Inactivated SARS-CoV-2 vaccine does not increase the risk of relapse in patients with clinically inactive adult-onset Still's disease.

OBJECTIVE: A succession of cases have reported flares of adult-onset Still's disease (AOSD) after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raising concerns. We aimed to investigate the impact of inactivated SARS-CoV-2 vaccines on disease activity in patients with AOSD. METHODS: We prospectively enrolled clinically inactive AOSD patients visiting the outpatient clinics of our department. The patients received SARS-CoV-2 vaccines (BBIBPCorV, Sinopharm, Beijing, China) voluntarily. The occurrence of relapse in the participants was recorded during the follow-up period and a propensity score matching (PSM) method was used to compare the relapse rates between vaccinated and unvaccinated patients. Localized and systemic symptoms were assessed in the vaccinated patients. RESULTS: A total of 122 patients with inactive AOSD were included, of which 49.2% (n = 60) voluntarily received the inactivated SARS-CoV-2 vaccine. The relapse rate did not increase significantly in vaccinated patients in comparison with unvaccinated patients (after PSM: 6.8% versus 6.8%), and no relapse occurred within one month after vaccination. No obvious adverse reactions were reported in 75.0% of the participants, and none of the patients reported severe reactions. CONCLUSION: Increased disease activity or relapse following vaccination with inactivated SARS-CoV-2 were rare in patients with inactive AOSD. Local and systemic adverse reactions were found to be mild and self-limiting. These safety profiles of inactivated SARS-CoV-2 vaccines in patients with AOSD may assist in eliminating vaccine hesitancy and increase the vaccination rate against SARS-CoV-2.

Reactivation of Parvovirus B19 Infection: An Uncommon Trigger of Macrophage Activation Syndrome in Adult-Onset Still's Disease.

A 40-year-old woman presented with four weeks of intermittent high-grade fever, cough, and joint pain, and two weeks of a generalized rash. She was found to have adult-onset Still's disease (AOSD) and rapidly developed macrophage activation syndrome (MAS) on the second day of admission. Among infectious etiologies, Epstein-Barr virus and members of the herpes virus family are common triggers of MAS. However, our patient was found to have reactivation/recurrence of parvovirus B19 infection as the cause; this is an uncommon trigger reported infrequently in the medical literature. Despite intensive treatment, the patient passed away.

SEVERE MYOCARDITIS WITH CARDIOGENIC SHOCK IN ADULT-ONSET STILL'S DISEASE AFTER mRNA COVID-19 VACCINATION: A CASE OF ATYPICAL PRESENTATION

Background/Aims Adult-onset Still's disease is a systemic inflammatory disease of unknown aetiology. Post-COVID-19 vaccine adult-onset Still's disease has been reported and was associated with only mild myocarditis. Here we report the first case of adult-onset Still's disease after mRNA COVID-19 vaccination presenting with severe myocarditis with acute heart failure and cardiogenic shock. Methods We described the case history of the patient. Results A 72-year-old Chinese woman developed gradual onset of fever, shortness of breath, sore throat, generalised arthralgia, malaise and poor appetite 15 days after receiving the first dose of BNT162b2 mRNA COVID-19 vaccine. Physical examination revealed fever, bilateral ankle oedema and elevated jugular venous pressure. Significant investigation results are shown in Table 1. Extensive viral panel tests (including enterovirus, influenza and cytomegalovirus) were all negative. Echocardiography showed severely reduced left ventricular ejection fraction of 20%. The acute heart failure was complicated by cardiogenic shock requiring intensive care unit admission. Myocarditis was later diagnosed. Although the heart condition subsequently improved, there were persistent fever and arthralgia, as well as the development of generalised maculopapular skin rash. In view of that, series of investigations were performed, which revealed persistent neutrophilic leucocytosis, hyper-ferritinaemia and liver function derangement, while autoimmune panel was grossly unremarkable and septic/viral workup was negative (Table 1). Contrast PET-CT scan showed no features of malignancy. Adult-onset Still's disease was diagnosed, and the patient was treated with oral prednisolone 40mg daily. The patient's condition responded to the treatment;the fever subsided and the leucocyte count and inflammatory markers were normalised, and she was subsequently discharged. Three months after discharge, the patient was clinically well with prednisolone tapered down to 5mg daily. Reassessment echocardiogram showed full recovery with LVEF 60%. Conclusion Severe myocarditis with acute heart failure and cardiogenic shock is a possible initial presentation of adult-onset Still's disease after mRNA COVID-19 vaccination. After exclusion of more common aetiologies, it is important to consider adult-onset Still's disease as one of the differential diagnoses in the presence of compatible features following COVID-19 vaccination, such that appropriate and timely workup and treatment can be offered. (Table Presented).

