMARD will be assigned to the JAKi category.ResultsThe questionnaire was answered by 1357 individuals with a median age of 57 years. 63% of participants were female. 33% are living in a household with children. 36% were diagnosed with RA, 34% with axSpA, 22% with PsA and 8% with another inflammatory rheumatic disease. A total of 100 patients were prescribed csDMARDs, 94 JAKi, 18 rituximab, 695 other b/tsDMARDs, and 450 patients received none of these treatments (Table 1). 10% of patients feel their general lives are affected by COVID-19 at a level of more than 7 out of a 10 scale. 3% of the participants report that COVID-19 impacts their social environment (family and friends) as a potentially dangerous disease at a level of more than 7 out of 10 scale. After being vaccinated against COVID-19, 33% of patients report no fear of the disease, however, 27% of participants still state that their anxiety against the virus remained unchanged. There is a trend towards persistence of fear in those taking rituximab (35%) compared to the participants in other groups (26% and 20% respectively in csDMARDs and JAKi takers). More than half of the population still wear masks, and rituximab users are the most likely to wear them (72% of these individuals still do), followed by individuals on JAKi (65%) (Figure 1).ConclusionOur study revealed that after around two years of the COVID-19 pandemic, the burden of COVID-19 in patients with inflammatory rheumatic diseases in Switzerland is generally low, although it appears higher in patients with JAKi and rituximab, and that for a minority the quality-of-life still remains impacted.References[1]Conway, R., et al., SARS–CoV-2 Infection and COVID-19-19 Outcomes in Rheumatic Diseases: A Systematic Literature Review and Meta-Analysis. 2022. 74(5): p. 766-775.[2]Goldman, J.D., et al., COVID-19-19 in immunocompromised populations: implications for prognosis and repurposing of immunotherapies. 2021. 9(6).Table 1.Basic characteristics of study population.VariableLevelOverallRituximabJAKiOther b/tsDMARDscsDMARDsNone of the aboveUnclearn13571894695100161289Gender (%)Men508 (37.4)3 (16.7)19 (20.2)291 (41.9)39 (39)63 (39)93 (32)Age (median)57595956595558Diagnosis Group (%)RA498 (36.7)18 (100)67 (71.3)188 (27)69 (69)33 (20.5)123 (42.6)axSpA462 (34)011 (11.7)270 (38.8)10 (10)87 (54)84 (29)PsA296 (21.8)011 (11.7)187 (26.9)15 (15)19 (11.8)64 (22)RZA/PMR13 (1)003 (0.4)07 (4.3)3 (1)UA88 (6.5)05 (5.3)47 (6.8)6 (6)15 (9.3)15 (5.2)Figure 1.Participants' description of their current situation concerning COVID-19 (YES/NO option per criteria): a. overall b. by treatment group.[Figure omitted. See PDF]Acknowledgements:NIL.Di closure of InterestsChristoph Blapp: None declared, Shekoofeh Yaghmaei Employee of: AstraZeneca, Adrian Ciurea: None declared, Almut Scherer: None declared, Marco Kuster Employee of: AstraZeneca, Kim Lauper Speakers bureau: Pfizer, Viatris and Galapagos, Consultant of: Pfizer, Grant/research support from: Eli-Lilly.

OUTCOME FOR PATIENTS WITH GIANT CELL ARTERITIS (GCA) TREATED WITH TOCILIZUMAB ACCORDING TO NICE GUIDANCE IN A SINGLE TERTIARY UK CENTRE

