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Annals of Medicine and Surgery (2012) May 2024Macrophage activation syndrome (MAS) is a severe form of hemophagocytic lymphohistiocytosis that is frequently associated with either a flare-up of rheumatologic...
INTRODUCTION AND IMPORTANCE
Macrophage activation syndrome (MAS) is a severe form of hemophagocytic lymphohistiocytosis that is frequently associated with either a flare-up of rheumatologic diseases, or infection and is characterized by intermittent fever, organomegaly, and multisystem dysfunction. Early diagnosis and treatment are crucial for outcome improvement.
CASE PRESENTATION
The authors present a 9-year-old male with systemic onset juvenile idiopathic arthritis who presented with fever, vomiting, and nose bleeding, as well as being jaundiced, and having hepatomegaly and ascites. Pancytopenia, hepatic dysfunction, and elevated ferritin levels were discovered, along with negative virological and immunological tests. He was given broad-spectrum antibiotics, and a high-dose steroid showed a good response, and he was discharged about a week later.
CLINICAL DISCUSSION
It is hypothesized that decreased natural killer cells' function could lead to the inability to clear the infection, and subsequent lymphocytes-induced macrophages activation. Despite being beneficial in this case, steroids led to no improvement in other similar cases.
CONCLUSION
MAS is a real life-threatening complication for patients with systemic Juvenile idiopathic arthritis (sJIA), and early diagnosis and prompt initial treatment can both offer a favourable result against such syndrome.
PubMed: 38694344
DOI: 10.1097/MS9.0000000000001900 -
International Journal of Cardiology.... Jun 2024The recent (CDACD) study showed enhanced aortic stiffness and wall thickness in adolescents with various chronic disorders. Enhanced aortic stiffness can increase left...
BACKGROUND
The recent (CDACD) study showed enhanced aortic stiffness and wall thickness in adolescents with various chronic disorders. Enhanced aortic stiffness can increase left ventricular (LV) afterload and trigger a cascade of adverse arterioventricular interaction. Here, we investigate the relation between aortic changes and LV function in the CDACD study participants.
METHODS
This cross-sectional study included 114 adolescents 12-18 years old with cystic fibrosis (CF, n = 24), corrected coarctation of the aorta (CoA, n = 25), juvenile idiopathic arthritis (JIA, n = 20), obesity (n = 20), and healthy controls (n = 25). Aortic pulse wave velocity (PWV), which reflects aortic stiffness, and aortic wall thickness (AWT) were assessed with cardiovascular magnetic resonance imaging (CMR). Echocardiography was employed to study conventional markers of LV function, as well as LV global longitudinal strain (LVGLS), which is an established (pre)clinical marker of LV dysfunction.
RESULTS
First, aortic PWV and AWT were increased in all chronic disease groups, compared to controls. Second, in adolescents with CoA, JIA, and obesity, echocardiography showed a decreased LVGLS, while LV dimensions and conventional LV function markers were similar to controls. Third, multivariable linear regression identified aortic PWV as the most important determinant of their decreased LVGLS (standardized β -0.522, p < 0.001).
CONCLUSIONS
The decreased LVGLS in several adolescent chronic disease groups was associated with enhanced aortic PWV, which might reflect adverse arterioventricular interaction. Whether the decreased LVGLS in the chronic disease groups could negatively impact their long-term cardiovascular outcomes requires further study.
PubMed: 38694268
DOI: 10.1016/j.ijcha.2024.101385 -
World Journal of Clinical Cases Apr 2024Various non-steroidal anti-inflammatory drugs (NSAIDs) have been used for juvenile idiopathic arthritis (JIA). However, the optimal method for JIA has not yet been...
BACKGROUND
Various non-steroidal anti-inflammatory drugs (NSAIDs) have been used for juvenile idiopathic arthritis (JIA). However, the optimal method for JIA has not yet been developed.
AIM
To perform a systematic review and network meta-analysis to determine the optimal instructions.
METHODS
We searched for randomized controlled trials (RCTs) from PubMed, EMBASE, Google Scholar, CNKI, and Wanfang without restriction for publication date or language at August, 2023. Any RCTs that comparing the effectiveness of NSAIDs with each other or placebo for JIA were included in this network meta-analysis. The surface under the cumulative ranking curve (SUCRA) analysis was used to rank the treatments. value less than 0.05 was identified as statistically significant.
