Background
The interleukin‐1 (IL‐1) mediated systemic autoinflammatory diseases, including the cryopyrin‐ associated periodic syndromes (CAPS), tumour necrosis factor receptor‐associated periodic ...syndrome (TRAPS), mevalonate kinase deficiency (MKD) and deficiency of the IL‐1 receptor antagonist (DIRA), belong to a group of rare immunodysregulatory diseases that primarily present in early childhood with variable multiorgan involvement. When untreated, patients with severe clinical phenotypes have a poor prognosis, and diagnosis and management of these patients can be challenging. However, approved treatments targeting the proinflammatory cytokine IL‐1 have been life changing and have significantly improved patient outcomes.
Objective
To establish evidence‐based recommendations for diagnosis, treatment and monitoring of patients with IL‐1 mediated autoinflammatory diseases to standardise their management.
Methods
A multinational, multidisciplinary task force consisting of physician experts, including rheumatologists, patients or caregivers and allied healthcare professionals, was established. Evidence synthesis, including systematic literature review and expert consensus (Delphi) via surveys, was conducted. Consensus methodology was used to formulate and vote on statements to guide optimal patient care.
Results
The task force devised five overarching principles, 14 statements related to diagnosis, 10 on therapy, and nine focused on long‐term monitoring that were evidence and/or consensus‐based for patients with IL‐1 mediated diseases. An outline was developed for disease‐specific monitoring of inflammation‐induced organ damage progression and reported treatments of CAPS, TRAPS, MKD and DIRA.
Conclusion
The 2021 EULAR/American College of Rheumatology points to consider represent state‐of‐the‐art knowledge based on published data and expert opinion to guide diagnostic evaluation, treatment and monitoring of patients with CAPS, TRAPS, MKD and DIRA, and to standardise and improve care, quality of life and disease outcomes.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Juvenile idiopathic inflammatory myopathies (JIIM) are rare, chronic autoimmune muscle diseases of childhood, with the potential for significant morbidity. Data on long-term outcomes is limited. In ...this study we investigate correlations between clinical and demographic features with long-term outcomes in a referral population of adult patients with JIIM.
Forty-nine adults with JIIM were assessed at two referral centers between 1994 and 2016. Features of active disease and damage at a cross-sectional assessment were obtained. Regression modeling was used to examine factors associated with long-term outcomes, defined by the presence of calcinosis or a higher adjusted Myositis Damage Index (MDI) score. A multivariable model of MDI was constructed using factors that were statistically significant in bivariate models.
At a median of 11.5 IQR 4.5–18.9 years following diagnosis, median American College of Rheumatology (ACR) functional class was 2 1.5–3.0, Health Assessment Questionnaire (HAQ) score was 0.4 out of 3.0 0.0–1.0, and manual muscle testing (MMT) score was 229 out of 260 212.6–256.8. Median MDI score was 6.0 3.5–8.9, with the most commonly damaged organ systems being cutaneous and musculoskeletal. Factors associated with an elevated MDI score were the presence of erythroderma and other cutaneous manifestations, disease duration, and ACR functional class. Calcinosis was present in 55% of patients. The strongest predictors of calcinosis were disease duration, periungual capillary changes, and younger age at diagnosis.
In a tertiary referral population, long-term functional outcomes of JIIM are generally favorable, with HAQ scores indicative of mild disability. Although most patients had mild disease activity and virtually all had significant disease damage, severe or systemic damage was rare. Certain clinical features are associated with long-term damage and calcinosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
With the advent of innovative therapies including biologics and Janus kinase inhibitors, children with rheumatic diseases are more likely to have improved outcomes. Despite these advances, some ...children do not respond, or they, or their parents fear adverse events and seek other alternatives. Increasingly, private companies are offering mesenchymal stem cells (MSC) as an alternative, which are described as natural therapies for rheumatic diseases, often insinuating them as a cure. MSC have immunomodulatory properties, and transplantation of these stem cells have been used to successfully treat immunologic conditions like graft-versus-host disease. Lately, MSC research in adult lupus has been encouraging, but the clinical trials are still underway and in most, MSC therapy is not a standalone treatment. This retrospective case series will highlight three cases of pediatric refractory autoimmune disease whose parents sought out and received MSC therapy as a self-decision without first seeking medical advice from our specialty. The three families felt that their children were improved and in two believed that their child was cured. MSC have the potential of beneficial immunomodulation and may be a powerful tool in the therapy of rheumatic disease, but well controlled clinical trials are necessary and should be designed and monitored by experts in childhood rheumatic disease.
Three children with three different rheumatic diseases; systemic lupus erythematosus, mixed connective tissue disease and juvenile idiopathic arthritis were under the care of pediatric rheumatology at a large, tertiary-care, teaching institution. Multiple non-biologic and biologic disease-modifying anti-rheumatic drugs failed to significantly decrease disease activity, and as a result, the families chose to undergo MSC therapy. After transplantation, all children improved per patient and parent report and tapered off conventional immunosuppressive drugs. No serious adverse events occurred in these three patients.
