BACKGROUNDUndifferentiated systemic autoinflammatory diseases (USAIDs) present diagnostic and therapeutic challenges. Chronic interferon (IFN) signaling and cytokine dysregulation may identify ...diseases with available targeted treatments.METHODSSixty-six consecutively referred USAID patients underwent underwent screening for the presence of an interferon signature using a standardized type-I IFN-response-gene score (IRG-S), cytokine profiling, and genetic evaluation by next-generation sequencing.RESULTSThirty-six USAID patients (55%) had elevated IRG-S. Neutrophilic panniculitis (40% vs. 0%), basal ganglia calcifications (46% vs. 0%), interstitial lung disease (47% vs. 5%), and myositis (60% vs. 10%) were more prevalent in patients with elevated IRG-S. Moderate IRG-S elevation and highly elevated serum IL-18 distinguished 8 patients with pulmonary alveolar proteinosis (PAP) and recurrent macrophage activation syndrome (MAS). Among patients with panniculitis and progressive cytopenias, 2 patients were compound heterozygous for potentially novel LRBA mutations, 4 patients harbored potentially novel splice variants in IKBKG (which encodes NF-κB essential modulator NEMO), and 6 patients had de novo frameshift mutations in SAMD9L. Of additional 12 patients with elevated IRG-S and CANDLE-, SAVI- or Aicardi-Goutières syndrome-like (AGS-like) phenotypes, 5 patients carried mutations in either SAMHD1, TREX1, PSMB8, or PSMG2. Two patients had anti-MDA5 autoantibody-positive juvenile dermatomyositis, and 7 could not be classified. Patients with LRBA, IKBKG, and SAMD9L mutations showed a pattern of IRG elevation that suggests prominent NF-κB activation different from the canonical interferonopathies CANDLE, SAVI, and AGS.CONCLUSIONSIn patients with elevated IRG-S, we identified characteristic clinical features and 3 additional autoinflammatory diseases: IL-18-mediated PAP and recurrent MAS (IL-18PAP-MAS), NEMO deleted exon 5-autoinflammatory syndrome (NEMO-NDAS), and SAMD9L-associated autoinflammatory disease (SAMD9L-SAAD). The IRG-S expands the diagnostic armamentarium in evaluating USAIDs and points to different pathways regulating IRG expression.TRIAL REGISTRATIONClinicalTrials.gov NCT02974595.FUNDINGThe Intramural Research Program of the NIH, NIAID, NIAMS, and the Clinical Center.
Multi-year observations from the network of ground-based observatories (ARFINET), established under the project ‘Aerosol Radiative Forcing over India’ (ARFI) of Indian Space Research Organization and ...space-borne lidar ‘Cloud Aerosol Lidar with Orthogonal Polarization’ (CALIOP) along with simulations from the chemical transport model ‘Goddard Chemistry Aerosol Radiation and Transport’ (GOCART), are used to characterize the vertical distribution of atmospheric aerosols over the Indian landmass and its spatial structure. While the vertical distribution of aerosol extinction showed higher values close to the surface followed by a gradual decrease at increasing altitudes, a strong meridional increase is observed in the vertical spread of aerosols across the Indian region in all seasons. It emerges that the strong thermal convections cause deepening of the atmospheric boundary layer, which although reduces the aerosol concentration at lower altitudes, enhances the concentration at higher elevations by pumping up more aerosols from below and also helping the lofted particles to reach higher levels in the atmosphere. Aerosol depolarization ratios derived from CALIPSO as well as the GOCART simulations indicate the dominance of mineral dust aerosols during spring and summer and anthropogenic aerosols in winter. During summer monsoon, though heavy rainfall associated with the Indian monsoon removes large amounts of aerosols, the prevailing southwesterly winds advect more marine aerosols over to landmass (from the adjoining oceans) leading to increase in aerosol loading at lower altitudes than in spring. During spring and summer months, aerosol loading is found to be significant, even at altitudes as high as 4 km, and this is proposed to have significant impacts on the regional climate systems such as Indian monsoon.
