Search Results (162)

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

Objective: The interactions between the central nervous system (CNS) and the immune system suggest that immune mechanisms may be effective in the pathogenesis of epilepsy and epileptic seizures. Although studies on the natural immune response and epilepsy are continuing, it is not yet clear whether the interaction of the current immune system is due to epilepsy itself or antiepileptic drugs (AEDs), since epileptic patients also use AEDs There are a limited number of studies that have reported an increased incidence of upper respiratory tract infections (URTIs) in patients during levetiracetam (LEV) treatment. Therefore, we aimed to report our experience regarding the effect of LEV monotherapy on the complete blood count (CBC), immunoglobulin (Ig) levels, and lymphocyte subgroups in the interictal period in children and adolescents with epilepsy. Methods: This study enrolled 31 children who presented with epilepsy and underwent LEV monotherapy for at least one year (patient group) and 43 healthy children (control group). The CBC parameters (hemoglobin (hb), lymphocytes, leukocytes, neutrophils, and platelets), Ig levels (IgA, IgM, IgG, and IgE), and lymphocyte subsets (CD3, CD4, CD8, CD4/CD8 ratio, CD19, CD56, NKT cells, and Treg cells) were measured and compared between the two groups. The patients were also investigated regarding the frequency and types of infections that they experienced in the first month and first year of the study, and these data were compared between the patient group and the control group. In addition, the same parameters and the frequency of infection were compared among the patient subgroups (focal and generalized seizures). Results: The results of the present study indicate that there were no significant differences in the CBC parameters, lymphocyte subsets, or Ig levels between the patient group and the control group. The comparison among the patient subgroups was similar; however, the CD4/CD8 ratio was lower in the patient subgroup with focal seizures. In addition, there were no significant differences in the frequency or type of infections experienced one month and one year of the study between the patient group and the control group, and likewise for the patient subgroups (focal and generalized seizures). Conclusions: The present study demonstrated that LEV monotherapy did not increase the incidence of infection, and there were no significant effects on the CBC or on the humoral or cellular immune system in epileptic children. These findings also suggest that the CD4/CD8 ratio among lymphocyte subgroups is lower in patients with focal seizures. However, the epilepsy subgroups had a relatively small sample size; therefore, further prospective studies involving a larger patient population are needed to establish the association between LEV monotherapy and lymphocyte subgroups in patients with epilepsy. Full article

In the context of IgE-mediated food allergies in children, the use of hypoallergenic foods may offer an appropriate solution for enabling informed dietary choices and reducing reactivity to allergenic foods. It is well established that certain foods can alter their allergenicity depending on the method of processing. As such, processed foods may serve both as an alternative dietary option and as a useful tool in oral immunotherapy for children with IgE-mediated food allergies. Nevertheless, an oral food challenge is always recommended when a pediatric allergist considers incorporating processed foods into a child’s diet. This review aims to explore the potential use of processed forms of the nine major food allergens in IgE-mediated food allergies, supporting pediatric allergists in partially liberalizing children’s diets and facilitating the development of tolerance. Full article

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder primarily affecting adults. The disease in pediatric age is unusual and preferentially affects adolescents. In contrast to adults, who commonly exhibit the involvement of multiple organs simultaneously or sequentially over time, young patients tend to present with a localized disease, typically affecting the orbits. Proptosis, ptosis, diplopia, and restricted eye movement may be observed in these patients. Symptoms are proteiform, and the disease is chronic and indolent with a relapsing–remitting course. Diagnostic criteria have been developed for adults, which may not fully capture the pediatric disease phenotype. If untreated or poorly managed, IgG4-RD can lead to progressive fibrosis and scarring of affected organs, potentially causing irreversible damage. We conducted a narrative review using the IMRAD approach, presenting a nonsystematic analysis of the literature on pediatric IgG4-RD. Original papers, case reports/series, and relevant reviews in English were selected from PubMed, EMBASE, and Web of Science up to January 2024. Keywords included “IgG4-Related Disease” and “pediatric” and, additionally, we presented two original pediatric cases. Our purpose is to offer an overview of IgG4-RD manifestations, and challenges in diagnosing and managing this rare condition in children. Full article

