Search Results (199)

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) represents a group of rare systemic autoimmune disorders marked by inflammation and damage to small- and medium-sized blood vessels. The clinical presentation of AAV is highly variable, ranging from isolated organ involvement to severe, life-threatening multisystem disease, posing significant challenges in diagnosis, treatment, and prognosis. Objective: To demonstrate the clinical heterogeneity and different outcomes in three pediatric cases of ANCA-positive disease and emphasize the importance of integrating clinical findings with laboratory and imaging investigations for accurate diagnosis. Methods: We present three pediatric patients (ages 12–15 years) with ANCA-positive results but distinct clinical presentations, evaluated at the Children’s Emergency Hospital “Louis Turcanu”, Timisoara, between 2020 and 2024. All cases were investigated according to EULAR/PRINTO/PReS criteria for pediatric vasculitis. Results: Case 1 (PR3-ANCA positive) developed severe multi-organ involvement, including granulomatosis with polyangiitis (GPA) with pulmonary hemorrhage, pericarditis, thrombotic events, and renal impairment, requiring intensive immunosuppression with cyclophosphamide, rituximab, and mycophenolate mofetil, ultimately developing chronic kidney disease stage 3a. Case 2 (BPI-ANCA positive) presented with purpuric lesions and painless joint swelling, responding favorably to corticosteroid therapy with subsequent remission. Case 3 (MPO-ANCA) manifested as polyarticular arthritis without other organ involvement and was ultimately diagnosed as seronegative juvenile idiopathic arthritis (JIA), achieving complete remission with adalimumab therapy. Conclusions: This case series highlights the diverse clinical and biological features of ANCA-positive conditions in children, emphasizing that ANCA positivity requires careful clinical correlation as it may indicate true vasculitis requiring aggressive treatment or alternative diagnoses such as JIA with incidental ANCA positivity. Tailored therapeutic strategies based on clinical presentation and continued research are essential to improve patient outcomes. Full article

Background/Objectives: We aimed to evaluate the etiologic distribution of markedly elevated IgE (≥2000 IU/mL) and the association of parasitic infections with longitudinal IgE dynamics and National Institutes of Health Hyper-IgE Syndrome (NIH-HIES) score trajectories in pediatric patients. Methods: We retrospectively enrolled 127 pediatric patients with IgE ≥2000 IU/mL and ≥1 year of longitudinal follow-up at a tertiary allergy clinic (2019–2024). The primary outcome was the IgE reduction percentage difference between parasitic and non-parasitic groups. Results: Atopic sensitization was identified in 81.0% of tested patients; genetic evaluation was performed in 40 patients (31.5%), with confirmed IEI in one patient (0.8% of the cohort; 2.5% of those evaluated). Parasitic infections were present in 24.4% of patients (n = 31; intestinal parasites 15.7%, scabies 8.7%, hydatid cyst 1.6%; two patients had concurrent intestinal parasitosis and scabies). Median IgE reduction was 63.8% vs. 27.0% in parasitic versus non-parasitic groups (p < 0.001), persisting after multivariable adjustment (p < 0.001). Parasitic infection independently predicted IgE normalization below 2000 IU/mL (OR = 8.26; 95% CI: 2.76–24.68; p < 0.001). All three NIH-HIES inflammatory components (IgE, eosinophilia, eczema) regressed more often in the parasitic group (all p ≤ 0.01); no patient reached the ≥40-point HIES threshold. Conclusions: Parasitic infections produce a clinical phenotype overlapping with hyper-IgE syndrome, constituting a reversible phenocopy of primary immune dysregulation. In populations with substantial parasitic prevalence, parasitological evaluation may be a useful consideration in children with markedly elevated IgE and indeterminate clinical scores; however, this approach should complement rather than replace comprehensive clinical assessment. Full article