BackgroundIn 2018 NICE and NHS England approved one year of weekly subcutaneous tocilizumab for use in relapsing or refractory GCA [1, 2]. During the COVID pandemic NHS England allowed extended use of tocilizumab in selected high risk patients [3]. This extension ended in March 2022. This has created a cohort of patients who are now no longer treated with tocilizumab and may be at risk of GCA flare. Currently, NHS England does not allow retreatment with tocilizumab.ObjectivesThis service evaluation used an intention-to-treat approach to retrospectively evaluate patients, who were ratified to receive tocilizumab for GCA according to the NICE guidance. We aimed to describe this cohort of patients for whom the use of tocilizumab had been approved, and their outcomes in terms of complications and disease control.Methods49 patients were ratified to receive tocilizumab between May 2019 and April 2022 by a specialist multidisciplinary team at a single tertiary rheumatology center. Their response was assessed in terms of relapse rates, steroid usage and complications as described below.Results80% of the 49 cohort of patients consisted of females (Table 1). 55% of patients were diagnosed with GCA on combination of clinical history, laboratory and temporal artery duplex findings. 94% (46/49) had at least a week's course of tocilizumab. Around half (51%) had relapsing disease. 6% had first dose as intravenous due to critical ischaemia. 27% (13/49) of patients developed complications whilst on treatment. Six developed cytopenia, 3 acquired infections and 4 stopped due to other reasons. As per guidelines, tocilizumab was stopped after 12 months in 25 patients (51%). 16% stopped treatment early due to complications. 18% had incomplete information. 10% had ongoing treatment. One patient died several months after finishing tocilizumab. 47% had methotrexate as DMARD therapy added prior to tocilizumab commencement (Figure 1). Out of 25 patients who completeted treatment, 24% (6/25) relapsed. 83% of these relapses were diagnosed on recurrence of symptoms and high inflammatory markers. In addition, 3 patients, who had tocilizumab suspended relapsed. 2/3 of these patients had treatment suspended due to infection. 5/9 relapse patients did not have preceding DMARD therapy. 22% (2/9) of relapse patients had PET-CT due to involvement of extra-cranial disease. 56% (5/9) relapsed following a median follow-up of 11 months. Of relapsed patients, seven were treated with increased dose of prednisolone and two patients received 6 months extension of tocilizumab with adequate tolerance and efficacy.ConclusionOur data shows good tolerability of tocilizumab and a 24% flare rate amongst patients who completed treatment. This is less than the 50% rate seen in GiACTA and other cohorts, where the majority of which occurred within 6 months of stopping treatment [4]. DMARD treatment may reduce relapse rate, but this will require further study. The data describing the efficacy of treatment beyond one year is limited [3]. However, with no established guidance for treating patients following tocilizumab, extension of treatment is a plausible option.References[1]Tocilizumab for treating giant cell arteritis, NICE Technology Appraisal Guidance, 18 April 2018. https://www.nice.org.uk/guidance/ta518/resources/tocilizumab-for-treating-giant-cell-arteritis-pdf-82606786726597[2]Stone J, Tuckwell K, Dimonaco S et al.Trial of Tocilizumab in Giant-Cell Arteritis. N Engl J Med 2017;377:317-328.[3]Regola F, Cerudelli E,Bosio G. Long-term treatment with tocilizumab in giant cell arteritis: efficacy and safety in a monocentric cohort of patients Rheumatology Adv Pract 2020;0:1–9.[4]Conway R, Putman MS, Mackie SL. Benchmarking tocilizumab use for giant cell arteritis. Rheumatol Adv Pract. 2022;6(2):rkac037.Figure 1.Table 1.GenderAge at time of diagnosisIndication for stopping treatmentMaleFemale50-5960-6970-7980-89Completed treatmentComplicationsOngoing treatmentIncomplete information18313162010251058Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Navigating Giant Cell Arteritis (Gca) Service during and Post Covid-19 Pandemic: An Audit of Gca Care at North Bristol Nhs Trust against the Bsr Quality Standards

Background/Aims GCA is a systemic vasculitis predominantly affecting the large vessels that requires prompt diagnosis and management. This clinical audit aims to study the impacts of COVID-19 pandemic on our GCA service and to identify areas for improvement to ensure good and safe practice amid healthcare crisis. Methods We audited referrals for suspected GCA from February 2021 until September 2022 and measured our patient care against the BSR quality standards. We performed retrospective data collection from digital care record systems and analysed our data using the IBM SPSS Statistics version 29. Results 106 patients with suspected GCA were included, 73% were female and the mean age was 70 years. 75% of the referrals were from primary care. Main presenting symptoms were headaches (95.7%), scalp tenderness (69.6%), tongue/jaw claudication (52.2%), visual symptoms (47.8%), constitutional symptoms (43.5%) and polymyalgic symptoms (21.7%). 33% of patients were diagnosed and treated as GCA. Mean CRP was 23.9mg/L and mean plasma viscosity was 1.89mPA. The mean referral-to-specialist review time has reduced to 1.6 days, compared with 2.7 days pre-pandemic. All patients had vascular ultrasound but only 7.5% had a temporal artery biopsy (TAB), compared with 41% pre-pandemic. Table 1 compares expected and achieved BSR quality standards. Conclusion Changes in work pattern during the pandemic meant that the time from referral to specialist review was significantly reduced, by implementing twice weekly registrar-led 'Hot' clinics and reserving ad hoc slot(s) in on-call consultant's clinics for GCA referrals. We have ramped up our vascular imaging capacity for vascular ultrasound during the pandemic in response to reduced surgical operating capacity for TAB. Strategies to address areas for improvement identified in this audit include: (1) clear and timely communication with referrer about steroid initiation and dosage, at the time of referral;(2) improving communication with primary care, emphasising need for urgent Ophthalmology input in patients with suspected GCA-related visual symptoms, through updating our regional GCA guideline for primary care;(3) standardising and implementing a GCA review proforma or checklist in our department to ensure that the BSR GCA care bundle is being implemented and addressed at the earliest opportunity. (Table Presented).

