IMPAIRED HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES: A CROSS-SECTIONAL ANALYSIS FROM AN INTERNATIONAL E-SURVEY

BackgroundComprehensive and large-scale assessment of health-related quality of life in patients with idiopathic inflammatory myopathies (IIMs) worldwide is lacking. The second COVID-19 vaccination in autoimmune disease (COVAD-2) study [1] is an international, multicentre, self-reported e-survey assessing several aspects of COVID-19 infection and vaccination as well as validated patient-reported outcome measures (PROMs) to outline patient experience in various autoimmune diseases (AIDs), with a particular focus on IIMs.ObjectivesTo investigate physical and mental health in a global cohort of IIM patients compared to those with non-IIM 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 obtained from the COVAD-2 survey.MethodsDemographics, AID diagnoses, comorbidities, disease activity, treatments, and PROMs were extracted from the COVAD-2 database. The primary outcomes were PROMIS Global Physical Health (GPH) and Global Mental Health (GMH) scores. Secondary outcomes included PROMIS physical function short form-10a (PROMIS PF-10a), pain visual analogue scale (VAS), and PROMIS Fatigue-4a scores. Each outcome was compared between IIMs, non-IIM AIRDs, NRAIDs, and controls. Factors affecting GPH and GMH scores in IIMs were identified using multivariable regression analysis.ResultsA total of 10,502 complete responses from 1582 IIMs, 4700 non-IIM AIRDs, 545 NRAIDs, and 3675 controls, which accrued as of May 2022, were analysed. Patients with IIMs were older [59±14 (IIMs) vs. 48±14 (non-IIM AIRDs) vs. 45±14 (NRAIDs) vs. 40±14 (controls) years, p<0.001] and more likely to be Caucasian [82.7% (IIMs) vs. 53.2% (non-IIM AIRDs) vs. 62.4% (NRAIDs) vs. 34.5% (controls), p<0.001]. Among IIMs, dermatomyositis (DM) and juvenile DM were the most common (31.4%), followed by inclusion body myositis (IBM) (24.9%). Patients with IIMs were more likely to have comorbidities [68.1% (IIMs) vs. 45.7% (non-IIM AIRDs) vs. 45.1% (NRAIDs) vs. 26.3% (controls), p<0.001] including mental disorders [33.4% (IIMs) vs. 28.2% (non-IIM AIRDs) vs. 28.4% (NRAIDs) vs. 17.9% (controls), p<0.001].GPH median scores were lower in IIMs compared to NRAIDs or controls [13 (interquartile range 10–15) IIMs vs. 13 (11–15) non-IIM AIRDs vs. 15 (13–17) NRAIDs vs. 17 (15–18) controls, p<0.001] and PROMIS PF-10a median scores were the lowest in IIMs [34 (25–43) IIMs vs. 40 (34–46) non-IIM AIRDs vs. 47 (40–50) NRAIDs vs. 49 (45–50) controls, p<0.001]. GMH median scores were lower in AIDs including IIMs compared to controls [13 (10–15) IIMs vs. 13 (10–15) non-IIM AIRDs vs. 13 (11–16) NRAIDs vs. 15 (13–17) controls, p<0.001]. Pain VAS median scores were higher in AIDs compared to controls [3 (1–5) IIMs vs. 4 (2–6) non-IIM AIRDs vs. 2 (0–4) NRAIDs vs. 0 (0–2) controls, p<0.001]. Of note, PROMIS Fatigue-4a median scores were the highest in IIMs [11 (8–14) IIMs vs. 8 (10–14) non-IIM AIRDs vs. 9 (7–13) NRAIDs vs. 7 (4–10) controls, p<0.001].Multivariable regression analysis in IIMs identified older age, male sex, IBM, comorbidities including hypertension and diabetes, active disease, glucocorticoid use, increased pain and fatigue as the independent factors for lower GPH scores, whereas coexistence of interstitial lung disease, mental disorders including anxiety disorder and depression, active disease, increased pain and fatigue were the independent factors for lower GMH scores.ConclusionBoth physical and mental health are significantly impaired in patients with IIMs compared to those with non-IIM AIDs or those without AIDs. Our results call for greater attention to patient-reported experience and comorbidities including mental disorders to provide targeted approaches and optimise global well-being in patients with IIMs.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.AcknowledgementsThe authors a e grateful to all respondents for completing the questionnaire. The authors also thank The Myositis Association, Myositis India, Myositis UK, the Myositis Global Network, Cure JM, Cure IBM, Sjögren's India Foundation, EULAR PARE for their contribution to the dissemination of the survey. Finally, the authors wish to thank all members of the COVAD study group for their invaluable role in the data collection.Disclosure of InterestsAkira Yoshida: None declared, Yuan Li: None declared, Vahed Maroufy: None declared, Masataka Kuwana Speakers bureau: Boehringer Ingelheim, Ono Pharmaceuticals, AbbVie, Janssen, Astellas, Bayer, Asahi Kasei Pharma, Chugai, Eisai, Mitsubishi Tanabe, Nippon Shinyaku, Pfizer, Consultant of: Corbus, Mochida, Grant/research support from: Boehringer Ingelheim, Ono Pharmaceuticals, Naveen Ravichandran: None declared, Ashima Makol Consultant of: Boehringer-Ingelheim, Parikshit Sen: None declared, James B. Lilleker: None declared, Vishwesh Agarwal: None declared, Sinan Kardes: None declared, Jessica Day Grant/research support from: CSL Limited, Marcin Milchert: None declared, Mrudula Joshi: None declared, Tamer A Gheita: None declared, Babur Salim: None declared, Tsvetelina Velikova: None declared, Abraham Edgar Gracia-Ramos: None declared, Ioannis Parodis Grant/research support from: Amgen, AstraZeneca, Aurinia Pharmaceuticals, Eli Lilly, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis, and F. Hoffmann-La Roche, Elena Nikiphorou Speakers bureau: Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Eli Lilly, Consultant of: Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Eli Lilly, Grant/research support from: Pfizer, Eli Lilly, Ai Lyn Tan Speakers bureau: AbbVie, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, UCB, Consultant of: AbbVie, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, UCB, Arvind Nune: None declared, Lorenzo Cavagna: None declared, Miguel A Saavedra Consultant of: AbbVie, GlaxoSmithKline, Samuel Katsuyuki Shinjo: None declared, Nelly Ziade Speakers bureau: AbbVie, Boehringer-Ingelheim, Eli Lilly, Janssen, Pfizer, Roche, Consultant of: AbbVie, Boehringer-Ingelheim, Eli Lilly, Janssen, Pfizer, Roche, Grant/research support from: AbbVie, Boehringer-Ingelheim, Eli Lilly, Janssen, Pfizer, Roche, Johannes Knitza: None declared, Oliver Distler Speakers bureau: AbbVie, Amgen, Bayer, Boehringer Ingelheim, Janssen, Medscape, Novartis, 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, Topadur, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Kymera, Mitsubishi Tanabe, Novartis, Roche, Hector Chinoy Grant/research support from: Eli Lilly, UCB, Vikas Agarwal: None declared, Rohit Aggarwal Consultant of: Mallinckrodt, Octapharma, CSL Behring, Bristol Myers-Squibb, EMD Serono, Kezar, Pfizer, AstraZeneca, Alexion, Argenx, Boehringer Ingelheim (BI), Corbus, Janssen, Kyverna, Roivant, Merck, Galapagos, Actigraph, Abbvie, Scipher, Horizontal Therapeutics, Teva, Biogen, Beigene, ANI Pharmaceutical, Nuvig, Capella, CabalettaBio, Grant/research support from: Bristol Myers-Squibb, Pfizer, Mallinckrodt, Janssen, Q32, EMD Serono, Boehringer Ingelheim, Latika Gupta: None declared.