Objectives: Lupus nephritis (LN) is a severe manifestation of pediatric systemic lupus erythematosus (SLE) requiring accurate disease activity assessment. This study evaluated the association of the Systemic Inflammation Response Index (SIRI) and the Systemic Immune-Inflammation Index (SII) with disease activity in children with LN. Methods: In this cross-sectional study, 52 children with LN aged 1 month to 18 years treated at Dr. Hasan Sadikin General Hospital, Indonesia, were included. SIRI and SII were calculated from complete blood counts, and disease activity was assessed using the Mexican Modification of the SLE Disease Activity Index (Mex-SLEDAI). Correlations were analyzed using Spearman’s test. Results: Median SIRI and SII values were 1511 and 789,544, respectively, with a median Mex-SLEDAI score of 7. SIRI showed a moderate positive correlation with disease activity (r = 0.443; p < 0.001), and SII also showed a significant positive correlation (r = 0.390; p = 0.004). Both indices increased with higher LN activity. Conclusions: SIRI and SII were significantly associated with disease activity in pediatric LN, with SIRI yielding a numerically higher correlation coefficient, though this difference was not formally compared. These indices may serve as simple, non-invasive biomarkers for assessing inflammatory activity in children with lupus nephritis. Full article

Background/Objectives: The co-occurrence of asthma and obesity presents a significant clinical challenge, but the underlying mechanisms remain unclear. Reduced adiponectin and vitamin D levels have been associated with both conditions, suggesting that their potential modulatory roles warrant further investigation. This study aimed to evaluate whether vitamin D and adiponectin levels differ among pediatric groups defined by their asthma and obesity status, to better characterize the metabolic and inflammatory profile of the obesityasthma phenotype. Methods: A total of 120 participants aged 6–18 were enrolled and categorized into four groups: Asthma (n = 30), Obesity (n = 30), Asthma + Obesity (n = 30), and Control group (n = 30). All participants underwent lung function testing, anthropometric assessment and measurement of fraction of exhaled nitric oxide (FeNO). Participants were further categorized according to BMI percentiles. Adiponectin levels were measured using ELISA, while vitamin D levels were detected using HPLC. Results: Vitamin D levels and lung function parameters did not differ across groups, although deficiency was most prevalent in the obesity group. FeNO was elevated in asthmatics relative to obese children (p = 0.038) and in obese asthmatics compared with both controls (p = 0.040) and obese children (p = 0.021). Adiponectin levels were lower in obese asthmatic children compared to the controls (p = 0.024). A similar difference was observed between the controls and obese asthmatics among children with low vitamin D levels (p = 0.014). Conclusions: The dominant mechanisms underlying the obesity–asthma phenotype remain unclear; however, our findings indicate a link between adiponectin dysregulation and heightened airway inflammation, as evidenced by increased FeNO levels, though the precise pathways involved are still not well-understood. The role of vitamin D appears less consistent. These results highlight the need for further research to clarify the interplay between metabolic and inflammatory pathways and to support more personalized management strategies in children with obesity-related asthma. Full article

Background: Studies on the clinical presentation of eosinophilic esophagitis and its outcome in children in the Middle East and North African region are scarce. The aim of this 10-year retrospective study was to describe the common clinical manifestations, endoscopic and histological findings, and the response to medication and dietary intervention in children and adolescents with eosinophilic esophagitis. Methods: This study was a retrospective chart review of patients aged 6 months to 18 years who attended the Pediatric Gastroenterology clinic at the American University of Beirut Medical Center between 1 January 2013 and 30 June 2023 and who were diagnosed with eosinophilic esophagitis. Results: A total of 15 patients met the inclusion criteria. The median age at diagnosis was 9 years. Male patients accounted for 73% of our cohort. The most frequent presenting symptoms were dysphagia (80%) and choking (47%). The esophagus appeared normal in 33% of subjects despite histologic confirmation of disease, highlighting the importance of routine biopsies. Adherence to therapy was variable, with 73% of subjects reporting symptom improvement following initial therapy, even in cases where histology remained active. This pattern suggests that symptomatic improvement alone may not reliably reflect disease control and underscores the importance of objective monitoring through follow-up biopsy. Conclusions: The recognition of manifestations of eosinophilic esophagitis in children, early diagnosis, and strict adherence to the diet and medication are essential to prevent long-term complications. In a resource-constrained country like Lebanon, the management remains challenging in view of the burden of dietary restrictions and high cost of procedures and biologics. Socioeconomic feasibility and long-term adherence to diet and medication is as critical as pharmacologic efficacy in determining outcomes in pediatric patients. Full article

