Search Results (46)

Background: Youth with chronic rheumatologic diseases undergo medical experiences that can lead to post-traumatic stress disorder (PTSD). Understudied in pediatric rheumatology, medical PTSD can be significantly distressing and impairing. Objective: This study explored the prevalence of medical PTSD symptoms in youth with chronic inflammatory arthritis and associated factors, including pain, disease activity, mental health history, and anxiety sensitivity. Methods: A cross-sectional study of 50 youth (ages 8–18) with juvenile idiopathic arthritis (JIA) and childhood-onset systemic lupus erythematous (cSLE) was conducted at a pediatric rheumatology clinic. Participants completed self-report measures assessing post-traumatic stress symptoms (CPSS-V), pain, anxiety sensitivity (CASI), pain-related self-efficacy (CSES), adverse childhood experiences (ACEs), and fibromyalgia symptoms (PSAT). Clinical data included diagnoses, disease activity, treatment history, and demographics. Results: Forty percent had trauma symptoms in the moderate or more severe range. The 14% likely meeting criteria for probable medical PTSD were older (median 17 vs. 15 years, p = 0.005), had higher pain scores (median 4 vs. 3, p = 0.008), more ACEs (median 3 vs. 1, p = 0.005), higher anxiety sensitivity scores (median 39 vs. 29, p = 0.008), and higher JIA disease activity scores (median cJADAS-10 11.5 vs. 7.5, p = 0.032). They were also more likely to report a history of depression (71 vs. 23%, p = 0.020). No associations were found with hospitalization or injected/IV medication use. Conclusions: Medical trauma symptoms are prevalent in youth with chronic inflammatory arthritis. Probable PTSD was associated with pain and psychological distress. These findings support the need for trauma-informed care in pediatric rheumatology. Full article

Introduction: The monitoring of autonomic nervous balance during childhood remains underexplored. However, heart rate variability (HRV) is widely recognized as a biomarker of health risk across the lifespan. Juvenile idiopathic arthritis (JIA), a group of chronic inflammatory joint disorders, is associated with persistent inflammation and pain, both of which contribute to increased cardiovascular risk, commonly linked to reduced HRV. Among HRV parameters, very-low frequency (VLF) components have been associated with physiological recovery processes. This study aimed to assess HRV during sleep in patients with JIA. Methods: We studied 10 patients with JIA and 10 age-, gender-, and Tanner stage-matched healthy controls. All participants underwent polysomnographic monitoring following an adaptation night in the sleep laboratory. HRV was analyzed using standard time and frequency domain measures over 5 min epochs across all sleep stages. Frequency components were classified into low- and high-frequency bands, and time domain measures included the standard deviation of the beat-to-beat intervals. Group differences in HRV parameters were assessed using nonparametric tests for independent samples, with a significance level set at p < 0.05. Results: JIA exhibited greater sleep disruption than controls, including reduced NREM sleep, longer total sleep time, and increased wake time after sleep onset. HRV analyses in both time and frequency domains revealed significant differences between groups across all stages of sleep. In JIA patients, the standard deviation of the normal-to-normal interval during slow wave sleep (SWS) and total power across all sleep stages (p < 0.05) was reduced. In JIA patients, the standard deviation of the normal-to-normal interval during slow wave sleep and total power across all sleep stages were significantly reduced (p < 0.05). VLF power was also significantly lower in JIA patients across all sleep stages (p = 0.002), with pronounced reductions during N2 and SWS (p = 0.03 and p = 0.02, respectively). A group effect was observed for total power across all stages, mirroring the VLF findings. Additionally, group differences were detected in LF/HF ratio analyses, although values during N2, SWS, and REM sleep did not differ significantly between groups. Notably, the number of affected joints showed a moderate positive correlation with the parasympathetic HRV parameter. Conclusions: Patients with JIA exhibited sleep disruption and alterations in cardiovascular autonomic functioning during sleep. Reduced HRV across all sleep stages in these patients suggests underlying autonomic nervous dysfunction. Addressing sleep disturbances in patients with chronic pain may serve as an effective strategy for managing their cardiovascular risk. Full article

