Progress in pediatrics in 2015: choices in allergy, endocrinology, gastroenterology, genetics, haematology, infectious diseases, neonatology, nephrology, neurology, nutrition, oncology and pulmonology

This review focuses key advances in different pediatric fields that were published in Italian Journal of Pediatrics and in international journals in 2015. Weaning studies continue to show promise for preventing food allergy. New diagnostic tools are available for identifying the allergic origin of allergic-like symptoms. Advances have been reported in obesity, short stature and autoimmune endocrine disorders. New molecules are offered to reduce weight gain and insulin-resistance in obese children. Regional investigations may provide suggestions for preventing short stature. Epidemiological studies have evidenced the high incidence of Graves' disease and Hashimoto's thyroiditis in patients with Down syndrome. Documentation of novel risk factors for celiac disease are of use to develop strategies for prevention in the population at-risk. Diagnostic criteria for non-celiac gluten sensitivity have been reported. Negative effect on nervous system development of the supernumerary X chromosome in Klinefelter syndrome has emerged. Improvements have been made in understanding rare diseases such as Rubinstein-Taybi syndrome. Eltrombopag is an effective therapy for immune trombocytopenia. Children with sickle-cell anemia are at risk for nocturnal enuresis. Invasive diseases caused by Streptococcus pyogenes are still common despite of vaccination. No difference in frequency of antibiotic prescriptions for acute otitis media between before the publication of the national guideline and after has been found. The importance of timing of iron administration in low birth weight infants, the effect of probiotics for preventing necrotising enterocolitis and perspectives for managing jaundice and cholestasis in neonates have been highlighted. New strategies have been developed to reduce the risk for relapse in nephrotic syndrome including prednisolone during upper respiratory infection. Insights into the pathophysiology of cerebral palsy, arterial ischemic stroke and acute encephalitis may drive advances in treatment. Recommendations on breastfeeding and complementary feeding have been updated. Novel treatments for rhabdomyosarcoma should be considered for paediatric patients. Control of risk factors for bronchiolitis and administration of pavilizumab for preventing respiratory syncytial virus infection may reduce hospitalization. Identification of risk factors for hospitalization in children with wheezing can improve the management of this disease. Deletions or mutations in genes encoding proteins for surfactant function may cause diffuse lung disease

Advances in paediatrics in 2016: Current practices and challenges in allergy, autoimmune diseases, cardiology, endocrinology, gastroenterology, infectious diseases, neonatology, nephrology, neurology, nutrition, pulmonology

Abstract This review reports main progresses in various pediatric issues published in Italian Journal of Pediatrics and in international journals in 2016. New insights in clinical features or complications of several disorders may be useful for our better understanding. They comprise severe asthma, changing features of lupus erythematosus from birth to adolescence, celiac disease, functional gastrointestinal disorders, Moebius syndrome, recurrent pneumonia. Risk factors for congenital heart defects, Kawasaki disease have been widely investigated. New diagnostic tools are available for ascertaining brucellosis, celiac disease and viral infections. The usefulness of aCGH as first-tier test is confirmed in patients with neurodevelopmental disorders. Novel information have been provided on the safety of milk for infants. Recent advances in the treatment of common disorders, including neonatal respiratory distress syndrome, hypo-glycemia in newborns, atopic dermatitis, constipation, cyclic vomiting syndrome, nephrotic syndrome, diabetes mellitus, regurgitation, short stature, secretions in children with cerebral palsy have been reported. Antipyretics treatment has been updated by national guidelines and studies have excluded side effects (e.g. asthma risk during acetaminophen therapy). Vaccinations are a painful event and several options are reported to prevent this pain. Adverse effects due to metabolic abnormalities are reported for second generation antipsychotic drugs

SIAIP position paper: provocation challenge to antibiotics and non-steroidal anti-inflammatory drugs in children

Drug hypersensitivity reactions (DHRs) in childhood are mainly caused by betalactam or non-betalactam antibiotics, and non-steroidal anti-inflammatory drugs (NSAIDs). Laboratory tests for identifying children who are allergic to drugs have low diagnostic accuracy and predictive value. The gold standard to diagnose DHR is represented by the drug provocation test (DPT), that aims of ascertaining the causative role of an allergen and evaluating the tolerance to the suspected drug. Different protocols through the administration of divided increasing doses have been postulated according to the type of drug and the onset of the reaction (immediate or non immediate reactions). DPT protocols differ in doses and time interval between doses. In this position paper, the Italian Pediatric Society for Allergy and Immunology provides a practical guide for provocation test to antibiotics and NSAIDs in children and adolescents