•Ground based and space borne observations supported by transport model simulations.•Meridional increase in the vertical spread of aerosols over India during spring.•Dominance of mineral dust aerosols during spring and summer at higher altitudes.
Objective
To characterize the early disease course in childhood‐onset antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) and the 12‐month outcomes in children with AAV.
Methods
...Eligible subjects were children entered into the Pediatric Vasculitis Initiative study who were diagnosed before their eighteenth birthday as having granulomatosis with polyangiitis (Wegener's), microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (Churg‐Strauss), or ANCA‐positive pauci‐immune glomerulonephritis. The primary outcome measure was achievement of disease remission (Pediatric Vasculitis Activity Score PVAS of 0) at 12 months with a corticosteroid dosage of <0.2 mg/kg/day. Secondary outcome measures included the rates of inactive disease (PVAS of 0, with any corticosteroid dosage) and rates of improvement at postinduction (4–6 months after diagnosis) and at 12 months, presence of damage at 12 months (measured by a modified Pediatric Vasculitis Damage Index PVDI; score 0 = no damage, score 1 = one damage item present), and relapse rates at 12 months.
Results
In total, 105 children with AAV were included in the study. The median age at diagnosis was 13.8 years (interquartile range 10.9–15.8 years). Among the study cohort, 42% of patients achieved remission at 12 months, 49% had inactive disease at postinduction (4–6 months), and 61% had inactive disease at 12 months. The majority of patients improved, even if they did not achieve inactive disease. An improvement in the PVAS score of at least 50% from time of diagnosis to postinduction was seen in 92% of patients. Minor relapses occurred in 12 (24%) of 51 patients after inactive disease had been achieved postinduction. The median PVDI damage score at 12 months was 1 (range 0–6), and 63% of patients had ≥1 PVDI damage item scored as present at 12 months.
Conclusion
This is the largest study to date to assess disease outcomes in pediatric AAV. Although the study showed that a significant proportion of patients did not achieve remission, the majority of patients responded to treatment. Unfortunately, more than one‐half of this patient cohort experienced damage to various organ systems early in their disease course.
Burden of childhood-onset arthritis Moorthy, Lakshmi N; Peterson, Margaret Ge; Hassett, Afton L ...
Pediatric rheumatology online journal,
07/2010, Letnik:
8, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Juvenile arthritis comprises a variety of chronic inflammatory diseases causing erosive arthritis in children, often progressing to disability. These children experience functional impairment due to ...joint and back pain, heel pain, swelling of joints and morning stiffness, contractures, pain, and anterior uveitis leading to blindness. As children who have juvenile arthritis reach adulthood, they face possible continuing disease activity, medication-associated morbidity, and life-long disability and risk for emotional and social dysfunction. In this article we will review the burden of juvenile arthritis for the patient and society and focus on the following areas: patient disability; visual outcome; other medical complications; physical activity; impact on HRQOL; emotional impact; pain and coping; ambulatory visits, hospitalizations and mortality; economic impact; burden on caregivers; transition issues; educational occupational outcomes, and sexuality.The extent of impact on the various aspects of the patients', families' and society's functioning is clear from the existing literature. Juvenile arthritis imposes a significant burden on different spheres of the patients', caregivers' and family's life. In addition, it imposes a societal burden of significant health care costs and utilization. Juvenile arthritis affects health-related quality of life, physical function and visual outcome of children and impacts functioning in school and home. Effective, well-designed and appropriately tailored interventions are required to improve transitioning to adult care, encourage future vocation/occupation, enhance school function and minimize burden on costs.