Inflammatory and Infectious Vasculopathies

Inflammatory and infectious disorders have been important, if uncommon, causes of stroke. Primary and secondary vasculitides may cause stroke affecting large and small blood vessels of the central nervous system. The pathology may include granulomatous, lymphocytic, and necrotizing lesions. The underlying antigens leading to vasculitis may include amyloid deposition from amyloid angiopathy, or even from infectious agents, although the mechanisms for these disorders remain poorly understood. Many of these conditions have a poor prognosis, although steroid and other immunosuppressive therapies may improve outcomes. Further research, including well-designed clinical trials, are needed. Although infections, such as syphilis, have been associated with stroke risk for more than a century, understanding the relationship between infection and stroke has taken on even greater urgency in the era of the coronavirus disease 19 pandemic. A multitude of pathogens, including bacteria, viruses, parasites, and fungi, have been associated with specific stroke syndromes, through a number of different mechanisms, including large vessel vasculopathy, aneurysmal dilatation, thrombophilia, and cardioembolism. Some infections may also contribute to the atherosclerotic process. This chapter will cover the clinical features, pathophysiology, and potential treatment (where available) for inflammatory and infectious causes and contributors to stroke risk. © 2022 Elsevier Inc.

Challenges in the Diagnosis and Investigation of Giant Cell Arteritis during Covid- 19 Pandemic Restrictions: Does the Southend Pretest Probability Score Help to Guide Clinical Diagnosis?

Background/Aims During 2020-2021 many usual hospital services were affected as focus turned towards managing COVID-19. Elective outpatient surgery ceased and rheumatology staff were redeployed to covid wards. This reduced the availability of temporal artery biopsy (TAB) and temporal artery ultrasound (TAUS) to aid in diagnosing giant cell arteritis (GCA). The rheumatology team making diagnoses of GCA or not-GCA were doing so often based entirely on clinical and laboratory findings. We aimed to determine referral patterns and investigations for suspected GCA during the covid pandemic, compare diagnoses at 6 months after initial assessment and retrospectively apply the Southend Pretest Probability Score (PTPS) and correlate with the diagnosis of GCA or not-GCA. Methods We reviewed all electronic referrals for suspected GCA from July 2020 - June 2021. Clinical details and investigations reviewed. PTPS applied giving a result of low, intermediate or high probability of GCA. Results 84 referrals for suspected GCA over 12 months. 20 diagnosed GCA/ large vessel vasculitis (LVV), 64 not-GCA. Peak referral months Nov 2020 and April 2021 with 13 and 16 referrals. Lowest in October 2020 with 1 referral. 57 female, 27 male. Mean age 70.1 years. 19% male referrals diagnosed GCA, 26% female diagnosed GCA. All LVV and PMR diagnoses were female. 27 TAUS, 6 TAB, 7 PET, 13 CT, 3 MRI performed. 30 patients had no additional investigations. Of 20 GCA;14 had supporting investigations, 6 were clinical diagnoses. All GCA diagnoses were consistent at 6 months. One not-GCA case was subsequently diagnosed with LVV on CTPET. All other not-GCA diagnoses were consistent at 6 months. The PTPS was retrospectively applied based on available clinical information in all except 2 cases, and compared to GCA/not-GCA diagnosis and investigations undertaken. Conclusion Referral numbers for suspected GCA were higher than previous years however the number of actual GCA diagnoses was similar. With limitations on diagnostic investigations due to covid, diagnoses of GCA with and without additional tests were accurate at 6 months, and correlated with a high probability score. The PTPS is a therefore valuable clinical tool in the assessment of GCA. (Table Presented).

