REDUCED HEALTH-RELATED QUALITY OF LIFE USING PROMIS IN PATIENTS WITH SYSTEMIC SCLEROSIS: A CROSS-SECTIONAL ANALYSIS FROM THE INTERNATIONAL COVAD-2 E-SURVEY

BackgroundThe second COVID-19 vaccination in autoimmune disease (COVAD-2) study [1] is an international, multicentre, self-reported e-survey designed to evaluate several facets covering COVID-19 infection and vaccination as well as validated patient-reported outcome measures (PROMs) in a variety of autoimmune diseases (AIDs), including systemic sclerosis (SSc). Detailed assessment of the health-related quality of life (HRQOL) and its drivers in patients with SSc is lacking.ObjectivesTo assess physical and mental health in a global cohort of SSc patients in comparison with non-SSc autoimmune inflammatory rheumatic diseases (AIRDs), non-rheumatic AIDs (NRAIDs), and those without AIDs (controls) using Patient-Reported Outcome Measurement Information System (PROMIS) global health data from the COVAD-2 survey.MethodsThe COVAD-2 database was used to extract demographics, AID diagnosis, comorbidities, disease activity, current therapies, and PROMs. PROMIS global physical health (GPH), global mental health (GMH) scores, PROMIS physical function short form-10a (PROMIS PF-10a), pain visual analogue scale (VAS), and PROMIS Fatigue-4a scores were compared between SSc, non-SSc AIRDs, NRAIDs, and controls. Outcomes were also compared between diffuse cutaneous SSc (dcSSc) vs limited cutaneous SSc (lcSSc). Multivariable regression analysis was performed to identify factors influencing GPH and GMH scores in SSc.ResultsA total of 10,502 complete responses from 276 SSc, 6006 non-SSc AIRDs, 545 NRAIDs, and 3675 controls as of May 2022 were included in the analysis. Respondents with SSc were older [SSc vs. non-SSc AIRDs vs. NRAIDs vs. controls: 55 (14) vs. 51 (15) vs. 45 (14) vs. 40 (14) years old, mean (SD), p < 0.001]. Among patients with SSc, 129 (47%) had dcSSc and 147 (53%) had lcSSc. SSc patients reported a significantly higher prevalence of ILD [SSc vs. non-SSc AIRDs vs. NRAIDs vs. controls: 30.4% vs. 5.5% vs. 1.5% vs. 0.2%, p < 0.001], and treatment with MMF [SSc vs. non-SSc AIRDs vs. NRAIDs vs. controls: 26.4% vs. 9.5% vs. 1.1% vs. 0%, p < 0.001].Patients with SSc had lower GPH and PROMIS PF-10a scores [SSc vs. non-SSc AIRDs vs. NRAIDs vs. controls: 13 (11–15) vs. 13 (11–15) vs. 15 (13–17) vs. 17 (15–18), median (IQR), p < 0.001;39 (33–46) vs. 39 (32–45) vs. 47 (40–50) vs. 49 (45–50), p < 0.001, respectively] and higher Pain VAS and PROMIS Fatigue-4a scores compared to those with NRAIDs or controls [SSc vs. non-SSc AIRDs vs. NRAIDs vs. controls: 3 (2–5) vs. 3 (1–6) vs. 2 (0–4) vs. 0 (0–2), p < 0.001;11 (8–14) vs. 11 (8–14) vs. 9 (7–13) vs. 7 (4–10), p < 0.001, respectively]. Patients with AIDs including SSc had lower GMH scores compared to controls [SSc vs. non-SSc AIRDs vs. NRAIDs vs. controls: 12.5 (10–15) vs. 13 (10–15) vs. 13 (11–16) vs. 15 (13–17), p < 0.001].Among SSc patients, GPH, GMH, and PROMIS PF-10a scores were lower in dcSSc compared to lcSSc [dcSSc vs. lcSSc: 12 (10–14) vs. 14 (11–15), p < 0.001;12 (10-14) vs. 13 (10-15), p<0.001;38 (30–43) vs. 41 (34–47), p < 0.001, respectively]. Pain VAS and PROMIS Fatigue-4a scores were higher in dcSSc compared to lcSSc [4 (2–6) vs. 3 (1–5), p < 0.001;12 (8–15) vs. 9 (8–13), p < 0.001, respectively].The independent factors for lower GPH scores in SSc were older age, Asian ethnicity, glucocorticoid use, and higher pain and fatigue scales, while mental health disorders and higher pain and fatigue scales were independently associated with lower GMH scores.ConclusionIn a global cohort, patient-reported physical and mental health were significantly worse in patients with SSc in comparison to those with non-SSc AIDs and without AIDs. Our findings support the critical need for more attention to patient's subjective experiences including pain and fatigue to improve the HRQOL in patients with SSc.Reference[1]Fazal ZZ, Sen P, Joshi M, et al. COVAD survey 2 long-term outcomes: unmet need and protocol. Rheumatol Int. 2022;42: 2151–58.Acknowledgements:NIL.Disclosure of InterestsKeina Yomono: None declared, Yuan Li: None dec ared, Vahed Maroufy: None declared, Naveen Ravichandran: None declared, Akira Yoshida: None declared, Kshitij Jagtap: None declared, Tsvetelina Velikova Speakers bureau: Pfizer and AstraZeneca, Parikshit Sen: None declared, Lorenzo Cavagna: None declared, Vishwesh Agarwal: None declared, Johannes Knitza: None declared, Ashima Makol: None declared, Dey Dzifa: None declared, Carlos Enrique Toro Gutierrez: None declared, Tulika Chatterjee: None declared, Aarat Patel: None declared, Rohit Aggarwal Consultant of: Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, Abbvie, Janssen, Kyverna Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, Roivant, Merck, Galapagos, Actigraph, Scipher, Horizon Therepeutics, Teva, Beigene, ANI Pharmaceuticals, Biogen, Nuvig, Capella Bioscience, and CabalettaBio, Grant/research support from: Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, Abbvie, Janssen, Kyverna Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, Roivant, Merck, Galapagos, Actigraph, Scipher, Horizon Therepeutics, Teva, Beigene, ANI Pharmaceuticals, Biogen, Nuvig, Capella Bioscience, and CabalettaBio, Latika Gupta: None declared, Masataka Kuwana Speakers bureau: Abbvie, Asahi-Kasei, Astellas, Boehringer-Ingelheim, Chugai, Eisai, MBL, Mochida, Nippon Shinyaku, Ono Pharmaceuticals, Tanabe-Mitsubishi, Consultant of: Astra Zeneka, Boehringer-Ingelheim, Chugai, Corbus, GSK, Horizon, Tanabe-Mitsubishi, Grant/research support from: Boehringer-Ingelheim, Vikas Agarwal: 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.

CLINICAL SIGNIFICANCE OF SERUM FERRITIN IN PATIENTS WITH SYSTEMIC SCLEROSIS

BackgroundThe main systemic sclerosis (SSc) manifestations are skin thickening, microangiopathy and ischemic changes in tissues, fibrotic damage to the lungs, heart, kidneys, and digestive system, arthritis, and myopathy. Acute phase reactants (APR) like erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) reflect inflammation activity in various inflammatory conditions. Ferritin is a protein bound to iron;low serum ferritin indicates iron deficiency and/or anemia. Instead, high ferritin levels are associated with inflammatory and non-inflammatory conditions such as dermatomyositis, pulmonary fibrosis, lupus, systemic COVID-19, vasculitis, tissue damage, thromboembolic complications, and metastatic cancer. The possible role of ferritin in SSc as APR is unclear.ObjectivesWe aimed to assess whether ferritin levels can reflect the severity of SSc and predict the outcome.Methods241 files of SSc patients with information on serum ferritin level (ferritin over 300 mg/dL is considered elevated) who visited the Rambam Rheumatology Institute in the years 2004-2021were used for retrospective analysis. Patients' demographic, clinical, laboratory, imaging, and respiratory function data were collected from electronic hospital files. Statistics included Student's T-test, Pearson's chi-squared test, and Kaplan-Meier curve;statistical significance was determined as p<0.05.Results36 patients (FerEl-SSc) had elevated ferritin values;the rest (n=205) represented the second group (FerNor-SSc). Significant differences were seen in gender (male 44.4% - 15.6%), disease duration (4.56 - 7.7 years), modified Rodnan skin score (12.3 - 6.9), as well as in incidence of lung (65.7% - 38.7%), heart (51.4% - 21.1%), and renal (28.6% - 5.9%) involvement. Increased ferritin correlated with elevated ESR, CRP, creatinine, creatine kinase, troponin, and reduced hemoglobin, impaired pulmonary function tests and reduced left ventricular ejection fraction on echocardiography. Patients with elevated ferritin had a significant increase in mortality rates (52.8% and 35.1%) and non-significant reduction in survival.ConclusionOur study demonstrated that ferritin has a potential as a sensitive marker for SSc severity in term of skin thickening, vital organ complications, and mortality. The ferritin test is simple and inexpensive, it can add to the complex SSc assessment and contribute to treatment decision-making in complicated SSc.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

