Pediatric chronic urticaria: Clinical and laboratory characteristics and factors linked to remission.

BACKGROUND: Chronic urticaria (CU) is defined as the occurrence of wheals/angioedema for ≥6 consecutive weeks. Until now, guidelines and publications addressing CU have focused mainly on adults. As a result, evidence and guidance in the pediatric population are scarce. METHODS: This study aims to describe clinical and laboratory findings in pediatric CU and to determine factors associated with remission. RESULTS: 185 patients, 54% female, median age at onset of 8.8 years. Angioedema was present in almost half. The most common type of CU was chronic spontaneous urticaria (CSU) in 74%. At least one atopic comorbidity was found in almost a third (35%). In addition, 8% had an autoimmune disorder (exclusively in CSU) and 9% had a psychiatric condition. Basopenia was found in 67% and was more frequently associated with CSU. The basophil activation test (BAT) was positive in 40%. With regard to remission, being of male sex, angioedema absence, the absence of physical triggers, and eosinophil counts >0.51 × 109 /L were associated with shorter CU duration. CONCLUSION: Atopy is a common condition in pediatric CU. CSU is the most common type. Autoimmune comorbidities and basopenia were significantly more common in CSU. In addition, ours is one of the few studies, assessing BAT utility in the pediatric population, being positive in a relevant percentage (40%). BAT positivity was more frequent in CSU. Our results suggest that the absence of angioedema and physical triggers, male sex, and eosinophil counts >0.51 × 109 /L appear to be associated with a better prognosis in terms of remission.

Serum hepcidin levels, iron status, and HFE gene alterations during the first year of life in healthy Spanish infants.

The aims of this study were to describe hepcidin levels and to assess their associations with iron status and the main variants in the HFE gene in healthy and full-term newborns during the first year of life, as a longitudinal study conducted on 140 infants. Anthropometric and biochemical parameters, hepcidin, hemoglobin (Hb), serum ferritin (SF), transferrin saturation (TS), mean corpuscular volume (MCV), and C-reactive protein (CRP), were assessed in 6- and 12-month-olds. Infants were genotyped for the three main HFE variants: C282Y, H63D, and S65C. Hepcidin levels increased from 6 to 12 months of age (43.7 ± 1.5 to 52.0 ± 1.5 ng/mL; p < 0.001), showing higher levels in infants with better iron status compared to those with iron deficiency (ID) (44.8 ± 1.5 vs 37.9 ± 1.3 ng/mL, p < 0.018, and 54.3 ± 1.5 vs 44.0 ± 1.4 ng/mL, p < 0.038, in 6- and 12-month-olds, respectively). In multivariate linear regression models, iron status was found to be associated with hepcidin levels in infants with wild-type HFE gene (p = 0.046 and p = 0.048 in 6- and 12-month-olds, respectively). However, this association was not found in HFE-alteration-carrying infants. Hepcidin levels increased in healthy infants during the first year of life and were positively associated with iron levels only in infants with wild-type HFE gene, a situation that requires further investigation.

Nasal obstructive disorders induce medical treatment failure in paediatric persistent allergic rhinitis (The NODPAR Study).

BACKGROUND: Allergic rhinitis (AR) is the most common chronic disease among children. To characterize the disease, a modified classification of severity (m-ARIA) has recently been validated in AR children. When medical treatment fails, surgery for nasal obstructive disorders (NOD) may be a therapeutic option. Our objective was to assess the prevalence of NOD and their influence in medical treatment response among children with persistent AR (PER). METHODS: In a prospective, real-life study, 130 paediatric PER patients (13.1 ± 2.8 years, females 31.5%, severe rhinitis 49%) referred from Allergy to ENT department were assessed for their response (R, responders; NR, non-responders) to medical treatment (intranasal steroids and antihistamines or antileukotrienes) by direct questioning and nasal symptom visual analogue scale, the presence of NOD (septal deformity, turbinate enlargement and adenoidal hyperplasia), comorbidities, nasal symptoms, rhinitis severity (modified ARIA criterion) and asthma control (International Consensus On Pediatric Asthma criterion). RESULTS: After 2 months of treatment, the NR group presented a higher prevalence of obstructive septal deformity and severe inferior turbinate enlargement when compared with the R group. Higher septal deformity and turbinate enlargement scores were strongly associated with treatment refractoriness. The prevalence of severe PER was also higher for the NR group. Higher asthma control scores were associated with the probability of treatment-induced improvement. CONCLUSIONS: In paediatric PER patients, medical therapy refractoriness was associated with NOD, mainly septal deformity and turbinate enlargement. In those patients, ENT examination will facilitate an early NOD diagnosis in order to indicate potential corrective surgery.

