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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 < 18 years. Fatal food anaphylaxis in Italian children and adolescents almost always occurs outside and is characterized by cardiorespiratory arrest; auto-injectable adrenaline intramuscular was available in few cases. Mortality from food anaphylaxis, especially in children, is a very rare event with stable incidence, but its risk deeply impacts the quality of life of patients with food allergy and their families. Prevention of fatal food anaphylaxis must involve patients and their families, as well as the general public, public authorities, and patients' associations. [ABSTRACT FROM AUTHOR]

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 < 18 years. Fatal food anaphylaxis in Italian children and adolescents almost always occurs outside and is characterized by cardiorespiratory arrest; auto-injectable adrenaline intramuscular was available in few cases. Mortality from food anaphylaxis, especially in children, is a very rare event with stable incidence, but its risk deeply impacts the quality of life of patients with food allergy and their families. Prevention of fatal food anaphylaxis must involve patients and their families, as well as the general public, public authorities, and patients' associations. [ABSTRACT FROM AUTHOR]

BNT162b2 vaccine, developed by BioNTech and Pfizer ha recently approved for use in children aged 5 to 11 years. Recent data show evidence of safety on the administration and serious adverse events have been rarely reported. However, allergic systemic reactions could occur. In some cases, a correct allergic evaluation allows identifying patients at risk of developing an anaphylactic reaction. Risk assessment of allergic reactions to COVID-19 vaccines is useful to limit contraindications to vaccination and help to safely vaccinate people supposed to be at risk of allergic reactions. [ABSTRACT FROM AUTHOR]

The diagnosis of drug‐induced enterocolitis syndrome (DIES), resembling the typical findings of a well‐known disease, the food protein‐induced enterocolitis syndrome (FPIES), was acknowledged in the first publication on the topic in 2014. Ten cases of DIES have been described so far. Unanswered questions concerning DIES include its pathogenetic mechanism, natural history, the possible presence of predisposing genetic factors, and the potential existence of its atypical forms. DIES is a recently defined and intriguing clinical entity, similar to FPIES but triggered by drugs. It seems well‐defined from the clinical point of view, but its pathogenetic mechanisms are not known. DIES deserves more attention among allergists, especially among the professionals who work with children, and all efforts should be conceived to improve its correct recognition and accurate management. [ABSTRACT FROM AUTHOR]

The diagnosis of drug‐induced enterocolitis syndrome (DIES), resembling the typical findings of a well‐known disease, the food protein‐induced enterocolitis syndrome (FPIES), was acknowledged in the first publication on the topic in 2014. Ten cases of DIES have been described so far. Unanswered questions concerning DIES include its pathogenetic mechanism, natural history, the possible presence of predisposing genetic factors, and the potential existence of its atypical forms. DIES is a recently defined and intriguing clinical entity, similar to FPIES but triggered by drugs. It seems well‐defined from the clinical point of view, but its pathogenetic mechanisms are not known. DIES deserves more attention among allergists, especially among the professionals who work with children, and all efforts should be conceived to improve its correct recognition and accurate management. [ABSTRACT FROM AUTHOR]

Available guidelines for asthma management represent an important and suitable tool to make the entire medical process evidence-based, effective, and safe for patients. Their purpose is to help doctors and patients formulate the best decisions in regard to asthma management by choosing the most appropriate strategies in each specific clinical situation. The Global Initiative for Asthma (GINA) document, together with other national and international recommendations, is one of the main documents used for asthma prevention and management in Italy, but several studies reported that these recommendations are often not applied in real-life clinical practice, which consequently results in inadequate asthma control. In this context, a substantial simplification of the GINA document and asthma guidelines may represent a feasible strategy to be pursued to ameliorate the knowledge among GPs, primary care pediatricians, and specialists taking care of children and adults with asthma. On the other hand, another critical factor that may explain unsatisfactory control of asthma is the limited importance that all recommendations place on asthma heterogeneity. In the era of personalized medicine and target therapies, phenotype-driven asthma management may become a desirable approach for optimizing the management of asthmatic patients. In addition, digital health strategies have been investigated in the literature to improve asthma monitoring and may represent a promising tool in the future from this point of view. Relevant stakeholders should continue to investigate how to optimize real-life asthma control to propose novel solutions to translate into clinical practice. [ABSTRACT FROM AUTHOR]