The three cases presented in this report reflect comparable beneficial outcomes and minimal risks published in adult studies. These were not controlled studies, however, and benefit was reported rather than documented. These cases suggest that MSC transplantation may prove a promising adjunctive treatment option; however, further research, development of standardized infusion therapy protocols, and well-designed monitored clinical trials are essential.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The novel human coronavirus of 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly swept throughout the entire world. As the ongoing pandemic has spread, recent studies ...have described children presenting with a multisystem inflammatory disorder sharing the features of Kawasaki disease (KD) and toxic shock syndrome, now named Multisystem Inflammatory Syndrome in Children (MIS-C). These cases report a similar phenotype of prolonged fever, multisystem involvement, and biomarkers demonstrating marked hyperinflammation that occurs temporally in association with local community spread of SARS-CoV-2. Herein, we describe the presentation, clinical characteristics, and management of an 11-year-old boy with prolonged fever, strikingly elevated inflammatory markers, and profound, early coronary artery aneurysm consistent with a hyperinflammatory, multisystem disease temporally associated with coronavirus disease 2019. We highlight our multidisciplinary team's management with intravenous immunoglobulin, methylprednisolone, and an interleukin-1 receptor antagonist, anakinra, as a strategy to manage this multisystem, hyperinflammatory disease process.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Abstract
Multisystem inflammatory syndrome in children (MIS-C) has been observed in temporal association with coronavirus disease 2019 (COVID-19), typically within 2 to 6 weeks of illness or ...exposure. We present a case of MIS-C occurring 16 weeks after initial COVID-19 illness to highlight the prolonged period of risk for developing MIS-C.
We describe the presentation, diagnostic evaluation, and management of an adolescent presenting with a multisystem inflammatory process sixteen weeks following COVID-19. We highlight an expanded risk period, longer then commonly reported, for MIS-C to bring heightened awareness to its possibility.
Despite routine implementation of cleaning and disinfection practices in clinical healthcare settings, high-touch environmental surfaces and contaminated equipment often serve as reservoirs for the ...transmission of pathogens associated with healthcare-associated infections (HAIs).
The current study involved the analysis of high-touch surface swabs using a metatranscriptomic sequencing workflow (CSI-Dx™) to assess the efficacy of cleanSURFACES® technology in decreasing microbial burden by limiting re-contamination. This is a non-human single center study conducted in the Emergency Department (ED) and on an inpatient Oncology Ward of Walter Reed National Military Medical Center that have followed hygienic practices during the COVID-19 pandemic environment.
Although there was no difference in observed microbial richness (two-tailed Wilcoxon test with Holm correction, P > 0.05), beta diversity findings identified shifts in microbial community structure between surfaces from baseline and post-intervention timepoints (Day 1, Day 7, Day 14, and Day 28). Biomarker and regression analyses identified significant reductions in annotated transcripts for various clinically relevant microorganisms' post-intervention, coagulase-negative staphylococci and
, at ED and Oncology ward, respectively. Additionally, post-intervention samples predominantly consisted of Proteobacteria and to a lesser extent skin commensals and endogenous environmental microorganisms in both departments.
Findings support the value of cleanSURFACES®, when coupled with routine disinfection practices, to effectively impact on the composition of active microbial communities found on high-touch surfaces in two different patient care areas of the hospital (one outpatient and one inpatient) with unique demands and patient-centered practices.
ObjectivesLong-term safety and efficacy of adalimumab among patients with juvenile idiopathic arthritis (JIA) was evaluated through 6 years of treatment.MethodsChildren aged 4–17 years with ...polyarticular JIA were enrolled in a phase III, randomised-withdrawal, double-blind, placebo-controlled trial consisting of a 16-week open-label lead-in period, 32-week randomised double-blind period and 360-week long-term extension. Patients were stratified by baseline methotrexate use. Adverse events (AEs) were monitored, and efficacy assessments included JIA American College of Rheumatology (JIA ACR) 30%, 50%, 70% or 90% responses and the proportions of patients achieving 27-joint Juvenile Arthritis Disease Activity Score (JADAS27) low disease activity (LDA, ≤3.8) and inactive disease (ID, ≤1).ResultsOf 171 patients enrolled, 62 (36%) completed the long-term extension. Twelve serious infections in 11 patients were reported through 592.8 patient-years of exposure. No cases of congestive heart failure-related AEs, demyelinating disease, lupus-like syndrome, malignancies, tuberculosis or deaths were reported. JIA ACR 30/50/70/90 responses and JADAS27 LDA were achieved in 66% to 96% of patients at week 104, and 63 (37%) patients achieved clinical remission (JADAS27 ID sustained for ≥6 continuous months) during the study. Attainment of JIA ACR 50 or higher and JADAS27 LDA or ID in the initial weeks were the best predictors of clinical remission. Mean JADAS27 decreased from baseline, 22.5 (n=170), to 2.5 (n=30) at week 312 (observed analysis).ConclusionsThrough 6 years of exposure, adalimumab was well tolerated with significant clinical response (up to clinical remission) and a relatively low retention rate.