Outcomes of Sars-Cov-2 Infection in Patients with Anca Associated Vasculitis. Data from the National Sar-Covid Registry

Objectives: To describe the clinical characteristics and outcomes of SARSCoV-2 infection in patients with systemic vasculitis. Method(s): Observational, multicenter, cross-sectional analytical study in patients 18 or older diagnosed with systemic vasculitis with confirmed SARSCoV-2 infection (RT-PCR or serology) included in the SAR-COVID registry. Patients were evaluated from July 2020 to February 2022. Patients diagnosed with ANCA-associated vasculitis (AAV), other systemic vasculitides (Giant cell arteritis, Takayasu), and a control group of patients with other rheumatological diseases matched by age, sex, comorbidities, and date of SARS-CoV-2 infection. The survival curve of the groups was studied by Kaplan-Meier and compared through the Log-Rank Test. A Cox regression model will be performed to adjust survival for different variables (sex, age, treatments for underlying disease, treatments for viral infection, smoking, obesity, d-dimer level, and disease activity). Result(s): A total of 282 out of 2694 patients in the SAR-COVID registry were included, 57.4%women with a mean age of 55.7 years (SD 14.1). Fifty-four patients in the AAV group, 32 in the other vasculitis group, and 196 controls were studied. Hospitalization was required in 53.7% of the AAV group, 37.5% in other vasculitides, and 26.2% in the control group. 5.6% of patients in the control group presented acute respiratory distress syndrome (ARDS), 15.6% in the other vasculitis group, and 22.2% in the AAV group (p alpha 0.001). Complete recovery was observed in 82.3% of patients in the control group, 75%in the other vasculitis group, and 63%in the AAV group.We observed that 5.7% of the patients in the control group died from COVID-19, 9.4%from other vasculitides, and 27.8% in the AAV group (p alpha 0.001). We found a lower survival in the AAV group compared to the control group (p alpha 0.005). In the multivariate Cox regression model, older age (HR:1.05 IC95%1.01-1.09 p = 0.01), BMI > 40 (HR:13.2 IC95% 2.1-83.2 p = 0.01), and high activity of the underlying disease (HR:16 95% CI 3.7-69.4 p alpha 0.005) were associated with lower survival. Conclusion(s): In conclusion, patients diagnosed with AAV presented a worse disease course during SARS-CoV-2 infection with a more frequent requirement for invasive mechanical ventilation. Likewise, these patients showed lower survival compared to patients with other autoimmune diseases.

Esophageal Mucosal Calcinosis: A Rare Site of Calcium Deposition in End-Stage Renal Disease

Introduction: Calciphylaxis, otherwise known as calcium uremic arteriolopathy, is defined as calcium deposition around blood vessels in skin and fat tissue which occurs in 1-4% of patients with end-stage renal disease (ESRD). Calcium deposition in the esophagus is extremely rare;to date, there have been only 4 cases reported worldwide. We report the fifth case of esophageal mucosal calcinosis occurring in a young male with ESRD. Case Description/Methods: A 37-year-old Thai man with ESRD on peritoneal dialysis since 2005 presented with generalized weakness and odynophagia due to oral ulcers, resulting in poor PO intake. He denied drinking alcohol, illicit drug use, or smoking. On exam his abdomen was soft, non-distended, non-tender, without any guarding. Past medical history included hypertension and COVID-19 in January 2022. Laboratory tests revealed neutropenia and pancytopenia, hyperphosphatemia, and hypocalcemia. EGD revealed distal esophageal esophagitis and hemorrhagic erosive gastropathy. Biopsy showed ulcerative esophagitis with dystrophic calcification, consistent with esophageal mucosal calcinosis .No intestinal metaplasia was noted. Immunohistochemistry was negative for CMV, HSV1, and HSV2. The patient was treated with pantoprazole 40mg IV every 12 hours, Magic Mouthwash 5ml qid, and Carafate 10mg qid. He was transferred to a cancer center where he had a bone marrow biopsy formed which was negative. His symptoms resolved and the patient was discharged to home (Figure). Discussion(s): Esophageal mucosal calcinosis is extremely rare. It is due to a combination of factors involving acidosis and the phenotypic differentiation (and apoptosis) of vascular smooth muscle cells (VSMC) into chondrocytes or osteoblast-like cells. These changes, along with the passive accumulation of calcium and phosphate, induce calcification. Acidosis is well-known to promote inflammation of the arterial walls, releasing cytokines that induce vascular calcification. The benefits of treatment with sodium thiosulfate remain unclear. An ample collection of cases should help devise standardized treatment options and establish management guidelines for this condition.