Background: Micro- and nanoplastics (MNPs) are widespread environmental contaminants with growing evidence linking them to adverse health effects, including progression and worsening of allergic diseases. As allergies are rapidly increasing among youth (affecting almost 30% of children), this demographic represents a vulnerable population facing emerging environmental threats. Since no prior study has investigated MNP risks perceptions in an allergic population, this study aimed to assess public awareness and risk perception of MNP in Croatian youth, focusing on the influence of urbanicity, education, and allergy status. Methods: A total of 1155 participants (aged 6–18 years) were recruited from three Croatian regions as part of the EU Horizon 2020 IMPTOX and the Horizon Europe EDIAQI studies. Allergy status was determined via skin prick tests (SPT), and standardized questionnaires were used to collect data on MNP awareness and perception. Results: Awareness was significantly higher among allergic individuals (89.5% vs. non-allergic 79%, FDR p value= 0.036) and those with university-level education (88.3% vs. elementary 63.3%, FDR p value = 0.050). Allergic participants were also more concerned about food contamination by MNPs (87.7%) compared to non-allergic individuals (79.2%), FDR p value = 0.005). Media and social media were the primary sources of information regarding MNPs (FDR p value = 0.026). Conclusions: Education and allergy status are the strongest predictors of MNP awareness and related risk perceptions in the Croatian population. Targeted public health communication and educational strategies are needed to translate basic awareness into informed behavioral and policy engagement. Full article

Background/Objectives: Severe infusion-related reactions to rituximab are rare; we aim to extend our knowledge about them in children, focusing on rituximab-induced serum sickness (RISS) and anaphylaxis. Methods: We conducted a monocentric retrospective study on children and adolescents who received rituximab. Patients were defined as having RISS if they had fever and at least rash and/or arthralgia, 1 to 30 days following infusion, and without another diagnosis to explain symptoms. Anaphylaxis was defined according to the diagnostic criteria proposed by the World Allergy Organization. Results: 1534 rituximab infusions in 391 patients were analyzed. Seven patients developed RISS; all received rituximab for an autoimmune disease, including four for immune thrombocytopenia (ITP). Six patients had fever, rash, and arthralgia. C-reactive protein or sedimentation rate was increased in all patients, and complement was decreased in 83%. Evolution was favorable within a few days with corticosteroids and/or intravenous immunoglobulins. Rituximab was reinfused in one patient, which resulted in an immediate anaphylactoid reaction. Lower doses of rituximab were less likely to induce RISS. RISS was associated with a greater chance of achieving ITP remission. Seven patients developed anaphylaxis; five successfully received further infusions using desensitization protocols. Conclusions: RISS in children is a severe complication of rituximab infusion. Our study suggests that it may be more frequent in individuals treated for autoimmune conditions, especially ITP. The classical triad of fever, rash, and arthralgia appeared to be frequently present, and biological inflammation and/or low complement can further support the diagnosis. In contrast to anaphylaxis, where rituximab may be safely rechallenged upon desensitization protocol, treatment alternatives should be pursued in patients experiencing RISS, given the higher risk of severe RISS recurrence. Full article