Bronchial asthma is a respiratory chronic disorder frequently affecting youth. It is characterized by a huge personal, familial, and societal impact. Biological and cellular studies in recent decades define asthma as a chronic inflammatory disease of the airways. Inflammation represents the major pathogenetic factor underlying the airflow obstruction and bronchial hyperactivity that peculiarly characterize asthma. When bronchial asthma is diagnosed after too long a delay and treated too late or inadequately, structural remodeling of the whole bronchial wall can occur and lead to persistent limitations in lung function and quality of life. Although adult asthma and asthma in youth may be recognized by some common pathogenetic mechanisms, there are some important differences that justify a peculiar approach to asthma in young individuals, worth particular attention. Anatomical, physiological, social, and emotional aspects that differentiate asthma in children and adolescence are briefly revised and highlighted in the present review. Full article

Background/Objectives: Recurring infections in children with allergies pose significant clinical challenges, with these conditions often exacerbating each other through complex immunological interactions. This narrative review examines the connection between recurring infections and allergic conditions in pediatric patients, focusing on how immune system dysfunction influences infection susceptibility in respiratory allergies. Methods: A comprehensive literature search across PubMed, Web of Science, and SciELO databases was conducted from January 2014 to May 2024. Studies involving children and adolescents up to 18 years old with diagnosed respiratory allergies were included, while reviews, opinion pieces, case reports, and studies not addressing immune–infection interactions were excluded. Results: Analysis reveals significant immune dysfunction in allergic children, affecting both innate and adaptive immunity components. Children with allergic rhinitis and asthma demonstrate decreased interferon-gamma production, increasing vulnerability to viral infections (particularly rhinovirus) and bacterial infections such as Mycoplasma pneumoniae. Rhinovirus represents the most common pathogen, present in 75% of asthma exacerbations. Atopic children exhibit markedly higher bacterial infection rates, with 27.1% showing Mycoplasma pneumoniae involvement versus 4.9% in non-atopic children. Conclusions: Recurring infections in allergic pediatric patients result from significant immune dysfunction involving altered cytokine production and immune cell function. These complex interactions highlight the need for targeted therapeutic approaches that enhance immune responses and reduce infection risks. Future research should focus on identifying specific biomarkers and immune mechanisms for developing more effective interventions. Full article

Objective: to seek for predictors of inactive disease (ID) in juvenile idiopathic arthritis (JIA) with artificial intelligence. Methods: The clinical charts of patients seen within 6 months after disease onset between 2007 and 2019 and with follow-up visits at 6, 12, 18, and 24 months were reviewed retrospectively. Sixty-eight potential predictors were recorded at each visit. The primary endpoint was ID at 24 months by 2004 Wallace criteria. Data obtained from diverse combinations of visits were examined to identify the best forecasting model. After pre-processing, the cohort was divided into training (50%) and testing (50%) cohorts. Multivariate time series forecasting, coupled with the Random Forest method, was used to train the machine learning (ML) forecasting model. Predictive performance was assessed through the Matthews correlation coefficient (MCC). Results: A total of 414 patients were included. The best performance in predicting ID at 24 months in the training cohort was provided by the 0–12 months interval (MCC = 0.68). In the testing cohort, the same ML model confirmed a high forecasting performance (MCC = 0.65). Assessment of feature importance and impact analysis showed that the most relevant predictor of ID was the physician’s global assessment (PhGA), followed by the count of active joints (AJC). Conclusions: PhGA and AJC values over the first 12 months were the strongest predictors of ID at 24 months. This finding highlights the importance of regular quantitative assessment of disease activity by the caring physician in monitoring the course of the patient toward achievement of complete disease quiescence. Full article