GENE ANALYSIS REVEALED THE USEFULNESS OF TRIPLE THERAPY WITH BARICITINIB, RITUXIMAB AND TACROLIMS FOR ANTI-MDA5 ANTIBODY POSITIVE DERMATOMYOSITIS (MDA5-DM)

BackgroundAnti-MDA5 antibody positive dermatomyositis (MDA5-DM) is characterized by high mortality due to rapid progressive ILD. MDA5 is a cytosolic protein and a family of RIG-I like receptor, which functions as a virus RNA sensor and induces the production of such as type-1 IFN. Although little is known about the pathogenesis of MDA5-DM, it is notable that the similarities were reported between COVID-19 infection and MDA5-DM. It may suggest that there is a common underlying autoinflammatory mechanism. We reported that in MDA5-DM, (1) RIG-I-like receptor signaling is enhanced and (2) antiviral responses such as type 1 IFN signaling are also enhanced as compare with anti-ARS-antibody positive DM, and (3) the key for survival is suppression of RIG-I-like and IFN signaling (EULAR2022, POS0390). We also found that a significant role for uncontrolled macrophage in the pathogenesis of ILD by our autopsy case. Recently, it has been reported that tacrolimus (TAC) and cyclophosphamide (CY) combination therapy (TC-Tx) has improved the prognosis of cases with early onset of the disease, but there are cases that cannot be saved. Therefore, we devised BRT therapy (BRT-Tx). The Tx combines baricitinib (BAR), which inhibits GM-CSF and IFN-mediated signaling and effectively suppresses uncontrolled macrophages, with rituximab (RTX) and TAC, which rapidly inhibits B and T cell interaction and ultimately prevents anti-MDA5 antibody production.ObjectivesTo determine the differences in gene expression between BRT and TC-Tx for MDA5-DM in peripheral blood.MethodsTotal of 6 MDA5-DM (TC: 3, BRT: 3) were included and all of them had multiple poor prognostic factors. Peripheral whole blood was collected at just before and 2-3 months after the treatment. RNA was extracted, and quantified using a next-generation sequencer. Differentially Expressed Genes (DEGs) were identified by pre vs. post treatment. Gene Ontology (GO), clustering and Gene Set Variation Analysis (GSVA) were performed to DEGs. As one BRT case was added since our last year's report, we also reanalyzed the surviving vs. fatal cases. The IFN signature was scored separately for Types 1, 2, and 3, and the changes between pre- and post-treatment were investigated.ResultsTwo of three cases with TC died during treatment, while all three cases on BRT recovered. The cluster analysis of the DEGs separated deaths from survivors, not by type of treatment. Comparing surviving and dead cases, GO analysis revealed that the immune system via immunoglobulins and B cells was significantly suppressed in surviving cases. GO analysis of DEGs in each therapeutic group showed that expression of B cell-related genes such as lymphocyte proliferation and B cell receptor signaling pathway were significantly suppressed in BRT-Tx. On the other hand, TC-Tx significantly suppressed such pathways as cell proliferation and cell surface receptor signaling, and was less specific for the target cells than BRT-Tx. The changes in IFN signature score after treatment showed an increase in type 2 and 3 IFN scores in all fatal cases and an increase in type 1 IFN score in one fatal case.ConclusionBRT-Tx significantly suppressed gene expression associated with B cells, while TC-Tx was characterized by low specificity of therapeutic targets and suppression of total cell proliferation. Comparison of surviving and dead cases revealed that the combination of RTX contributed to the success of treatment, as suppression of the immune system mediated by immunoglobulins and B cells is the key for survival. Analysis of the IFN signature revealed an increase in IFN score after treatment in fatal cases, indicating that the combination of BAR is beneficial. The superiority of BRT-Tx seems clear from the fact that all patients survived with BRT-Tx while only one/three patients survived with TC-Tx.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsMoe Sakamoto: None declared, Yu Nakai: None declared, Yoshiharu Sato: None declared, Yoshinobu Koyama Speakers bureau: Abbvie, Asahikasei, Ayumi, BMS, Esai, Eli-Lilly, Mitsubishi Tanabe, Grant/research support from: Abbvie, GSK.