VALIDITY AND RELIABILITY OF MEASUREMENT OF PERIPHERAL OXYGEN SATURATION DURING THE 6-MINUTE WALK TEST IN PATIENTS WITH SYSTEMIC SCLEROSIS

BackgroundThe 6-Minute Walk Test (6MWT) is a standardised method routinely used to screen for and monitor interstitiel lunge disease and/or pulmonary arterial hypertension in patients with systemic sclerosis (SSc). Studies shows that esaturations during the 6MWT are associated with severity of pulmonary manifestations in patients with SSc [1]. Digital sensors are commonly used to measure peripheral oxygen saturation (SpO2) during the 6MWT. However, digital-based sensors may have important limitations in patients with SSc due to disease-related microangiopathy, Raynaud's phenomenon, sclerodactyly and motion artifacts during the 6MWT [2]. Sensors located at more central body positions may therefore be more accurate as these as less prone to Raynaud attacks.ObjectivesTo determine the validity and re-test reliability of peripheral oxygen saturation measured at the finger, forehead, and ear during the 6MWT in patients with SSc.Methods82 patients with SSc had an arterial line placed while performing the 6MWT. Peripheral oxygen saturation was simultaneously measured by finger, forehead, and earlobe sensors and compared to the arterial oxygen saturation (SaO2) measured before and after the 6MWT. 40 patients repeated the 6MWT one week later. We used Bland-Altman plots to display the agreement between SpO2 and SaO2, and between the minimal SpO2 (minSpO2) one week apart. The intraclass correlation coefficient (ICC, 95% confidence interval 95% CI]) for repeated measurement of minSpO2 was calculated.ResultsThe mean difference (SpO2 - SaO2, ± standard deviation [SD]) after the 6MWT was –3.3% (±4.82), 0.15% (±1.55), and 1.36% (±1.93) for the finger, forehead, and earlobe, respectively (Table 1).The finger minSpO2 also demonstrated the poorest re-test reliability: The mean difference in minSpO2 (visit2-visit1, ±SD) was 1.28% (±5.3), 0.74% (±4.36) and –1.10% (±2.87),). The ICC (95% CI) showed good agreement using the ear and forehead probe (ICCear = 0.89 [0.80;0.94];ICCforehead = 0.88 [0.60;0.87]), while a modest reliability was found using the finger probe (ICCfinger = 0.65 [0.43;0.80]).ConclusionPeripheral oxygen saturation should be measured using either the earlobe or forehead during the 6MWT in patients with SSc.References[1]Villalba, W. O. et al. Six-minute walk test for the evaluation of pulmonary disease severity in scleroderma patients. Chest 131, 217–222 (2007).[2]Pathania, Y. S. Alternatives for erroneous finger probe pulse oximetry in systemic sclerosis patients during COVID-19 pandemic. Rheumatol. Int. 41, 2243–2244 (2021).Table 1.Validity and re-test reliability of peripheral oxygen during the 6MWT (n= 82)Finger probeForehead probeEar probeMean difference SpO2 - SaO2  Mean difference pre-test (+/-SD)–0.68% (±1.88)0.13% (±1.26)1.54% (±0.69)  Mean difference post--test (+/-SD)–3.30% (±4.82)0.15% (±1.55)1.36% (±1.93)Mean difference of the minSpO2 (visit2-visit1)  Mean difference (±SD)1.28% (±5.3)0.74% (±4.36)1.10% (±2.87)Abbreviations: SpO2, Peripheral oxygen saturation;SaO2, Arterial oxygen saturation;SD, Standard deviation.Acknowledgements:NIL.Disclosure of InterestsAmanda Lynggaard Riis: None declared, Esben Naeser Paid instructor for: Boehringer Ingelheim Denmark, Katja Thorup Aaen: None declared, Henrik Hovgaard: None declared, Peter Juhl-Olsen: None declared, Elisabeth Bendstrup Speakers bureau: Hoffman-la-Roche.Boehringer Ingelheim.Glaxo Smith Kleine.Daichii Sankyo, Klaus Soendergaard Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Grant/research support from: Boehringer Ingelheim.

REFERRAL BEHAVIOUR OF PRIMARY CARE DOCTORS TO RHEUMATOLOGY CLINIC IN MALAYSIA

BackgroundThe workload at rheumatology clinics have been growing relentlessly and an audit on new.referrals helps to identify referral behaviour of primary care doctors and improvement can be done by providing further training.ObjectivesTo audit on new referral cases to rheumatology clinic from 2020-2022 and to identify new cases with misdiagnosis for future training purpose.MethodsThis was a retrospective study. The medical records of all new referral to rheumatology clinic Hospital Sultan Ismail and Hospital Pakar Sultanah Fatimah from 1st January 2020 to 31th November 2022 were reviewed. The referral diagnosis and final diagnosis were identified and analysed.ResultsThere were total of 927 new cases referral throughout the 35 months during Covid-19pandemic. Majority of them were diagnosed to have rheumatoid arthritis (217/927)followed by systemic lupus erythematosus (190/927), psoriatic arthritis (147/927),gout (62/927), osteoarthritis (58/927), systemic sclerosis (25/927), ankylosing spondylitis (25/927), soft tissue rheumatism (24/927), Sjogren syndrome (24/927),mixed connective tissue disease (14/927), vasculitis (11/927), fibromyalgia (10/927),polymyositis (7/927) and miscellaneous (39/927).45 out of the new cases were diagnosed as unlikely rheumatic diseases. There were 29pending cases awaiting final diagnosis.212 of the referrals were identified as misdiagnosis with the highest as nodal osteoarthritis.(55/212) followed by unlikely rheumatic disease (43/212), soft tissue rheumatism (24/212),psoriatic arthritis (20/212), Sjogren syndrome (14/212), gout (8/212), rheumatoid arthritis (7/212), fibromyalgia (6/212), systemic lupus erythematosus (5/212), ankylosing spondylitis (4/212), mixed connective tissue disease (3/212), systemic sclerosis (2/212), polymyositis (2/212) and others (19/212): diffuse idiopathic skeletal hyperostosis, hypermobility syndrome, RS3PE syndrome, idiopathic uveitis, graft versus host disease, juvenile idiopathic arthritis, antiphospholipid syndrome, hypothyroidism, post streptococcal arthritis, prolapsed intervertebral disc, cerebrovascular disease, traumatic sternoclavicular joint subluxation, ledderhose disease, paraspinal muscle spasm and viral myalgia).ConclusionNodal osteoarthritis and soft tissue rheumatism can be great mimicker for inflammatory.arthritis and if wrongly diagnosed will lead to unnecessary anxiety or wrong treatment. More training is needed to improve clinical skills amongst primary care doctors.ReferencesNA.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

CLINICAL CHARACTERISTICS OF PEDIATRIC PATIENTS WITH RHEUMATIC DISEASES UNDER TREATMENT WITH BIOLOGICAL THERAPY: INFORMATION FROM BIOBADAMEX