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

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

The specialized pro-resolving lipid mediator Protectin D1 affects macrophages differentiation and activity in Adult-onset Still's disease and COVID-19, two hyperinflammatory diseases sharing similar transcriptomic profiles.

Introduction: COVID-19 and autoinflammatory diseases, such as Adult-onset Still's Disease (AOSD), are characterized by hyperinflammation, in which it is observed massive production and uncontrolled secretion of pro-inflammatory cytokines. The specialized pro-resolving lipid mediators (SPMs) family is one the most important processes counteracting hyperinflammation inducing tissue repair and homeostasis restoration. Among SPMs, Protectin D1 (PD1) is able to exert antiviral features, at least in animal models. The aim of this study was to compare the transcriptome of peripheral blood mononuclear cells (PBMCs) from patients with AOSD and COVID-19 and to evaluate the role of PD1 on those diseases, especially in modulating macrophages polarization. Methods: This study enrolled patients with AOSD, COVID-19, and healthy donors HDs, undergoing clinical assessment and blood sample collection. Next-generation deep sequencing was performed to identify differences in PBMCs transcripts profiles. Plasma levels of PD1 were assessed by commercial ELISA kits. Monocyte-derived macrophages were polarized into M1 and M2 phenotypes. We analyzed the effect of PD1 on macrophages differentiation. At 10 days, macrophages were analyzed for surface expression of subtypes markers by flow cytometry. Cytokines production was measured in supernatants by Bio-Plex Assays. Results: In the transcriptomes from AOSD patients and COVID-19 patients, genes involved in inflammation, lipid catabolism, and monocytes activation were specifically dysregulated in AOSD and COVID-19 patients when compared to HDs. Patients affected by COVID-19, hospitalized in intensive care unit (ICU), showed higher levels of PD1 when compared to not-ICU hospitalized patients and HDs (ICU COVID-19 vs not-ICU COVID-19, p= 0.02; HDs vs ICU COVID-19, p= 0.0006). PD1 levels were increased in AOSD patients with SS ≥1 compared to patients with SS=0 (p=0.028) and HDs (p=0.048). In vitro treatment with PD1 of monocytes-derived macrophages from AOSD and COVID-19 patients induced a significant increase of M2 polarization vs control (p<0.05). Furthermore, a significant release of IL-10 and MIP-1ß from M2 macrophages was observed when compared to controls (p<0.05). Discussion: PD1 is able to induce pro-resolutory programs in both AOSD and COVID-19 increasing M2 polarization and inducing their activity. In particular, PD1-treated M2 macrophages from AOSD and COVID-19 patients increased the production of IL-10 and enhanced homeostatic restoration through MIP-1ß production.

The Great Still-Usion: Unmasking Adult-Onset Still's Disease Masquerading As Upper Respiratory Tract Infection.

Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology that presents with high-grade fever, arthritis, evanescent rash, and multiorgan involvement. It is a rare disorder and is a diagnosis of exclusion. AOSD is often misdiagnosed initially as viral exanthems or upper respiratory tract infections leading to a delay in diagnosis. Management includes non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and conventional or biologic disease-modifying antirheumatic drugs (DMARDs). We report a case of a 53-year-old female with prolonged fever, sore throat, arthralgia, and rash. She was initially presumed to have infectious pharyngitis but did not respond to antimicrobial therapy. After extensive evaluation that excluded infectious, malignant, and other rheumatological etiologies, she was noted to satisfy multiple Yamaguchi criteria and was subsequently diagnosed with AOSD. Glucocorticoids and biologic DMARDs were initiated, leading to improved clinical manifestations and a decline in inflammatory markers.

ADULT STILL'S DISEASE: NEW HORIZONS.

Still's disease in children (systemic juvenile idiopathic arthritis - JIA) and adult Still's disease (ASD) are considered as systemic autoinflammatory diseases of unknown etiology, which are based on similar immunopathogenetic mechanisms associated with genetically determined disorders of the mechanisms of innate immunity. ASD was first described 50 years ago by the English rheumatologist Eric George Lapthorne Bywaters. The molecular basis of ASD immunopathogenesis is the activation of innate immunity associated with NLRP3 inflammasome-dependent mechanisms of inflammation, characterized by the overproduction of "pro-inflammatory" cytokines - interleukin (IL) 1 and IL-18, inducing the synthesis of other proinflammatory inflammatory mediators. A review of new data concerning the mechanisms of immunopathology, clinical polymorphism, laboratory biomarkers and the possibilities of ASD pharmacotherapy is presented. Particular attention is paid to the prospects for the use of monoclonal antibodies to IL-1beta - canakinumab. The problems associated with the generality of clinical and laboratory disorders, pathogenetic mechanisms and pharmacotherapy of ASD and coronavirus disease 2019 (COVID-19) are considered.Copyright © 2021 Authors. All rights reserved.

ADULT STILL'S DISEASE: NEW HORIZONS.

Still's disease in children (systemic juvenile idiopathic arthritis - JIA) and adult Still's disease (ASD) are considered as systemic autoinflammatory diseases of unknown etiology, which are based on similar immunopathogenetic mechanisms associated with genetically determined disorders of the mechanisms of innate immunity. ASD was first described 50 years ago by the English rheumatologist Eric George Lapthorne Bywaters. The molecular basis of ASD immunopathogenesis is the activation of innate immunity associated with NLRP3 inflammasome-dependent mechanisms of inflammation, characterized by the overproduction of "pro-inflammatory" cytokines - interleukin (IL) 1 and IL-18, inducing the synthesis of other proinflammatory inflammatory mediators. A review of new data concerning the mechanisms of immunopathology, clinical polymorphism, laboratory biomarkers and the possibilities of ASD pharmacotherapy is presented. Particular attention is paid to the prospects for the use of monoclonal antibodies to IL-1beta - canakinumab. The problems associated with the generality of clinical and laboratory disorders, pathogenetic mechanisms and pharmacotherapy of ASD and coronavirus disease 2019 (COVID-19) are considered.Copyright © 2021 Authors. All rights reserved.

Safety of Gam-COVID-Vac (Sputnik V) Combined Vector Vaccine in Patients With Immunoinflammatory Rheumatic Diseases: Preliminary Data.