Aircraft measurements of the vertical profiles of aerosol total number concentrations and size distributions (in the size range of 0.5–20 μm) were made over seven geographically diverse locations of ...the Indian mainland during two contrasting seasons, winter (December 2012) and spring (April–May 2013), as a part of the regional aerosol warming experiment (RAWEX). Our observations revealed an increase in the vertical extent of aerosol loading during spring having a significant enhancement in coarse mode aerosols in the lower free-troposphere (FT) over western and central parts of India and the Indo-Gangetic plains (IGP). The particulate depolarisation ratio (PDR) derived from the Cloud Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) over the same region showed the presence of dust (including polluted dust) at higher altitudes in spring. Concurrent and collocated measurements of aerosol scattering and absorption properties aboard the aircraft revealed that the FT enhancement in coarse mode aerosol loading during spring is associated with a decrease in single scattering albedo and an increase in columnar absorption aerosol optical depth. This confirms that the elevated layers of coarse mode aerosols seen during spring are absorbing in nature, especially over the IGP. The presence of such coarse-mode absorbing aerosols plays a crucial role in governing the radiation balance over the IGP in spring through the diabatic heating of the upper atmosphere.
The impact of the COVID-19 pandemic on new diagnoses of recurrent fevers and autoinflammatory diseases is largely unknown. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) PFAPA/AID ...Working Group aimed to investigate the impact of the COVID-19 pandemic on the number of pediatric patients evaluated for recurrent fevers and autoinflammatory diseases in North America. The absolute number of new outpatient visits and the proportion of these visits attributed to recurrent fever diagnoses during the pre-pandemic period (1 March 2019-29 February 2020) and the first year of the COVID-19 pandemic (1 March 2020-28 February 2021) were examined. Data were collected from 27 sites in the United States and Canada. Our results showed an increase in the absolute number of new visits for recurrent fever evaluations in 21 of 27 sites during the COVID-19 pandemic compared to the pre-pandemic period. The increase was observed across different geographic regions in North America. Additionally, the proportion of new visits to these centers for recurrent fever in relation to all new patient evaluations was significantly higher during the first year of the pandemic, increasing from 7.8% before the pandemic to 10.9% during the pandemic year (
< 0.001). Our findings showed that the first year of the COVID-19 pandemic was associated with a higher number of evaluations by pediatric subspecialists for recurrent fevers. Further research is needed to understand the reasons behind these findings and to explore non-infectious triggers for recurrent fevers in children.
Objective
Few data are available regarding the rates of serious adverse events (SAEs) and important medical events (IMEs) outside of product‐based registries and clinical trials for juvenile ...idiopathic arthritis (JIA). The Enhanced Drug Safety Surveillance Project (EDSSP) was developed to pilot a novel system to collect SAEs/IMEs in children with JIA. This analysis reports the results from this 4‐year (2008–2012) EDSSP.
Methods
Participating physicians were surveyed monthly to ascertain whether their JIA patients experienced an SAE or IME. Sites were surveyed every 6 months to determine the number of unique JIA patients seen at each site during that 6‐month period. Reporting rates were calculated per 100 person‐years and 95% confidence intervals (95% CIs) were calculated based on a Poisson distribution.
Results
Thirty‐seven Childhood Arthritis and Rheumatology Research Alliance sites with 115 physicians participated. The mean response rate to the monthly surveys was 65%. There were 147 total SAEs and 145 total IMEs. The largest proportion of SAEs and IMEs occurred in children with polyarticular JIA (39% and 37%, respectively). The majority of SAEs and IMEs were reported for patients receiving therapy with biologic agents (76% and 69%, respectively). The total event rate for SAEs and IMEs combined was 1.07 events per 100 person‐years (95% CI 0.95–1.19). The rates for SAEs and IMEs were 0.54 per 100 person‐years (95% CI 0.45–0.63) and 0.53 per 100 person‐years (95% CI 0.49–0.62), respectively.
Conclusion
The EDSSP provided a simple tool for SAE/IME reporting within an established research network and resulted in a similar range of reported events as captured by a traditional product‐based registry.
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