Allergic diseases share a type 2 immune reaction and elevated oxidative stress, contributing to disease pathogenesis and exacerbations. Vitamin C (ascorbic acid), a fundamental exogenous antioxidant, has been hypothesized to attenuate these pathological mechanisms. This narrative review critically examined the most recent evidence concerning the role of vitamin C in preventing and managing allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis. This narrative review consisted of three steps: conducting the search, reviewing abstracts and full texts, and discussing results. For this reason, we consulted the PubMed database to detect the pertinence of studies according to the review’s conduct. The final search ended in March 2025 and included English-language-based international articles, online reports, and electronic books. The keywords “vitamin C and allergic disease” and “vitamin C and immune system” were used. After the complete search, we read the abstracts to ensure that they concerned the topic of interest. Recent evidence suggests a protective role for vitamin C in asthma, with several studies reporting reduced oxidative stress markers, improved lung function, and decreased airway inflammation following regular intake or supplementation. Higher dietary vitamin C intake correlates with lower asthma prevalence and severity, particularly in pediatric populations. Conversely, the findings regarding allergic rhinitis and atopic dermatitis are heterogeneous. While topical ascorbic acid derivatives show promise in atopic dermatitis models, oral vitamin C intake does not appear to affect allergic rhinitis or dermatitis risk significantly. Vitamin C demonstrates potential as an add-on therapy in asthma management by attenuating oxidative stress and type 2 respiratory inflammation. However, its role in allergic rhinitis and atopic dermatitis remains less clear. Further multicentric, well-designed clinical trials are necessary to establish definitive guidelines for vitamin C supplementation in allergic disease management. Full article

Background: The pathophysiology of non-IgE-mediated cow’s milk allergy is mostly unknown. Previous studies suggested a mechanism mediated by T cells, but this was not confirmed in subsequent studies. The aim of this study was to investigate the immunological mechanisms, especially the role of regulatory T cells (Tregs), in the pathophysiology of allergic proctocolitis (FPIAP). Methods: A prospective observational study was conducted on infants with FPIAP and a control group of healthy infants with similar ages. The main variables were lymphocyte populations, included Tregs, which were extracted from peripheral blood and processed immediately by flow cytometry at two time points: in the acute phase (“T0”) and after clinical resolution (“Tres”). Results: A total of 32 patients with FPIAP and 10 healthy infants were enrolled. There was a higher T-CD4 memory cell count, increased numbers of regulatory B cells and a higher percentage of Tregs (p < 0.01) in patients with acute FPIAP in contrast to the healthy group. The levels of granulocytes (mainly eosinophils), dendritic cells (mDC2) and NK16+56- cells were also significantly higher in the FPIAP group. NK16+56- cells and the number of granulocytes appeared to be the best markers for distinguishing between the healthy and FPIAP infants based on the ROC curves. Conclusions: FPIAP does not appear to have an immune mechanism mediated by T cells, but it may be associated with innate immunity responses characterized by an increase in NK16+56- cells, eosinophils and dendritic cells. These cells could be evaluated in future studies as possible markers of non-IgE-mediated cow’s milk protein allergy. Full article