BackgroundThe advent of biologic treatment (bDMARD) in childhood rheumatic diseases (RD) has changed their evolution and prognosis. Evidence is robust for diseases such as juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE), but in other diseases we still have to learn which is the ideal therapy, time to discontinuation and the potential adverse events (AE) in short and long term.ObjectivesIdentify the clinical and treatment characteristics of pediatric patients with rheumatic diseases with bDMARD treatment and describe the development of AE.MethodsBIOBADAMEX is a prospective ongoing cohort of Mexican patients with RD using bDMARDs since 2016. We included all patients younger than 18 years of age registered in BIOBADAMEX. Descriptive statistics were used for the baseline characteristics and the Chi-square test to analyze the differences between the characteristics of the groups in relation to the development of AE.ResultsA total of 45 patients were included, 31 (69%) of them female, mean age of 13.3 (±3.6) years. (Table 1).The most frequent diagnosis was JIA 25 (56%), followed by SLE 9 (20%), uveitis 5 (11%), polymyositis/dermatomyositis and hidradenitis 2 (4%) respectively;systemic sclerosis and CINCA 1 patient (2%) respectively. The mean duration disease in years was 4.67 (±2.1). Nine patients (20%) used a biologic prior to the current;23 (51%) patients had comorbidities.The most frequent bDMARDs used was Adalimumab (ADA) in 17 (38%) patients followed by Rituximab in 15 (33%) and Tocilizumab in 10 (22%), Infliximab, Abatacept and Canakinumab were used in one patient respectively.When compared by groups, ADA and Tocilizumab were the most used bDMARDs in JIA, Rituximab the only one used in SLE and PM/DM, and ADA the only one for uveitis.15 patients discontinued biological treatment, 4 (27%) due to AE. 82% used an additional synthetic DMARD, being methotrexate the most used in 48% of patients. Steroids were used by 21 (47%) of the patients with a median dose of 10mg (IQR 5 - 25).Fifteen AEs were recorded: 7 (47%) were infections, 5 of these (71%) were COVID;allergies and neutropenia in 2 (13%) patients respectively. By disease infections were more frequent in patients with JIA and Uveitis;neutropenia only occurred in patients with JIA (p 0.95). 87% of the AEs were non-serious, 1 patient with JIA presented a severe AE and one patient with SLE a fatal AE associated with COVID (p 0.93), with no statistically significant difference between groups.ConclusionJIA is the most frequent indication to use bDMARD as worldwide reported. The AE in this analysis are similar to previous registries in terms of the prevalence of infections, in our group the most frequent infectious complication was COVID, being fatal in one patient related with rituximab in SLE. Our study did not find statistically significant differences in the development of AE between diseases;however, they will continue to be reported and the number of patients in the registry will increase.References[1] Sterba,Y.et al. Curr Rheumatol Rep 2016;18,45[2] Fuhlbrigge RC, et al. 2021;47(4):531-543.Table 1.Baseline CharacteristicsBaseline characteristics (n = 45)n%Female, n(%)3168.9Age, media (SD)13.3 (±3.6)Index Body Mass, media (SD)19.6 (±4.9)Dx n(%)n %- JIA25 55.6- SLE9 20- PM/DM2 4.4- Uveitis5 11.1- Hidradenitis2 4.4- Systemic sclerosis1 2.2- CINCA1 2.2Disease duration(years) media (IQR)4.67±2.1Current treatment n(%)n %- Infliximab1 2.2- Adalimumab17 37.8- Rituximab15 33.3- Abatacept1 2.2- Tocilizumab10 22.2- Canakinumab1 2.2Treatment duration (months) median (IQR)4.5 (0.56 – 36.9)Treatment suspension, n(%)15 (33.2)Months to suspension, median (IQR)0.66 (0.46 – 1)Discontinue cause, n(%)n %- Inefficacy1 6.6- Remission1 6.6- Side effects4 26.6- Others5 33.3- Unknown4 26.6Steroids use, n(%):21 46.7Steroids dose (mg), median (IQR)10 5 – 25DMARDs use n(%):37 82.2AE, n(%):15 33.3By disease:AE TypeInfectionAllergyNeutropeniaOtherChi2JIA31230.95SLE1101Uveitis3000Acknowledgements:NIL.Disclosure of InterestsSamara Mendieta: None declare , Alfonso Torres: None declared, Fedra Irazoque-Palazuelos: None declared, Sandra Sicsik: None declared, Iris Jazmin Colunga-Pedraza: None declared, Daniel Xavier Xibille Friedmann: None declared, Deshire Alpizar-Rodriguez Employee of: Scientific advisor in GSK-Mexico, VIJAYA RIVERA TERAN: None declared.

DERMATO-NEURO SYNDROME PRECIPITATED BY COVID-19 INFECTION IN THE SETTING OF SCLEROMYXEDEMA

BackgroundA black female in her 40s presented with a nonpruritic rash for 10 months consisting of bumps on the face, hands, forearms, and thighs. She had no prior treatment. Past medical history was significant for pulmonary embolism (PE) 6 years prior. She had no personal or family history of autoimmune disease. Physical exam revealed numerous smooth 2-3 mm skin-colored papules over the bilateral forearm dorsa, hands, anterior thighs, and face. Serum protein electrophoresis revealed monoclonal IgG lambda gammopathy. Skin biopsy of her left elbow showed dermal fibroplasia with mucin deposition. IgG was less than 1.5 grams/deciliter;bloodwork was otherwise stable. The diagnosis of scleromyxedema was rendered.ObjectivesThe objective of this clinical case was to evaluate a neurologic sequela of COVID-19 infection in a patient with scleromyxedema.MethodsOne month following diagnosis of scleromyxedema, our patient was diagnosed with COVID-19 five days before admission to the emergency department with altered mental status and aphasia. Rheumatology was consulted due to malignant hypertension and acute kidney injury with question of scleroderma-like renal crisis in the setting of recently diagnosed COVID-19 infection, although she had no other features of systemic sclerosis. The infectious disease team was consulted due to COVID-19-induced inflammatory reaction.ResultsThe patient's creatinine kinase and brain natriuretic peptide were elevated. Creatinine and potassium trended upwards. She developed seizures and became hemodynamically unstable with rapidly declining clinical status. She was transferred to the intensive care unit, where she developed respiratory arrest, shock, hyperkalemia, and acidemia. She received escalating doses of pressors but experienced frequent arrhythmic disturbances and developed asystole. Resuscitation efforts were unsuccessful;she expired within 24 hours of consultation.ConclusionDermato-neuro syndrome (DNS) is a potential complication of scleromyxedema associated with confusion, dysarthria, seizures, and coma. The patient's clinical presentation is consistent with DNS in the setting of scleromyxedema likely precipitated by COVID-19. Intravenous immunoglobulins are first-line treatment for scleromyxedema;however, it is associated with risk of venous thromboembolism. The patient was considered for treatment as an outpatient but deferred due to history of PE. She was reevaluated for treatment upon presentation to the hospital, but given the severity and rapidity of her condition, it was already too late. This is the second reported case of COVID-19 induced DNS in a patient with scleromyxedema. Given the severity, we recommend early initiation of treatment in patients with scleromyxedema and aggressive treatment for those contracting COVID-19.References[1] Haber R, Bachour J, El Gemayel M. Scleromyxedema treatment: a systematic review and update. Int J Dermatol. 2020;59:1191-1201.[2] Flannery MT, Humphrey D. Deep Venous Thrombosis with Pulmonary Embolism Related to IVIg Treatment: A Case Report and Literature Review. Case Rep Med. 2015;971321.[3] Lee YH, Sahu J, O'Brien MS, D'Agati VD, Jimenez SA. Scleroderma Renal Crisis-Like Acute Renal Failure Associated With Mucopolysaccharide Accumulation in Renal Vessels in a Patient With Scleromyxedema. J Clin Rheumatol. 2011;17:318-322.[4] Hoffman-Vold AM, Distler O, Bruni C, et al. Systemic sclerosis in the time of COVID-19. Lancet Rheumatol. 2022;4:e566-575.[5] Fritz M, Tinker D, Wessel AW, et al. SARS-CoV-2: A potential trigger of dermato-neuro syndrome in a patient with scleromyxedema. JAAD Case Rep. 2021;18:99-102.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