Efficacy of sildenafil and high-dose anakinra in an MIS-C patient with pulmonary vasculitis: A case report

Multisystem inflammatory syndrome in children (MIS-C) is a newly identified clinical entity still not very well known in terms of epidemiology, pathogenesis, and long-term outcome. Pulmonary involvement with acute respiratory failure is an unusual life-threatening complication of MIS-C, often a reason for admission to the pediatric intensive care unit (PICU) and the use of mechanical ventilation. We present a case of a 7-year-old male patient, previously healthy, hospitalized for MIS-C, treated with intravenous immunoglobulins (IVIG), high dose methylprednisolone, and anakinra. After 2 days of the aforementioned therapy, the patient presented with hypoxia (SatO2: 85% in ambient air room) and breathing difficulties. A chest computed tomography (CT) scan showed the presence of multiple bilateral basal parenchymal thickening and small basal pleural effusion and an arterial blood gas analysis revealed severe hypoxia (PaO2/FiO2 ratio, 170 mmHg). Because of a worsening of respiratory distress, the patient was transferred to the PICU, where invasive mechanical ventilation and a continuous infusion of anakinra (12 mg/kg/day) were started. An echocardiogram was performed, which showed an increase in pulmonary pressure (40 mmHg) with normal heart ejection fraction (55%), and the hypothesis of pulmonary vasculitis involving the pulmonary arterioles was made. Therefore, therapy with sildenafil (0.15 mg/kg/day) was promptly set up, with an immediate improvement of the clinical picture of respiratory failure, reduction of pulmonary pressure (23 mmHg), and subsequent extubation at 36 h with a regular clinical course until discharge. As far as we know, our case represents the first report of pulmonary vasculitis in an MIS-C patient. The use of sildenafil and high-dose continuous anakinra may represent a rescue therapy in cases of MIS-C with pulmonary vasculitis or with difficulty in extubation, allowing a short-term hospitalization in intensive care and improving the long-term outcome in these patients

Preliminary data revealing efficacy of Streptococcus salivarius K12 (SSK12) in Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome: A multicenter study from the AIDA Network PFAPA syndrome registry

Objective: To evaluate the potential role of Streptococcus salivarius K12 (SSK12) in controlling febrile flares in patients with Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome. Further aims were to assess the impact of SSK12 on (i) flare duration, (ii) variation in the degree of the highest body temperature during flares, (iii) steroid-sparing effect, and (iv) change of PFAPA accompanying symptoms before and after SSK12 introduction. Patients and methods: The medical charts from 85 pediatric patients with PFAPA syndrome (49 males and 36 females) enrolled in the AIDA registry and treated with SSK12 for a median period of 6.00 ± 7.00 months in the period between September 2017 and May 2022 were examined. Children recruited had a median time of disease duration of 19.00 ± 28.00 months. Results: The number of febrile flares significantly decreased comparing the 12 months before [median (IQR), 13.00 (6.00)] and after SSK12 initiation [median (IQR), 5.50 (8.00), p < 0.001]. The duration of fever was significantly reduced from 4.00 (2.00) days to 2.00 (2.00) days [p < 0.001]. Similarly, the highest temperature in°C was found significantly lower in the last follow-up assessment [median (IQR), 39.00 (1.00)] compared to the period prior to SSK12 start [median (IQR), 40.00 (1.00), p < 0.001]. Steroid load (mg/year) of betamethasone (or any equivalent steroid) significantly decreased between 12 months before treatment with SSK12 [median (IQR), 5.00 (8.00) mg/year] and the last follow-up visit [median (IQR), 2.00 (4.00) mg/year, p < 0.001]. The number of patients experiencing symptoms including pharyngitis/tonsillitis (p < 0.001), oral aphthae (p < 0.001) and cervical lymphadenopathy (p < 0.001) significantly decreased following SSK12. Conclusion: SSK12 prophylaxis given for at least 6.00 months was found to reduce febrile flares of PFAPA syndrome: in particular, it halved the total number per year of fever flares, shortened the duration of the single febrile episode, lowered body temperature by 1°C in the febrile flare, provided a steroid-sparing effect, and significantly reduced the accompanying symptoms related to the syndrome