Background/Objectives: Growth in childhood and adolescence is influenced by a complex interaction of genetic, environmental, and hormonal factors, with growth hormone (GH) and insulin-like growth factor 1 (IGF-1) playing crucial roles in linear growth and development. However, chronic inflammation, often detected in situations like inflammatory bowel disease and juvenile idiopathic arthritis, can significantly disrupt the GH/IGF-1 axis, causing a relevant growth impairment. Methods: We conducted a retrospective review focusing on the role of cytokines in the GH-IGF-1 axis and growth. Results: Inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 have been shown to contribute to GH resistance through an array of mechanisms that involve the downregulation of GH receptors and alterations in IGF-1 metabolism. This disruption negatively impacts the growth plate, particularly by impairing chondrocyte proliferation and differentiation, which are essential for proper bone elongation. This review delves into the intricate relationship among growth, chronic inflammation, and GH-IGF-1 axis, emphasizing the contribution of inflammatory cytokines in modulating GH signaling. It also highlights how cytokines can interfere with the molecular pathways that regulate skeletal growth, ultimately leading to growth disturbances in children suffering from chronic inflammatory diseases. Conclusions: The findings underscore the importance of controlling inflammation in affected individuals to mitigate its detrimental effects on growth and ensure that children may reach their growth full potential. Full article

Background: The aim of this study was to investigate the effects of multimodal rheumatologic complex treatment (MRCT) in childhood and adolescence. MRCT means a high-frequency treatment program of at least 11 h per week. Methods: MRCTs in children, carried out between May 2009 and May 2022 at the Department of Pediatrics of the University Hospital in Halle (Saale), were included in this study. The effects of the MRCT were evaluated based on inflammatory activity, functionality (using the Childhood Health Assessment Questionnaire (CHAQ)), subjective statements regarding pain intensity, state of health, and coping with the illness, as well as the objective determination of joint mobility. Data were analyzed retrospectively using t-tests to compare different groups and values before and after treatment. Results: During the study period, N = 133 MRCTs were conducted in n = 95 children. The most common diagnosis was juvenile idiopathic arthritis (83.2%). The c-reactive protein (CRP) fell from an average of 25.3 mg/L to 7.3 mg/L, and the erythrocyte sedimentation rate (ESR) fell from 29.5 mm in the first hour to 17.9 mm. Pain intensity was reduced from 5.4 to 4.0. The state of health and coping with the illness also improved. The disability index showed a moderate reduction from 0.92 to 0.81. Furthermore, an improvement in joint mobility was observed. Positive effects were also shown in patients with somatoform disorders. Conclusions: Due to the positive effects of MRCT on subjective well-being and physical health, the treatment program can be recommended for affected children, including patients with an additional diagnosed somatoform disorder. Full article

Objective: The study analyzed the role of traumatic experiences and psychosomatic components as potential predictors of the likelihood of chronic pain patients having or not having fibromyalgia. Methods: We examined the role of stressful life events (Traumatic Experiences Checklist), psychosomatic syndromes (Toronto Alexithymia Scale and Diagnostic Criteria for Psychosomatic Research), pain, and psychological distress (Beck Depression Inventory—II and State-Trait Anxiety Inventory) in 104 patients with fibromyalgia compared with a sample of 104 patients with rheumatoid arthritis. Results: Patients with fibromyalgia reported significantly more traumatic events, a higher prevalence of psychosomatic syndromes, and higher levels of pain, anxiety and depressive symptoms compared with patients with rheumatoid arthritis (all p < 0.01). Hierarchical binary logistic regression with group membership as the dependent variable showed that somatization syndromes (OR = 3.67), pain (OR = 1.56), and childhood trauma (OR = 1.11) were statistically significant predictors of group belonging, and the model explained 67% of the variance in diagnosis [χ²(9) = 143.66, p < 0.001]. Conclusion: These results highlighted that patients with fibromyalgia are characterized primarily by marked somatization and a high prevalence of early stressful life events compared with patients with rheumatoid arthritis, a primarily nociceptive chronic pain condition. A better knowledge of these mechanisms could allow clinicians to develop tailored interventions that take greater account of the psychological dimension of the disease. Full article

Background/objectives: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood, leading to severe disability and negatively affecting patients’ health-related quality of life (HRQoL). The aim of this systematic review was to evaluate the adoption, reporting and assessment methodology of HRQoL in phase III clinical trials involving children with JIA. Methods: An electronic and manual search was conducted to identify primary and secondary publications of pharmacological trials conducted between 2012 and 2023. Data were extracted and recorded in duplicate. Results: A total of 222 studies were screened and 24 articles (22 primary and 2 secondary publications) were included in the review. HRQoL was not listed among the endpoints in 10 trials (45.5%), while it was a secondary endpoint in 12 trials (54.5%). The proportion of trials that did not consider HRQoL was equally relevant in both for-profit and no-profit settings (44.4% versus 50.0%), but it was higher in studies on systemic JIA compared to other JIA subtypes (62.5%), and on IL inhibitor treatment (72.7%) with respect to other disease-modifying antirheumatic drugs. Information on HRQoL was usually collected from parents/caregivers, and only three studies were categorized as “probably robust” with regard to HRQoL assessment. Conclusions: Systematic incorporation of HRQoL measures represents an urgent need in pediatric rheumatology, aiding clinicians in their decision-making in relation to treatment effectiveness and considering the children’s perspective. Full article