CLINICAL CHARACTERISTICS & OUTCOMES AMONG PATIENTS WITH SYSTEMIC AUTOIMMUNE RHEUMATIC DISEASES AND SARS-CoV-2 INFECTION: 2-YEAR DATA FROM A TERTIARY RHEUMATOLOGY CENTRE IN GREECE

BackgroundPatients with autoimmune rheumatic diseases (ARDs) under moderate/severe immunosuppression are considered a high-risk population to develop severe Covid-19 infection.ObjectivesThe aim of our study was to describe the clinical characteristics and the outcome of patients with ARD who contracted a Sars-Cov-2 infection.MethodsAmong patients with ARD being followed in our tertiary outpatient rheumatology clinic, we retrospectively identified those infected with SARS-CoV-2 between the beginning of the pandemic and August 2022. Patients' medical files were reviewed for demographics (age, gender and comorbidities) and disease-related characteristics, as well as coronavirus disease (COVID-19) characteristics, including vaccination status, treatment, and outcomes (covid-19 severity, hospitalization, death).ResultsA total of 209 cases of ARD patients with confirmed Covid-19 infection were recorded. Most of them were women (62.7%), with a mean age of 52.4± 13.8 years. The most prevalent ARDs were seronegative spondyloarthropathies (28.7%), systematic lupus erythematosus (21.5%), rheumatoid arthritis (16.5%), and systemic sclerosis (11.5%). More than half of the patients received corticosteroids (57.8%), while the most frequently used immunosuppressants were hydroxychloroquine (30.9%), TNF inhibitors (26.5%), mycophenolate mofetil (24.0%), methotrexate (19.1%) and rituximab (15.2%). One hundred and fifty-eight (76%) patients were either on remission or had mild disease activity. Most of the patients (131/209) had at least one comorbidity, more commonly arterial hypertension (48.5%) and pulmonary disease (45.2%). Most of the patients were vaccinated against Sars-Cov-2 (73.7%), either with two doses (38.0%), three doses (57.0%) or four doses (5.0%) of mRNA-based vaccines. The big majority of the patients (83.3%) were asymptomatic or had mild Covid-19 disease. About half of the patients (53.1%) reported to have received Covid-19 treatment. Thirty-two of them (15.3%) needed hospitalization, and five death cases were reported overall. Among the demographic characteristics, age (p<0.0001 for hospitalization) and comorbidities were associated with worse covid-19 outcomes. In particular, cardiovascular disease (OR 5.37, p=0.001 for covid-19 severity, OR 6.89, p=0.001 for hospitalization), pulmonary disease (OR 3.02, p=0.006 for hospitalization), and obesity (OR 3.46, p=0.044 for hospitalization) had the stronger associations. Non-vaccination status was also associated with a higher risk for hospitalization (OR 2.68, p=0.015). In relation to ARD-related factors, treatment with rituximab (OR 4.11, p=0.002 for hospitalization), systemic sclerosis diagnosis (OR 3.45, p=0.03 for Covid-19 severity) and myositis diagnosis (OR 4.91, p=0.033 for hospitalization) were associated with worse Covid-19 outcomes. On the other hand, spondyloarthropathies appear to be negatively associated with Covid-19 severity (OR=0.27, p=0.035).ConclusionAccording to our study, most ARD patients recovered uneventfully from Covid-19. However, there are several indications that we should be vigilant for patients who remain unvaccinated, are older, have a systemic sclerosis or myositis diagnosis, and/or receive intense immunosuppressive regiments such as rituximab.References[1]Papagoras C, Fragoulis GE, et al. Better outcomes of COVID-19 in vaccinated compared to unvaccinated patients with systemic rheumatic diseases. Ann Rheum Dis. 2021 Nov 10.[2]Strangfeld A, Schäfer M, et al. Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis. 2021 Jul;80(7):930-942.Table 1.N=209ARD Diagnosisn (%)Rheumatoid arthritis34 (16.3)Seronegative spondyloarthropathies60 (28.7)Systemic lupus erythematosus45 (21.5)Systemic sclerosis24 (11.5)Sjogren's syndrome15 (7.2)Vasculitis19 (9.1)Myositis9 (4.3)Other3 (1.4)Acknowledgements:NIL.Disclosure of InterestsNone Declared.

SYSTEMIC SCLEROSIS AND COVID-19 VACCINE-ASSOCIATED DELAYED ADVERSE EVENTS: INSIGHTS FROM THE COVAD-2 STUDY

BackgroundWe have previously reported short term safety of the COVID-19 vaccination in patients with Systemic sclerosis (SSc) but delayed adverse events (ADEs) (occurring >7 days post-vaccination) are poorly characterized in this rare yet vulnerable disease group.ObjectivesWe analyzed delayed COVID-19 vaccine-related ADEs among patients with SSc, other systemic autoimmune and inflammatory disorders (SAIDs) and healthy controls (HC) using data from the ongoing 2nd global COVID-19 Vaccination in Autoimmune Diseases (COVAD-2) study [1].MethodsThe COVAD-2 study was a cross-sectional, patient self-reporting e-survey utilizing an extensively validated, pilot tested questionnaire, translated into 19 languages, circulated by a group of 157 physicians across 106 countries from February to June 2022.We captured data on demographics, SSc/SAID disease characteristics (including skin subset, treatment history and self-reported disease activity), autoimmune and non-autoimmune comorbidities, COVID-19 infection history and course, and vaccination details including delayed ADEs as defined by the CDC.Delayed ADEs were categorized into local injection site pain/soreness;minor and major systemic ADEs, and hospitalizations. We descriptively analyzed the risk factors for overall and specific ADEs in SSc and SAIDs, and further triangulated clinically significant variables in binominal logistic regression analysis with adjustment for age, gender, ethnicity, comorbidity, and immunosuppressive therapy to analyze the survey responses.ResultsFrom among 17 612 respondents, 10 041 patients (median age 51 (18-58) years, 73.4% females, 44.9% Caucasians) vaccinated against COVID-19 at least once (excluding incomplete responses and trial participants) were included for analysis. Of these, 2.6 % (n=258) had SSc, 63.7% other SAIDs, and 33.7% were HCs. BNT162b2 Pfizer (69.4%) was the most administered vaccine, followed by MRNA-1273 Moderna (32.25%) and ChadOx1 nCOV-19 Oxford/AstraZeneca (12.4%) vaccines.Among the patients with SSc, 18.9% reported minor while 8.5% experienced major delayed ADEs, and 4.6% reported hospitalization. These values were comparable to those of the ADEs reported in other SAIDs and HCs. Patients with SSc reported higher frequency of difficulty in breathing than HCs [OR=2.3 (1.0-5.1), p=0.042].Individuals receiving Oxford/AstraZeneca reported more minor ADEs [OR=2.5 (1.0-6.0), p=0.045];whereas patients receiving Moderna were less likely to develop myalgia and body ache [OR=0.1 (0.02-1.0), p=0.047 and OR=0.2 (0.05-1.0), p=0.044 respectively].Patients with diffuse cutaneous SSc experienced minor ADEs and specifically fatigue more frequently [OR=2.1 (1.1-4.4), p=0.036, and OR=3.9 (1.3-11.7), p=0.015] than those with limited cutaneous SSc. Self-reported active disease pre-vaccination did not confer any increased risk of vaccine ADEs in the adjusted analysis. Unlike our previous observations in myositis, autoimmune and non-autoimmune comorbidities did not affect the risk of delayed ADEs in SSc. SSc patients with concomitant myositis reported myalgia [OR=3.4 (1.1-10.7), p=0.035] more frequently, while those with thyroid disorders were more prone to report a higher frequency of joint pain [OR=5.5 (1.5-20.2), p=0.009] and dizziness [OR=5.9 (1.3-27.6), p=0.024] than patients with SSc alone. Patients with SSc-interstitial lung disease did not report increased frequency of ADEs.ConclusionA diagnosis of SSc did not confer a higher risk of delayed post COVID-19 vaccine-related ADEs than other SAIDs and HCs. Diffuse cutaneous phenotype and certain co-existing autoimmune conditions including myositis and thyroid disease can increase the risk of minor ADEs. These patients may benefit from pre-vaccination counselling, close monitoring, and early initiation of appropriate care in the post COVID-19 vaccination period.Reference[1]Fazal ZZ, Sen P, Joshi M, Ravichandran N, Lilleker JB, et al. COVAD survey 2 long-term outcomes: unmet need and protocol. Rheumatol Int 2022 Dec;42(12):2151-2158AcknowledgementsCOVAD Study Team.Disclosure of InterestsBo dana Doskaliuk: None declared, Parikshit Sen: None declared, Mrudula Joshi: None declared, Naveen Ravichandran: None declared, Ai Lyn Tan Speakers bureau: Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB, Consultant of: Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB, Samuel Katsuyuki Shinjo: None declared, Sreoshy Saha: None declared, Nelly Ziade Speakers bureau: Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis,Boehringer Ingelheim, Janssen, and Pierre Fabre, Consultant of: Pfizer, Roche, Abbvie, Eli Lilly,NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, and Pierre Fabre, Grant/research support from: Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, and.Pierre Fabre, Tulika Chatterjee: None declared, Masataka Kuwana: None declared, Johannes Knitza: None declared, Oliver Distler Speakers bureau: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur, Consultant of: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur, Grant/research support from: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur, Rohit Aggarwal Consultant of: Mallinckrodt, Octapharma, CSL Behring, Bristol Myers-Squibb, EMD Serono, Kezar, Pfizer, AstraZeneca, Alexion, Argenx, Boehringer Ingelheim, Corbus, Janssen, Kyverna, Roivant, Merck, Galapagos, Actigraph, Abbvie, Scipher, Horizontal Therapeutics, Teva, Biogen, Beigene, ANI Pharmaceutical, Nuvig, Capella, CabalettaBio, Grant/research support from: Mallinckrodt, Pfizer, Bristol Myers-Squibb, Q32, EMD Serono, Janssen, Boehringer Ingelheim (BI), Ashima Makol: None declared, Latika Gupta: None declared, Vikas Agarwal: None declared.

