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Abstract Idiopathic anaphylaxis (IA) remains a frustrating challenge for both patients and physicians. The aim of this paper is to focus on IA in pediatric ages and suggest possible diagnostic algorithms according to specific age ranges (infants, children, and adolescents). In fact, in a variable percentage of patients, despite extensive diagnostic tests, the cause of anaphylactic episodes cannot be identified. Moreover, the lack of a unanimous IA definition requires a careful and detailed diagnostic workup. Prompt recognition of signs and symptoms, especially in younger children, and an accurate clinical history often allow a choice of the most appropriate diagnostic tests and a correct differential diagnosis.

Abstract Exercise-induced bronchoconstriction (EIB) is characterized by the narrowing of airways during or after physical activity, leading to symptoms such as wheezing, coughing, and shortness of breath. Distinguishing between EIB and exercise-induced asthma (EIA) is essential, given their divergent therapeutic and prognostic considerations. EIB has been increasingly recognized as a significant concern in pediatric athletes. Moreover, studies indicate a noteworthy prevalence of EIB in children with atopic predispositions, unveiling a potential link between allergic sensitivities and exercise-induced respiratory symptoms, underpinned by an inflammatory reaction caused by mechanical, environmental, and genetic factors. Holistic management of EIB in children necessitates a correct diagnosis and a combination of pharmacological and non-pharmacological interventions. This review delves into the latest evidence concerning EIB in the pediatric population, exploring its associations with atopy and sports, and emphasizing the appropriate diagnostic and therapeutic approaches by highlighting various clinical scenarios.

Abstract Imported allergens are involved in many allergic reactions, with unexpected and unusual implications. They can be involved in developing asthma, allergic rhinoconjunctivitis, Hymenoptera venom allergies and food allergies. Imported allergens can be implied in respiratory allergies attributable to commercial practices and accidental diffusion through air currents that have introduced non-native species in new geographical contexts. Ambrosia artemisiifolia L., a plant native to North America and currently in the western part of Lombardy, represents an example. Moreover, a variation in the pollen concentration in the Northwest Tuscany area and Trentino Alto-Adige was observed. Cannabis sativa is another imported allergen used frequently by adolescents. Regarding potential imported food allergens, there is no validated list. Imported food allergens derive from ethnic foods, referring to Mexican/Latin American, Chinese/Japanese, Southeast Asian, Arab/Middle Eastern and African cuisine. Four insect flours were recently introduced to the European and Italian markets (Acheta domesticus, Alphitobius diaperinus, Tenebrio molitor and Locusta migratoria). The association between the accidental introduction through commercial traffic, climate change, and the absence of natural enemies in the destination ecosystem is related to the introduction of a specific Hymenoptera, Vespa velutina, in Italy and Europe. External events attributable to human activities, such as climate change and the introduction of non-native plants, foods and Hymenoptera through trade, have contributed to the issue of imported allergens. Making the correct diagnosis and guiding the diagnostic and therapeutic path in this particular context represent the concerns of the pediatric allergist.

Abstract Anaphylaxis is a life-threatening reaction characterized by the acute onset of symptoms involving different organ systems and requiring immediate medical intervention. The incidence of fatal food anaphylaxis is 0.03 to 0.3 million/people/year. Most fatal food-induced anaphylaxis occurs in the second and third decades of life. The identified risk factors include the delayed use of epinephrine, the presence of asthma, the use of recreational drugs (alcohol, nicotine, cannabis, etc.), and an upright position. In the United Kingdom (UK) and Canada, the reported leading causal foods are peanuts and tree nuts. In Italy, milk seems to be the most common cause of fatal anaphylaxis in children

Abstract Hypersensitivity pneumonitis (HP) is a rare disease in childhood with the prevalence of 4 cases per 1 million children and an incidence of 2 cases per year. The average age of diagnosis at pediatric age is approximately 10 years. The pathogenesis of HP is characterized by an immunological reaction caused by recurrent exposure to triggering environmental agents (mostly bird antigens in children). The clinical picture of HP is complex and variable in children, often presenting in subacute forms with cough and exertion dyspnea. A diagnosis of HP should be considered in patients with an identified exposure to a triggering antigen, respiratory symptoms, and radiologic signs of interstitial lung disease. Blood tests and pulmonary function tests (PFT) support the diagnosis. Bronchoscopy (with bronchoalveolar lavage and tissue biopsy) may be needed in unclear cases. Antigen provocation test is rarely required. Of note, the persistence of symptoms despite various treatment regimens may support HP diagnosis. The avoidance of single/multiple triggers is crucial for effective treatment. No evidence- based guidelines for treatment are available; in particular, the role of systemic glucocorticoids in children is unclear. With adequate antigen avoidance, the prognosis in children with HP is generally favorable.