Background Several cases of pine nut allergies and anaphylaxis have been reported in the literature, but only few pine nut allergens have been characterized. The aim of this research is to identify through immunoelectrophoretic techniques the major pine nut allergens in a group of children monosensitized to pine nuts. Methods We studied five children with pine nut allergies and no other sensitization to food except to pine nuts, confirmed by in vivo (prick test, prick-to-prick) and in vitro tests (specific Ig E determinations [ CAP- FEIA]). The protein profile of pine nuts was analyzed by Sodium Dodecyl sulfate Polyacrylamide Gel Electrophoresis ( SDS- PAGE). Immunoblotting was performed after incubation of membranes with the sera from the children included in the present study. Results Immunoblotting ( SDS- PAGE) demonstrated five similar bands between 6 and 47 kDa in all the subjects studied. Conclusion These bands should be considered the potential allergens for pine nut allergic children. [ABSTRACT FROM AUTHOR]

Objective. Vernal keratoconjunctivitis (VKC) is a chronic conjunctivitis that affects children mainly in temperate areas, with exacerbations in spring and summer. Eyelashes provide natural protection for the eyes from sunshine, wind, and foreign bodies. These factors induce a worsening of signs and symptoms in VKC, whereas mechanical protection of the eyes produces relief. The aim of this study was to evaluate eyelash length in a large series of VKC patients and in age-and gender-matched healthy subjects. Methods. Upper eyelash length was measured in 93 VKC patients (mean age: 8.7 years; range: 4-18 years) with a digital caliper. History, clinical form, type of presentation, degree of severity, and drug therapy were evaluated. Skin tests and serum-specific immunoglobulin E for common allergens, serum-total immunoglobulin E, peripheral blood eosinophil counts, and serum eosinophil cationic protein were determined. Two age- and gender-matched control subjects for each VKC patient underwent the same eyelash measurement. Results. The upper eyelashes were significantly longer in VKC patients than in control subjects (mean ± SD: 8.9 ± 1.17 mm vs 7.9 ± 1.07 mm). In healthy subjects, a negative correlation was found between eyelash length and age. With multivariate analysis, unlike control subjects, the eyelash length in VKC patients did not correlate with age, was positively correlated with the degree of severity of VKC, and was negatively correlated with the use of topical cyclosporine. Conclusions. Patients with VKC had longer eyelashes than healthy matched subjects. The ocular inflammation, by unknown chemical mediators, was likely responsible for the excessive eyelash growth. The finding may represent a defensive mechanism against physical agents that might have a crucial role in the etiopathogenesis of this disease. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

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 FROM AUTHOR]

Notwithstanding the efforts made in the last decades to mitigate the consequences of natural rubber latex allergy, this disease continues to be a major health problem, especially in developing countries. The categories of patients with greater and frequent exposure to latex (such as health care professionals and, in the pediatric field, subjects who undergo repeated surgery, e.g., those suffering from spina bifida and urogenital malformations) have an increased risk of developing sensitization and allergy to latex. Herein we provide an overview of the current knowledge and practical recommendations with a focus on epidemiology, diagnostics, and management (including both prevention and therapy) in order to guide a correct recognition and containment of this potentially fatal condition. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the case of a six-year-old female child, who has been referred to the Allergy Unit of Anna Meyer Children's Hospital for suspected drug-induced enterocolitis syndrome (DIES).