Development and implementation of the AIDA International Registry for patients with Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis syndrome

Objective: Aim of this paper is to illustrate the methodology, design, and development of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to patients with the Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome. Methods: This is a physician-driven, non-population- and electronic-based registry proposed to gather real-world demographics, clinical, laboratory, instrumental and socioeconomic data from PFAPA patients. Data recruitment is realized through the on-line Research Electronic Data Capture (REDCap) tool. This registry is thought to collect standardized information for clinical research leading to solid real-life evidence. The international scope and the flexibility of the registry will facilitate the realization of cutting-edge study projects through the constant updating of variables and the possible merging and transfer of data between current and future PFAPA registries. Results: A total of 112 centers have already been involved from 23 countries and 4 continents starting from August 24th, 2021, to April 6th, 2022. In total 56/112 have already obtained the formal approval from their local Ethics Committees. The platform counts 321 users (113 principal investigators, 203 site investigators, two lead investigators, and three data managers). The registry collects retrospective and prospective data using 3,856 fields organized into 25 instruments, including PFAPA patient's demographics, medical histories, symptoms, triggers/risk factors, therapies, and impact on the healthcare systems. Conclusions: The development of the AIDA International Registry for PFAPA patients will enable the on-line collection of standardized data prompting real-life studies through the connection of worldwide groups of physicians and researchers. This project can be found on NCT 05200715

Development and Implementation of the AIDA International Registry for Patients With Still's Disease

Objective: Aim of this paper is to present the design, construction, and modalities of dissemination of the AutoInflammatory Disease Alliance (AIDA) International Registry for patients with systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD), which are the pediatric and adult forms of the same autoinflammatory disorder. Methods: This Registry is a clinical, physician-driven, population- and electronic-based instrument implemented for the retrospective and prospective collection of real-world data. The collection of data is based on the Research Electronic Data Capture (REDCap) tool and is intended to obtain evidence drawn from routine patients' management. The collection of standardized data is thought to bring knowledge about real-life clinical research and potentially communicate with other existing and future Registries dedicated to Still's disease. Moreover, it has been conceived to be flexible enough to easily change according to future scientific acquisitions. Results: Starting from June 30th to February 7th, 2022, 110 Centers from 23 Countries in 4 continents have been involved. Fifty-four of these have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 175 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry collects baseline and follow-up data using 4449 fields organized into 14 instruments, including patient's demographics, history, clinical manifestations and symptoms, trigger/risk factors, therapies and healthcare access. Conclusions: This international Registry for patients with Still's disease will allow a robust clinical research through collection of standardized data, international consultation, dissemination of knowledge, and implementation of observational studies based on wide cohorts of patients followed-up for very long periods. Solid evidence drawn from "real-life " data represents the ultimate goal of this Registry, which has been implemented to significantly improve the overall management of patients with Still's disease. NCT 05200715 available at

Pollen-food allergy syndrome in età pediatrica: fenotipi evolutivi e storia naturale. Uno studio multicentrico di coorte longitudinale.