SAFETY AND PHARMACOKINETICS OF IGPRO20 (SUBCUTANEOUS IMMUNOGLOBULIN) AND IGPRO10 (INTRAVENOUS IMMUNOGLOBULIN) IN ADULTS WITH SYSTEMIC SCLEROSIS (SSC) – RESULTS FROM A PHASE 2 TRIAL

BackgroundSystemic sclerosis (SSc) is a severe, progressive multisystem rheumatic disease with high mortality, but without approved disease-modifying treatment to stop or reverse course of disease. Intravenous immunoglobulin G (IgG) may have a positive impact on SSc based upon available literature reports. However, to date, there have been no clinical trials evaluating subcutaneous IgG (SCIG) in SSc. In particular, the impact of pathologically altered skin in SSc on local safety and pharmacokinetics (PK) of SCIG has not been explored yet.ObjectivesThe primary and secondary objectives of this trial (NCT04137224) included safety, including local infusion safety, and bioavailability of subcutaneous IgG (IgPro20) in adults with diffuse cutaneous SSc (dcSSc).MethodsThis was a randomized, open-label, crossover study. Adult subjects with dcSSc diagnosis within 5 years from first non-Raynaud's phenomenon and modified Rodnan Skin Score of 15-45 at screening were randomized 1:1 to sequence A (IgPro20, 20% normal human subcutaneous immunoglobulin followed by IgPro10, 10% normal human intravenous immunoglobulin) or sequence B (IgPro10 followed by IgPro20). Each subject was to complete two treatment periods (16 weeks each), with up to 40 weeks (including screening) study duration for an individual subject. Doses received were 0.5g/kg/week split over two sessions for IgPro20, and 2g/kg/4 weeks split over 2-5 days for IgPro10. The primary endpoint was safety of IgPro20, described as treatment-emergent adverse events (TEAEs) and changes in clinical observations.Results27 subjects were randomized, with 13 subjects to sequence A and 14 subjects to sequence B. In total, 25 subjects completed the study. Of 27 treated subjects, 107 TEAEs occurred in 22 subjects (81.5%) over the 36-week study period, the majority of which were mild or moderate. The most common TEAEs (>10% of subjects) by preferred term (PT) were headache (12 events occurring in 6 subjects [22.2%]), COVID-19 (3 events occurring in 3 subjects [11.1%]), diarrhoea (3 events occurring in 3 subjects [11.1%]), and vomiting (3 events occurring in 3 subjects [11.1%]).A total of 10 serious AEs (SAEs) were reported in 6 subjects (Viral infection, Chronic gastritis, Vomiting, Dehydration, Upper gastrointestinal haemorrhage, Chest pain, Myocardial infarction, Myocardial ischemia, Breast cancer, Interstitial lung disease). Among these, one subject experienced 2 SAEs (myocardial ischemia & myocardial infarction) and was discontinued from study treatment. None of the SAEs were considered related to study treatment by the investigator, and no deaths were reported.For IgPro20, 14 infusion site reactions (ISRs) occurred in 5 subjects (19.2%), all were mild or moderate in severity. The most common ISRs were infusion site pain and infusion site swelling (3 events in 2 subjects each, 7.7%). In total, 686 IgPro20 infusions were performed, resulting in an overall ISR rate per infusion of 0.02, ie 2 ISRs per 100 infusions. No ISRs were reported for IgPro10.No clinically relevant trends in vital signs, body weight, clinical laboratory tests, electrocardiograms, or pulmonary function tests were observed.PK profiles and bioavailability in dcSSc subjects were similar to those observed in other approved indications such as Primary Immunodeficiency. Population relative bioavailability of IgPro20, based on dose-normalized, baseline-corrected AUC0-tau was 0.761 (90% CI: 0.7033, 0.8232), ie 76.1% compared to IgPro10 (intravenous IgG).ConclusionThe overall safety profiles of IgPro20 and IgPro10 in subjects with dcSSc were consistent with that in approved indications such as CIDP, including a relatively low ISR rate for IgPro20. PK profiles and bioavailability were also similar to other indications. This study indicates that subcutaneous administration of IgPro20 has acceptable safety, bioavailability and PK profiles in patients with dcSSc. AcknowledgementsEditorial assistance was provided by Meridian HealthComms Ltd., funded by CSL Behring.Disclosure of InterestsChristopher P Denton Speakers bureau: Ja ssen, Boehringer Ingelheim, Consultant of: GSK, CSL Behring, Boehringer Ingelheim, Merck, Roche, Sanofi, Grant/research support from: GSK, CSL Behring, Inventiva, Horizon, Otylia Kowal-Bielecka Speakers bureau: Abbvie, Janssen-Cilag, Boehringer Ingelheim, Medac, MSD, Novartis, Pfizer, Sandoz, Consultant of: Boehringer Ingelheim and Novartis, Grant/research support from: Received congress support from Abbvie, Boehringer Ingelheim, and Medac, Susanna Proudman Speakers bureau: Boehringer Ingelheim, Grant/research support from: Janssen, Marzena Olesińska Consultant of: AstraZeneca, Margitta Worm Consultant of: Novartis Pharma GmbH, Sanofi-Aventis Deutschland GmbH, DBV Technologies S.A, Aimmune Therapeutics UK Limited, Regeneron Pharmaceuticals, Inc, Leo Pharma GmbH, Boehringer Ingelheim Pharma GmbH &Co.KG, ALK-Abelló Arzneimittel GmbH, Kymab Limited, Amgen GmbH, Abbvie Deutschland GmbH & Co. KG, Pfizer Pharma GmbH, Mylan Germany GmbH (A Viatris Company), AstraZeneca GmbH, Lilly Deutschland GmbH and GlaxoSmithKline GmbH & Co. KG., Nicoletta Del Papa Speakers bureau: Janssen Cilag, Boehringer Ingelheim., Marco Matucci-Cerinic Speakers bureau: Biogen, Sandoz, Boehringer Ingelheim, Consultant of: CSL Behring, Boehringer Ingelheim, Grant/research support from: MSD, Chemomab, Jana Radewonuk Shareholder of: CSL Behring, Employee of: CSL Behring, Jeanine Jochems Shareholder of: CSL Behring, Employee of: CSL Behring, Amgad Shebl Shareholder of: CSL Behring, Employee of: CSL Behring, Anna Krupa Shareholder of: CSL Behring, Employee of: CSL Behring, Jutta Hofmann Shareholder of: CSL Behring, Employee of: CSL Behring, Maria Gasior Shareholder of: CSL Behring, Employee of: CSL Behring.