RESULTS
We included 8 RCTs (1127 patients) comparing 8 different instructions including meloxicam (0.125 qd and 0.250 qd), Celecoxib (3 mg/kg bid and 6 mg/kg bid), piroxicam, Naproxen (5.0 mg/kg/d, 7.5 mg/kg/d and 12.5 mg/kg/d), inuprofen (30-40 mg/kg/d), Aspirin (60-80 mg/kg/d, 75 mg/kg/d, and 55 mg/kg/d), Tolmetin (15 mg/kg/d), Rofecoxib, and placebo. There were no significant differences between any two NSAIDs regarding ACR Pedi 30 response. The SUCRA shows that celecoxib (6 mg/kg bid) ranked first (SUCRA, 88.9%), rofecoxib ranked second (SUCRA, 68.1%), Celecoxib (3 mg/kg bid) ranked third (SUCRA, 51.0%). There were no significant differences between any two NSAIDs regarding adverse events. The SUCRA shows that placebo ranked first (SUCRA, 88.2%), piroxicam ranked second (SUCRA, 60.5%), rofecoxib (0.6 mg/kg qd) ranked third (SUCRA, 56.1%), meloxicam (0.125 mg/kg qd) ranked fourth (SUCRA, 56.1%), and rofecoxib (0.3 mg/kg qd) ranked fifth (SUCRA, 56.1%).
CONCLUSION
In summary, celecoxib (6 mg/kg bid) was found to be the most effective NSAID for treating JIA. Rofecoxib, piroxicam, and meloxicam may be safer options, but further research is needed to confirm these findings in larger trials with higher quality studies.
PubMed: 38680254
DOI: 10.12998/wjcc.v12.i12.2056 -
Genes Apr 2024Juvenile idiopathic arthritis is a heterogeneous group of diseases characterized by arthritis with poorly known causes, including monogenic disorders and multifactorial...
Juvenile idiopathic arthritis is a heterogeneous group of diseases characterized by arthritis with poorly known causes, including monogenic disorders and multifactorial etiology. 22q11.2 proximal deletion syndrome is a multisystemic disease with over 180 manifestations already described. In this report, the authors describe a patient presenting with a short stature, neurodevelopmental delay, and dysmorphisms, who had an episode of polyarticular arthritis at the age of three years and eight months, resulting in severe joint limitations, and was later diagnosed with 22q11.2 deletion syndrome. Investigation through Whole Genome Sequencing revealed that he had no pathogenic or likely-pathogenic variants in both alleles of the gene or in genes associated with monogenic arthritis (, , , , , , , , , , ). However, the patient presented 41 risk polymorphisms for juvenile idiopathic arthritis. Thus, in the present case, arthritis seems coincidental to 22q11.2 deletion syndrome, probably caused by a multifactorial etiology. The association of the gene in individuals previously described with juvenile idiopathic arthritis and 22q11.2 deletion seems unlikely since it is located in the distal and less-frequently deleted region of 22q11.2 deletion syndrome.
Topics: Humans; Arthritis, Juvenile; Male; DiGeorge Syndrome; Whole Genome Sequencing; Intramolecular Oxidoreductases; Child, Preschool; Macrophage Migration-Inhibitory Factors; Child
PubMed: 38674447
DOI: 10.3390/genes15040513 -
Pediatric Rheumatology Online Journal Apr 2024Juvenile idiopathic arthritis (JIA) is the most prevalent rheumatic disease in children, and the inflammatory process is widely studied, primarily characterized by its...
BACKGROUND
Juvenile idiopathic arthritis (JIA) is the most prevalent rheumatic disease in children, and the inflammatory process is widely studied, primarily characterized by its impact on joint health. Emerging evidence suggests that JIA may also affect the central nervous system (CNS). This study investigates the potential CNS involvement in JIA by analyzing the presence of astrocyte-derived extracellular vesicles (EVs) and the S100B protein in plasma, both of which are indicative of astrocyte activity and blood-brain barrier (BBB) integrity.
METHODS
EDTA plasma from 90 children diagnosed with JIA and 10 healthy controls, matched by age and gender, was analyzed for extracellular vesicles by flow cytometric measurement. Astrocyte-derived EVs were identified using flow cytometry with markers for aquaporin 4 (AQP-4) and glial fibrillary acidic protein (GFAP). Levels of the S100B protein were measured using a commercial ELISA. Disease activity was assessed using the Juvenile Arthritis Disease Activity Score (JADAS27, 0-57), and pain levels were measured using a visual analogue scale (VAS, 0-10 cm).