Background: Numerous studies have established a link between adverse childhood experiences (ACEs) and the development of depression in later life. However, the interactive relationships between ACEs, depression, and chronic diseases are still not well understood. In this study, the aim was to investigate the impact of ACEs on depressive trajectories among middle-aged and elderly individuals in China, as well as to examine the mediating roles of chronic diseases in this association. Methods: Data were drawn from 6921 participants aged 45 and older, using the China Health and Retirement Longitudinal Study (CHARLS) data from 2011, 2013, 2015, and 2018, combined with the 2014 life history survey. Depressive symptom scores were assessed using the widely recognized CES-D-10 scale. The trajectories of depressive symptoms were identified via group-based trajectory modeling (GBTM). The association between ACEs and depressive trajectories was analyzed using multinomial logistic regression, and the KHB method was employed to test the mediating effects of different chronic diseases. Results: The age of the 6921 participants was 57.2 ± 8.0 years, with females comprising 53.9% and males 46.1%. We found that approximately 70% of Chinese middle-aged and older adults had experienced at least one ACE, and 4.8% had experienced four or more ACEs. The following four distinct trajectories of depressive symptoms were identified: continuing-low (N = 1897, 27.4%), continuing-low-to-middle (N = 2937, 42.4%), continuing-middle-to-high (N = 1649, 23.8%), and continuing-high (N = 438, 6.3%). Compared to individuals without ACEs, those with four or more ACEs had a significantly higher likelihood of following the continuing-low-to-middle trajectory (OR = 2.407, 95%CI: 1.633–3.550), the continuing-middle-to-high trajectory (OR = 7.458, 95%CI: 4.999–11.127), and the continuing-high trajectory (OR = 20.219, 95%CI: 12.115–33.744), rather than the continuing-low trajectory. Exposure to a greater number of ACEs was associated with an increased risk of following an adverse trajectory of depressive symptoms. Multiple chronic diseases significantly mediated the relationship between ACEs and depressive trajectories, with arthritis or rheumatism exerting the largest mediating effect, followed by digestive and respiratory diseases. Conclusions: These findings indicated that ACEs were associated with a higher risk of worse depressive symptom trajectories, with different chronic diseases mediating this relationship. Therefore, developing public measures to prevent ACEs can reduce the risk of chronic diseases and depression in middle-aged and elderly people. Additionally, strengthening the prevention and management of chronic diseases in individuals exposed to ACEs may further reduce their subsequent risk of depression. Full article

Dysbiosis of the gastrointestinal tract is the most common cause of disease in childhood and adulthood. The formation of the intestinal microbiome begins in utero, and composition modification during life depends mainly on various genetic, nutritional, and environmental factors. The main cause of intestinal dysbiosis is improper nutrition due to a short period of breastfeeding, insufficient intake of fresh fruits and vegetables, and/or consumption of a large amount of processed food. The benefits of a diet based on grains, legumes, fruits, and vegetables are reflected in reducing the risk of cancer, cardiovascular diseases, myocardial infarction, stroke, rheumatoid arthritis, high blood pressure, asthma, allergies, and kidney stones. Anaerobic fermentation of fibers produces short-chain fatty acids (SCFA) that have an anti-inflammatory role and great importance in shaping the intestinal microbiota. Factors associated with high fiber in a plant-based diet promote increased insulin sensitivity. Insulin and insulin-like growth factor 1 (IGF-I) act as promoters of most normal and pre-neoplastic tissues. Conclusion: A plant-based diet high in fiber prevents disease by creating metabolites in the gut that reduce oxidative stress. Full article