CYCLOPHOSPHAMIDE THERAPY DURING THE COVID19 PANDEMIC

BackgroundDuring the Coronavirus disease (COVID-19) pandemic, one of the biggest concerns of rheumatologists and rheumatology patients has been whether the risk or severity of the disease will increase with immunosuppressive therapy. Some drugs have been reported to be associated with adverse Covid19 outcomes [1,2]. Cyclophosphamide (CYC) is a drug that has been used in rheumatology practice for many years. There is not enough data in the literature on the frequency or consequences of COVID-19 while receiving CYC therapy.ObjectivesThe aim of this study is to examine the frequency and outcomes of Covid19 in patients who received CYC therapy during the Covid19 pandemic.MethodsThe files of patients who received CYC therapy protocol between March 2020 and March 2022 at Başkent University Faculty of Medicine Ankara Hospital, Rheumatology outpatient clinic were retrospectively reviewed. In our clinic, CYC therapy is administered as an intravenous treatment protocol of 500 mg three times every 10 days, then 500 mg every two weeks. Although the cumulative dose varies depending on the disease and the patient, it is usually planned to be at least three gram. The diagnosis of Covid 19 was made in the patients with clinically compatible radiology and SARS-CoV-2 PCR test results.ResultsA total of 36 patients received CYC during the specified period. CYC indications were ANCA-associated vasculitis in 12 patients, interstitial lung disease associated with undifferentiated connective tissue disease in 5 patients, SLE in 5 patients, scleroderma in 4 patients, Sjögren's syndrome in 4 patients, Behçet's disease in 1 patient, vasculitis associated with sarcoidosis in 1 patient, rheumatoid vasculitis in 1 patient, leukocytoclastic vasculitis in 1 patient, polymyositis in 1 patient and Takayasu disease in 1 patient.The median age (q1-q3) was 62 (52-68) years. Covid19 infection was detected in only 3 patients (8%) during the CYC therapy protocol. The median cumulative CYC dose for these patients was 3.5 g. One out of 3 patient was hospitalized for Covid 19 pneumonia. There was no death due to Covid19.ConclusionIn this study, it has been shown that CYC therapy was safe during the Covid19 pandemic period.References[1]Samanta J, Naidu G, Deo P, Mittal S, Prasad CB, Das D, Dhir V, Sharma SK, Ramachandran R, Rathi M, Nada R, Minz RW, Jain S, Sharma A. Managing ANCA-associated vasculitis during COVID-19 pandemic: a single-center cross-sectional study. Rheumatol Int. 2022 Dec;42(12):2159-2166.[2]Singh N, Madhira V, Hu C, Olex AL, Bergquist T, Fitzgerald KC, Huling JD, Patel RC, Singh JA. Rituximab is associated with worse COVID-19 outcomes in patients with rheumatoid arthritis: A retrospective, nationally sampled cohort study from the U.S. National COVID Cohort Collaborative (N3C). Semin Arthritis Rheum. 2023 Feb;58:152149.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

FLARES AFTER COVID-19 INFECTION IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES: RESULTS FROM THE COVAD STUDY

BackgroundViral infections are known triggers of disease flares in idiopathic inflammatory myopathies (IIMs). Reports of post-COVID-19 flares of IIMs have raised suspicion of a possible role of SARS-COV-2 in their onset [1,2]. However, despite rising flare rates in this vulnerable patient group during the pandemic, the risk factors for post-COVID-19 IIMs flares remain unknown [3,4].ObjectivesDisease flares among patients with idiopathic inflammatory myopathies (IIMs) can lead to significant disability, though are poorly explored in the post-COVID-19 period. We analysed risk factors for post-COVID-19 flares in a global sample of IIM patients in a subset analysis as part of the ongoing COVID-19 Vaccination in Autoimmune Diseases (COVAD) study.MethodsA cross-sectional patient self-reporting survey was circulated by the international COVAD study group (157 collaborators, 106 countries) to patients with autoimmune diseases and healthy controls from February-June 2022. Data was collected on demographics, autoimmune disease details, treatment history, comorbidities, COVID-19 history and course and COVID-19 vaccination details. Patients with IIMs who flared post COVID-19 were compared to those who did not using the χ2 test, factors found significant in univariate analysis and deemed clinically important, underwent multivariable analysis (binary logistic regression using the Enter method) with adjustment for age, gender, ethnicity, vaccine type, immunosuppression, autoimmune and non-autoimmune comorbidities, COVID-19 antibody status, and clinical symptoms of COVID-19. Statistical analyses were performed using IBM SPSS version 28.0, with statistical significance considered at p<0.05.Results15,165 respondents completed the survey of whom 1,169 contracted COVID-19. Of these, 207 had IIMs [median (IQR) age 57.0 (47.0-67.0), 71% female, 74.4% Caucasian]. We noted with concern that nearly a third of patients with IIMs (63/207, 30.4%) reported experiencing a flare. A past medical history significant for Asthma, (34.9% vs 6.9%, multivariable OR: 7.1;95%CI: 3.1-16.4, p<0.001) and specific clinical symptoms during COVID-19 including joint pains (multivariable OR: 6.05;95%CI: 1.60-22.9, p=0.008), and difficulty in breathing (multivariable OR: 3.43;95%CI: 1.09-10.8, p=0.036) were found to confer conferred a higher risk of flares (Table 1).Table 1Patient Reported Flares following COVID-19 infection among IIM patientsTotal IIMs (n=207)IIMs with flare after COVID-19 (n=63)IIMs without flare after COVID-19 (n=144)OR (95%CI)PAge (median, IQR) years57.0 (47.0-67.0)53.0 (47.0-62.0)59.0 (47.0-69.0)-0.024GenderMale Female60 (29.0) 147 (71.0)7 (11.1) 56 (88.9)53 (36.8) 91 (63.2)0.2 (0.09-0.5)< 0.001ComorbiditiesAsthma ILD32 (15.5) 31 (15.0)22 (34.9) 11 (17.5)10 (6.9) 20 (13.9)7.1 (3.1-16.4) 1.3 (0.5-2.9)<0.001 00.508Clinical features in previous COVID-19 infectionFatigue Myalgia Arthralgia Difficulty in breathing134 (64.7) 94 (45.4) 56 (27.1) 41 (19.8)52 (82.5) 44 (69.8) 36 (57.1) 27 (42.9)82 (56.9) 50 (34.7) 20 (13.9) 14 (9.7)3.5 (1.7-7.4) 4.3 (2.3-8.2) 8.2 (4.1-16.4) 6.9 (3.3-14.6)<0.001 <0.001 <0.001 <0.001ConclusionWe observed a high frequency of patients with IIM experiencing post-COVID-19 disease flares. A past history of Asthma and those with certain acute COVID-19 symptoms were at higher risk.References[1]Saud A, Naveen R, Aggarwal R, Gupta L. COVID-19 and Myositis: What We Know So Far. Curr Rheumatol Rep 2021;23:63.[2]Gokhale Y, Patankar A, Holla U, Shilke M, Kalekar L, Karnik ND, et al. Dermatomyositis during COVID-19 Pandemic (A Case Series): Is there a Cause Effect Relationship? J Assoc Physicians India 2020;68:20–4.[3]Gupta L, Lilleker JB, Agarwal V, Chinoy H, Aggarwal R. COVID-19 and myositis - unique challenges for patients. Rheumatology (Oxford) 2021;60:907–10.[4]Naveen R, Sundaram TG, Agarwal V, Gupta L. Teleconsultation experience with the idiopathic inflammatory myopathies: a prospective observational cohort study during the COVID-19 pandemic. Rheumatol Int 2021;41:67–76.Acknowledgements:NIL.Disclosure of InterestsSa dia Sasha Ali: None declared, Naveen Ravichandran: None declared, Parikshit Sen: None declared, Jessica Day Grant/research support from: JD has received research funding from CSL Limited., Mrudula Joshi: None declared, Sreoshy Saha: None declared, Rohit Aggarwal Consultant of: RA has a consultancy relationship with and/or has received research funding from the following companies: Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, Abbvie, Janssen, Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, and Roivant., Grant/research support from: RA has a consultancy relationship with and/or has received research funding from the following companies: Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, Abbvie, Janssen, Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, and Roivant., Vikas Agarwal: None declared, Hector Chinoy Speakers bureau: Speaker for UCB, and Biogen. HC was supported by the National Institution for Health Research Manchester Biomedical Research Centre Funding Scheme., Grant/research support from: Has received grant support from Eli Lilly and UCB, consulting fees from Novartis, Eli Lilly, Orphazyme, Astra Zeneca, Oliver Distler Speakers bureau: OD has consultancy relationships with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued "mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Consultant of: OD has consultancy relationships with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued "mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Grant/research support from: OD has consultancy relationships with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last three years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, Baecon, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Mitsubishi Tanabe, Novartis, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued "mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Carlo Vinicio Caballero: None declared, Carlos Enrique Toro Gutierrez: None declared, Dey Dzifa: None declared, Ashima Makol: None declared, Ai Lyn Tan Speakers bureau: Has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB., Consultant of: has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB., Samuel Katsuyuki Shinjo: None declared, Vishwesh Agarwal: None declared, Latika Gupta: None declared.