RESULTS
Our analyses revealed a significantly higher concentration of astrocyte-derived EVs in the plasma of children with JIA compared with healthy controls. Furthermore, children with JADAS27 scores of 1 or higher exhibited notably higher levels of these EVs. The S100B protein was detectable exclusively in the JIA group.
CONCLUSION
The elevated levels of astrocyte-derived EVs and the presence of S100B in children with JIA provide evidence of BBB disruption and CNS involvement, particularly in those with higher disease activity. These findings underscore the importance of considering CNS health in the comprehensive management of JIA. Further research is required to elucidate the mechanisms behind CNS engagement in JIA and to develop treatments that address both joint and CNS manifestations of the disease.
Topics: Humans; Arthritis, Juvenile; Child; Male; Blood-Brain Barrier; Female; Cross-Sectional Studies; Extracellular Vesicles; Astrocytes; S100 Calcium Binding Protein beta Subunit; Adolescent; Case-Control Studies; Child, Preschool; Permeability
PubMed: 38671467
DOI: 10.1186/s12969-024-00984-2 -
Rheumatology and Therapy Jun 2024Emapalumab is a fully human monoclonal antibody that targets free and receptor-bound interferon-gamma (IFNγ), neutralizing its biological activity. IFNγ levels differ...
INTRODUCTION
Emapalumab is a fully human monoclonal antibody that targets free and receptor-bound interferon-gamma (IFNγ), neutralizing its biological activity. IFNγ levels differ by orders of magnitude between patients with primary hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS; a form of secondary HLH) in systemic juvenile idiopathic arthritis (sJIA). Therefore, this study aimed to develop a population pharmacokinetic model for emapalumab across a patient population with a wide range of total (free and emapalumab-bound) IFNγ levels using observations from patients with primary HLH or MAS in sJIA in clinical trials.
METHODS
Pharmacokinetic data were pooled (n = 58; 2709 observations) from studies enrolling patients administered emapalumab for primary HLH or MAS in sJIA. Patients with primary HLH were administered emapalumab 1 mg/kg (potentially increasing to 3, 6, and up to 10 mg/kg based on clinical response) every 3 days. Patients with MAS in sJIA were administered emapalumab 6 mg/kg, followed by 3 mg/kg every 3 days until day 15 and twice weekly until day 28. An earlier population PK model was re-parameterized using this data.
RESULTS
The final model for emapalumab comprised a 2-compartment model with first-order elimination. Emapalumab clearance remains constant when the total IFNγ concentration (free and emapalumab-bound) is < ~ 10,000 pg/ml but increases proportionally to total IFNγ concentration above this threshold. Emapalumab clearance was estimated to be 0.00218, 0.00308, 0.00623 and 0.01718 l/h at total serum IFNγ concentrations of 10, 10, 10 and 10 pg/ml, respectively, with corresponding terminal half-lives of 19.2, 13.8, 7.18 and 3.12 days for a 1-year-old patient weighing 10 kg with primary HLH. The median terminal half-life for emapalumab in patients with MAS in sJIA was estimated to be 24.0 (range, 6.13-32.4) days, which is similar to observations in healthy volunteers.
CONCLUSIONS
Emapalumab pharmacokinetics in patients with primary HLH and MAS in sJIA were described by a two-compartment model with fixed allometric exponents and an age-related effect. Differences in total IFNγ levels between patients with primary HLH and MAS may affect emapalumab pharmacokinetics, suggesting that each indication may require different dosing to rapidly control hyperinflammation.
TRIAL REGISTRATION
Clinicaltrials.gov identifiers: NCT01818492, NCT03311854 and NCT02069899.
PubMed: 38662147
DOI: 10.1007/s40744-024-00669-y -
Frontiers in Immunology 2024
Topics: Humans; Arthritis, Juvenile; Interleukin-1beta; Cell-Derived Microparticles; Macrophages; Biomarkers; Thrombosis; Inflammation
PubMed: 38655252
DOI: 10.3389/fimmu.2024.1397527 -
Reumatologia Clinica Apr 2024Magnetic resonance imaging (MRI) sensitivity and specificity seem to be less studied in enthesitis-related arthritis (ERA). We aimed to determine the ability of...