Ataxia-telangiectasia is a rare autosomal recessive disorder that is difficult to diagnose due to its unpredictable presentation. It is characterized by cerebellar degeneration, telangiectasias, immunodeficiency, frequent pulmonary infections, and tumors. Immune system abnormalities manifest as disruptions in both cellular and humoral immunity. The most common findings include decreased levels of immunoglobulin classes (IgA, IgM, IgG, and IgG subclasses) and a reduced number of T and B lymphocytes. A four-year-old girl was initially evaluated and treated for skin lesions that presented as crusts spreading across her body. She was monitored by a pulmonologist due to frequent bronchial obstructions. Over time, she developed bilateral scleral telangiectasia, saccadic eye movements, and impaired convergence. Her gait was wide-based and unstable, with truncal ataxia and a positive Romberg sign. Laboratory tests revealed decreased immunoglobulin G levels, subclass IgG4 levels, elevated alpha-fetoprotein, and a reduced number of T and B lymphocytes. Brain magnetic resonance imaging showed cerebellar atrophy. Whole-exome sequencing identified heterozygous variants c.1564-165del, p.(Glu5221lefsTer43), and c.7630-2A>C in the serine/threonine-protein kinase ATM (ataxia-telangiectasia mutated) gene, confirming the diagnosis of ataxia-telangiectasia. Following diagnosis, treatment with intravenous immunoglobulin replacement was initiated along with infection prevention and management. The goal of this case report is to raise awareness of the atypical initial presentation that may lead to a diagnostic delay. We emphasize the importance of considering ataxia-telangiectasia in the differential diagnosis, even when classical neurological signs are not yet evident. Full article

Background: Idiopathic histaminergic angioedema (IH-AAE) is a pathological entity poorly described in the literature. It overlaps with some forms of chronic urticaria, especially in pediatrics. Objective: This study is a descriptive analysis of this form of angioedema’s natural history and prognosis. The aim is to describe long-term data about the course of this clinical entity, including clinical presentation, recurrence, and response to therapy, emphasizing follow-up and outcome. Methods: We performed a retrospective monocentric descriptive study at the Allergy Unit, Department of Pediatrics of the Institute for Maternal and Child Health of Trieste, Italy. We selected pediatric patients (0–18 years old) visiting the outpatient clinic from January 2010 to December 2020 who received a diagnosis of IH-AAE. We analyzed the disease recurrence, the remission rate, the time and frequency of recurrences, and the body sites involved. Results: The median follow-up was 57 months. Among the 36 individuals examined at follow-up, 9 (25%) still had episodes of angioedema, while 27 (75%) reported the absence of attacks. Disease remission was established in 24 patients (66.6%). The median remission time was 13 months (IQR: 7–28). When comparing AE recurrence at onset and follow-up, in all children, the number of episodes decreased (in 4/9 patients) or remained unchanged over time (in 5/9 patients). Moreover, within this group, AE recurrence was recorded as high, intermediate, and low, respectively, in one (11.1%), two (22.2%), and six patients (66.7%). The median number of monthly episodes was one (IQR: 0.2–3), and eight was the maximum value. The initial recurrence of AE attacks has no impact on the time and rate of remission (p = 0.56). According to these data, 36% of the patients will go into remission in 1 year, 54% in 2 years, and 71% in 6.5 years, while 14% of the children will still present with AE after 8 years of disease. Conclusions: IH-AAE is a benign and self-limiting condition that can sometimes last several years. Over time, the number of episodes per month decreases or, at most, remains unchanged. No patients reported disease worsening. The frequency of attacks at onset does not correlate with the possibility of recovery or the remission time. Full article

Background: Dried ivy leaf extract EA 575^® (Prospan^®) is commonly used to treat coughs and may help reduce inappropriate antibiotic use for the common cold. This retrospective study investigated whether prescribing EA 575 is associated with reduced subsequent antibiotic use in children and adolescents with the common cold. Repeated EA 575 prescriptions were also analyzed to estimate treatment satisfaction. Methods: Data were sourced from the IQVIA Disease Analyzer database, including patients under 18 diagnosed with a common cold and prescribed either EA 575 or antibiotics between 2017 and 2020 (index date). Propensity score matching controlled for confounding factors. Antibiotic prescriptions were assessed 4–30 and 31–365 days after the index date, along with bacterial infections 4–40 days post-index. Repeated EA 575 prescriptions 2–5 years post-index were analyzed as a proxy for treatment satisfaction. Results: Overall, 10,390 children and adolescents were included in each matched cohort. Compared to antibiotics, EA 575 prescriptions were associated with significantly lower odds of antibiotic use 4–30 days (OR: 0.56; 95% CI: 0.49–0.64; p < 0.001) and 31–365 days (OR: 0.58; 95% CI: 0.54–0.62; p < 0.001) after the index date. The odds of bacterial infection 4–30 days after EA 575 prescription were also lower (OR: 0.67; 95% CI: 0.45–0.99; p = 0.047). Of the 42,677 patients in the EA 575 analysis, 50.5% had at least one repeated prescription, with the highest rates among children aged 0–2 years (54.7%) and the lowest in those aged 13–17 years (19.9%). Conclusions: EA 575 prescription was associated with reduced subsequent antibiotic use in children and adolescents with common colds. Frequent repeated prescription rates emphasize the therapeutic value of EA 575 as a treatment option for cold symptoms, especially in younger children. Full article