Abstract Eosinophilic esophagitis (EoE) is a chronic clinical-pathologic disease characterized by eosinophilic infiltration of the esophageal epithelium with esophageal dysfunction symptoms. EoE can occur at any age and has different clinical manifestations depending on the age onset. To date, esophago-gastroduodenal endoscopy (EGD) with biopsy is the gold-standard for EoE diagnosis. According to the recent consensus guidelines, proton pump inhibitors, corticosteroids and elimination diets could be a first-line therapy option. The aim of the treatment is clinical and histological remission for preventing long-lasting untreatable fibrosis. A multidisciplinary approach (allergist, gastroenterology, dietitian, and pathologist) is recommended for managing patients affected by EoE, given the complexity of its treatment. This review will provide a practical guide to assist pediatricians treating children with EoE. Moreover, it highlights the unmet needs in diagnosis and treatment that require urgent attention from the scientific community in the aim of improving the management of patients with EoE.

Abstract Background Solar urticaria represents an uncomfortable form of chronic inducible urticaria. First and second-line treatments are ineffective in some patients, leading to an impairment in their quality of life. Omalizumab represents a safe therapeutic option in case of refractory solar urticaria. Case presentation We update a case of a 21-year-old Caucasian girl affected by solar urticaria from the age of 14. Poor disease control was achieved with standard or high-dose of H1-antihistamines. Several omalizumab courses, including a 1-year-long course, were practiced resulting in clinical remission and significant improvement in patient’s quality of life. Conclusion Our experience confirms the effectiveness and safety of omalizumab for the management of refractory solar urticaria. Future studies are awaited in order to monitor long term effects and chronic doses of this treatment, particularly in patients who need concomitant therapy with antihistamines.

Abstract Background Currently, severe allergic asthma and food allergy in children represent an important public health problem with medical, psychosocial and economic impacts. Omalizumab is a humanized monoclonal anti-IgE antibody, approved for refractory allergic asthma and chronic urticaria. It has been widely used in clinical practice as add-on therapy in patients with severe uncontrolled allergic asthma. In recent years there has seen the emergence of an allergic epidemic with increasing food allergy, which represents the main cause of anaphylaxis in children. The standard of care for food allergy is strictly dietary allergen avoidance and emergency treatment, but recent clinical trials have suggested that omalizumab may have a role to play as an adjuvant to oral immunotherapy (OIT). We present a case series of patients treated at our institution with omalizumab for severe allergic asthma and food allergy. Methods Patients received omalizumab according to a standard reference nomogram after failing standard therapies. In children with comorbid severe food allergy, omalizumab was administered in conjunction with an oral immunotherapy protocol. Results Omalizumab was effective in controlling symptoms of allergic asthma, allergic rhinitis and rhinosinusitis, but not eosinophilic esophagitis, while aiding successful oral desensitization of comorbid severe food allergies. Conclusions Omalizumab appears to be an excellent therapeutic option in children with inadequately controlled severe allergic asthma, allergic rhinitis and rhinosinusitis, with or without food allergy.

Abstract 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.

Abstract Allergen immunotherapy (AIT) is the only currently available immune-modifying and aetiological treatment for patients suffering from IgE-mediated diseases. In childhood, it represents a suitable therapeutic option to intervene during the early phases of respiratory allergic diseases such as rhino-conjunctivitis and asthma, which is when their progression may be more easily influenced. A growing body of evidence shows that oral immunotherapy represents a promising treatment option in children with persistent IgE- mediated food allergy. The efficacy of AIT is under investigation also in patients with extrinsic atopic dermatitis, currently with controversial results. Furthermore, AIT might be a strategy to prevent the development of a new sensitization or of a (new) allergic disease. However, there are still some methodological criticisms, such as: a) the regimen of administration and the amount of the maintenance dose are both largely variable; b) the protocols of administration are not standardized; c) the description and classification of side effects is variable among studies and needs to be standardized; d) quality of life and evaluation of health economics are overall missing. All these aspects make difficult to compare each study with another. In addition, the content of major allergen(s) remains largely variable among manufacturers and the availability of AIT products differences among countries. The interest and the attention to AIT treatment are currently fervent and increasing. Well-designed studies are awaited in the near future in order to overcome the current gaps in the evidence and furtherly promote implementation strategies.

Abstract Background The diagnosis of IgE-mediated cow’s milk allergy is often based on anamnesis, and on specific IgE (sIgE) levels and/or Skin Prick Tests (SPT), which have both a good sensitivity but a low specificity, often causing positive results in non-allergic subjects. Thus, oral food challenge is still the gold standard test for diagnosis, though being expensive, time-consuming and possibly at risk for severe allergic reactions. Aim The aim of the present study was to perform a systematic review of the studies that have so far analyzed the positive predictive values for sIgE and SPT in the diagnosis of allergy to fresh and baked cow’s milk according to age, and to identify possible cut-offs that may be useful in clinical practice. Methods A comprehensive search on Medline via PubMed and Scopus was performed August 2017. Studies were included if they investigated possible sIgE and/or SPT cut-off values for cow’s milk allergy diagnosis in pediatric patients. The quality of the studies was evaluated according to QUADAS-2 criteria. Results The search produced 471 results on Scopus, and 2233 on PubMed. Thirty-one papers were included in the review and grouped according to patients’ age, allergen type and cooking degree of the milk used for the oral food challenge. In children