Background. Patients with autoimmune and inflammatory rheumatic diseases (AIRDs) are at high risk of developing COVID-19. Vaccination is an effective method of preventing this disease, which may be unsafe for patients with AIRDs. The aim of the study is to assess the safety of Gam-COVID-Vac in patients with IVRD in real clinical practice. Material and methods. A cross-sectional study was carried out. The main group consisted of patients with AIRDs, the control group consisted of individuals without AIRDs. All participants were interviewed by the research physician using a unified questionnaire, additional information was obtained from medical records. Results. The study included 222 patients with AIRDs (119 with rheumatoid arthritis, 36 with ankylosing spondylitis, 17 with psoriatic arthritis, 17 with Sjogren's disease, 10 with undifferentiated spondyloarthritis, 8 with systemic lupus erythematosus, 4 with metabolic arthritis, 3 with systemic scleroderma, 3 with systemic vasculitis, 2 with polymyalgia rheumatica, 2 with undifferentiated systemic connective tissue disease, 1 with adult Still's disease) and 111 patients without AIRDs. The number of patients with AIRDs who had a combination of local and systemic adverse events (AE) on the introduction of the first component of the vaccine was significantly less than in the control group (22.1 and 44.1%, respectively, P<0.001). Similar differences were also noted after the introduction of the second component (14.0 and 29.7%, respectively, P<0.001). AEs such as pain at the injection site without restriction of movement, weakness, fever, arthralgia/myalgia, headache, and chills were significantly more common in the control group after the introduction of the first component of the vaccine. After complete immunization, AEs were absent in 35.6% of patients with AIRDs and in 21.6% of control group patients (P=0.01). Exacerbations of AIRDs and new autoimmune phenomena were not registered in any cases. Conclusions. According to preliminary data, immunization of patients with AIRDs with the Gam-COVID-Vac combined vector vaccine appears to be quite safe.Copyright © Team of Authors, 2022.

Risk of Exacerbation of Rheumatic Disease after COVID-19 Vaccination

Objectives: To investigate the risk of flare-ups after COVID-19 vaccination in patients with rheumatic disease. Method(s): A total of 1,617 patients with rheumatic diseases were identified from three rheumatology clinics. Patients were interviewed for demographic data, disease activity, and vaccination status. Disease flare-up was determined clinically by independent rheumatologists. Change of serum markers and medications were retrieved from medical records. The risk of exacerbation of rheumatic disease, change in serum markers, and escalation of rheumatic medications between vaccinated and nonvaccinated patients were determined using Cox, linear, and logistic regression models, respectively. Possible confounding factors were also taken into consideration. Result(s): Among 562 (34.76%) patients who received COVID-19 vaccination, rheumatic disease (HR = 2.10, P < 0.001), inflammatory arthritis (HR = 2.71, P < 0.001), rheumatoid arthritis (RA) (HR = 2.03, P = 0.002), spondyloarthritis (SpA) (HR = 4.78, P < 0.001), autoimmune disease (HR = 1.77, P = 0.01), and systemic lupus erythematosus (SLE) (HR = 1.99, P = 0.02) were associated with postvaccination clinical flare-up. Adult Still's disease (B = 12.76, P = 0.03) was associated with increased serum C-reactive protein (CRP). No association was found between vaccination and escalation of rheumatic medication. Subgroup analyses showed that only the mRNA vaccine was associated with flare-ups. Conclusion(s): COVID-19 vaccination was associated with minor disease flare-up but not escalation of rheumatic medications. In the absence of absolute contraindications, COVID-19 vaccination is recommended in patients with rheumatic disease. KEY MESSAGES 1. Vaccination is effective in the prevention of morbidity due to COVID-19 in patients with autoimmune diseases. 2. The mRNA vaccine was associated with mild rheumatic disease flare-up. 3. Inactivated virus vaccine is preferable to mRNA vaccine in patients with active autoimmune disease. Copyright © 2023 The Author(s).

Case report: Coronavirus Disease 2019 (COVID-19) modified RNA vaccination-induced Adult-Onset Still's Disease with fulminant myocarditis as initial presentation.

Myocarditis is a rare complication of Coronavirus Disease 2019 (COVID-19) vaccination. We report a case of an elderly female who presented initially with acute myocarditis, fulminant heart failure, and atrial fibrillation after receiving a modified ribonucleic acid (mRNA) vaccine (BNT162b2). Unlike other patients with vaccine-induced myocarditis, she developed persistent fever, sore throat, polyarthralgia, diffuse macular rash, and lymphadenopathy. After extensive investigation, she was diagnosed with post-vaccination Adult-Onset Still's Disease. The systemic inflammation gradually subsided after the use of non-steroidal anti-inflammatory drugs and systemic steroids. She was discharged from hospital with stable hemodynamics. Methotrexate was subsequently given to maintain long-term remission.