Allergic proctocolitis (AP) is a benign condition, frequent in childhood, that is classified as a non-IgE-mediated food allergy. The prevalence is unknown; however, its frequency appears to be increasing, especially in exclusively breastfed infants. Clinical manifestations typically begin in the first few months of life with the appearance of bright red blood (hematochezia), with or without mucus, in the stool of apparently healthy, thriving infants. Most cases of AP are caused by cow's milk proteins; however, other allergens, such as soy, egg, corn, and wheat, may be potential triggers. Diagnosis is based on the patient's clinical history and on the resolution of signs and symptoms with the elimination of the suspected food antigen from the diet and their reappearance when the food is reintroduced into the diet. The treatment of AP is based on an elimination diet of the trigger food, with resolution of the symptoms within 72–96 h from the beginning of the diet. The prognosis of AP is good; it is a self-limiting condition, because most children can tolerate the trigger food within one year of life, with an excellent long-term prognosis. The purpose of this review is to provide an update on the current knowledge and recommendations in epidemiological, diagnostic, and therapeutic terms to the pediatricians, allergists, and gastroenterologists who may find themselves managing a patient with AP. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder in childhood. Skin barrier impairment exposes infants to food allergens, potentially causing sensitization followed by IgE-mediated food allergy. We describe the case of an infant with severe AD in whom several sensitizations to foods are detected, with consequently difficult weaning, and a history of anaphylaxis to cashew nut. Foods for which skin tests were negative were introduced into the infant's diet. Then, when AD control was managed, oral food challenges (OFCs) for foods to which the patient was sensitized, with the exception of cashew nut, were performed. The simultaneous presence of sensitization toward multiple foods made it difficult to introduce them using classic OFC. Therefore, it was decided to perform the low-dose, gradual controlled OFC. This led to an introduction of sensitized foods into the infant's diet, with the exception of cashew nut, avoiding allergic reactions. Absolute recommendations on how, when, and where to perform OFCs with allergenic food to which the child with AD is sensitized are lacking so far. In our opinion, OFCs and the subsequent ntroduction of allergenic foods should be individualized, evaluating some factors such as their social and nutritional importance, the patient's age and clinical phenotype (including the history of anaphylaxis), and the sensitization profile. There is agreement on the fact that the dietary approach in children with moderate-severe AD should no longer include a strict elimination diet. We believe that an early, gradual controlled introduction of all allergenics to identify the amount of food tolerated in the absence of reactions, even if low dose, may improve patients' and families' quality of life. However, even if discussing a vast relevant literature, the limitation of our work is that we describe the management of a single patient. Extensive and high-quality research is needed in this field to improve the available evidence in the area. [ABSTRACT FROM AUTHOR]

Angioedema (AE) is a vascular reaction of subcutaneous and submucosal tissues that identifies various clinical pictures and often is associated with wheals. AE without wheals (AEwW) is infrequent. The ability to distinguish between AEwW mediated by mast cells and bradykinin-mediated or leukotriene-mediated pathways is often crucial for a correct diagnostic–therapeutic and follow-up approach. AEwW can be hereditary or acquired. Factors typically correlated with hereditary angioedema (HAE) are a recurrence of episodes, familiarity, association with abdominal pain, onset after trauma or invasive procedures, refractoriness to antiallergic therapy, and lack of pruritus. The acquired forms of AE can present a definite cause based on the anamnesis and diagnostic tests. Still, they can also have an undetermined cause (idiopathic AE), distinguished according to the response to antihistamine in histamine-mediated and non-histamine-mediated forms. Usually, in childhood, AE responds to antihistamines. If AEwW is not responsive to commonly used treatments, it is necessary to consider alternative diagnoses, even for pediatric patients. In general, a correct diagnostic classification allows, in most cases, optimal management of the patient with the prescription of appropriate therapy and the planning of an adequate follow-up. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

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 FROM AUTHOR]

In 2014, drug‐induced enterocolitis syndrome (DIES) was described for the first time. It is still a poorly known disease with symptoms that typically resemble those of food protein–induced enterocolitis syndrome (FPIES). To date, six more cases of DIES have been described and new clinical diagnostic criteria have been proposed based on those in the international guidelines for FPIES. In this paper, the authors describe three more cases of DIES. In addition, similarities and differences with FPIES have been deeply analyzed. To date, several unanswered questions need to be addressed, but clinicians must be instructed how to identify DIES, in order to make an allergy workup and give definite therapeutic indications to patients, especially in children where DIES seems to be more frequent. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is the most common immune-mediated skin disease in childhood. Several treatment options for pediatric AD, both topical and systemic, are currently available. We carried out a single-center observational study with the aim of describing characteristics and treatment patterns in pediatric AD patients. Methods: The study included 867 patients aged ≤16 years (females 50.5%, mean patient's age 5.9 years, standard deviation ±3.6 years) with a previous doctor-confirmed diagnosis of AD who underwent balneotherapy at the Comano Thermal Spring Water Center (Comano, Trentino, Italy) from April to October 2014. Results: Among the patients included in the study, 41.2% had mild (SCORing Atopic Dermatitis, SCORAD 0-15), 43.6% moderate (SCORAD 16–40) and 15.2% severe AD (SCORAD > 40). A higher occurrence of reported food allergy was observed among children with more severe AD (p < 0.0001), while no association was found between AD severity and reported inhalant allergy or passive smoking (p = 0.15 and 0.92, respectively). Emollients (55.1%) and topical corticosteroids (TCS; 45.7%) were the main treatment options used in the previous month. The use of oral steroids and topical calcineurin inhibitors (TCI) was considerably less common (6.3 and 4.5%, respectively), while no patients were on systemic agents other than steroids. Among patients with severe AD, 9.8% had not used TCS, TCI or any systemic treatments. Moreover, 20.0% of the patients in the study population had followed elimination diets, although only 27.2% of them had a reported food allergy. Conclusions: A significant difference in the prevalence of reported food allergy emerged across the different AD severity categories. Furthermore, although further data are necessary to confirm our findings, undertreatment in children with AD appeared to be very common, at least among those attending the Comano Thermal Spring Water Center. Moreover, many patients followed elimination diets in the absence of reported food allergy. [ABSTRACT FROM AUTHOR]