Background/Objectives: Juvenile idiopathic arthritis (JIA) is a chronic childhood disease that often persists into the reproductive years. JIA may impact long-term fertility due to the prolonged exposure to immunosuppressive therapies. Methods: A total of 35 adult JIA female patients of childbearing age and 20 age-matched healthy controls were studied to test their anti-Müllerian hormone (AMH) serum levels as a biomarker of ovarian reserve. Demographic characteristics, disease duration, previous and current treatments, disease activity (DAS44), and a health assessment questionnaire (HAQ) were recorded. Results: JIA patients had a mean age of 22.3 ± 2.9 years, a disease duration of 12.3 ± 6.1 years, and a DAS44 of 1.24 ± 0.61. No differences were found in AMH serum levels between JIA and controls (5.78 ± 2.37 ng/mL vs. 6.60 ± 2.68 ng/mL, respectively; p = 0.17). Among the patients, 22 (62.9%) were receiving a stable dose of methotrexate (MTX) and 19 (54.3%) a dose of TNFα inhibitors. No difference in AMH serum levels was observed between JIA patients who were or were not exposed to MTX (p = 0.29) or to TNFα inhibitors (p = 0.50). Conclusions: Ovarian reserve as assessed by AMH serum levels appears to be comparable between those with JIA and age-matched controls and does not appear to be influenced by disease characteristics or prior/concomitant exposure to immunosuppressive drugs. Full article

EBV infects more than 90% of people globally, causing lifelong infection. The phases of the EBV life cycle encompass primary infection, latency, and subsequent reactivation or lytic phase. The primary infection usually happens without noticeable symptoms, commonly in early life stages. If it manifests after childhood, it could culminate in infectious mononucleosis. Regarding potential late consequences, EBV is associated with multiple sclerosis, rheumatoid arthritis, chronic active EBV infection, lymphomas, and carcinomas. Previous reports that the lytic phase plays a negligible or merely secondary role in the oncogenesis of EBV-related tumors are steadily losing credibility. The right mechanisms through which the lytic cycle contributes to carcinogenesis are still unclear, but it is now recognized that lytic genes are expressed to some degree in different cancer-type cells, implicating their role here. The lytic infection is a persistent aspect of virus activity, continuously stimulating the immune system. EBV shows different strategies to modulate and avoid the immune system, which is thought to be a key factor in its ability to cause cancer. So, the principal goal of our review is to explore the EBV’s lytic phase contribution to oncogenesis. Full article

Feto-maternal microchimerism is the bidirectional transfer of cells through the placenta during pregnancy that can affect the health of both the mother and the offspring, even in childhood or adulthood. However, microchimerism seems to have different consequences in the mother, who already has a developed immune system, than in the fetus, which is vulnerable with immature defense mechanisms. Studies have shown that the presence of fetal microchimeric cells in the mother can be associated with reduced fetal growth, pre-eclampsia, miscarriage, premature birth, and the risk of autoimmune disease development in the future. However, some studies report that they may also play a positive role in the healing of maternal tissue, in cancer and cardiovascular disease. There are few studies in the literature regarding the role of maternal microchimeric cells in fetal autoimmunity. Even fewer have examined their association with the potential triggering of autoimmune diseases later in the offspring’s life. The objectives of this review were to elucidate the mechanisms underlying the potential association between maternal cells and autoimmune conditions in offspring. Based on our findings, several hypotheses have been proposed regarding possible mechanisms by which maternal cells may trigger autoimmunity. In Type 1 diabetes, maternal cells have been implicated in either attacking the offspring’s pancreatic β-cells, producing insulin, differentiating into endocrine and exocrine cells, or serving as markers of tissue damage. Additionally, several potential mechanisms have been suggested for the onset of neonatal lupus erythematosus. In this context, maternal cells may induce a graft-versus-host or host-versus-graft reaction in the offspring, function as effectors within tissues, or contribute to tissue healing. These cells have also been found to participate in inflammation and fibrosis processes, as well as differentiate into myocardial cells, potentially triggering an immune response. Moreover, the involvement of maternal microchimeric cells has been supported in conditions such as juvenile idiopathic inflammatory myopathies, Sjögren’s syndrome, systemic sclerosis, biliary atresia, and rheumatoid arthritis. Conversely, no association has been found between maternal cells and celiac disease in offspring. These findings suggest that the role of maternal cells in autoimmunity remains a controversial topic that warrants further investigation. Full article

Juvenile idiopathic arthritis (JIA) is a chronic arthritis of unknown cause that develops in patients younger than 16 years of age and persists for at least 6 weeks. It is an important cause of short- and long-term physical and mental impairments in children. The goal of treatment for JIA is remission. A T2T (treatment-to-target) has been proposed and practiced as a means of achieving remission. The method of evaluating the disease activity of JIA depends on the disease type. For systemic JIA, disease activity is determined by comprehensively considering joint findings, systemic inflammatory findings, changes in inflammatory and synovitis markers, imaging findings, and other factors. For articular JIA other than systemic JIA, the Juvenile Arthritis Disease Activity Score (JADAS-27) is used to evaluate disease activity. The CHAQ (Childhood Health Assessment Questionnaire) and the Japanese version of the modified Rankin Scale (mRS) are mainly used to assess the physical function and ADL. The CHAQ is a global standard assessment method with the advantage that it can be transitioned to the HAQ used in adults, making it useful for international comparisons. The mRS is used to classify the severity of JIA as a chronic disease, and is an indispensable evaluation method in the specific disease procedure in Japan. It is necessary to have pediatric-specific knowledge of growth and development and routine childhood immunizations and to consider transition support tailored to the patient’s situation. Ultimately, the goal is to foster the patient’s independence and to provide an uninterrupted follow-up in the adult care department. Continuous follow-up will be provided during the schooling (and later, employment) period, and the relationship with the patient will be tailored to their developmental stage. It is also important to understand and communicate the importance of contraception and the drugs that cannot be used during pregnancy. Full article