New-Onset Arthritis Following COVID-19 Vaccination: A Systematic Review of Case Reports.

Coronavirus disease 2019 (COVID-19) vaccine has effectively suppressed the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and alleviated its symptoms, but there are also many adverse events. Joint diseases caused by COVID-19 vaccine have been reported in many studies. Some are well-controlled arthritis patients who developed arthritis after COVID-19 vaccination, while others are new-onset joint pain and swelling problems after COVID-19 vaccination. The purpose of this systematic review is to examine the literature reports in existing databases and analyze the incidence of new-onset arthritis after COVID-19 vaccination. We included 31 eligible articles and described 45 patients, ranging in age from 17 to over 90, with more females than males. The majority (84.4%) of patients received the adenovirus vector vaccine (ChAdOx1) and the mRNA-based vaccine (BNT126b2 and mRNA-1273). Most (64.4%) patients developed joint-related symptoms after the first dose of vaccine, and 66.7% developed symptoms within the first week of vaccination. The joint symptoms involved were mainly joint swelling, joint pain, limited range of motion, and so on. A total of 71.1% of the patients involved multiple joints, both large and small; 28.9% of patients involved only a single joint. Some (33.3%) patients were confirmed by imaging, and the most common diagnoses were bursitis and synovitis. Two nonspecific inflammatory markers, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), were monitored in almost all cases, and all patients showed varying degrees of increase in these two markers. Most of the patients received the treatment of glucocorticoid drugs or nonsteroidal anti-inflammatory drugs (NSAIDs). Clinical symptoms markedly improved in most patients, with 26.7% making a full recovery and no relapse after a few months of follow-up. To determine whether there is a causal relationship between COVID-19 vaccination and the triggering of arthritis, large-scale and well-controlled research studies are needed in the future to verify this relationship and to further study its pathogenesis in detail. Clinicians should raise awareness of this complication with a view to early diagnosis and appropriate treatment.

An Unforeseen Outcome of COVID-19: The Triggering of Adult-Onset Still's Disease.

Background: Adult-onset Still's disease (AOSD) is a rare auto-inflammatory disorder with unknown etiology by which an infectious trigger is usually responsible for the onset of the disease. It is diagnosed by exclusion when certain clinical, biochemical, and radiological criteria are met after excluding all other potential causes. Besides, SARS­CoV­2 infection is increasingly being reported to have autoimmune complications. In the literature, 3 AOSD cases have been reported to be triggered by SARS­CoV­2 infection and here we report the fourth. Case presentation: A 24-year-old female doctor suffered from fever, sore throat, and mild cough a few days after a shift in the COVID-19 ward. A week later, she developed polyarthritis, salmon-colored rash, and high-grade fever, and the laboratory findings were indicating an inflammatory syndrome. COVID-19 IgM antibodies were positive indicating recent infection. After running a battery of tests, infectious, neoplastic, and rheumatic causes of these symptoms that persisted for about 50 days were excluded which led to a diagnosis of AOSD after fulfilling its criteria with subsequent treatment with methylprednisolone. Drastic improvement was achieved with no recurrence until the date of reporting. Conclusion: This case presents a new consequence of COVID-19 and adds to the emerging cumulative experiences with this disease. We encourage health care professionals to report such cases to further understand the nature of this infection and its possible outcomes.