Background: Chronic urticaria (CU), daily wheals or angioedema that lasts more than 6 weeks, is a common skin disease; CU is classified as spontaneous (no specific eliciting factor involved) or inducible (specific eliciting factor involved). Recent EAACI guidelines for management of CSU recommend second‐generation non‐sedating H1 antihistamines (sgAH1s) as initial treatment in children (weight‐adjusted) as in adults, followed by increased doses (up to 4 times) if the standard dose is not effective. The efficacy and tolerability of fourfold updosing in adults are known, but there is little documentation regarding updosing in the pediatric population. This retrospective study evaluates the efficacy and tolerability of the updosing of sgAH1s in children with CSU in a tertiary care pediatric hospital. Methods: The electronic charts of patients diagnosed with CSU and referred to the Allergy Unit of Meyer Children's University hospital were reviewed during a period of 4 years. For each patient, an examination of demographic characteristics, diagnostic workup, efficacy, and tolerability of the treatment was performed. Disease activity was monitored using UAS7. Results: Sixty‐six cases of CSU were identified, and all of them were treated initially with a standard dose of sgAH1s, followed by increased doses up to fourfold when standard dosing was not effective. 44/66 patients (66.7%) treated with sgAH1s responded: 25 with a standard dose, 16 with a double, 2 with threefold dose, and 1 with fourfold dose. 12/66 (18.2%) patients began a therapy with omalizumab. As for the remaining patients, 10/66 (15.1%), they are still undergoing therapy with sgAH1s because of the relapse of the symptoms after the stepped‐down dosage. Regarding tolerability, 9/66 (13.6%) patients treated with sgAH1s experienced side effects: three that required treatment change and six that did not. Conclusion: Our data were consistent with the tolerability of updosing of sgAH1s in children with CSU, although the efficacy appears to be limited to double the standard dose. [ABSTRACT FROM AUTHOR]

Allergic diseases have different frequencies. In particular, allergic rhinitis and asthma have high frequencies of about 20% and 10%, respectively. Other allergic diseases have lower frequencies; for example, food allergy has a frequency of 1%‐4%. There are also rare allergic diseases, with a prevalence of 5 cases per 10 000 people in the general population, and they are included in Orphanet. However, other extremely rare allergic diseases still need to be properly known in order to be possibly recognized as rare diseases and cataloged in Orphanet. [ABSTRACT FROM AUTHOR]

Adverse reactions to natural rubber latex (NRL) represent a group of clinical manifestations that include non-allergic reactions and immediate-type or delayed-type allergic reactions. NRL sublingual immunotherapy (SLIT) has been demonstrated to be an effective and safe practice for latex clinical manifestations with good patient tolerance. A pediatric case of NRL allergy managed with an effective tailored SLIT is described. This case is compelling because the girl, who did not have an atopic background, suffered from NRL allergy with high reactivity and unique monosensitization. To the best of our knowledge, this is the first case with this characteristic described to date. Moreover, the SLIT follow-up time reported was unusually long, extending from childhood to adulthood. The case described highlights several problems of real-life management, and it demonstrates how the pediatric allergist plays a key role in the management of all these issues in order to succeed in guiding the patient through the immunotherapy process with a personalized approach, in line with the precision medicine principles. However, further long-term clinical studies are needed to better define the natural history of NRL allergy and find new potential biomarkers of response to NRL immunotherapy. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has surprised the entire population. The world has had to face an unprecedented pandemic. Only, Spanish flu had similar disastrous consequences. As a result, drastic measures (lockdown) have been adopted worldwide. Healthcare service has been overwhelmed by the extraordinary influx of patients, often requiring high intensity of care. Mortality has been associated with severe comorbidities, including chronic diseases. Patients with frailty were, therefore, the victim of the SARS-COV-2 infection. Allergy and asthma are the most prevalent chronic disorders in children and adolescents, so they need careful attention and, if necessary, an adaptation of their regular treatment plans. Fortunately, at present, young people are less suffering from COVID-19, both as incidence and severity. However, any age, including infancy, could be affected by the pandemic. Based on this background, the Italian Society of Pediatric Allergy and Immunology has felt it necessary to provide a Consensus Statement. This expert panel consensus document offers a rationale to help guide decision-making in the management of children and adolescents with allergic or immunologic diseases. [ABSTRACT FROM AUTHOR]