An Audit of Demographics, Symptoms & Investigations: Part of the Survey of Gca in the Sehsct during the Covid-19 Pandemic

Background/Aims Giant cell arteritis (GCA) is the most common vasculitis in adults aged over 50 years old with the highest incidence among persons aged 70- 79. It is more commonly seen in female patients. Most cases have been reported in whites of Northern European descent. A broad range of symptoms can be reported including headache, jaw or tongue claudication, visual disturbances, PMR and other systemic features including weight loss, fever and sweats. In recent years new evidence has emerged regarding the investigation and treatment of GCA. This audit is to review the demographics, symptoms and investigations of patients who presented to the Rheumatology Department in SEHSCT with features concerning for possible GCA. Methods Retrospective collection of data from January 2020 to July 2021 using the regional Electronic Care Record NI with reference to presentations, investigation results, clinic records and follow-up letters. Results 70 patients were included (24 males and 46 females). Mean age was 72 years old. Table 1 shows the percentages of clinical symptoms reported. All patients investigated had an ESR (mean 57.8) and CRP (mean 54.1) checked. 43 patients had ANCA checked with 3 positive results. 40 patients underwent CT brain with 2 abnormalities reported unrelated to GCA. TA ultrasound was performed on one occasion with a positive result demonstrating ''halo'' sign recorded. 6 patients underwent CTPET with 3 diagnoses of LVV and 1 of PMR. 70 TAB performed with 12 positive results and 4 'suggestive' of GCA. Conclusion Our cohort of patients demonstrated demographics similar to the current global geographic trends in GCA. There are a broad range of clinical symptoms that can present in GCA, none of which are entirely specific or pathognomonic. Clinical diagnosis is based on clinical symptoms, signs and laboratory tests, each of which are imperfect markers for GCA. Our audit demonstrated that the use of additional confirmatory diagnostic tests including temporal artery ultrasound and CTPET was being under-utilized in the SEHSCT. Use of these tests may improve the diagnostic yield in this challenging condition. As a result of this audit, a quality improvement project to provide a rapid access GCA pathway is being designed. (Table Presented).

A Systematic Review of New Rheumatic Immune-Mediated Inflammatory Diseases (R-Imid) Following Sars-Cov-2 Vaccinations

Background/Aims There are sporadic reports about the development of new rheumatic immune-mediated inflammatory diseases (R-IMIDs) in adults after receiving SARS-CoV-2 vaccines. This systematic review (SR) aimed to critically review and summarize the clinical profile, patient demographics, treatment, and prognosis of new-onset R-IMIDs following SARS-CoV-2 vaccination. Methods We retrieved English-language articles (Case reports and series and observational studies) on new-onset R-IMIDs following SARS-CoV-2 vaccination, published until June 2022, from standard databases (MEDLINE, Embase, Cochrane). The search strings used during the literature search incorporated 'SARS-CoV-2 vaccination' (along with related MeSH terms) and various key terms for R-IMIDs [which included (but was not limited to) inflammatory arthritis, connective tissue disease (CTD), vasculitis, systemic lupus erythematosus, Sjogren's syndrome, sarcoidosis, systemic sclerosis, idiopathic inflammatory myositis, anti-synthetase syndrome, Adult-onset Stills disease (AOSD), giant cell arteritis (GCA), and polymyalgia rheumatica (PMR)]. The protocol was registered in PROSPERO (CRD42022318561). Results Of the total 2179 articles retrieved, 1986 articles were excluded following the title- screening, and 107 articles that did not meet inclusion criteria. We included the remaining 86 articles (130 cases) upon full-text screening. Furthermore, we added four articles (six cases) based on a manual search, comprising 90 articles (136 cases) for final analysis. These 136 new R-IMID cases were reported from 27 different countries. Of these, more than one-third of the cases were reported from three countries (viz., Italy, Japan, and the USA). The patients had a mean age of 57 (range:17-90) years, and the majority were females (63.0%). Most patients developed R-IMIDs after receiving Pfizer-BioNTech vaccine (76;55%), followed by Oxford AstraZeneca vaccine (35;25%). The mean duration between SARSCoV- 2 vaccination and R-IMIDs development was 9.2 (range:1-90) days. The second dose of the vaccine resulted in more R-IMIDs (74;54%) than the first (53;39%). CTDs (34;25%) and small vessel vasculitis (33;24%) were the commonest R-IMID manifestations, followed by inflammatory arthritis and AOSD, each in 13 (9.5%) cases. Nearly half of the patients with CTDs had Idiopathic Inflammatory Myositis. PMR and GCA accounted for 16 (11.7%) and 5 (3.6%) cases, respectively. However, no cases of axial spondylarthritis were reported. Most (118;86%) R-IMID patients were treated with corticosteroids, with a small number receiving steroid-sparing drugs, such as methotrexate, rituximab and cyclophosphamide. Most (125;91%) went into either disease remission or improvement following the treatment. Only three patients were admitted to the intensive care unit (ICU) to manage their disease;One of them died due to fatal myositis and rhabdomyolysis;two surviving ICU patients had ANCA-associated vasculitis with lung involvement. Conclusion Although rare, this SR highlights the emergence of de novo R-IMIDs following SARS-CoV-2 vaccination. We cannot confirm the causality between the vaccination and the onset of R-IMID. However, further research is warranted in this area.