CLINICAL AND IMMUNOLOGICAL PROFILES OF PATIENTS WITH ANTI-SYNTHETASE SYNDROME: A RETROSPECTIVE COHORT STUDY FROM A TERTIARY CENTRE

BackgroundAnti-synthetase syndrome (ASS) is a rare auto-immune condition that combines autoantibodies and specifics clinical manifestations, including myositis, interstitial lung disease (ILD), polyarthritis, mechanic's hands, Raynaud's phenomenon, and unexplained fever. The hallmark of this syndrome is the presence of anti-aminoacyl-tRNA-synthetase (ARS) antibodies. Several anti-ARS antibodies have been described, anti-Jo1 being the most common, followed by anti-PL7, anti-PL12, anti-OJ, anti-EJ, anti-KS, anti-YRS, and anti-Zo. According to a recent epidemiological survey, the rising number of patients with autoimmune diseases, including idiopathic inflammatory myopathies (IIM) coincides with the COVID-19 pandemic.ObjectivesTo evaluate the clinical characteristics of ASS patients with different anti-ARS antibodies from a tertiary rheumatology center.MethodsWe conducted a retrospective, single-centered study on consecutive patients diagnosed with ASS from 1 January 2015 to 31 December 2022. Clinical and serologic data were obtained by medical records review from hospital database. Myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) were tested using commercial ELISA kits. We included all patients fulfilling Connor's criteria for ASS.ResultsSixty-one patients (44 females) with mean age 54.4 (13.8) years were included. The most frequently reported clinical manifestation was arthralgia (68.8%), followed by Raynaud's phenomenon (67.2%), ILD (65.6%), myositis (46%), mechanic's hands (44.3%), arthritis (39.3%), and fever (18.0%). The typical triad for ASS, including myositis, arthritis and ILD was present in 17 patients. Twenty-eight (45.9%) patients were PL7+, 21 (34.4%) were Jo1+, 3 (4.9%) were PL12+, and 2 (3.2%) were OJ+. Seven patients were positive for more than two anti-ARS antibodies. The most frequently found MAA was anti-Ro52 (n=23, 37.7%). Of the 61 patients included, 41 (67.2%) patients were diagnosed in the last 3 years (COVID-19 pandemic). The most frequently detected MSA in ASS patients diagnosed during COVID-19 pandemic was anti-PL7 (25/28), while anti-Jo1 was the most common MSA in ASS patients diagnosed before 2020 (p<0.05) (Fig 1).The anti-Jo1+ patients were younger, have significantly more frequent muscle involvement and significantly higher levels of CK than anti-PL7+ patients (p<0.05). The co-occurance of anti-Ro52 antibodies was more frequently observed in anti-Jo1+ patients (n=11, 52.4%) than in anti-PL7+ patients (n=6, 21.4%) (p<0.05). We did not find statistically significant differences between ASS groups regarding sex, disease duration, clinical manifestations including dermatologic lesions, Raynaud's phenomenon, arthralgia/arthritis, ILD, fever, and cancers (all p>0.05).ConclusionASS patients have heterogenous manifestations, and different types of anti-ARS antibodies are associated to distinct clinical and immunological features. The COVID-19 pandemic led to increase prevalence of ASS cases and to a remarkable shift in the anti-ARS antibodies profile, with increased frequency of anti-PL7 antibodies. Further studies are needed to investigate the link between SARS-CoV-2 infections and myositis.References[1]Witt LJ, et al. The Diagnosis and Treatment of Antisynthetase Syndrome. Clin Pulm Med. 2016 Sep;23(5):218-226.[2]Gracia-Ramos AE, et al. New Onset of Autoimmune Diseases Following COVID-19 Diagnosis. Cells. 2021 Dec 20;10(12):3592.[3]Connors GR, et al. Interstitial lung disease associated with the idiopathic inflammatory myopathies: what progress has been made in the past 35 years? Chest. 2010 Dec;138(6):1464-74.[4]García-Bravo Let al. Association of anti-SARS-COV-2 vaccine with increased incidence of myositis-related anti-RNA-synthetases auto-antibodies. J Transl Autoimmun. 2022 Jun 30;5:100160.Figure 1.ASS patients with positive anti-ARS antibodies per year (from 2015 to 2022). The green line shows the PL7+ patients;and the orange line shows the Jo1+ cases.[Figure omitted. See PDF]AcknowledgementsI have no acknowledgements to declare.Disclosure of Inter stsNone Declared.