Atopic eczema (AE) is the most common inflammatory skin disease in infancy and its prevalence is rising worldwide. It has a wide social impact on the affected children and their families' lives. AE can have a chronic and heterogeneous course, with periods of remission and relapse of the clinical manifestations. For this reason, its severity assessment through standardized outcome measures becomes a fundamental guide for health professionals, who can manage AE following evidence-based medicine principles in their everyday clinical practice or in clinical trials. Several scoring systems have been recognized to assess the clinical manifestations of AE, both from the physician's and the patient's point of view. Despite the scoring systems standardized for adults, there are very few published options about the expression of a patient/caregiver-centered global severity assessment specifically for pediatric AE. For this reason, the aim of our study was to evaluate a new, quick, user-friendly and feasible caregiver-reported global severity assessment for pediatric AE. Based on a 0–10 numerical rating scale in pediatric AE, we named this scoring system the Comano score. We carried out a cross-sectional observational study enrolling a total of 867 patients aged from 1 to 16 years (males 49.5%, mean patient's age 5.9 years, standard deviation ±3.6 years) with a previous doctor-confirmed diagnosis of AE, who underwent balneotherapy at Comano Thermal Center (Comano, Trentino, Italy). A strong correlation between Comano score and SCORing Atopic Dermatitis (SCORAD) was observed (r = 0.74, p < 0.0001). According to our results, the Comano score may be a promising new tool for the expression of a caregiver-reported global severity assessment in pediatric AE. However, further data are needed to confirm our preliminary findings before health professionals can use this scoring system in their everyday clinical practice to manage pediatric AE. Still, as a patient-focused measure, the Comano score may facilitate delivering person-centered care so as to define a measure for a clinical impact that can be meaningful to the subject, which is gaining importance in modern medicine. [ABSTRACT FROM AUTHOR]

Are oral food challenges for introduction of high-risk foods in children with food protein-induced enterocolitis syndrome needed? Abbreviations FPIES Food protein-induced enterocolitis syndrome OFC Oral food challenge PbP Prick by prick s-IgEs Serum specific IgEs SPTs Skin prick tests The cornerstone of the management of acute food protein-induced enterocolitis syndrome (FPIES) is the elimination of the culprit food from the patient's diet. We found that only 6 out of 183 OFCs (3.3%) with high-risk foods were positive and three patients with positive OFCs had FPIES to multiple foods. [Extracted from the article]

Background: Hymenoptera venom allergy (HVA) is an underestimated condition representing an important cause of morbidity and mortality worldwide. Preventing future allergic reactions in patients who have already developed a systemic reaction is based on the correct management of the acute phase of the reaction followed by a correct diagnosis and, where indicated, prescription of adrenaline autoinjectors and VIT. A possible strategy to optimize care processes and to improve outcomes is the implementation of a Diagnostic and Therapeutic Care Pathways, also known as Integrated Care Pathways or Clinical Pathways (CPWs). The aim of the care pathway is to enhance the quality of care by improving risk‐adjusted patient outcomes, promoting patient safety, increasing patient satisfaction, and optimizing the use of resources. To our knowledge, currently in Italy as well as in Europe, there is no CPWs codified for the management of HVA patients. This paper describes the development of the clinical content of a care pathway for the management of HVA. Methods: The methodology applied is based on the eight step method to build the clinical content of an evidence-based care pathway suggested by Lodewijckx et al. Results: Three hundred and seventeen different clinical activities were extracted from the selected literature. The expert panel was involved in their evaluation, expressing a judgment of relevance through the Delphi study. As a result, 126 clinical activities were appraised to be valid and feasible. The final recommendations (126) were translated into 123 key interventions. Six indicators were produced by the clinical activities. Conclusion: A set of 123 key interventions and of six process indicators were found to be appropriate for the development and standardization of the clinical content of the Hymenoptera venom allergy care pathway. [ABSTRACT FROM AUTHOR]