Hemorrhagic Cardiac Tamponade as a Complication of Limited Cutaneous Systemic Sclerosis.

Cardiac tamponade is an uncommon complication of systemic sclerosis (SSc) with a high mortality rate. Here, we report a case of a 58-year-old patient with limited cutaneous systemic sclerosis (lcSSc), gastroesophageal reflux disease (GERD), diabetes mellitus, pulmonary hypertension (PHTN), and COVID-19 infection, which occurred one month ago, presenting with a large hemorrhagic pericardial effusion and early cardiac tamponade. The patient had an acute onset of progressive dyspnea and anasarca. On examination, she was tachypneic, tachycardic, desaturating on room air, and hypotensive. Pitting edema up to thighs and bilateral basilar crackles were also appreciated. Labs were remarkable for negative troponin, chest X-ray with pulmonary congestion, D-dimer at 6.01, CT angiogram negative, brain natriuretic peptide level at 73 pg/mL, C-reactive protein level at 7.64 mg/dL, normal complement levels, and negative COVID-19 test results. Echocardiography showed early tamponade and a large circumferential effusion with chamber collapse. Right heart catheterization was performed finding PHTN at 54 mmHg. Pericardiocentesis drained 500 mL of the hemorrhagic effusion. Fluid analysis showed RBC at 220,000/uL, WBC at 5000/uL, protein 4.8 g/dL, lactate dehydrogenase level of 1275 U/L, and negative cytology. The patient was treated for serositis from lcSSc flare with mycophenolate mofetil and steroids, and responded very well. Hemorrhagic cardiac tamponade is a very rare phenomenon in limited scleroderma. A recent COVID-19 infection could have served as a trigger factor for our patient's lcSSc in long remission to flare up. Clinicians should maintain a high index of suspicion and a low threshold for intervention when lcSSc patients have an acute onset of cardiac compromise, especially with a history of a recent COVID-19 infection.

Scleromyxedema in an adult following Sinopharm BBIBP-CorV vaccination: An extremely rare phenomenon.

Introduction: The Sinopharm BBIBP-CorV vaccine produces a variety of cutaneous adverse effects. Scleromyxedema is a mucinous connective tissue disorder that causes skin thickness and sclerodermoid changes. According to our findings, this is the first case of scleromyxedema induced by the Sinopharm immunization. Case description: We discuss the case of a 75-year-old woman who acquired progressive thickening of the skin in her limbs and trunk after getting the Sinopharm vaccination. Examination, laboratory testing, and a biopsy were used to verify scleromyxedema diagnosis. Intravenous immunoglobulins, mycophenolate mofetil, and prednisolone were used in the treatment of the patient. The outcomes from the 4-month follow-up were reassuring. Conclusion: This study emphasizes the need of considering scleromyxedema as a connective tissue pathology in patients who have recently received Sinopharm vaccine and have similar cutaneous signs.

[The impact of COVID-19 in a cohort of patients with systemic sclerosis]

Background: COVID-19 brought with it unknowns related to systemic sclerosis. Objective: To know the clinical evolution and prognosis of COVID-19 in a cohort of patients with systemic sclerosis. Methods: During the pandemic, we had digital contact with a cohort of 197 patients with SSc. If they had any condition that met the suspected definition of COVID-19, they underwent polymerase chain reaction testing for SARS-CoV-2;they were treated on an outpatient or hospital basis without interfering with their treatment. They followed their evolution every 24 hours until they became asymptomatic or died. Results: Thirteen patients (6.6%), nine diffuse cutaneous (dcSSc), and four limited cutaneous (lcSSc) developed COVID-19 during nine months of follow-up. The immunosuppressants used at the time of the disease were: mycophenolate mofetil, methotrexate, and prednisone, in low doses. Seven patients had interstitial lung disease (ILD). The main symptoms were chest pain, cough, dyspnea, dysgeusia, and anosmia, 1 with mild symptoms without pneumonia, 11 with mild pneumonia, and one with severe pneumonia that required hospital management. Only one (7.7%) presented severe pneumonia, was hospitalized, and died. Conclusions: COVID-19 disease in patients with SSc can be overcome in most cases, even when they are ILD and were using immunosuppressants at the time of infection with the SARS-CoV-2 virus. Copyright © 2023 Revista Medica del Instituto Mexicano del Seguro Social.

Covid-19 Booster Vaccine Related Dermatitis: A Case Study

Case Report: A 28 year old male with a past medical history of hypothyroidism and positive ANA presented to an outpatient dermatology clinic with a diffuse pruritic rash two weeks after the administration of his first Moderna COVID booster vaccine. He denied any other accompanying symptoms such as fever or chills as well as any similar rashes to prior doses of the Moderna COVID vaccine. The rash consisted of pink erythematous minimally scaly papules, thin plaques and patches involving the left and right dorsal hands, forearms, wrists, face, neck and left shoulder. The remainder of the patient's skin including the bilateral lower extremities, the eyelids, conjunctiva and oral mucosa was clear. The patient denied any similar rashes in the past. The patient denied any allergies to medications, or food or environmental allergies. He denied any notable contact allergen exposures, including to soaps, lotions, and cosmetic products. The patient also denied any significant family history or past surgical history. The patient was on Armour Thyroid for hypothyroidism and testosterone for low levels since age eighteen. The patient was started on cetirizine 10 mg once daily for the rash with minimal improvement. Autoimmune workup for the rash was notable for an elevated anti-RNP and as the patient's past medical history included Raynaud's phenomenon and ANA positivity for ten years, the patient was diagnosed with mixed connective tissue disease (MCTD). Autoimmune conditions can often have an indolent course, where symptoms progressively develop and worsen. MCTD is an autoimmune overlap syndrome that can consist of the following three connective tissue diseases: systemic lupus erythematosus, scleroderma, and polymyositis. Millions of individuals across the world are receiving COVID vaccines to protect themselves and members of their community, and it is of utmost importance that we continue to investigate adverse events. Although of low incidence, these rare effects have the ability to impact large numbers of people within both healthy and immunocompromised populations. It is critical that we examine and document them in a rigorous manner, to ensure safe vaccine delivery and reassure the public about vaccine safety overall.