TYPE I INTERFERON SCORE IS ASSOCIATED WITH THE SEVERITY AND POOR PROGNOSIS IN ANTI-MDA5 ANTIBODY-POSITIVE DERMATOMYOSITIS PATIENTS

BackgroundAnti-MDA5 antibody-positive dermatomyositis (anti-MDA5+DM) is a rare autoimmune disease associated with a high mortality rate due to rapid-progressive interstitial lung disease (RP-ILD), particularly in East Asia[1]. MDA5, acts as a cytoplasmic sensor of viral RNA, thus activating antiviral responses including the type I interferon (IFN) signaling pathway[2]. The involvement of type 1 IFN in the pathogenesis of MDA5+DM has been proposed based on the significantly elevated expression of its downstream stimulated genes(ISG) in muscle, skin, lung, and peripheral blood[3;4]. Janus kinase inhibitor, which targets the IFN pathway, combined with glucocorticoid could improve the survival of early-stage MDA5+DM-ILD patients[5]. In clinical practice, there is still an urgent demand for sensitive biomarkers to facilitate clinical risk assessment and precise treatment.ObjectivesThis study aimed to investigate the clinical significance of interferon score, especially IFN-I score, in patients with anti-MDA5+DM.MethodsDifferent subtypes of idiopathic inflammatory myopathy, including anti-MDA5+DM(n=61), anti-MDA5-DM(n=20), antisynthetase syndrome(ASS,n=22),polymyositis(PM,n=6) and immune-mediated necrotizing myopathy(IMNM,n=9), and 58 healthy controls were enrolled.. A multiplex quantitative real-time PCR(RT-qPCR) assay using four TaqMan probes was utilized to evaluate two type I ISGs (IFI44, MX1, which are used for IFN-I score), one type II ISG (IRF1), and one housekeeping gene (HRPT1). Clinical features and disease activity index were compared between high and low IFN-I score groups in 61 anti-MDA5+DM patients. The association between laboratory findings and the predictive value of baseline IFN-I score level for mortality was analyzed.ResultsThe IFN scores were significantly higher in patients with anti-MDA5+DM than in HC (Figure 1A). The IFN-I score correlated positively with serum IFN α(r = 0.335, P =0.008), ferritin (r = 0.302, P = 0.018), and Myositis Disease Activity Assessment Visual Analogue Scale (MYOACT) score(r=0.426, P=0.001). Compared with patients with low IFN-I scores, patients with high IFN-I scores showed increased MYOACT score, CRP, AST, ferritin, and the percentages of plasma cells (PC%) but decreased lymphocyte count, natural killer cell count, and monocyte count. The 3-month survival rate was significantly lower in patients with IFN-I score > 4.9 than in those with IFN-I score ≤ 4.9(72.9% vs. 100%, P=0.044)(Figure 1B).ConclusionIFN score, especially IFN-I score, detected by multiplex RT-qPCR, can be a valuable biomarker for monitoring disease activity and predicting mortality in anti-MDA5+DM patients.References[1]I.E. Lundberg, M. Fujimoto, J. Vencovsky, R. Aggarwal, M. Holmqvist, L. Christopher-Stine, A.L. Mammen, and F.W. Miller, Idiopathic inflammatory myopathies. Nat Rev Dis Primers 7 (2021) 86.[2]G. Liu, J.H. Lee, Z.M. Parker, D. Acharya, J.J. Chiang, M. van Gent, W. Riedl, M.E. Davis-Gardner, E. Wies, C. Chiang, and M.U. Gack, ISG15-dependent activation of the sensor MDA5 is antagonized by the SARS-CoV-2 papain-like protease to evade host innate immunity. Nat Microbiol 6 (2021) 467-478.[3]G.M. Moneta, D. Pires Marafon, E. Marasco, S. Rosina, M. Verardo, C. Fiorillo, C. Minetti, L. Bracci-Laudiero, A. Ravelli, F. De Benedetti, and R. Nicolai, Muscle Expression of Type I and Type II Interferons Is Increased in Juvenile Dermatomyositis and Related to Clinical and Histologic Features. Arthritis Rheumatol 71 (2019) 1011-1021.[4]Y. Ye, Z. Chen, S. Jiang, F. Jia, T. Li, X. Lu, J. Xue, X. Lian, J. Ma, P. Hao, L. Lu, S. Ye, N. Shen, C. Bao, Q. Fu, and X. Zhang, Single-cell profiling reveals distinct adaptive immune hallmarks in MDA5+ dermatomyositis with therapeutic implications. Nat Commun 13 (2022) 6458.[5]Z. Chen, X. Wang, and S. Ye, Tofacitinib in Amyopathic Dermatomyositis–Associated Interstitial Lung Disease. New England Journal of Medicine 381 (2019) 291-293.AcknowledgementsThis work was supported by the National Natural Science Foundation of China [81974251], and Shanghai Hospital Develop ent Center, Joint Research of New Advanced Technology Project [SHDC12018106]Disclosure of InterestsNone Declared.