Background: Severe cutaneous adverse reactions (SCARs) are delayed‐type hypersensitivity reactions to drugs including as follows: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Stevens‐Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN) and Acute Generalized Exanthematous Pustulosis (AGEP). Incidence, triggers and management of SCARs have not been investigated in large‐scale epidemiological studies on children. Objective: The aim of our study was to collect epidemiological, clinical and aetiological data from children with SCARs referred to our tertiary care paediatric hospital of Florence. Methods: From 2010 to 2018 charts of children with diagnosis of SCAR were reviewed, and data collected during the acute phase and/or the subsequent allergy evaluation. Patients underwent patch tests, intradermal tests and lymphocyte transformation tests. All children were investigated for infectious diseases. Results: Incidence of SCARs in hospitalized children was 0.32% over a 9‐year period. Fifty‐four children were enrolled (31 M; 23 F; median age 6.5 years): 17 cases of DRESS, 30 SJS, 3 TEN, 2 AGEP, 1 linear immunoglobulin A bullous disease (LABD) and 1 pemphigus. Twenty‐eight out of 54 patients underwent drug allergy investigations, and 50% of them resulted positive. Combining clinical history and results of allergy work‐up, 74% SCARs seem to be caused by drugs, 18.6% by both drugs and infections, 3.7% by infections, and 3.7% remained idiopathic. No deaths occurred. Conclusions: In this study, SCARs incidence is in line with literature data. Drugs were most commonly the leading cause. Management of SCARs requires cooperation among professional figures for an early diagnosis and a prompt treatment. Mortality rate seems to be lower in children. [ABSTRACT FROM AUTHOR]

Forty-five out of 60 patients (75%) passed the OFC, and the children who managed the first day of OFC tolerated the whole meal without any problems; in those who failed (25%), the symptoms were milder without specifying the time latency from the last dose. Choosing the most appropriate OFC protocol is complex, in fact, as the onset of FPIES symptoms is delayed, it is difficult to know the smallest symptom trigger dose. Patients can eat a whole serving dose before the onset of reactions, and however, it is not known whether the same reactions would have occurred even after a smaller dose of the trigger foods. In conclusion, our results, as the method 2 of Infante,[9] show that a quarter of the full dose, as a trigger dose, is sufficient for eliciting reactions and that the temporal latency between the first and second dose should be longer than the 30 minutes as recommended by the current guidelines. [Extracted from the article]

Introduction: Penicillins and cephalosporins are the most frequent causes of hypersensitivity reactions (HRs) to drugs in children. Among cephalosporins for intravenous use, ceftriaxone (CT) is the most frequently prescribed in Italy. The aims of this study were to evaluate the diagnostic methods for CT hypersensitivity in a population of children with suspected HRs to this drug and their tolerance toward amoxi-cillin/clavulanic acid (AMX/CLV). Materials and Methods: From 2012 to 2018, 90 children were investigated for suspected HRs to CT according to the European Academy of Allergy Asthma and Clinical Immunology (EAACI) guidelines. Results: Ninety children had a history of reaction to CT. The majority (79/90; 77.8%) had a history of immediate reactions (IRs). CT hypersensitivity was confirmed in 26/90 patients (28.9%). In case of IRs, skin tests can be useful (24% of positive CT intradermal tests – IDTs) particularly in cases of anaphylaxis (81.8% of positive CT IDTs). Only 5 out of 28 drug provocation tests were positive. Serum-specific IgE (sIgE) determination for CT correlated with positivity upon skin/drug provocation tests (high specificity 95.6%) but had a low sensitivity; sIgE for AMX had a very low positive predictive value (14.3%), advocating against its use. In case of non-IRs, only 7/11 patients reached a confident diagnosis, but the low number of children does not enable proper conclusions. Only 2 children showed cross- and/or co-allergy (2.2%) between CT and AMX/CLV. Conclusion: IDTs seem to be useful for diagnosing CT IRs. Hypersensitivity to CT is confirmed in 28.9% of children, although a large fraction of parents refused an intravenous rechallenge (45.6%). It remains unknown whether this is due to the fact this was intravenous rather than a rechallenge with the culprit, but it reflects a clinical reality. Otherwise, cross- and/or co-allergy between CT and AMX/CLV is a rare event. [ABSTRACT FROM AUTHOR]