Background: Evidence linking adenoid hypertrophy (AH) and atopy is conflicting. We examined whether Cassano-graded AH severity is more closely associated with inflammatory markers than with IgE-mediated sensitization. Methods: We retrospectively included children aged 3–12 years diagnosed with AH between December 2022 and December 2025. AH was graded according to the Cassano classification and dichotomized as advanced AH (Stage III–IV). Atopic features were evaluated separately as clinical atopy, IgE-mediated sensitization, elevated total IgE, and eosinophilia. Multivariable logistic regression analyses were performed to assess factors associated with clinical atopy, sensitization, and advanced AH. Results: Among 426 children, clinical atopy was present in 28.2%, sensitization in 23.0%, elevated total IgE in 16.4%, and eosinophilia in 27.7%; 39.2% had advanced AH. In multivariable analysis, clinical atopy was independently associated with family history of atopy (aOR 13.9; 95% CI 7.9–24.4), elevated total IgE (aOR 3.86; 95% CI 2.10–7.08), and passive smoking exposure (aOR 1.73; 95% CI 1.07–2.79). Sensitization was independently associated only with family history of atopy (aOR 4.99; 95% CI 1.99–12.53). Advanced AH was independently associated only with eosinophilia (aOR 2.07; 95% CI 1.30–3.29). Conclusions: AH severity was associated with eosinophilia rather than classical IgE-mediated sensitization. Assessment of eosinophilia may aid routine severity evaluation in children with AH. Full article

Background/Objectives: Familial Mediterranean fever (FMF) is the most common periodic fever syndrome worldwide, and persistent subclinical inflammation has been reported in 10–20% of cases during attack-free periods. Although the immunomodulatory effects of vitamin D, vitamin B12 and folate have been investigated in various conditions, data on their relationship with subclinical inflammation in FMF patients remain limited. This study aimed to evaluate the association between micronutrient levels and subclinical inflammation in pediatric FMF. Methods: Children aged 2–18 years with an FMF diagnosis of more than two years, receiving regular colchicine therapy, and attack-free for at least two months were included. Patients with other autoinflammatory diseases, colchicine resistance, concomitant renal disease, active infection, or inadequate follow-up were excluded. Demographic, clinical, genetic, and biochemical data were analyzed. Results: A total of 253 patients were included, with a median age of 14 years (range, 3–18), and 133 (52.6%) were female. Persistent subclinical inflammation was observed in 31 patients (12.3%). Genetic analysis revealed homozygous M694V mutations in 71 patients (28%). Median vitamin levels were as follows: vitamin D 17.3 ng/mL (IQR 10.6–27.1), vitamin B12 288 pg/mL (IQR 214–367), and folate 6.4 ng/mL (IQR 4.8–7.6). Comparison between patients with and without subclinical inflammation showed no significant differences in micronutrient levels. Conclusions: Although micronutrients have been reported to play immunomodulatory roles, we did not observe significant association between vitamin levels and subclinical inflammation in pediatric FMF patients in our study. Full article

Vernal keratoconjunctivitis (VKC) represents far more than a typical allergic eye disease. It is a distinct and often underestimated chronic inflammatory condition that primarily affects children during critical stages of physical and emotional development. Though frequently grouped with seasonal allergic conjunctivitis, VKC differs significantly in its immunopathology, clinical presentation, and long-term implications. Its intense ocular symptoms and its potential for corneal damage and substantial psychosocial burden require, rather than symptom control, coordinated and multidisciplinary management. This narrative review explores VKC from every angle, with a particular focus on its implications for pediatric care. VKC, in fact, represents a genuine clinical challenge: as its symptoms can mimic milder forms of conjunctivitis, its course is often unpredictable, and its treatment requires balancing efficacy and safety in vulnerable age groups. We examined the immunological mechanisms that make it a model of localized Th2 inflammation, the diagnostic pitfalls that delay recognition, and the evolving treatment landscape, from conventional therapies like cyclosporine A and tacrolimus to innovative agents such as omalizumab and dupilumab. We also highlighted the role of emerging biomarkers, the influence of environmental and microbiome factors, and the urgent need for standardized care pathways. As research continues to expand our understanding, VKC is emerging as a prime example of how personalized medicine and translational science can intersect to address complex immune-mediated diseases in children. For the ones treating pediatric allergic disorders, VKC is no longer a rare curiosity: it is a clinical challenge worth understanding deeply. Full article

