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ObjectivesTo determine factors associated with COVID-19-related death in people with rheumatic diseases.MethodsPhysician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category.ResultsOf 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66–75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death.ConclusionAmong people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

BACKGROUNDPediatric SARS-CoV-2 infection can be complicated by a dangerous hyperinflammatory condition termed multisystem inflammatory syndrome in children (MIS-C). The clinical and immunologic spectrum of MIS-C and its relationship to other inflammatory conditions of childhood have not been studied in detail.METHODSWe retrospectively studied confirmed cases of MIS-C at our institution from March to June 2020. The clinical characteristics, laboratory studies, and treatment response were collected. Data were compared with historic cohorts of Kawasaki disease (KD) and macrophage activation syndrome (MAS).RESULTSTwenty-eight patients fulfilled the case definition of MIS-C. Median age at presentation was 9 years (range: 1 month to 17 years); 50% of patients had preexisting conditions. All patients had laboratory confirmation of SARS-CoV-2 infection. Seventeen patients (61%) required intensive care, including 7 patients (25%) who required inotrope support. Seven patients (25%) met criteria for complete or incomplete KD, and coronary abnormalities were found in 6 cases. Lymphopenia, thrombocytopenia, and elevation in inflammatory markers, D-dimer, B-type natriuretic peptide, IL-6, and IL-10 levels were common but not ubiquitous. Cytopenias distinguished MIS-C from KD and the degree of hyperferritinemia and pattern of cytokine production differed between MIS-C and MAS. Immunomodulatory therapy given to patients with MIS-C included intravenous immune globulin (IVIG) (71%), corticosteroids (61%), and anakinra (18%). Clinical and laboratory improvement were observed in all cases, including 6 cases that did not require immunomodulatory therapy. No mortality was recorded in this cohort.CONCLUSIONMIS-C encompasses a broad phenotypic spectrum with clinical and laboratory features distinct from KD and MAS.FUNDINGThis work was supported by the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Institute of Allergy and Infectious Diseases; Rheumatology Research Foundation Investigator Awards and Medical Education Award; Boston Children's Hospital Faculty Career Development Awards; the McCance Family Foundation; and the Samara Jan Turkel Center.

ObjectivesCOVID-19 outcomes in people with rheumatic diseases remain poorly understood. The aim was to examine demographic and clinical factors associated with COVID-19 hospitalisation status in people with rheumatic disease.MethodsCase series of individuals with rheumatic disease and COVID-19 from the COVID-19 Global Rheumatology Alliance registry: 24 March 2020 to 20 April 2020. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Age, sex, smoking status, rheumatic disease diagnosis, comorbidities and rheumatic disease medications taken immediately prior to infection were analysed.ResultsA total of 600 cases from 40 countries were included. Nearly half of the cases were hospitalised (277, 46%) and 55 (9%) died. In multivariable-adjusted models, prednisone dose ≥10 mg/day was associated with higher odds of hospitalisation (OR 2.05, 95% CI 1.06 to 3.96). Use of conventional disease-modifying antirheumatic drug (DMARD) alone or in combination with biologics/Janus Kinase inhibitors was not associated with hospitalisation (OR 1.23, 95% CI 0.70 to 2.17 and OR 0.74, 95% CI 0.37 to 1.46, respectively). Non-steroidal anti-inflammatory drug (NSAID) use was not associated with hospitalisation status (OR 0.64, 95% CI 0.39 to 1.06). Tumour necrosis factor inhibitor (anti-TNF) use was associated with a reduced odds of hospitalisation (OR 0.40, 95% CI 0.19 to 0.81), while no association with antimalarial use (OR 0.94, 95% CI 0.57 to 1.57) was observed.ConclusionsWe found that glucocorticoid exposure of ≥10 mg/day is associated with a higher odds of hospitalisation and anti-TNF with a decreased odds of hospitalisation in patients with rheumatic disease. Neither exposure to DMARDs nor NSAIDs were associated with increased odds of hospitalisation.

The COVID-19 pandemic has compelled the global community to work together to understand SARS-CoV-2 and mitigate its effects, but it has also highlighted health disparities faced by people from minority racial or ethnic groups and other marginalized populations. International collaboration needs to be leveraged to address these disparities and inequities.

Background Limited data are available on the experiences of patients with autoinflammatory diseases (AIDs) and their families along the path to diagnosis and treatment. We sought to describe these experiences in patients with AIDs including tumor necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyperimmunoglobulin D syndrome (MKD/HIDS), and familial Mediterranean fever (FMF). Methods Ninety-minute, semi-structured qualitative interviews and 5-day written/video diaries were used to gather information on the experiences of patients with AIDs and their families. Results Twelve families of patients from the US (TRAPS [ n  = 4], MKD/HIDS [ n  = 5], FMF [ n  = 5]) participated in this study from August to November 2015. The study included two families with multiple afflicted siblings. Patients’ ages ranged from 1 to 28 years. Most parents reported realizing that something was seriously wrong with their child after medical emergencies and/or hospitalizations, which initiated the difficult path to diagnosis. For most, the process included multiple specialist visits, extensive and repeated testing, and many misdiagnoses. Over time, 92% of parents reported losing confidence in the healthcare system’s ability to find an answer to their child’s symptoms, while they also struggled with unsupportive school personnel and dismissive friends and relatives. Patients and their parents reported holding on to memories of “what life was like” before the onset of symptoms and mourning their subsequent loss of “normalcy.” Even after diagnosis, patients and parents continued to feel uncertain about what to expect in the future. Conclusions All families emphasized the need for efficient early diagnosis of AIDs. Initiatives that improve the speed and accuracy of diagnosis, provide more comprehensive patient education, and support patients and families through the illness have the potential to significantly improve the quality of life of patients with AIDs and their families. Healthcare providers should be aware of the impact of the long diagnostic journey on families and work to create an environment of trust and collaboration in the face of a difficult and prolonged diagnostic process.