Dermatomyositis with Specific Autoantibodies Appearing after Sars-Cov-2 Infection or Mrna Vaccination: Hints at a Shared Pathogenetic Mechanism

Background. Environmental factors such as infections and vaccines are known to trigger dermatomyositis (DM), and during the recent SARS-CoV-2 pandemic this has become even clearer. SARS-CoV-2 infection may share features with anti-MDA5 DM, such as rapidly progressive lung involvement, cutaneous lesions and cytokine release syndrome. A few case reports of DM following SARSCoV-2 vaccination have been published, suggesting the onset of an aberrant immune response leading to DM with specific autoantibody signatures and severe organ impairment. Methods. Clinical and laboratory data of the 2 case reports were obtained from electronic clinical charts in Humanitas Research Hospital (Rozzano, Milan, Italy). Autoantibody analysis was performed by protein-immunoprecipitation for anti-MDA5 and immunoblot for anti-Ro52 and TIF1gamma antibodies as per protocol. Results. Case report 1 is a 71-year-old woman who developed fever, cough, and anosmia, which resolved spontaneously in two weeks, but did not undergo a nasopharyngeal swab, while her relatives were diagnosed with SARS-CoV-2 infection. When symptoms improved, she developed arthralgia and skin lesions on her face, chest, and hands for which she started topical treatment, with negative SARSCoV-2 nasopharyngeal swab and positive serum test for IgG against SARS-CoV-2 spike protein. For the persistence of the skin rash and arthralgia, she was admitted to our Department in March 2021. Blood tests showed mild elevation of C reactive protein (2.1 mg/L -normal value NV<5), aspartate (84 UI/L) and alanine aminotransferase (133 UI/L -NV<35), ferritin (595 ng/ml -NV<306), troponin I (19 ng/L -NV<14), and BNP (251 pg/ml -NV<100) with normal complete blood cell count, creatine kinase, C3 and C4. IgG antibodies for SARS-CoV-2 spike protein were confirmed to be elevated (96 AU/ml -NV<15). Autoantibodies associated with connective tissue diseases were tested and only anti-MDA5 antibodies were positive at immunoprecipitation. A punch biopsy of a Gottron-like lesion on the left hand showed leukocytoclastic vasculitis. We observed reduced capillary density with neoangiogenesis and ectasic capillaries at the nailfold capillaroscopy. EKG and ecocardiography were normal, while cardiac magnetic resonance detected abnormalities in the parametric sequences, consistent with signs of previous myocarditis. A lung CT scan revealed pulmonary emphysema while respiratory function tests demonstrated reduced volumes (FVC 82%, FEV1 64%, inadequate compliance CO diffusion test). Based on the biochemical and clinical findings, a diagnosis of anti-MDA5-associated DM with skin and heart involvement was made and treatment with low-dose methylprednisolone (0.25 mg/kg daily) and azathioprine 100 mg was started, then switched to mycophenolate because not effective on skin lesions. Case report 2 is an 84-year-old woman with history of colon cancer (surgical treatment) and oral lichen treated with low doses steroids in the last 2 years. After the 2nd dose of SARS-CoV-2 mRNA vaccination, in March 2021 she developed skin rash with V-sign, Gottron's papules, periungueal ulcers, muscle weakness and fatigue, thus she performed a rheumatologic evaluation. Blood tests showed mild elevation of creatine kinase (484 UI/L, NV <167), CK-MB (9.6ng/ml, NV <3.4), BNP (215 pg/ml -NV<100) with normal values of complete blood cell count, C3 and C4. Anti-Ro52kDa and TIF1gamma were positive at immunoblot, thus we confirmed a diagnosis of DM. The clinical evaluation also showed active scleroderma pattern at nailfold capillaroscopy, normal echocardiography, bronchiectasia but not interstitial lung disease at lung CT, and normal respiratory function tests (FVC 99%, FEV1 99%, DLCO 63%, DLCO/VA 81%). A PET-CT scan was performed to exclude paraneoplastic DM, and treatment with steroids and mycophenolate was started. Conclusions. SARS-CoV-2 may induce mechanisms for escaping the innate immunity surveillance and causing autoimmune diseases, but more clinical and functional studies are needed to demonstrate this possible association.

Hyaluronic Acid in Facial Rehabilitation—A Narrative Review

Background: Hyaluronic acid fillers (HAF) are a versatile tool in esthetic medicine. They also have a potential for medical indications including facial rehabilitation. Materials and methods: We performed a literature search on PUBMED and Google Scholar until December 2022. Clinical trials, clinical studies, review articles, systematic reviews, meta-analyses, case series, and case reports were considered for review. Keywords "facial rehabilitation”, "acne scars”, "traumatic scars”, "oral restoration”, "facial lipoatrophy”, "facial asymmetry”, "periocular correction”, "nasal obstruction”, "ear lobe restoration”, "morphea”, AND "hyaluronic acid filler” were used to select articles. Results: We prepared a narrative review on the use of HAF for correction of facial asymmetry and asymmetric lips, improvement of different types of scars, improvement of the jaw line, improvement of ear lobes, periocular and oral restoration, and the treatment of nasal obstruction and morphea en coub de sabre. The amount of HA used in these indications is often less than 1 mL. The bolus technique, fanning, and dual-plane injections can be utilized for treatment. Duration of clinical effects depends upon the anatomical region and is usually maintained between 2 months and 2 years. Adverse events are often mild and temporary. Vascular occlusion is a severe adverse event, but it has not been reported yet for these medical indications. Repeated injections are recommended to obtain a longer-lasting improvement. In cases of morphea, only stable and non-inflammatory plaques should be treated. The advantage of HAF compared to permanent and semipermanent fillers is the availability of hyaluronidase for rapid removal of filler material and to revise overcorrection. Conclusions: HAF play an auxiliary role in facial rehabilitation. Knowledge of filler qualities, anatomy, and underlying diagnoses is important for their safe application. More prospective controlled trials are necessary to improve evidence.

Intramuscular Polydeoxyribonucleotides in Fibrotic and Atrophic Localized Scleroderma: An Explorative Prospective Cohort Study.

Effective options in the quiescent, scantily inflammatory phase of localized scleroderma (morphea) are lacking. A cohort study in patients with histologically confirmed fibroatrophic morphea explored the therapeutic value of the anti-dystrophic A2A adenosine agonist polydeoxyribonucleotide (PDRN, one daily 5.625 mg/3 mL ampoule for 90 days with a three-month follow-up). Primary efficacy endpoints: Localized Scleroderma Cutaneous Assessment Tool mLoSSI and mLoSDI subscores for disease activity and damage in eighteen areas; Physicians Global Assessment for Activity (PGA-A) and Damage (PGA-D) VAS scores; skin echography. Secondary efficacy endpoints: mLoSSI, mLoSDI, PGA-A, PGA-D, and morphea areas (photographs) over time; Dermatology Life Quality Index (DLQI); skin biopsy scores and induration over time. Twenty-five patients enrolled; 20 completed the follow-up period. Highly significant improvements at the end of the 3-month treatment period: mLoSSI-73.7%, mLoSDI-43.9%, PGA-A-60.4%, PGA-D-40.3%, with further improvements at follow-up visit for all disease activity and damage indexes. Overall, the outcomes suggest that a daily PDRN ampoule intramuscularly for 90 days reduces disease activity and damage rapidly and significantly in quiescent, modestly inflammatory morphea with few currently therapeutic options. The COVID-19 pandemic and lockdowns caused difficulties in enrollment, and some patients were lost to follow-up. Due to low final enrollment, the study outcomes may have only an exploratory value, yet they appear impressive. The anti-dystrophic potential of the PDRN A2A adenosine agonist deserves further in-depth exploration.

Oral health education for systemic sclerosis patients: A booklet report.

Purpose/objectives: Systemic sclerosis (SSc) is a rare chronic autoimmune disease characterized by vascular abnormalities and connective tissue disorders. In 2021, the multidisciplinary team of the university hospital recognized a demand for oral health information among SSc patients. This study aims to describe the development of an SSc oral health booklet and its validation by people with SSc. Methods: For the development of the booklet, the project creators employed the action research methodology involving ten stages. SSc patients evaluated the material by filling out a digital form. Results: One hundred and thirty-one people with SSc evaluated the booklet. It received an average score of 9.73 (SD: 0.80) in relevance, 9.82 (SD: 0.47) in explicitness, and 9.49 (SD: 0.93) in aesthetics. The final version was emailed to the participants and posted on social media. Innovation: This is the first booklet that deeply addresses these issues in Portuguese and constitutes a soft technology to instruct and assist patients with SSc. Conclusion: The production of high-quality educational materials on oral health for patients with SSc is necessary. The online distribution increased its reach and had great importance in the context of the COVID-19 pandemic.