INTRODUCTION AND OBJECTIVES
Magnetic resonance imaging (MRI) sensitivity and specificity seem to be less studied in enthesitis-related arthritis (ERA). We aimed to determine the ability of sacroiliac MRI to diagnose ERA patients.
MATERIALS AND METHODS
We conducted a retrospective study including 44 patients with juvenile idiopathic arthritis (JIA). Each patient had a sacroiliac joint MRI. We divided patients into two groups: G1 patients with ERA and G2 patients with non-ERA subtype.
RESULTS
ERA was noted in 61% of the cases. Sacroiliac joints were painful in 15 patients (34%). MRI was normal in 25 patients (57%) (G1:11 versus G2:14) and showed bone marrow edema in the sacroiliac joints in 19 patients (34%) (G1=16 versus G2=3, p=0.005). Sacroiliac joints MRI's sensitivity and specificity in the ERA diagnosis were 61.54% and 82.35%, respectively. Positive and negative predictive values were 84.21% and 58.33%, respectively. Furthermore, sacroiliac joint pain in the clinical examination was able to predict sacroiliac bone edema in MRI with an odds ratio of 6.8 (95% CI 1.68-28.09; p=0.006).
CONCLUSION
Our study showed that sacroiliac joint MRI has good specificity and positive predictive value in the diagnosis of ERA patients among JIA patients. This underlines the usefulness of sacroiliac joint MRI in the early diagnosis of ERA patients.
Topics: Humans; Sacroiliitis; Retrospective Studies; Male; Female; Magnetic Resonance Imaging; Arthritis, Juvenile; Child; Sensitivity and Specificity; Adolescent; Sacroiliac Joint; Child, Preschool
PubMed: 38644029
DOI: 10.1016/j.reumae.2023.12.008 -
Pediatric Rheumatology Online Journal Apr 2024Adolescents with juvenile idiopathic arthritis (JIA) tend to engage in less physical activity than their typically developing peers. Physical activity is essential for...
BACKGROUND
Adolescents with juvenile idiopathic arthritis (JIA) tend to engage in less physical activity than their typically developing peers. Physical activity is essential for bone development and reduced physical activity may detrimentally effect bone health. Thus, we examined differences in total body bone mineral content (BMC) and areal bone mineral density (aBMD) between adolescents with JIA and adolescent controls without JIA. We also examined associations between moderate-to-vigorous physical activity (MVPA), lean mass, and bone outcomes.
METHODS
Participants included 21 adolescents with JIA (14 females, 7 males) and 21 sex- and age-matched controls aged 10-20 years. Assessments included: height; weight; triple-single-leg-hop distance (TSLH); MVPA by accelerometry; and total body BMC, aBMD, and lean mass measured using dual X-ray absorptiometry. Height-adjusted z-scores were calculated for BMC and aBMD and used for all analyses. Multiple linear mixed effects models examined group differences in BMC and aBMD, adjusting for sex, maturity, MVPA, TSLH, and lean mass. Participants clusters, based on sex and age (within 18 months), were considered random effects.
RESULTS
Adolescents with JIA had lower total body aBMD z-scores [β (95% CI); -0.58 (-1.10 to -0.07), p = 0.03] and BMC z-scores [-0.47 (-0.91 to -0.03), p = 0.04] compared with controls. Mean daily MVPA was 22.0 min/day lower in adolescents with JIA than controls; however, MVPA was not associated with aBMD [-0.01 (-0.01 to 0.01), p = 0.32] or BMC [0.00 (-0.01 to 0.00), p = 0.39]. Lean mass was positively associated with aBMD [0.05 (0.01 to 0.09) g/cm, p = 0.03] and BMC [0.06 (0.03 to 0.10) g, p < 0.001].
CONCLUSION
Adolescents with JIA had lower total body aBMD and BMC compared with sex- and age-matched controls without JIA. Group differences in bone outcomes were not associated with the lower MVPA participation of adolescents with JIA. Despite this, physical activity should still be encouraged as it promotes physical well-being.
Topics: Male; Female; Humans; Adolescent; Bone Density; Arthritis, Juvenile; Cross-Sectional Studies; Case-Control Studies; Absorptiometry, Photon; Exercise
PubMed: 38641611
DOI: 10.1186/s12969-024-00982-4