Background/Objectives: Food allergy (FA) is a substantial health burden in children. FA is often associated with malnutrition and malabsorption, due to restrictive food avoidance diets, which can significantly impair the patient’s and their family’s quality of life. To this date, population-based data combining sensitization and clinical allergy remain limited. This study aimed to assess the patterns of sensitization rates to food and food allergy prevalence rates in Croatian children and to evaluate differences according to age, sex, and region of origin. Materials and Methods: In this cross-sectional study, 1948 preschool and school-aged children from three Croatian regions (Zagreb, Dalmatia, and Slavonia) were included. Participants underwent skin prick testing to common food and inhalant allergens. Data on personal and family medical history were collected using questionnaires and medical records. FA prevalence was evaluated using self-reported data in school-aged children and physician-diagnosed FA data in preschool children. Results: Overall, 41% of participants were sensitized to at least one allergen, while 13% were sensitized to at least one food allergen. Tree nuts—particularly hazelnut—were the most common food-derived sensitizers, followed by hen’s egg, cow’s milk, and fish. Boys exhibited higher total sensitization rates than girls (44.2% vs. 37.5%; p = 0.001), higher food allergen sensitization rates (14.7% vs. 11.4%; p = 0.037), and higher total polysensitization rates (30.7% vs. 22.6%; p < 0.001). School-aged children showed higher total sensitization (44.8% vs. 33.4%; p < 0.001) and polysensitization rates (29.8% vs. 20.5%; p < 0.001) than preschool children, while sensitization to food allergens did not differ between age groups. Food allergen sensitization rates differed by region, with higher prevalence in Zagreb compared with Dalmatia and Slavonia (p = 0.0055), whereas total sensitization rates did not differ regionally. The agreement between sensitization and self-reported FA among school-aged children was low (κ = 0.22; p < 0.001), as was the agreement between sensitization and physician-diagnosed FA in preschool children (κ = 0.13; p < 0.001), despite high specificity in both analyses (95% and 99%%, respectively). Conclusions: Allergic sensitization is common among Croatian children, but it poorly predicts clinically relevant food allergy. These findings highlight the multifactorial nature of allergen sensitization in children and emphasize the need for improvements in diagnostic pathways, targeted prevention strategies, and continued surveillance to optimize allergy prevention and management in children. Full article

Background: Pediatric bronchoscopy and bronchoalveolar lavage (BAL) are valuable procedures, used by pediatric pulmonologists in a wide variety of clinical scenarios. Reports of indications for BAL include investigations of infectious processes, for unusual or poorly responsive pneumonia, and non-infections reasons, including interstitial lung disease and aspiration syndromes. BAL in pediatric asthma is occasionally done in severe and uncontrolled asthma, to rule out co-morbid conditions or to investigate asthma phenotypes. We report here the results of BAL in young children with global pre-BAL diagnoses, with comprehensive analysis of the BAL cellularity and culture results, and with a post hoc review by an allergist. The results of BAL in children with enigmatic pulmonary processes were compared to the expected BAL cellularity in normal children, obtained by an expanded historical mini review. Methods: The initial objective was to perform a mini review of the collective published data for normal/control children with BAL differential cell counts with the purpose of using the results to compare normals to the information obtained on the symptomatic children with BAL results from pulmonologists in our combined allergy–pulmonary division. The exploratory study group was children 0–6 years of age who underwent a BAL from 2000 to 2024 at an academic pulmonary-allergy division. The children had presumptive diagnoses requiring investigation, including the most common diagnoses of asthma, chronic cough, aspiration, or refractory bronchitis, and in this post hoc protocol only the diagnoses provided on the pre- and/or post-operative summary by the divisional pulmonologist(s) performing the BAL were used in the post hoc analysis. Secondarily, the operative day pre- and/or post-lavage diagnoses were used to divide the children into groups (based on operative day diagnoses) to stratify their lavage results, based on eosinophils, neutrophils, culture positivity and lipid-laden macrophages. Normative data collected from the literature was used as the historically expected results for the BAL group(s) analysis. Results: A mini review of BAL cellularity across 25+ years of literature was performed to establish normative data for our subsequent analysis. Both eosinophils and neutrophils are low or absent in normal children based on the comprehensive literature review. As a part of a larger cohort of 500 children ages 0–20 years, 317 children ages 0–6 were selected for review. The protocol was approved by the University Institutional Review Board. Using the mini review as reference, we found that eosinophil counts of one or more were recovered in over 20% of all children, regardless of bronchoscopy indication. Neutrophilia > 50% of cells and/or bacteria colony counts > 100,000 organisms were also frequent findings (>50 percent of the children). As a separate observation, lipid-laden macrophages did not isolate to aspiration indications for the bronchoscopy and lavage. Conclusions: An updated mini review of the cellularity expected in control children provided a context to the findings in our studied exploratory sample population. There was a high recovery of neutrophils coupled with culture positivity found across all children undergoing BAL. Eosinophils > 1 were present in up to 25% with a pre-lavage asthmatic symptom indication, but almost an equal percentage in other children with non-asthma-like conditions was surprising. Lipid-laden macrophage data was unhelpful. Full article