CLINICAL COURSE IN COVID 19 DISEASE IN IMMUNOSUPRESSED PATIENTS DIAGNOSED WITH RHEUMATIC DISEASES

BackgroundPatients with pre-existing rheumatic diseases may be exacerbated during SARS-CoV-2 infection, or may develop new autoimmune features. Furthermore, immunosuppressive agents used to treat autoimmunity-inflammation as well as comorbidities can also affect the disease outcome.ObjectivesTo evaluate the outcome of rheumatic diseases after Covid 19 infection in patients diagnosed with rheumatic diseases, under various immunosuppressive treatment, as well as the effects of vaccines against Covid or antiviral treatment in this sensitive population group.MethodsDuring the pandemic, 1493 patients with autoimmune or autoinflammatory disease who were continuously followed up in two tertiaries hospitals in northern and northwestern Greece were included in the current study. The patients were compared with 769 controls after adjustment for age, sex, weight, vaccination status and comorbidities. Of the 1493 patients, 648 had rheumatoid arthritis, 282 psoriatic arthritis, 173 ankylosing spondylitis, 122 systemic lupus erythematosus, 98 Sjogren's syndrome, 43 polymyalgia rheumatica, 34 mixed connective tissue disease or overlapping syndromes, 31 vasculitis, 27 systemic sclerosis, 18 myositis, 10 Behcet syndrome, 5 primary antiphospholipid syndrome and 2 had Familial Mediterranean Fever. The vast majority of patients and controls were fully vaccinated (82%) and 397 patients received antiviral treatment, 94% of them were fully vaccinated.ResultsCovid 19 disease in vaccinated patients with rheumatic diseases was shown to perform the same or about the same as those in the control group after adjustment for risk factors for severe disease. 19 of our patients required admission in the intensive care unit (62% full vaccinated) while a total of 12 died (66% non vaccinated). Major risk factors for severe disease were previous respiratory failure, chronic renal impairment, obesity, and failure to receive antiviral therapy. It was also shown that infection with Covid led to an exacerbation or induction of autoimmune disorders in 25 of the participants.ConclusionIn this large cohort, Covid 19 disease was shown to affect patients with autoimmune rheumatic diseases the same or approximately the same way as the general population if they are fully vaccinated and if they start timely antiviral treatment where indicated. Further research and monitoring of the results after the multiple mutations of the virus is advisable.ReferencesNone.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Severe juvenile dermatomyositis with specific liver involvement onset concomitant with COVID-19 infection: A case report

Juvenile Dermatomyositis (JDM) is an autoimmune disease that involves skin, muscle and internal organ disorders. Its mechanisms still not well established, but the triggering role of viral infections has been described. In this context, the effect of the COVID-19 on the onset of autoimmune disorders such as JDM remains a matter of study and research. We report a severe JDM, following a confirmed COVID-19 infection in a previously healthy 8 year-old boy who presented with various skin lesions and a cholestatic liver involvement. Laboratory findings were consistent with an inflammatory myositis and an autoimmune liver disease. Skin and muscle biopsies confirmed the diagnosis of JDM. The therapy choice was difficult. Finally, he received a second line therapy of the JDM with a favorable outcome. The liver fragment analysis showed a steatosis. This case supports the hypothesis of COVID-19 triggering role in the genesis of JDM and autoimmune diseases.Copyright © 2023 Scientific Publishers of India. All rights reserved.

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.

INCIDENCE, FEATURES AND OUTCOME OF DISEASE RELAPSE AFTER COVID-19 VACCINATION IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES

BackgroundThe approved COVID-19 vaccines showed clear safety and efficacy in reduction of severe SARS-CoV-2 disease. Patients with idiopathic inflammatory myopathies (IIM) were not well represented in these vaccine trials and there are limited data in the literature about development of confirmed disease flare after COVID-19 vaccination.ObjectivesTo evaluate frequency, features and outcome of disease relapses in patients with IIM following SARS–CoV-2 vaccination.MethodsA cohort of 176 IIM patients (mean age:57.6 years, 117 females, 59 males, 106 PM, 70 DM) were interviewed after the 3rd wave of COVID-19 pandemic and prospectively followed. Relapses were determined using the IMACS disease state criteria, outcome of the flares with myositis response criteria, calculating the total improvement score (TIS).ResultsA total of 146 (82.9%) patients received vaccination and 17/146 (11.6%) patients had relapse within 3 months and 13/146 (8.9%) patients within one month. The relapse rate of unvaccinated patients (1/30;3.3%) was not significantly different (p>0.1). No fatal flare has been observed. Three months after the post-vaccination relapses, 70.6% of the patients (12/17) achieved improvement of disease activity (average TIS score:30±15.81;7 minor, 5 moderate and 0 major improvement). Six months after flares improvement was detected in 14/16 (87.5%) of relapsed patients (average TIS score: 43±20.17;3 minimal, 7 moderate and 4 major). Forward stepwise logistic regression analysis revealed that the active state of myositis at time of injection (p<0.0001;OR: 31.2 CI: 9.0 – 108) and the application of BNT162b2 vaccination (p=0.026;OR: 4.06 CI: 1.1 – 14.7) were significantly associated with the occurrence of relapse.ConclusionMinority of the vaccinated IIM patients had confirmed disease flare after COVID-19 vaccination and majority of the relapses improved after individualized treatment. Active disease state at the time of vaccination probably contributes to the increased risk of post vaccination myositis flare.REFERENCES:NIL.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.