Nasal obstructive disorders impair health-related quality of life in adolescents with persistent allergic rhinitis: A real-life study.

BACKGROUND: We previously reported a higher prevalence of nasal obstructive disorders (NOD) in pediatric patients with persistent allergic rhinitis (PER) not responding to medical treatment. The aim of this study was to determine the impact of NOD on quality of life (QoL) in this population. METHODS: Real-life prospective study including 142 patients (41 children, 6-11 years old and 101 adolescents, 12-17 years old) with moderate and severe PER. After 2 months of medical treatment (intranasal steroids and antihistamines), patients were asked whether their symptoms had improved (yes/no) and classified accordingly in R, responders and NR, non-responders. Nasal symptoms (visual analog scale, VAS), NOD (nasal endoscopy), and QoL (PRQLQ, AdolQRLQ) were also assessed. RESULTS: Sixty-nine adolescents and 24 children were included in the NR group. NR presented worse QoL overall scores in adolescents (3.16±1.1 vs 1.63±0.99; P=.00001) and children (2.19±0.82 vs 1.51±0.77, P=.02). Medical treatment failure was associated with worse outcomes in QoL (adolescents OR: 1.6, P<.0001; children OR: 1.04, P=.036). Female adolescents presented worse QoL scores than males (3.19 vs 2.36, P=.001). The presence of obstructive septal deviation (OR: 1.02, P=.005), obstructive turbinate hyperplasia (OR: 1.03, P=.0006), and coexistence of both (OR=2.06, P=.001) was associated with worse QoL in adolescents. A strong and highly significant correlation was found between nasal symptoms VAS and QoL. CONCLUSION: The presence of NOD, particularly in adolescents, is associated with poor QoL outcomes. Assessment of NOD in pediatric PER should be considered an essential approach to determine the response to treatment and its impact on patient's QoL.

Are there early inflammatory biomarkers that affect neurodevelopment in infancy?

Few studies have investigated the relationship between post-natal inflammatory biomarkers at early age and child neurodevelopment outcomes. The main aim of this study was to examine the relationship between IL-6, IL-1ß, IL-4 cytokines, as well as cortisol at 6 and 12months of age, and neurodevelopment and psychological problems at 30months of age. The study was conducted on a sample of 51 full-term newborns who were followed up at 6, 12, and 30months of age. Infant neurodevelopment was assessed using the Bayley Scales of Infant Development-II, psychological problems were assessed with the Child Behavior Checklist 1.5-5 (CBCL 1.5-5) and the mother's emotional symptoms were assessed with the General Health Questionnaire-28. When the infants were 6 and 12months old, IL-6, IL-1ß, IL-4 cytokines, and cortisol were measured in blood samples. The results showed that higher IL-6 at 12months predicted higher scores in internalizing (emotionally reactive, anxious/depressed, withdrawn and attention problems) and externalizing problems (aggressive behavior) at 30months. By contrast, high levels of IL-1ß at 6months were related to worse motor skills. Inflammatory biomarkers were not related to mental performance. IL-6 and IL-1ß could be early markers of later psychological problems and psychomotor disabilities.

Influence of nasal septum deformity on nasal obstruction, disease severity, and medical treatment response among children and adolescents with persistent allergic rhinitis.

OBJECTIVE: To evaluate the impact of different types of nasal septum deformity (NSD) on nasal obstruction, rhinitis severity and response to medical treatment among pediatric persistent allergic rhinitis (PER) patients. METHODS: In a prospective, real-life study, 150 children and adolescents (mean age 13 ± 2.8 years, females 32.6%) diagnosed with PER according to ARIA guidelines were assessed by nasal endoscopy for NSD according to Mladina's classification, their response to medical treatment (intranasal steroids and antihistamines or antileucotriens), the presence of comorbidities, rhinitis severity (modified-ARIA criterion) and nasal obstruction visual analog scale score (VAS). RESULTS: Most patients (87%) had 1 of the 7 types of septal deformities. There was a high prevalence of bilateral (types 4 and 6; 46%) and anterior unilateral (types 1 and 2; 25%) NSD in patients not responding to medical treatment. Type 4 (OR = 6.4; p = 0.005) or type 6 (OR = 4.4; p = 0.03) NSD increased the risk of lack of improvement with medical treatment. Coexistence of anterior unilateral or bilateral NSD with severe turbinate enlargement increased >20-fold the risk of lack of improvement. Patients with bilateral NSD presented greater rhinitis severity. Non-responder adolescents displayed higher prevalence of bilateral NSD than children (53% vs. 23%; p = 0.02). Nasal obstruction VAS was higher for patients with anterior than posterior NSD, and greater for patients with bilateral NSD than any other type of septal morphology. CONCLUSION: Nasal endoscopy shows that bilateral and unilateral anterior nasal septum deformities are strongly associated with a poor response to medical treatment, greater rhinitis severity and higher nasal obstruction VAS. Consequently, nasal endoscopy is necessary in the PER patients to understand the disease severity as well as to plan a specific surgical treatment in order to improve nasal obstruction, disease severity, and patient's quality of life.