Objective: Adolescents with chronic rheumatic disease must increasingly take on more responsibility for disease management from parents as they transition from pediatric to adult care. Yet, there are limited resources to inform and support parents about transition. Here, we evaluate the impact of a Transition Toolkit, geared towards parents and adolescents, on transition readiness, and explore the potential impact of parent–adolescent communication. Methods: A prospective cohort study of youths aged 14–18 years old and their parents was performed. Participant demographics, disease characteristics, transition readiness scores (Transition-Q, max 100), and parent–adolescent communication scores (PACS, max 100) were collected at enrollment (when the Transition Toolkit was shared with adolescents and their parents. Generalized estimating equation (GEE) analyses determined the influence of the Toolkit on transition readiness and explored the role of parent–adolescent communication quality. Subgroup analyses were conducted by sex. Results: A total of 21 patients were included; 19 completed one post-intervention Transition-Q and 16 completed two. Transition-Q scores increased over time and the rate of increase doubled after the Toolkit was shared (β = 7.8, p < 0.05, and β = 15.5, p < 0.05, respectively). Conclusion: Transition readiness improved at each follow-up, the greatest increase was seen after the Toolkit was shared. Parent–adolescent communication quality did not appear to impact changes in transition readiness. Full article

Juvenile Idiopathic Arthritis (JIA), the leading childhood rheumatic condition, has a chronic course in which persistent disease activity leads to long-term consequences. In the era of biologic therapy and tailored treatment, precise disease activity assessment and aggressive intervention for high disease activity are crucial for improved outcomes. As inflammation is a fundamental aspect of JIA, evaluating it reflects disease severity. Recently, there has been growing interest in investigating cellular immune inflammation indices such as the neutrophil-to-lymphocyte ratio (NLR) and systemic immune inflammation index (SII) as measures of disease severity. The aim of this retrospective study was to explore the potential of the SII in reflecting both inflammation and disease severity in children with JIA. The study comprised 74 JIA patients and 50 healthy controls. The results reveal a notable increase in median SII values corresponding to disease severity, exhibiting strong correlations with traditional inflammatory markers, including CRP and ESR (ρ = 0.714, ρ = 0.661), as well as the JADAS10 score (ρ = 0.690). Multiple regression analysis revealed the SII to be independently associated with JADAS10. Furthermore, the SII accurately distinguished patients with high disease activity from other severity groups (AUC = 0.827, sensitivity 81.5%, specificity 66%). These findings suggest that integrating the SII as an additional measure holds potential for assessing disease activity in JIA. Full article

Carditis in childhood is a rare disease with several etiologies. We report a case of infant death due to pericarditis and myocarditis after the mRNA vaccine against COVID-19 (COVIDmRNAV). A 7-year-old male child received the first dose of the COVIDmRNAV and presented with monoarthritis and a fever non-responsive to oral antibiotics. The laboratory investigation showed signs of infection (leukocytosis, high levels of c-reactive protein). His condition rapidly deteriorated, and the patient died. The autopsy identified pericardial fibrin deposits, hemorrhagic areas in the myocardium, and normal valves. A diffuse intermyocardial inflammatory infiltrate composed of T CD8+ lymphocytes and histiocytes was identified. An antistreptolysin O (ASO) dosage showed high titers. The presence of arthritis, elevated ASO, and carditis fulfills the criteria for rheumatic fever. However, valve disease and Aschoff’s nodules, present in 90% of rheumatic carditis cases, were absent in this case. The temporal correlation with mRNA vaccination prompted its inclusion as one of the etiologies. In cases of myocardial damage related to COVID-19mRNAV, it appears to be related to the expression of exosomes and lipid nanoparticles, leading to a cytokine storm. The potential effects of the COVID-19mRNAV must be considered in the pathogenesis of this disease, whether as an etiology or a contributing factor to a previously initiated myocardial injury. Full article