BackgroundWe describe the early experiences of adults with systemic rheumatic disease who received the COVID-19 vaccine.MethodsFrom 2 April to 30 April 2021, we conducted an online, international survey of adults with systemic rheumatic disease who received COVID-19 vaccination. We collected patient-reported data on clinician communication, beliefs and intent about discontinuing disease-modifying antirheumatic drugs (DMARDs) around the time of vaccination, and patient-reported adverse events after vaccination.ResultsWe analysed 2860 adults with systemic rheumatic diseases who received COVID-19 vaccination (mean age 55.3 years, 86.7% female, 86.3% white). Types of COVID-19 vaccines were Pfizer-BioNTech (53.2%), Oxford/AstraZeneca (22.6%), Moderna (21.3%), Janssen/Johnson & Johnson (1.7%) and others (1.2%). The most common rheumatic disease was rheumatoid arthritis (42.3%), and 81.2% of respondents were on a DMARD. The majority (81.9%) reported communicating with clinicians about vaccination. Most (66.9%) were willing to temporarily discontinue DMARDs to improve vaccine efficacy, although many (44.3%) were concerned about rheumatic disease flares. After vaccination, the most reported patient-reported adverse events were fatigue/somnolence (33.4%), headache (27.7%), muscle/joint pains (22.8%) and fever/chills (19.9%). Rheumatic disease flares that required medication changes occurred in 4.6%.ConclusionAmong adults with systemic rheumatic disease who received COVID-19 vaccination, patient-reported adverse events were typical of those reported in the general population. Most patients were willing to temporarily discontinue DMARDs to improve vaccine efficacy. The relatively low frequency of rheumatic disease flare requiring medications was reassuring.

A Girl with Abdominal Pain and Bloody DiarrheaA 16-year-old girl was admitted with abdominal pain and bloody diarrhea of 5 weeks’ duration. Colonoscopy revealed multiple friable lesions in the sigmoid colon. A diagnostic test was performed.

Oligoarticular juvenile idiopathic arthritis (oligo JIA) is the most common form of chronic inflammatory arthritis in children, yet the cause of this disease remains unknown. To understand immune responses in oligo JIA, we immunophenotyped synovial fluid T cells with flow cytometry, bulk RNA-Seq, single-cell RNA-Seq (scRNA-Seq), DNA methylation studies, and Treg suppression assays. In synovial fluid, CD4 + , CD8 + , and γδ T cells expressed Th1-related markers, whereas Th17 cells were not enriched. Th1 skewing was prominent in CD4 + T cells, including Tregs, and was associated with severe disease. Transcriptomic studies confirmed a Th1 signature in CD4 + T cells from synovial fluid. The regulatory gene expression signature was preserved in Tregs, even those exhibiting Th1 polarization. These Th1-like Tregs maintained Treg-specific methylation patterns and suppressive function, supporting the stability of this Treg population in the joint. Although synovial fluid CD4 + T cells displayed an overall Th1 phenotype, scRNA-Seq uncovered heterogeneous effector and regulatory subpopulations, including IFN-induced Tregs, peripheral helper T cells, and cytotoxic CD4 + T cells. In conclusion, oligo JIA is characterized by Th1 polarization that encompasses Tregs but does not compromise their regulatory identity. Targeting Th1-driven inflammation and augmenting Treg function may represent important therapeutic approaches in oligo JIA.

To assess the practice patterns of pediatric rheumatology and infectious diseases subspecialists in the diagnosis and treatment of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. An online survey assessing diagnostic and treatment approaches was sent to 424 members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) and 980 members of the Pediatric Infectious Disease Society (PIDS). 277 physicians (123 from CARRA and 154 from PIDS representing 21% of the total membership) completed the survey. To diagnose PFAPA, most respondents agreed that patients must have the following features of the diagnostic criteria: stereotypical fever episodes (95%), asymptomatic intervals between episodes (93%), and normal growth and development (81%). However, 71% of the respondents did not require age of onset <5 years, 33% did not require regular intervals between episodes, and 79% did not require the concomitant signs of aphthous stomatitis, adenitis, or pharyngitis during episodes as long as episodes were regular. Over half (58%) considered episode resolution with steroids to be diagnostic of PFAPA. Corticosteroids, antipyretics, tonsillectomy, and cimetidine were the most commonly prescribed treatments, while steroids and tonsillectomy were most effective. Subspecialists in pediatric rheumatology and infectious diseases showed limited adherence to the complete published criteria for diagnosing PFAPA suggesting heterogeneity in the characteristics of patients diagnosed with the disorder. These findings emphasize the need to develop consensus diagnostic and treatment guidelines in well-characterized patient populations.