Background: Impedance pneumography (IP) is a non-invasive technique for assessing tidal breathing in young children and enables home-based recordings without active patient cooperation. By deriving tidal breathing flow–volume (TBFV) curves and indices such as the expiratory variability index (EVI), IP has been proposed as a tool for identifying obstructive breathing patterns and monitoring airway function in early childhood. However, its clinical role in asthma and wheezing disorders has not been systematically evaluated. This review aimed to assess the evidence of IP in differentiating healthy children from those with asthma or recurrent wheeze, in reflecting treatment-related changes or acute bronchial obstruction, and in relation to other lung function tests. Methods: A systematic literature search of PubMed, Medline, Embase, and the Cochrane Library databases was conducted on 5 January 2026. Original studies using IP in children aged 0–7 years with asthma or wheeze were eligible. Study selection followed PRISMA guidelines, and risk of bias (RoB) was assessed using the Newcastle–Ottawa Scale (NOS). Due to substantial heterogeneity in study design, populations, and outcome measures, results were synthesized narratively. Results: Five studies were included, with a total of 376 participants aged 0.5–7.0 years. Three studies reported significantly lower EVI values and TBFV profile variation in children with asthma or recurrent wheeze compared with healthy controls. Two studies found an association between EVI and markers of airway obstruction. Changes in IP measures following inhaled corticosteroid treatment or medication withdrawal were reported, suggesting sensitivity to treatment-related changes. However, study quality was moderate to low, with small sample sizes, heterogeneous outcome definitions, and limited diagnostic validation. Conclusions: Current evidence suggests that IP-derived indices, particularly EVI, capture clinically relevant features of obstructive breathing patterns in young children and may be useful for longitudinal monitoring of airway function. However, evidence supporting a diagnostic role for IP in childhood asthma remains limited. Larger, independent, and methodologically robust studies are needed before IP can be integrated into routine clinical practice. Full article

Background: Food allergy [FA] is a growing public health concern among school-age children, with schools and childcare/daycare settings representing high-risk environments for accidental exposure and anaphylaxis. Objective: To systematically review evidence on digital health interventions supporting FA education, prevention, and management in school settings. Methods: A systematic search of PubMed, Scopus, Web of Science, and CINAHL was conducted to identify studies published between January 2015 and December 2025 [PROSPERO CRD420251185553]. Eligible studies evaluated e-learning, mHealth, or web-based programs targeting school staff, parents, or students. Results: Sixteen studies met inclusion criteria. Digital health emerged as a catalyst for professional development, interprofessional communication, and health equity within school communities. Interventions consistently improved knowledge, preparedness, and self-efficacy in anaphylaxis management among school staff, strengthened parental empowerment and communication with schools, and supported coping and inclusion among allergic children. Evidence on clinical outcomes; however, remains limited. Conclusions: Digital health can meaningfully enhance school preparedness and reduce inequalities in allergy management. Integrating digital tools into national school health frameworks—particularly where school nursing is not yet institutionalized—may represent a pivotal step toward safer, more equitable inclusion of children with food allergy. Full article