Introduzione La pollen-food allergy syndrome (PFAS) rappresenta una comorbidità della rinocongiuntivite allergica stagionale (SAR), manifestandosi come reazione avversa all'ingestione di alimenti polline-correlati. La sua prevalenza in età pediatrica è superiore a quanto precedentemente riportato e le caratteristiche cliniche e di sensibilizzazione allergica sono complesse nei paesi del Sud Europa. Poco è noto sull’evoluzione della PFAS nel tempo dal punto di vista clinico e atopico. Il nostro studio ha presentato l’obiettivo di investigare le caratteristiche cliniche e la sensibilizzazione allergica della popolazione PAN-PED in sei anni di osservazione per identificare i fattori predittivi potenziali di persistenza/remissione o nuova insorgenza della PFAS. Metodi Sono stati valutati 429 pazienti negli anni 2015-2017 (follow-up) della popolazione di studio “Panallergen in Pediatrics” reclutati nel 2009-2011 (baseline), survey multicentrica italiana di bambini con SAR. Sono state esaminate le informazioni cliniche della patologia allergica e gli alimenti scatenanti PFAS (questionario, AllergyCARD, TPS, Italia). In entrambi i controlli sono stati eseguiti prick test cutanei per un pannello di allergeni inalanti con estratti commerciali e prelievo ematico per determinare i livelli delle IgE specifiche per i panallergeni Phl p 12 (profilina), Bet v 1 (PR-10) e Pru p 3 (nsLTP) con ImmunoCAP FEIA. Risultati Al baseline, centouno pazienti riportavano PFAS a seguito dell’ingestione di almeno un alimento vegetale (23.5%) con un incremento al follow-up manifestandosi in 155 pazienti (36.1%). La PFAS è rimasta persistente in 64 pazienti (63.4%) ed è stata remittente in 37 pazienti (36.6%). Nella popolazione dei pazienti che non presentavano PFAS al baseline, 91 hanno mostrato PFAS incidente al follow-up (27.7%). Gli alimenti vegetali più frequentemente riportati come causa di sintomi al cavo orale nella popolazione con PFAS erano il kiwi e la pesca in entrambi i controlli. Il sottogruppo di pazienti con PFAS persistente mostrava: a) polisensibilizzazione pollinica; b) un numero elevato di alimenti trigger; c) frequente comorbidità con asma; d) una maggior frequenza dell’endotipo “multi-panallergen” e dell’endotipo “PR-10”. Il sottogruppo di pazienti con PFAS incidente presentava: a) numerosi alimenti trigger; b) numerose comorbidità allergiche; c) una maggior frequenza dell’endotipo “LTP”. Conclusioni La PFAS è una patologia clinicamente eterogenea e dinamica nella sua evoluzione clinica sin dall’età pediatrica. Un work-up diagnostico integrato comprendente le caratteristiche cliniche e la diagnostica molecolare rappresenta l’elemento di valutazione della PFAS in età pediatrica. Sono necessari ulteriori studi per analizzare la PFAS e supportare un approccio diagnostico e terapeutico patient-tailored della multimorbidità allergica.Introduction Pollen-food allergy syndrome (PFAS) represents a comorbidity of seasonal allergic rhinoconjunctivitis (SAR), manifesting as an adverse reaction after the ingestion of pollen-related foods. Its prevalence in childhood is higher than previously reported and the clinical and allergic sensitization characteristics are complex in Southern European countries. Little is known about the evolution of PFAS over time from the clinical and atopic point of view. Our study aimed at investigating the clinical features and allergic sensitization patterns of the PAN-PED population over six years to identify potential predictors of persistence/remission or new onset of PFAS. Methods We evaluated 429 patients in the years 2015-2017 (follow-up) from the study population "Panallergen in Pediatrics" recruited in 2009-2011 (baseline), Italian multicentric survey of children affected by SAR. Clinical information of allergic morbidity and foods triggering PFAS were obtained by questionnaire, AllergyCARD, TPS, Italy. In both controls, patients performed skin prick tests for a panel of inhalant allergens with commercial extracts and blood sampling for specific IgE levels to panallergens: Phl p 12 (profilin), Bet v 1 (PR-10) and Pru p 3 (nsLTP) with ImmunoCAP FEIA. Results At baseline, one hundred and one patients reported PFAS after the ingestion of at least one vegetable food (23.5%) increasing to 155 patients at follow-up (36.1%). PFAS was persistent in 64 patients (63.4%) and remittent in 37 patients (36.6%). In the population of patients without PFAS at baseline, 91 showed incident PFAS at follow-up (27.7%). The most frequent vegetable foods triggering oral symptoms were kiwi and peach in both controls. The subset of patients with persistent PFAS showed: a) pollen polysensitization; b) a large number of trigger foods; c) recurrent comorbidity with asthma; d) a higher frequency of "multi-panallergen" endotype and "PR-10" endotype. The subgroup of patients with incident PFAS had: a) numerous triggering foods; b) numerous allergic comorbidities; c) higher frequency of the "LTP" endotype. Conclusions The evolution of PFAS is clinically heterogeneous at pediatric and adolescent age. An integrated diagnostic work-up including clinical features and component-resolved diagnostics is the key element for the evaluation of PFAS in children. Further studies are needed to analyze PFAS during childhood to support a patient-tailored diagnostic and therapeutic approach for allergic multimorbidity