Global disparities in the treatment of idiopathic inflammatory myopathies: results from an international online survey study.

OBJECTIVES: We aimed to explore current practice and interregional differences in the treatment of idiopathic inflammatory myopathies (IIMs). We triangulated these observations considering countries' Gross National Income (GNI), disease subtypes, and symptoms using patient-reported information. METHODS: A cross-sectional ancillary analysis of the "COVID-19 vaccination in auto-immune disease" (COVAD) e-survey containing demographic characteristics, IIM subtypes (dermatomyositis (DM), polymyositis (PM), inclusion-body myositis (IBM), anti-synthetase syndrome (ASSD), immune-mediated necrotizing myopathy (IMNM), overlap myopathies (OM)), current symptoms (surrogate for organ involvement), and treatments (corticosteroids (CS), immunomodulators (IM), i.e., antimalarials, immunosuppressants (IS), intravenous immunoglobulins (IVIG), biological treatments, and targeted-synthetic small molecules). Treatments were presented descriptively according to continents, GNI, IIM, and organ involvement, and associated factors were analyzed using multivariable binary logistic regressions. RESULTS: Of 18,851 respondents from 94 countries, 1,418 with IIM were analyzed (age 61 years, 62.5% females). DM (32.4%), IBM (24.5%), and OM (15.8%) were the most common subtypes. Treatment categories included IS (49.4%), CS (38.5%), IM (13.8%), and IVIG (9.4%). Notably, treatments varied across regions, GNI categories (IS mostly used in higher-middle income, IM in lower-middle income, IVIG and biologics largely limited to high-income countries), IIM subtypes (IS and CS associated with ASSD, IM with OM and DM, IVIG with IMNM, and biological treatments with OM and ASSD) and disease manifestations (IS and CS with dyspnea). Most inter-regional treatment disparities persisted after multivariable analysis. CONCLUSION: We identified marked regional treatment disparities in a global cohort of IIM. These observations highlight the need for international consensus-driven management guidelines considering patient-centered care and available resources.

Post Covid-19 Vaccination Inflammatory Syndrome: A Case Report.

A previously healthy 24-year-old male patient was referred to our clinic with bilateral lower extremity pain and dark urine, which developed two weeks after receiving the second dose of BNT162b2 vaccine against SARS-CoV-2. Laboratory tests indicated rhabdomyolysis. Lower extremity magnetic resonance imaging was compatible with myositis. Myositis-related antibodies were negative. Biopsy taken from gastrocnemius muscle revealed muscle necrosis and striking expression of major histocompatibility complex class I antigen. He was successfully treated, and his complaints resolved. One week later at follow-up, he reported new-onset exertional dyspnea with palpitations. ST-segment depressions were spotted on electrocardiography. Troponin T was found elevated as 0.595 ng/mL (normal <0.014 ng/mL). Echocardiography showed hypokinetic left ventricle with ejection fraction of 40%, and pericardial effusion of 2mm. An appropriate treatment plan was formulated for the diagnosis of myocarditis, eventually the patient recovered within ten days. BNT162b2 mRNA vaccine was felt to cause the aforementioned condition since no other etiology could be identified. Although it is known that BNT162b2 may induce myocarditis, myositis concomitant myocarditis appears to be a very rare adverse effect of this vaccine.

Scurvy in a Pediatric Patient Unable to Bear Weight: A Case Report.

Pediatric scurvy is uncommon in the twenty-first century but cases have been reported in children with neurodevelopmental issues and restricted diets. We are reporting a two-year and nine-month-old boy who had a coronavirus disease (COVID) infection and then presented with a refusal to walk. By careful history-taking, he was found to have a restricted diet, speech delay, and gum bleeding suggestive of scurvy, which was confirmed by extremely low levels of ascorbic acid. In this case, the diagnosis of scurvy was established before establishing the diagnosis of neurodevelopmental delay. Treatment with ascorbic acid resulted in a remarkable improvement in his symptoms. This case highlights the importance of collecting a thorough history, connecting exam findings to the history, and including scurvy in differential diagnoses for the presentation of inability to bear weight.

High fatigue scores in patients with idiopathic inflammatory myopathies: a multigroup comparative study from the COVAD e-survey.