Safety of Gam-COVID-Vac (Sputnik V) Combined Vector Vaccine in Patients With Immunoinflammatory Rheumatic Diseases: Preliminary Data

Background. Patients with autoimmune and inflammatory rheumatic diseases (AIRDs) are at high risk of developing COVID-19. Vaccination is an effective method of preventing this disease, which may be unsafe for patients with AIRDs. The aim of the study is to assess the safety of Gam-COVID-Vac in patients with IVRD in real clinical practice. Material and methods. A cross-sectional study was carried out. The main group consisted of patients with AIRDs, the control group consisted of individuals without AIRDs. All participants were interviewed by the research physician using a unified questionnaire, additional information was obtained from medical records. Results. The study included 222 patients with AIRDs (119 with rheumatoid arthritis, 36 with ankylosing spondylitis, 17 with psoriatic arthritis, 17 with Sjögren's disease, 10 with undifferentiated spondyloarthritis, 8 with systemic lupus erythematosus, 4 with metabolic arthritis, 3 with systemic scleroderma, 3 with systemic vasculitis, 2 with polymyalgia rheumatica, 2 with undifferentiated systemic connective tissue disease, 1 with adult Still's disease) and 111 patients without AIRDs. The number of patients with AIRDs who had a combination of local and systemic adverse events (AE) on the introduction of the first component of the vaccine was significantly less than in the control group (22.1 and 44.1%, respectively, P<0.001). Similar differences were also noted after the introduction of the second component (14.0 and 29.7%, respectively, P<0.001). AEs such as pain at the injection site without restriction of movement, weakness, fever, arthralgia/myalgia, headache, and chills were significantly more common in the control group after the introduction of the first component of the vaccine. After complete immunization, AEs were absent in 35.6% of patients with AIRDs and in 21.6% of control group patients (P=0.01). Exacerbations of AIRDs and new autoimmune phenomena were not registered in any cases. Conclusions. According to preliminary data, immunization of patients with AIRDs with the Gam-COVID-Vac combined vector vaccine appears to be quite safe.

Risk of exacerbation of rheumatic disease after COVID-19 vaccination

Objectives: To investigate the risk of flare-ups after COVID-19 vaccination in patients with rheumatic disease. Method(s): A total of 1617 patients with rheumatic diseases were identified from three rheumatology clinics. Patients were interviewed for demographic data, disease activity, and vaccination status. Clinical disease flare up was determined independently by expert opinion by managing rheumatologists. Change of serum markers and medications were retrieved from medical records. The risk of exacerbation of rheumatic disease, change in serum markers, and escalation of rheumatic medications between vaccinated and non-vaccinated patients were determined using cox, linear and logistic regression models respectively. Possible confounding factors were also taken into consideration. Result(s): There were 562 (34.76%) patients received COVID-19 vaccine. After vaccination, rheumatic disease (HR = 2.10, P < 0.001), inflammatory arthritis (HR = 2.71, P < 0.001), rheumatoid arthritis (RA) (HR = 2.03, P = 0.002), spondyloarthritis (SpA) (HR = 4.78, P < 0.001), autoimmune disease (HR = 1.77, P = 0.01), and systemic lupus erythematosus (SLE) (HR = 1.99, P = 0.02) were associated with clinical flare up. Adult still's disease (B = 12.76, P = 0.03) was associated with an increase in CRP level. Escalation of rheumatic medications were not associated with COVID-19 vaccination in all diseases. Subgroup analyses showed only mRNA vaccine was associated with disease flare ups. Conclusion(s): COVID-19 vaccine was associated with minor disease flare up but not escalation of rheumatic medications. In the absence of absolute contraindications, full COVID-19 vaccination in patients with rheumatic disease should be encouraged by managing rheumatologists.

New-onset Adult-onset Still's Disease Following COVID-19 Vaccination: Three Case Reports and a Literature Review.

Since December 2020, coronavirus disease 2019 (COVID-19) vaccines have been distributed in most countries to prevent the onset and aggravation of COVID-19. There is little information regarding the long-term safety of the vaccines. We report three cases and a literature review of new-onset adult-onset Still's disease (AOSD) that occurred following COVID-19 vaccination. Our cases include moderate to severe AOSD, and two were complicated with macrophage activation syndrome. Seventeen cases of new-onset or relapse of AOSD following COVID-19 vaccination, including 14 identified in the literature review and our 3 patients, were all treated successfully with glucocorticoid therapy, immunosuppressive drugs, or biologic agents.