A Novel Large-Vessel Arteritis in SARS-CoV-2-Related Multisystem Inflammatory Syndrome in Children (MIS-C).

Multisystem inflammatory syndrome in children (MIS-C) is a newly defined condition associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The syndrome has been described as a "Kawasaki disease"-like illness and the spectrum of associated abnormalities, including vascular complications, remain to be fully defined. The novel findings of a large-vessel arteritis in this report will add to the understanding of this syndrome and its associated vascular complications.

Unusual Myositis of the Temporalis Muscle Occurring with Acute Covid-19

Background. SARS-CoV-2 infection can be accompanied by neuromuscular disorders. Rhabdomyolysis and Guillain-Barre syndrome have been described repeatedly. There are case reports of inflammatory myopathies manifesting during COVID-19, presenting as dermatomyositis, polymyositis or immune-mediated necrotizing myopathy, with dermatomyositis-like presentations most commonly reported. Larger cases series are from postmortem examinations of COVID-19 patients, where variable inflammatory pathology of the skeletal muscle has been found frequently but without local detection of the actual virus. Thus, autoimmune mechanisms or the systemic interferon response are discussed as causes. We report a case of focal inflammatory myopathy with perimysial pathology of the temporalis muscle occurring with acute, but mild COVID-19. Methods. Case report of clinical observations, cranial MRI, histopathological, and laboratory findings. 3T cranial MRI was performed with gadolinium contrast. Open temporalis muscle biopsy was performed. The sample underwent standard cryohistological studies as well as immunohistochemistry with antibodies against MHC-I and II, CD3, CD4, CD19, CD68, anti-MAC, p62 and MxA. Testing for auto-antibodies was based on immunoblots or ELISA. RT-PCR for SARS-CoV-2 was run with RNA extracted from cryopreserved muscle. Results. A Caucasian woman in her 60s with no history of autoimmune or muscle complaints developed swelling and pain of the right jaw musculature five days after testing positive for SARS-CoV-2 due to respiratory tract symptoms. In addition, she experienced trismus, but no further neuromuscular complaints. The course of respiratory tract symptoms stayed mild. She had been vaccinated previously with single shot SARS-CoV-2 vector vaccine. Due to persistent swelling and complaints, giant cells arteritis was excluded by unresponsiveness to five days oral steroids and sonography of the temporal artery. Cranial MRI was performed nearly four weeks after the SARS-CoV-2 infection and showed marked swelling and oedema of the temporalis muscle. Its biopsy showed numerous CD68 and acid phosphatase positive cells infiltrating from perimysial perivascular foci towards the endomysium with perimysial damage but little damage of adjacent, perifascicular muscle fibres. Muscle fibres did not react with anti-MHC-II, anti-MAC or -MxA. Capillaries did not react with anti-MAC or -MxA. SARS-CoV-2 RNA was not detected in muscle tissue. Serum creatine kinase was not elevated in the subacute phase. Slightly elevated ANA titre led to detection of autoantibodies against proliferating cell nuclear antigen (PCNA). No pathological results for other autoantibodies, including myositis-specific antibodies and anti-ds-DNA, were found in blood. Neither were antibodies against hepatitis C and B viruses. Retesting 15 weeks after infection, anti-PCNA immunoblot was still positive, but ELISA did not indicate a pathologic titre. The swelling, myalgia and trismus regressed spontaneously a month after onset, yet the latter still persists at the time of reporting. Conclusion. Our case diverges from the majority of COVID-19 associated my-ositis reports in the unusual location of the focal myositis and the histopathological pattern of predominantly perimysial damage and histiocytic infiltration. It concurs with the literature as no SARS-CoV2 RNA could be detected in the muscle. Anti-PCNA is associated very rarely with myositis. Other associated disorder (systemic lupus erythematosus, chronic viral hepatitis B or C) were not found. Increased levels of autoantibodies are reported in COVID-19 and mostly attributed to loss of self-tolerance during the acute disease phase. Interestingly, the structural protein M of SARS-CoV-2 appears to interact notably with PCNA in infected cells. Still, the causal connection between the myositis and COVID-19 in this case is based on the close temporal association in the absence of alternative, competing explanations from the medical history and findings.

