Somatic NOD2 mosaicism in Blau syndrome de Inocencio, Jaime, MD, PhD; Mensa-Vilaro, Anna, MD; Tejada-Palacios, Pilar, MD, PhD ...
Journal of allergy and clinical immunology,
08/2015, Letnik:
136, Številka:
2
Journal Article
Recenzirano
Odprti dostop
During the past few years, the clinical diversity of BS has increased as the number of diagnosed patients has increased. ...we currently know that some patients never developed some of the symptoms ...of the classical triad, whereas other patients developed symptoms beyond the triad.4,9 The phenotype of the patient described here resembles that detected in patients with BS affected exclusively with the triad, although differences in the articular involvement should be highlighted. ...the child will carry a germline mutation and it is conceivable that his or her phenotype will be even more severe than that observed in patients carrying a somatic mutation.\n Cell sorting was performed using the BD FACSAria II system (BD Biosciences Pharmingen).
Juvenile dermatomyositis (JDM) is the most common form of juvenile idiopathic inflammatory myopathy. We report a child with steroid-dependent JDM refractory to hydroxychloroquine and subcutaneous ...methotrexate who experienced systemic reactions to intravenous immunoglobulin and was successfully treated with subcutaneous immunoglobulin. This form of therapy has been shown to be safe, has a very low rate of adverse effects, does not require hospital admission, reduces the number of missed school days, and decreases the costs associated with treatment.
Objective
To develop and test a hybrid measure of muscle strength for juvenile dermatomyositis (JDM), which is based on the combination of the Manual Muscle Testing in 8 muscles (MMT‐8) and the ...Childhood Myositis Assessment Scale (CMAS) but is more comprehensive than the former and more feasible than the latter.
Methods
The hybrid MMT‐8/CMAS (hMC) is composed of all 8 items of the MMT‐8 and 3 items of the CMAS: time of head lift, assessment of abdominal muscles, and floor rise. The score ranges 0–100, with 100 indicating normal muscle strength. Validation procedures were conducted using 3 large multinational patient samples, including a total of 810 JDM patients.
Results
The hMC revealed face and content validity, good construct validity, excellent test–retest reliability (intraclass correlation coefficient = 0.99), and internal consistency (Cronbach's α = 0.94), strong responsiveness to clinical change over time (standardized response mean = 0.8 among patients judged as improved by the caring physician), and satisfactory capacity to discriminate patients judged as being in the states of inactive disease or low, moderate, or high disease activity by the physician (P < 0.001) or patients whose parents were satisfied or not satisfied with the illness course (P < 0.001).
Conclusion
The hMC was found to possess good measurement properties in a large population of patients with a wide range of disease activity and severity. The new tool, which is primarily intended for use in routine clinical care, should be further tested in other populations of patients evaluated prospectively.
Recurrent pericarditis is a troublesome complication of idiopathic acute pericarditis and occurs more frequently in pediatric patients after cardiac surgery (postpericardiotomy syndrome). ...Conventional treatment with nonsteroidal antiinflammatory drugs, corticosteroids, and colchicine is not always effective or may cause serious adverse effects. There is no consensus, however, on how to proceed in those patients whose disease is refractory to conventional therapy. In such cases, human intravenous immunoglobulin, immunosuppressive drugs, and biological agents have been used. In this report we describe 2 patients with refractory recurrent pericarditis after cardiac surgery who were successfully treated with 3 and 5 monthly high-dose (2 g/kg) intravenous immunoglobulin until resolution of the effusion. Our experience supports the effectiveness and safety of this therapy.
This study aimed to assess the baseline characteristics and clinical outcomes of coronavirus disease 2019 (COVID-19) in pediatric patients with rheumatic and musculoskeletal diseases (RMD) and ...identify the risk factors associated with symptomatic or severe disease defined as hospital admission, intensive care admission or death.
An observational longitudinal study was conducted during the first year of the SARS-CoV-2 pandemic (March 2020-March 2021). All pediatric patients attended at the rheumatology outpatient clinics of six tertiary referral hospitals in Madrid, Spain, with a diagnosis of RMD and COVID-19 were included. Main outcomes were symptomatic disease and hospital admission. The covariates were sociodemographic and clinical characteristics and treatment regimens. We ran a multivariable logistic regression model to assess associated factors for outcomes.