Acute lymphocytic leukemia (ALL) often presents with musculoskeletal concerns such as pain or swelling, even before appearance of blasts in the peripheral blood. Such presentation may lead to ...misdiagnosis of a child with juvenile rheumatoid arthritis (JRA). This study was designed to identify the predictive factors for leukemia using basic clinical and laboratory information.
A retrospective chart review was performed using a simple questionnaire to compare the clinical and laboratory findings present during the initial visit to a pediatric rheumatology clinic for 277 children who were ultimately diagnosed with either JRA (n = 206) or ALL (n = 71). Sensitivity and specificity analysis of a variety of parameters, both singly and in combination, was performed to identify predictive value for ALL.
The majority (75%) of children with ALL did not have blasts in the peripheral blood at the time of evaluation by pediatric rheumatologists. In children presenting with unexplained musculoskeletal complaints, the 3 most important factors that predicted a diagnosis of ALL were low white blood cell count (< 4 x 10(9)/L), low-normal platelet count (150-250 x 10(9)/L), and history of nighttime pain. In the presence of all 3, the sensitivity and specificity for a diagnosis of ALL were 100% and 85%, respectively. Other findings, including antinuclear antibody, rash, and objective signs of arthritis, were not helpful in differentiating between these diagnoses because they occurred at similar rates in both groups.
When a child develops new-onset bone-joint complaints, the presence of subtle complete blood count changes combined with nighttime pain should lead to consideration of leukemia as the underlying cause.
Objective
To differentiate juvenile polymyositis (PM) and muscular dystrophy, both of which may present with chronic muscle weakness and inflammation.
Methods
We studied 39 patients with probable or ...definite juvenile PM and 9 patients with muscular dystrophies who were initially misdiagnosed as having juvenile PM. Differences in demographic, clinical, and laboratory results; outcomes; and treatment responses were evaluated by Fisher's exact and rank sum tests. Random forests classification analysis and logistic regression were performed to examine significant differences in multivariable models.
Results
Clinical features and serum muscle enzyme levels were similar between juvenile PM and dystrophy patients, except 89% of dystrophy patients had muscle atrophy compared with 46% of juvenile PM patients. Dystrophy patients had a longer delay to diagnosis (median 12 versus 4 months) and were less frequently hospitalized than juvenile PM patients (22% versus 74%). No dystrophy patients, but 54% of juvenile PM patients, had a myositis autoantibody. Dystrophy patients more frequently had myopathic features on muscle biopsy, including diffuse variation of myofiber size, fiber hypertrophy, and myofiber fibrosis (44–100% versus 8–53%). Juvenile PM patients more frequently had complex repetitive discharges on electromyography and a complete response to treatment with prednisone or other immunosuppressive agents than dystrophy patients (44% versus 0%). Random forests analysis revealed that the most important features in distinguishing juvenile PM from dystrophies were myositis autoantibodies, clinical muscle atrophy, and myofiber size variation on biopsy. Logistic regression confirmed muscle atrophy, myofiber fibrosis, and hospitalization as significant predictors.
Conclusion
Muscular dystrophy can present similarly to juvenile PM. Selected clinical and laboratory features are helpful in combination in distinguishing these conditions.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Activated STING in a Vascular and Pulmonary Syndrome Liu, Yin; Jesus, Adriana A; Marrero, Bernadette ...
New England journal of medicine/The New England journal of medicine,
08/2014, Volume:
371, Issue:
6
Journal Article
Peer reviewed
Open access
The stimulator of interferon genes (STING) protein bridges sensors of cytosolic DNA and the inflammatory pathway mediated by interferon-β. Activating mutations in the
STING
gene cause a vascular and ...pulmonary syndrome.
Studies involving children with monogenic autoinflammatory disease have provided insights into the regulation of key proinflammatory cytokine pathways and their role in causing systemic and organ-specific inflammation.
1
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2
We studied six patients who presented in early infancy with systemic inflammation and violaceous, scaling lesions of fingers, toes, nose, cheeks, and ears that progressed to acral necrosis in most of the patients and did not respond to therapy. A mixed histologic pattern was observed, consisting of a prominent dermal inflammatory infiltrate with features of leukocytoclastic vasculitis and microthrombotic angiopathy of small dermal vessels. Three of the patients had severe interstitial lung . . .
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