Background: Lymphopenia is associated with disease activity in adult patients with systemic lupus erythematosus (SLE), but no similar studies exist among children. Furthermore, lymphopenia has only been used as a parameter of disease activity in the SLE disease activity index (SLEDAI), but not as an independent marker. Objectives: This study aimed to ascertain lymphopenia as an independent marker related to disease activity in children with SLE. Methods: This was a retrospective cohort study on patients newly diagnosed with SLE. The data were collected from January 2009 to March 2017, including clinical manifestations, complete blood counts, anti-dsDNA, and Mexican-SLEDAI (MEX-SLEDAI) scores. Statistical analysis was performed using the Chi-square test, Student’s t-test, and ROC curve analysis. Results: A total of 103 patients, aged from 12 to 18 years, participated in the study. Of these, 58 patients (56.3%) exhibited lymphopenia. The most commonly observed clinical manifestations in the lymphopenia group included nephritis (72.4%), hypertension (24.1%), and leukopenia (36.2%), with p < 0.05. Furthermore, neuropsychiatric SLE was found exclusively in the lymphopenia group. A negative correlation was observed between lymphocyte counts and anti-dsDNA levels (r = −0.24), as well as between lymphocyte counts and the MEX-SLEDAI score (r = −0.63, with p < 0.05). The receiver operating characteristic (ROC) curve indicated that a lymphocyte count with a cut-off point of ≤1738/mm³ is significant for predicting anti-dsDNA reactivity. Conclusions: Lymphopenia is significantly correlated with higher anti-dsDNA levels and increased disease activity, potentially serving as an independent marker of disease activity in children with SLE. However, further research is needed. Full article

Background: FIRES is a rare and catastrophic presentation of a de novo refractory status epilepticus (RSE) in healthy individuals following mild febrile illness. It carries a high burden of morbidity and an estimated mortality of 12% in children. In over half of patients, an underlying cause is not discovered (cryptogenic FIRES). The theory that post-infectious inflammation promotes aberrant neuronal excitation has led to the use of immunomodulatory therapies as treatment for FIRES. High-dose glucocorticoids and intravenous immunoglobulin (IVIG) are used as first-line therapies but are ineffective in most cases. A comprehensive initial evaluation is critical in directing second-line therapies; however, an autoimmune and inflammatory workup is seldom completed prior to treatment. Despite recent trends toward using cytokine-directed therapies, outcomes remain poor. Methods: This single-institution retrospective case series describes three cases of FIRES in similarly aged children. Each patient experienced super-refractory status epilepticus (SRSE) resistant to first-line systemic immunotherapy (SIT). The novel use of baricitinib, a non-selective JAK inhibitor, proved effective for one patient, while IL-1 and IL-6 inhibition were effective in the other two. All patients suffered moderate-to-severe neurologic and cognitive impairment at the time of discharge. Conclusions: FIRES is a poorly understood catastrophic presentation of refractory status epilepticus (RSE) requiring a multimodal approach to treatment. Cytokine profiling can be helpful in identifying cryptogenic cases from those with an underlying cause if conducted early in the clinical course. The early use of second-line immunomodulatory therapies may aid in decreasing neuroinflammation and improve outcomes. Full article