First report of a patient meeting criteria for both multisystem inflammatory syndrome in children and adult onset Still's disease.

BACKGROUND: COVID-19 is associated with a postinfectious hyperinflammatory disorder, multisystem inflammatory syndrome in children (MIS-C), that shares characteristics with still's disease, known as systemic juvenile idiopathic arthritis (SJIA) in children younger than 16, and adult onset Still's disease (AOSD) in children 16 and older. Both MIS-C and SJIA/AOSD can be complicated by macrophage activation syndrome (MAS), a potentially fatal condition of cytokine storm. CASE PRESENTATION: We present a 16 year-old male who developed quotidian fever, headache, conjunctival injection, sore throat, nausea and vomiting, diarrhea, rash, and symmetrical polyarticular arthralgia/arthritis 4 weeks after exposure to SARS-CoV-2 and 2 weeks after his first vaccination against COVID-19. Our patient's laboratory results were significant for elevated inflammatory markers and acute phase reactants. He met criteria for diagnosis with both MIS-C and AOSD. After receiving first-line treatment for both diseases, IVIG and methylprednisolone, our patient improved. CONCLUSION: MAS is a life-threatening rheumatological emergency, and physicians must be able to identify diseases, like MIS-C and AOSD, that may be complicated by MAS. Our patient's distinguishing feature on presentation was symmetrical polyarticular arthralgia/arthritis, which has not been associated with MIS-C. Simultaneously, AOSD-which is associated with polyarticular arthralgia/arthritis-is only now being recognized as a possible post-infectious entity in the aftermath of COVID-19 infection. In patients like our own, who meet criteria for both MIS-C and AOSD, administering first line treatment for both diseases may be best practice.

A More Unique Than Rare Myopericarditis - a Case Report

A 33yo man, ex-convict, with a history of IV substance abuse, without previous cardiological history, was admitted at our emergency department in the clinical context of an acute pericarditis, intermittent fever in the last 10 days and non-itchy maculo-papular erythema of palms and thorax. EKG documented a diffuse ST-segment elevation, chest X-rays revealed a bilateral pleural effusion and echocardiography documented a normal biventricular morphology and function, normal valvular function, and a circumferential pericardial effusion (14mm). The patient was admitted at our Cardiology Unit after a negative PCR SARS-CoV-2 test. Blood chemistry showed elevated WBC count with an important neutrophilia (24.000/mm3;90% neutrophils), elevated TnI-HS (236 ng/L;n.v. <18 ng/L), elevated C-reactive protein (340 mg/L;n.v. < 5mg/L). A classic anti-inflammatory therapy was set up with indomethacin + colchicine with little clinical benefit. Blood cultures, bacterial serology (i.e., Tubercolosis, T.gondii, Syphilis, Leptospirosis) and viral serology (i.e., HIV, HCV, HBV, EBV, HSV) resulted negative. However, an empirical antibiotic coverage was set up: sequentially with Piperacillin/Tazobactam, Vancomycin, Linezolid and Ceftriaxone. None of the antibiotics improved patient's clinical status. On the contrary, the patient developed an allergic reaction to Vancomycin and Linezolid. All autoantibodies tested resulted negative. After 10 days of hospitalization, the patient's clinical status continued to deteriorate. The intermittent fever (max 41degreeC) was not responsive to any treatment. The evanescent skin rash had spread to the whole body and was concomitant with the fever peaks. The indexes of inflammation were rising (C-reactive protein 400 mg/ L) and so were the WBC count (36.000/mm3). The patient lost weight (-8kg), developed hand and feet arthralgia, diffuse myalgia, painful retronucal lymph nodes, pharyngodynia and abdominal pain. An abdominal echography and CT were performed with evidence of mild abdominal effusion and splenomegaly. Hepatic cytolysis indices began to rise (AST 100 U/L;ALT 150 U/L;LDH 385 U/L). At that point, on the basis of Yamaguchi's Criteria, we suspected our patient could be affected by Adult-onset Still's disease (AOSD) with an initial stage of hemophagocytic lymphohistiocytosis (HLH). Prednisone (IV 2 mg/kg/die) was administered for 72h with an incomplete clinical and biochemical response (C-reactive Protein 180 mg/L). Subsequently, Anakinra (SC 100 mg/die) was administered with a complete clinical response in less than 72h. AOSD is very uncommon. The annual incidence is 0.16/100.000 with an equal distribution between sexes. HLH have been observed in 15% of patients, meanwhile myopericarditis is a rare complication. Although rare, it is fair to know and consider AOSD in the complicated and tricky diagnostic process of myopericarditis. A noteworthy point of this case report is the extreme efficacy of Anakinra in contexts of systemic inflammation and myopericarditis. A point still to be clarified concerns the duration of the treatment and the down-titration of Anakinra in these complicated contexts..