Background: Hazelnut allergy (HA) is one of the more common food allergies (FAs) in Europe with a prevalence of 0.2%. The gold standard for diagnosing FA is oral food challenge (OFC) with the culprit food. Another purpose of OFC is to identify the "threshold level" of food as the dose that elicits symptoms. In this way it is possible to avoid a strict elimination diet and to determine the minimal quantity of the culprit food tolerated by the patient. Objective: The aim of our study was to assess the efficacy and tolerability of hazelnut low-dose OFC (H-LDOFC) in children with HA. Methods: From January 2015 to December 2016, we retrospectively analyzed the charts of patients referred to Allergy Unit of Meyer Children's Hospital, Florence, Italy for a history of HA. Prick by prick (PbP) and specific serum IgE (s-IgE) to hazelnut were performed. We proposed conducting an H-LDOFC to parents of children with HA. The H-LDOFC was considered completed when a cumulative dose of 2.5 g of hazelnut was reached. We divided the patients who underwent the H-LDOFC into an asymptomatic and a symptomatic group. For statistics we used SPSS for Windows version 16.0 and conducted a t test for comparing the averages, considering a p value of < 0.05 significant. Results: Forty-three out of 70 patients (61.4%) with HA underwent an H-LDOFC. The PbP to hazelnut (mean ± SD) was 7.2 ± 2.9 mm and the s-IgE to hazelnut 25.3 ± 32.5 kU/L. Twenty-eight out of the 43 patients (65.1%) who underwent H-LDOFC reached the cumulative dose of 2.5 g of hazelnut. During the H-LDOFC, 20/43 patients (46.5%) had no reactions and 23/43 patients had a total of 55 reactions: 34 (61.8%) oral allergy syndrome, 8 (14.5%) rash, 6 (10.9%) abdominal pain, 2 (3.6%) urticaria, 2 (3.6%) angioedema, and 3 (5.4%) dyspnea. Atopic dermatitis was found to present the only statistically significant difference (p = 0.002) in patients with symptoms compared to asymptomatic patients during H-LDOFC. Conclusions: To our knowledge, this was the first study to assess the efficacy and tolerability of H-LDOFC in a pediatric population. Our study suggests that in children with HA, H-LDOFC is well accepted and safe because adverse reactions are mild and the majority are represented by localized symptoms (oral allergy syndrome) and efficient, especially in terms of improvement of quality of life. For these reasons it could be more extensively used in the treatment of HA. [ABSTRACT FROM AUTHOR]

Keywords: hymenoptera venom allergy; real-life stings; venom immunotherapy EN hymenoptera venom allergy real-life stings venom immunotherapy 209 211 3 02/24/21 20210201 NES 210201 To the Editor, It is known that a Hymenoptera sting cannot be avoided with absolute certainty in a patient affected by Hymenoptera venom allergy (HVA). Indeed, for example, it has been established for particular extracts of VIT for honeybees, that the content of the relevant allergens is mainly represented by Api m 1, and the other allergens make up only to 0.6-2% of their dry weight.12 On the other side, it has been shown that honeybee venom, in addition to Api m 1, contains multiple allergens such as Api m 2, Api m 3, Api m 4, Api m 5 and Api m 10. Component-resolved evaluation of the content of major allergens in therapeutic extracts for specific immunotherapy of honeybee venom allergy. [Extracted from the article]

When all the pins elicited the wheals, it was considered "severe" dermatographism.[2] The chi-square test was used to assess the relationship between the different forms of urticaria and dermatographism and between atopy and dermatographism. Investigating the degree of dermatographism, severe dermatographism was present in 17/92 (18.5%) patients with dermatographism and, in particular, in 16 cases and one control. The statistical analysis showed a significant correlation ( I P i < .001) between dermatographism and urticaria and between severe dermatographism and urticaria. [Extracted from the article]

The article presents two case studies to demonstrate T-cell activation in patients with Stevens-Johnson syndrome (SJS) after receiving amoxicillin-clavulanic acid. It mentions that in the first case drug was stopped and he received supportive therapies, including a short course of corticosteroids, fluid replacement with electrolyte solution and analgesic therapy. The case study points out that SJS requires hospitalization in childhood, and role of pathogens in it remain unidentified.