The study population included 77 pediatric patients. Mean age was 11.88 (4.04) years Of these, 30 patients (38.96%) were asymptomatic, 41 (53.25%) had a mild-moderate COVID-19 and 6 patients (7.79%) required hospital admission. The median length of hospital admission was 5 (2-20) days, one patient required intensive care and there were no deaths. Previous comorbidities increased the risk for symptomatic disease and hospital admission. Compared with outpatients, the factor independently associated with hospital admission was previous use of glucocorticoids (OR 3.51; p = 0.00). No statistically significant risk factors for symptomatic COVID-19 were found in the final model.
No differences in COVID-19 outcomes according to childhood-onset rheumatic disease types were found. Results suggest that associated comorbidities and treatment with glucocorticoids increase the risk of hospital admission.
NF-κB1 is a master regulator of both acquired and innate responses.
loss-of-function mutations elicit a wide clinical phenotype with asymptomatic individuals at one end of the spectrum and patients ...with common variable immunodeficiency, combined immunodeficiency or autoinflammation at the other. Impairment of acquired and innate immunity and disseminated
infection expands the clinical and immunological phenotype of NF-κB1 deficiency.
Functional and molecular characterization of a patient with a novel phenotype of NF-κB1 deficiency.
Circulating T, B, dendritic cell subsets and innate or unconventional T-cells were quantified. The cytokine production in stimulated whole blood samples was assessed and molecular characterization by next generation sequencing and gene expression assays were also performed.
We report a patient presenting with features of combined immunodeficiency (CID) and disseminated
infection. Sequencing of genomic DNA identified a novel synonymous mutation (c.705G > A) in
gene which resulted in exon 8 skipping and haploinsufficiency of the NF-κB1 subunit p50. The susceptibility to atypical mycobacterial infection has not been previously reported and may be the result of a dendritic cell deficiency. A selective deficiency of circulating follicular helper T (cTFH) cells responsible for mediating the differentiation of naive B cells into memory and plasma cells was also present in the patient. It could affect the maturation of innate or unconventional T cells where NF-κB1 could also be involved.
These findings showed that the role of NF-κB1 in humans could be critical for the development of acquired and innate immunity and further highlights the role of human T cells in anti-mycobacterial immunity.
Background Etanercept (ETN) and adalimumab (ADA) are considered equally effective biologicals in the treatment of arthritis in juvenile idiopathic arthritis (JIA) but no studies have compared their ...impact on patient-reported well-being. The objective of this study was to determine whether ETN and ADA have a differential effect on patient-reported well-being in non-systemic JIA using real-world data. Methods Biological-naive patients without a history of uveitis were selected from the international Pharmachild registry. Patients starting ETN were matched to patients starting ADA based on propensity score and outcomes were collected at time of therapy initiation and 3-12 months afterwards. Primary outcome at follow-up was the improvement in Juvenile Arthritis Multidimensional Assessment Report (JAMAR) visual analogue scale (VAS) well-being score from baseline. Secondary outcomes at follow-up were decrease in active joint count, adverse events and uveitis events. Outcomes were analyzed using linear and logistic mixed effects models. Results Out of 158 eligible patients, 45 ETN starters and 45 ADA starters could be propensity score matched resulting in similar VAS well-being scores at baseline. At follow-up, the median improvement in VAS well-being was 2 (interquartile range (IQR): 0.0 - 4.0) and scores were significantly better (P = 0.01) for ETN starters (median 0.0, IQR: 0.0 - 1.0) compared to ADA starters (median 1.0, IQR: 0.0 - 3.5). The estimated mean difference in VAS well-being improvement from baseline for ETN versus ADA was 0.89 (95% CI: -0.01 - 1.78; P = 0.06). The estimated mean difference in active joint count decrease was -0.36 (95% CI: -1.02 - 0.30; P = 0.28) and odds ratio for adverse events was 0.48 (95% CI: 0.16 -1.44; P = 0.19). One uveitis event was observed in the ETN group. Conclusions Both ETN and ADA improve well-being in non-systemic JIA. Our data might indicate a trend towards a slightly stronger effect for ETN, but larger studies are needed to confirm this given the lack of statistical significance. Keywords: Juvenile idiopathic arthritis, Etanercept, Adalimumab, Patient-reported outcomes, Epidemiology, Real-world data, Propensity score analysis
PDF