Intravenous anakinra to curb cytokine storm in adult-onset Still's disease and in macrophage activation syndrome: A case series.

OBJECTIVE: Adult-onset Still's disease (AOSD) is an auto-inflammatory polygenic disorder, for which the diagnosis is essentially clinical. The exclusion of mimickers [such as common bacterial and viral infections, hematologic malignancies, and, more recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] is necessary to confirm the diagnosis. Anti-interleukin (IL)-1 therapy is considered a treatment milestone for AOSD. Herein, we present a short series of newly-diagnosed AOSD or upcoming macrophage activation syndrome (MAS) cases who received intravenous (IV) anakinra, an IL-1 receptor blocker. METHODS: Four patients with newly-diagnosed AOSD or upcoming MAS were treated with IV anakinra at the Rheumatology Unit of Padova University Hospital, Italy. We obtained informed consent from the patients for use of their cases and medical images for publication purposes. RESULTS: All patients presented with AOSD or MAS during the COVID-19 pandemic, making diagnosis challenging due to similar immunological and clinical characteristics across both pathologies. All patients presented with hyperpyrexia and elevated inflammatory markers; two patients had a skin rash typically seen in AOSD. IV anakinra slowed down AOSD progression in all patients, prevented severe outcomes and mitigated the risk of multiorgan failure. All cases improved within 24hours of anakinra administration. CONCLUSION: We found that administration of anakinra in patients with newly-diagnosed AOSD and/or upcoming MAS reduced hyperinflammation and prevented life-threatening complications. The IV route appears to be preferable in the hospital setting, where comorbidities such as coagulopathies and thrombocytopenia can complicate the use of other routes of administration.

Comprehensive description of adult-onset Still's disease after COVID-19 vaccination.

Cases of adult-onset Still's disease (AOSD) have been reported after COVID-19 vaccination. Here we provide a comprehensive description and analysis of all cases of AOSD reported in the literature and in pharmacovigilance databases through April 2022. Disproportionality analyses of pharmacovigilance data were performed in order to further explore the association between vaccination and AOSD. We included 159 patients, 144 from the World Health Organization pharmacovigilance database and 15 from the literature. Detailed clinical characteristics were described for the cases from the literature and from the French pharmacovigilance database (n = 9). The cases of AOSD after COVID-19 vaccination concerned women in 52.2% of cases. The median age was 43.4 years. More than 80% of AOSD reports occurred during the first three weeks and concerned mostly the BNT162b2 mRNA vaccine. We identified 14.5% of disease flare with a median time-to-onset of AOSD flare-up significantly shorter than for the new onset form. More than 90% patients received steroids. Although all cases were considered serious and required hospitalization, most cases presented a favorable outcome (67.1%) with a good response to corticosteroid therapy with a mean time to recovery of 7.2 days. Disproportionality analyses suggested that AOSD was associated with COVID-19 vaccines as well as other vaccines. AOSD was nearly five times more frequently reported with COVID-19 vaccines than with all other drugs. Clinicians should be informed about the potential risk of AOSD onset or flare following COVID vaccines and the importance of its early detection to optimize its management.