Idiopathic inflammatory myopathies (IIMs) confer a significant risk of disability and poor quality of life, though fatigue, an important contributing factor, remains under-reported in these individuals. We aimed to compare and analyze differences in visual analog scale (VAS) scores (0-10 cm) for fatigue (VAS-F) in patients with IIMs, non-IIM systemic autoimmune diseases (SAIDs), and healthy controls (HCs). We performed a cross-sectional analysis of the data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) international patient self-reported e-survey. The COVAD survey was circulated from December 2020 to August 2021, and details including demographics, COVID-19 history, vaccination details, SAID details, global health, and functional status were collected from adult patients having received at least one COVID-19 vaccine dose. Fatigue experienced 1 week prior to survey completion was assessed using a single-item 10 cm VAS. Determinants of fatigue were analyzed in regression models. Six thousand nine hundred and eighty-eight respondents (mean age 43.8 years, 72% female; 55% White) were included in the analysis. The overall VAS-F score was 3 (IQR 1-6). Patients with IIMs had similar fatigue scores (5, IQR 3-7) to non-IIM SAIDs [5 (IQR 2-7)], but higher compared to HCs (2, IQR 1-5; P < 0.001), regardless of disease activity. In adjusted analysis, higher VAS-F scores were seen in females (reference female; coefficient -0.17; 95%CI -0.21 to -13; P < 0.001) and Caucasians (reference Caucasians; coefficient -0.22; 95%CI -0.30 to -0.14; P < 0.001 for Asians and coefficient -0.08; 95%CI -0.13 to 0.30; P = 0.003 for Hispanics) in our cohort. Our study found that patients with IIMs exhibit considerable fatigue, similar to other SAIDs and higher than healthy individuals. Women and Caucasians experience greater fatigue scores, allowing identification of stratified groups for optimized multidisciplinary care and improve outcomes such as quality of life.

COVID-19 musculoskeletal involvement in children.

Since the early phases of the COVID-19 pandemic, it has become clear that children are affected by mild respiratory symptoms rather than the critical pneumonia typical in adults. Nevertheless, it took longer to understand that pediatric patients with SARS-COV2 may develop a severe multisystem inflammatory response (a.k.a. multisystem inflammatory syndrome in children (MIS-C)), which can include musculoskeletal symptoms, and/or arthritis and myositis independently from MIS-C. Diagnostic imaging significantly contributed to the assessment of pulmonary disease due to COVID-19 but it has been rarely applied to evaluate musculoskeletal involvement in children with or without previous rheumatic diseases. Despite the paucity of radiological literature, muscle edema at magnetic resonance and synovitis at ultrasound have been described. Further use of diagnostic imaging for children with articular and muscular symptoms due to COVID-19 is strongly encouraged.

A machine learning analysis to evaluate the outcome measures in inflammatory myopathies.

OBJECTIVE: To assess the long-term outcome in patients with Idiopathic Inflammatory Myopathies (IIM), focusing on damage and activity disease indexes using artificial intelligence (AI). BACKGROUND: IIM are a group of rare diseases characterized by involvement of different organs in addition to the musculoskeletal. Machine Learning analyses large amounts of information, using different algorithms, decision-making processes and self-learning neural networks. METHODS: We evaluate the long-term outcome of 103 patients with IIM, diagnosed on 2017 EULAR/ACR criteria. We considered different parameters, including clinical manifestations and organ involvement, number and type of treatments, serum creatine kinase levels, muscle strength (MMT8 score), disease activity (MITAX score), disability (HAQ-DI score), disease damage (MDI score), and physician and patient global assessment (PGA). The data collected were analysed, applying, with R, supervised ML algorithms such as lasso, ridge, elastic net, classification, and regression trees (CART), random forest and support vector machines (SVM) to find the factors that best predict disease outcome. RESULTS AND CONCLUSION: Using artificial intelligence algorithms we identified the parameters that best correlate with the disease outcome in IIM. The best result was on MMT8 at follow-up, predicted by a CART regression tree algorithm. MITAX was predicted based on clinical features such as the presence of RP-ILD and skin involvement. A good predictive capacity was also demonstrated on damage scores: MDI and HAQ-DI. In the future Machine Learning will allow us to identify the strengths or weaknesses of the composite disease activity and damage scores, to validate new criteria or to implement classification criteria.

SARS-CoV-2-induced myopathy: Clinical aspects, paraclinical changes, and therapeutic options

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a considerable global effect, posing notable challenges for clinicians, the pandemic becoming one of the most imperative international health emergencies lately. Among other more frequent manifestations, SARS-CoV-2 disease may also give rise to skeletal muscle involvement. Viral-induced skeletal muscle involvement is a potentially severe manifestation of COVID-19 (Coronavirus Disease 2019) and may be either acute, or in the context of "long-COVID”. The present review aimed to illustrate few aspects about pathomechanisms, clinical and paraclinical frames, and treatment options for SARS-CoV-2-induced muscle involvement. Notably, it has been stated that SARS-CoV-2 may have the ability to invade muscle myocytes directly, the disease having a variety of clinical manifestations, from myalgia and muscle weakness to rhabdomyolysis. Nevertheless, it is also important to take into account that most of patients with severe forms receiving mechanical ventilation for more than one week may have complications such as CIM (critical illness myopathy) and/or CIP (critical illness polyneuropathy) that may be clinically similar to SARS-CoV-2-induced myositis, yet may be differentiated paraclinically from it. Additionally, it was hypothesized that SARS-CoV-2 infection may constitute a trigger for autoimmune diseases such as polymyositis/ dermatomyositis. Presently, there are no diagnosis criteria and no specific therapeutic strategy for SARS-CoV-2-induced myositis. © 2022, Amaltea Medical Publishing House. All rights reserved.