HLA DRB1*15/DRB1*16 might not be protective alleles in COVID-19- induced large vessel giant cell arteritis

Case report Background: Giant cell arteritis (GCA) is an immune-mediated vasculitis affecting large arteries. It has been hypothesized that pathogens including viruses may trigger inflammation within the vessel walls. Human leukocyte antigens' (HLA) genetic studies have previously reported HLA-DR4 (HLA-DRB1* 04 and HLA-DRB1* 01) as susceptibility, and HLA-DR2 (HLA-DRB1* 15 and HLA-DRB1* 16) as protective alleles for GCA. Here we report two cases of large vessel (LV) GCA diagnosed in patients previously suffered from mild coronavirus disese 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2). Case presentation: First case, a 69-year- old male, had a mild COVD-19 three months before the appearance of headache, malaise, and a febrile state associated with extremely increased inflammatory parameters (CRP 2847 mg/dl and IL-6 802.3 pg/ml). Computed tomography examination of the aorta (CTA) and the branches, performed in two occasions six months apart, showed an interesting picture of a migratory arteritis. HLA typing showed: HLA-A* 2,-A* 24;-B* 51,-B* 57;-DRB1* 15,-DRB1* 16;-DQB1* 05,-DQB1* 06;Second case, a 64-year- old female, was evaluated for LV-GCA two months after a mild COVID-19, when she presented with elevated CRP (183mg/dl) and systemic symptoms. Thickening of the ascending aorta and the aortic arch was seen on CTA. Typing of HLA revealed: HLA-A* 2,-A* 11;-B* 27,-B* 35;-DRB1* 14,-DRB1* 15;-DQB1* 05,-DQB1* 06;A whole-body 18F-FDG- PET/ CT performed in both cases revealed inflammation of the ascending, aortic arch, thoracic and abdominal aorta. The first patient had appearance of the inflammatory involvement of the iliac and femoral arteries, while the second patient had an additional pulmonary trunk inflammation. Corticosteroid treatment was introduced in both cases. Due to a progressive inflammatory course of LV-GCA in the first case, the IL-6 inhibitor (tocilizumab) was initiated, leading to a clinical and laboratory improvement. In conclusion, LV-GCA may be considered as an autoimmune disease triggered by SARS-CoV- 2, as one of the broad spectrum of manifestation within the post acute COVID-19. None of the previously known HLA susceptibility alleles for GCA were detected in our patients. In contrast, both patients had DRB1*15 allele, and one of them was DRB1*15/DRB1*16 carrier, suggesting a possibility of losing their protective effect in LV-GCA induced by COVID-19.

Management of Patients Affected by Giant Cell Arteritis during the COVID-19 Pandemic: Telemedicine Protocol TELEMACOV.

Giant cell arteritis (GCA) is the most common primary systemic vasculitis in western countries, prevalently affecting elderly people. Both early diagnosis and regular monitoring are necessary for the correct management of GCA. Following the outbreak of the COVID-19 pandemic, government decisions aiming at reducing the contagion led to reductions in health activities, limiting them to urgent cases. At the same time, remote monitoring activities have been implemented through telephone contacts or video calls carried out by specialists. In line with these deep changes affecting the worldwide healthcare system and in consideration of the high risk of GCA morbidity, we activated the TELEMACOV protocol (TELEmedicine and Management of the patient affected by GCA during the COVID-19 pandemic) in order to remotely monitor patients affected by GCA. The aim of this study was to evaluate the effectiveness of telemedicine in the follow-up of patients already diagnosed with GCA. This was a monocenter observational study. Patients with a previous diagnosis of GCA admitted to the Rheumatology Unit of the University Hospital "Città della Salute e della Scienza" in Turin were monitored every 6-7 weeks by means of video/phone calls from 9 March to 9 June 2020. All patients were asked questions concerning the onset of new symptoms or their recurrence, exams carried out, changes in current therapy, and satisfaction with video/phone calls. We performed 74 remote monitoring visits in 37 GCA patients. Patients were mostly women (77.8%) and had a mean age of 71.85 ± 9.25 years old. The mean disease duration was 5.3 ± 2.3 months. A total of 19 patients received oral glucocorticoids (GC) alone at the time of diagnosis with a daily dose of 0.8-1 mg/kg (52.7 ± 18.3 mg) of prednisone, while 18 patients were treated with a combination of oral steroids (at the time of diagnosis, the prednisone mean dose was 51.7 ± 18.8 mg) and subcutaneous injections of tocilizumab (TCZ). During the follow-up, patients additionally treated with TCZ reduced their GC dose more than patients treated with GC alone (p = 0.03). Only one patient, who was treated with GC alone, had a cranial flare and needed to increase the dosage of GC, which led to rapid improvement. Furthermore, all patients proved very adherent to the therapies (assessed by Medication Adherence Rating Scale (MARS)) and considered this type of monitoring very satisfactory according to a Likert scale (mean score 4.4 ± 0.2 on a 1-5 range). Our study shows that telemedicine can be safely and effectively used in patients with GCA under control as a possible alternative, at least for a limited period of time, to traditional visits.