Molecular diagnosis in house dust mite-allergic patients suggests that Der p 23 is clinically relevant in asthmatic children

BACKGROUND: Patterns of sensitization to house dust mites depend on geographic area and are important in clinical practice. However, the role of molecular diagnosis is not currently defined. We sought to characterize a pediatric population by focusing on sensitization to different mite species and major mite components in order to assess the clinical relevance of sensitization to allergenic components in our practice. METHODS: Consecutive children with respiratory allergy sensitized to house dust mites (determined by skin prick test [SPT]) were recruited. We determined specific IgE to nDer p 1, rDer p 2, and rDer p 23 using ImmunoCAP and sIgE using ImmunoCAP-ISAC microarray. Patients were followed up for 3 years. RESULTS: A total of 276 children were recruited. The frequency of sensitization was 86.6% for nDer p 1, 79.3% for rDer p 2, and 75.8% for rDer p 23. Lepidoglyphus species was the most common storage mite detected by SPT. Twenty-six patients (9.4%) were not sensitized to Der p 1 or Der p 2. It is noteworthy that IgE binding to Der p 23 was positive in 14 (53.8%). Asthmatic patients, especially those with a persistent moderate-severe phenotype, more frequently recognized the 3 major allergens. CONCLUSIONS: Most patients with mite allergy were sensitized to the major allergens Der p 1, Der p 2, and Der p 23. Of the allergens evaluated, 5% were sensitized to Der p 23 but not to Der p 1 or Der p 2. Sensitization to Der p 23 should be considered in the diagnosis and treatment of mite allergy, especially in patients with moderate-severe asthma, because it may worsen the clinical phenotype

ANTECEDENTES: El perfil de sensibilización a los ácaros del polvo depende del área geográfica y es importante en la práctica clínica. Sin embargo, el papel del diagnóstico molecular no ha sido del todo definido. Nuestro objetivo fue la caracterización del perfil de sensibilización de una población pediátrica a diferentes especies de ácaros; y evaluar la sensibilización a componentes alergénicos y su relevancia en nuestra práctica clínica. MÉTODOS: Se reclutaron de forma consecutiva pacientes con alergia respiratoria y sensibilización a ácaros del polvo doméstico mediante pruebas cutáneas. Se determinó la IgE específica por ImmunoCAP a nDer p 1, rDer p 2, rDer p 23 y la sIgE mediante el microarray de ImmunoCAP ISAC. Los pacientes fueron evaluados durante tres años según práctica cínica habitual. RESULTADOS: Se reclutaron un total de 276 niños. La sensibilización fue de 86,6% a nDer p 1, 79,3% a rDer p 2 y 75,8% a rDer p 23. Lepidoglyphus fue el ácaro de almacén más común según prueba cutánea. Un total de veintiséis pacientes (9,4%) no estaban sensibilizados a Der p 1 ni Der p 2; cabe destacar que 14 de ellos (53,8%) presentaban IgE positiva a Der p 23. Los pacientes con asma, y en especial los de fenotipo persistente moderado y grave, reconocieron con mayor frecuencia los tres alérgenos mayores. CONCLUSIONES: La mayoría de nuestra población pediátrica con alergia a ácaros está sensibilizada a los alérgenos mayores Der p 1, Der p 2 y Der p 23. Un 5% estaba sensibilizado a Der p 23, pero no a Der p 1 ni a Der p 2. La sensibilización a Der p 23 debe considerarse en el diagnóstico y tratamiento de la alergia a ácaros, especialmente en pacientes con asma persistente moderada y grave