Incidence and Clinical Outcomes of Newonset Autoimmune Connective Tissue Diseases after Covid-19 Infection- a Systematic Literature Review

Background/Aims Cases of new autoimmune and autoinflammatory conditions have been reported among COVID-19 survivors. A literature review on newonset autoimmune connective tissue diseases (ACTDs) following infection with COVID-19 is lacking.This systematic literature review aimed to evaluate the potential association between COVID-19 infection and the development of new-onset ACTDs in adults. Methods Articles published until September 2022, investigating the association between COVID-19 infection and new-onset ACTDs were included. The ''population'' searched was patients with disease terms for autoimmune connective tissue diseases, including (but not limited to) systemic lupus erythematosus (SLE), Sjogren's syndrome, systemic sclerosis (SSc), any idiopathic inflammatory myositis (IIM), antisynthetase syndrome, mixed CTD and undifferentiated CTD (and related MeSH terms), with ''intervention'' as COVID-19 and related terms. For terms for COVID-19, a dedicated search strategy developed by the National Institute for Clinical Excellence was used.Medline, Embase, and Cochrane databases were searched, restricted to English-language articles only. Eligible articles were: case reports and series (of any sample size), observational studies, qualitative studies and randomised controlled trials. Patients developing ACTDs without prior COVID-19 or reporting flares of existing ACTDs were excluded. Information was extracted on patient demographics, new ACTDs' onset time, clinical characteristics, COVID-19 and ACTD treatment, and COVID-19 and ACTDs outcomes. The protocol was registered in PROSPERO (CRD42022358750). Results After deduplication, 2239 articles were identified. After screening title and , 2196 papers were excluded, with 43 proceeding to fulltext screening. Ultimately, 28 articles (all single case reports) were included. Of the 28 included patients, 64.3% were female. The mean age was 51.1 years (range 20-89 years). The USA reported the most cases (9/28). ACTD diagnoses comprised: 11 (39.3%) IIM (including 4 cases of dermatomyositis);7 (25%) SLE;4 (14.3%) anti-synthetase syndrome;4 (14.3%) SSc;2 (7.1%) other ACTD (one diagnosed with lupus/MCTD overlap). Of eight, four (14.3%) patients (including that with lupus/MCTD) were diagnosed with lupus nephritis. The average onset time from COVID-19 infection to ACTD diagnosis was 23.7days. A third of the patients were admitted to critical care, one for ACTD treatment for SLE with haemophagocytic lymphohistiocytosis (14 sessions of plasmapheresis, rituximab and intravenous corticosteroids) and nine due to COVID-19. The majority (80%) of patients went into remission of ACTD following treatment, while two (10%) patients died- one due to macrophage activation syndrome associated with anti-synthetase syndrome and two from unreported causes. Conclusion Our results suggest a potential association between COVID-19 infection and new-onset ACTDs, predominantly in young females, reflective of wider CTD epidemiology. The aetiology and mechanisms by which ACTDs arise following COVID-19 infection remain unknown and require more robust epidemiological data.

Rare Case of Immune-Mediated Necrotizing Myopathy With Isolated Dysphagia as Presenting Symptom

Introduction: Immune mediated necrotizing myopathy (IMNM) is a rare, but progressive disease that accounts for about 19% of all inflammatory myopathies. Dysphagia occurs in 20-30% of IMNM patients. It often follows proximal muscle weakness and ensues in the later stages of the disease. We report a rare case of IMNM, presenting with dysphagia as the initial symptom, followed by proximal muscle weakness. Case Description/Methods: A 74-year-old male with a past medical history of coronary artery disease, hypertension, and hyperlipidemia presented to the ED with 2-3 weeks of intractable nausea, vomiting, and dysphagia for solids and liquids. Vital signs were stable, and initial labs displayed an AST of 188 U/L and ALT of 64 U/L with a normal bilirubin. Computed tomogram of the chest, abdomen, and pelvis were negative. An esophagram showed moderate to severe tertiary contraction, no mass or stricture, and a 13 mm barium tablet passed without difficulty. Esophagogastroduodenoscopy exhibited a spastic lower esophageal sphincter. Botox injections provided no significant relief. He then developed symmetrical proximal motor weakness and repeat labs demonstrated an elevated creatine kinase (CK) level of 6,357 U/L and aldolase of 43.4 U/L. Serology revealed positive PL-7 autoxantibodies, but negative JO-1, PL-12, KU, MI-2, EJ, SRP, anti-smooth muscle, and anti-mitochondrial antibodies. Muscle biopsy did not unveil endomysial inflammation or MHC-1 sarcolemmal upregulation. The diagnosis of IMNM was suspected. A percutaneous endoscopic gastrostomy feeding tube was placed as a mean of an alternative route of nutrition. He was started on steroids and recommended to follow up with outpatient rheumatology. He expired a month later after complications from an unrelated COVID-19 infection. Discussion(s): The typical presentation of IMNM includes painful proximal muscle weakness, elevated CK, presence of myositis-associated autoantibodies, and necrotic muscle fibers without mononuclear cell infiltrates on histology. Dysphagia occurs due to immune-mediated inflammation occurring in the skeletal muscle of the esophagus, resulting in incoordination of swallowing. Immunotherapy and intravenous immunoglobulin are often the mainstay of treatment. Our patient was unique in presentation with dysphagia as an initial presenting symptom of IMNM, as well as elevated enzymes from muscle breakdown. It is critical as clinicians to have a high degree of suspicion for IMNM due to the aggressive nature of the disease and refractoriness to treatment.