Increased incidence of giant cell arteritis and associated stroke during the COVID-19 pandemic in Spain: A nation-wide population study.

INTRODUCTION: SARS-CoV-2 infection and COVID-19 vaccines might have increased the incidence of giant-cell arteritis (GCA) and the risk of associated stroke in Spain. METHODS: Retrospective nation-wide observational analysis of all adults hospitalized with GCA in Spain during 5 years (Jan-2016 and Dec-2021). The incidence and proportion of admissions with or because of GCA and GCA-associated stroke were compared between pre-pandemic (2016-2019) and pandemic (2020 and 2021) years. Sensitivity analyses were conducted for the different COVID-19 waves and vaccine timing schedules. RESULTS: A total of 17,268 hospital admissions in patients diagnosed with GCA were identified. During 2020 there were 79.3 and 8.1 per 100,000 admissions of GCA and GCA-associated stroke, respectively. During 2021 these figures were 80.8 and 7.7 per 100,00 admissions, respectively. As comparison, yearly admissions due to GCA and GCA-associated stroke were 72.4 and 5.7 per 100,00, respectively, during the pre-pandemic period (p < 0.05). Coincident with the third wave of COVID-19 (and first vaccine dosing), the rate of GCA-associated stroke admissions increased significantly (from 6.7 to 12%; p < 0.001). Likewise, there was an increase in GCA-associated stroke (6.6% vs 4.1%, p = 0.016) coincident with the third dose vaccination (booster) in patients older than 70 at the end of 2021. In multivariate analysis, only patients admitted during the third COVID-19 wave (and first vaccine dosing) (OR = 1.89, 95% CI 1.22-2.93), and during the third vaccination dosing in patients older than 70 (booster) (OR = 1.66, CI 1.11-2.49), presented a higher GCA-associated stroke risk than the same months of previous years after adjustment by age, sex, classical cardiovascular risk factors and COVID-19 diagnosis. CONCLUSIONS: The COVID-19 pandemic led to an increased incidence of GCA during 2020 and 2021. Moreover, the risk of associated stroke significantly risen accompanying times of COVID-19 vaccine dosing, hypothetically linked to an increased thrombotic risk of mRNA-SARS-CoV-2 vaccines. Hence, forthcoming vaccine policies and indications must weigh the risk of severe COVID-19 with the risk of flare or stroke in patients with GCA.

Outcomes during and after long-term tocilizumab treatment in patients with giant cell arteritis.

OBJECTIVE: To assess outcomes in giant cell arteritis (GCA) patients during and after long-term tocilizumab (TCZ) treatment. METHODS: Retrospective analysis of GCA patients treated with TCZ at a single centre (2010-2022). Time to relapse and annualised relapse rate during and after TCZ treatment, prednisone use, and safety were assessed. Relapse was defined as reappearance of any GCA clinical manifestation that required treatment intensification, regardless of C reactive protein levels and erythrocyte sedimentation rate. RESULTS: Sixty-five GCA patients were followed for a mean (SD) of 3.1 (1.6) years. The mean duration of the initial TCZ course was 1.9 (1.1) years. The Kaplan-Meier (KM)-estimated relapse rate at 18 months on TCZ was 15.5%. The first TCZ course was discontinued due to satisfactory remission achievement in 45 (69.2%) patients and adverse events in 6 (9.2%) patients. KM-estimated relapse rate at 18 months after TCZ discontinuation was 47.3%. Compared with patients stopping TCZ at or before 12 months of treatment, the multivariable adjusted HR (95% CI) for relapse in patients on TCZ beyond 12 months was 0.01 (0.00 to 0.28; p=0.005). Thirteen patients received >1 TCZ course. Multivariable adjusted annualised relapse rates (95% CI) in all periods on and off TCZ aggregated were 0.1 (0.1 to 0.2) and 0.4 (0.3 to 0.7), respectively (p=0.0004). Prednisone was discontinued in 76.9% of patients. During the study, 13 serious adverse events occurred in 11 (16.9%) patients. CONCLUSION: Long-term TCZ treatment was associated with remission maintenance in most patients with GCA. The estimated relapse rate by 18 months after TCZ discontinuation was 47.3%.