Background: The basophil activation test (BAT), has been proposed as a possible assay for the diagnosis of immediate-type allergy to beta-lactams (BLs). The aim of this study was to assess the utility of BAT in the diagnosis of amoxicillin (AMX) or AMX-clavulanate (AMX-C) IgE-mediated hypersensitivity in children and adults. Material and methods: Eighteen children and 21 adults, with clinical history of immediate reactions to AMX or AMX-C, were referred to Anna Meyer Children's Hospital and San Giovanni di Dio Hospital, respectively. They underwent in vivo tests (skin prick test and intradermal test). Moreover, BAT with AMX or AMX-C was performed within 6 months from the reaction. Results: In the pediatric group, the concordance between the skin tests (ST) and BAT results was 83.3%. Upon comparing the symptom grades and ST results to the BAT results, we found that the reaction severity and ST positivity did not correlate with BAT results in children. In the adult group, the concordance between the ST and BAT results was 61.9%. Upon comparing patients with severe reactions and patients with mild reactions in terms of BAT results, we found a BAT sensitivity of 38.5% and a specificity of 100%. When comparing the symptom grades to the BAT results, we found that no patients with mild symptoms had a positive BAT result, whereas 38.5% of patients with severe symptoms had a positive BAT result. Conclusions: BAT does not seem to be a useful tool to increase the sensitivity of an allergy work-up to diagnose immediate hypersensitivity to AMX or AMX-C. [ABSTRACT FROM AUTHOR]

The aim of this paper is to provide an alternative and more efficient screening test for allergy with respect to traditional UNICAP and prick skin tests, which are commercially available nowadays. The proposed test is aimed at monitoring the interaction of the IgE protein with the allergen in an allergic subject. The idea relies on the fact that the interaction between the IgE and the corresponding allergen happens through binding mechanisms between the IgE and the allergen structure, changing the ionic content of the serum. This latter can be monitored by impedance measurements and confirmed by reactive oxygen species (ROS) evaluation in leukocyte subpopulations. Therefore, in this paper we propose a novel system for the detection of allergies based on impedance measurements and confirmed by ROS measurements. This type of measurement approach has never been presented in the literature for this purpose. A measurement protocol has been developed to guarantee reproducibility and repeatability of the assay. This paper describes both the instrument—specifically designed for impedance evaluation—and the measurement protocols for both methodologies, defining univocally, in this way, the overall measurement technique. [ABSTRACT FROM AUTHOR]

Background: The study describes the demographic features, culprit foods, clinical features and outcomes for children presenting with acute fish and/or shellfish food protein-induced enterocolitis syndrome (FPIES) infour Italian paediatric allergy centres. Methods: A retrospective/prospective study was undertaken. All children diagnosed with fish or shellfish FPIES were enrolled. The diagnosis of FPIES was based on Sicherer's or Miceli Sopo clinical criteria. Skin prick tests (SPT) were performed in all patients, at the time of diagnosis and prior to OFC. Results: Seventy children were enrolled. Mean age at first episode was 14 months (range 6-46 months); mean age at diagnosis was 34 months (range 6-164 months). Sole and cod were the fish most commonly implicated. Fifty-seven of 70 (81%) children had FPIES exclusively to fish, 37 of 57 (65%) children had single-fish FPIES, 20 of 57 (35%) multiple-fish FPIES, nine of 70 (13%) presented adverse reactions exclusively to shellfish, and four of 70 (6%) presented adverse reactions to both fish and shellfish. Only four (5.7%) children presented episodes of acute FPIES with different foods (2 to cow's milk, 1 to egg, 1 to beef); in all cases, onset was prior to that of fish or shellfish FPIES. Fifteen of 70 (21%) children tolerated fish other than the offending fish. Twenty-four of 70 (34%) children achieved tolerance (age range 24- 102 months). Conclusions: The chief peculiarities of acute fish and shellfish FPIES, compared to more frequent cow's milk or soy FPIES, are (i) later age of onset, (ii) longer persistence and (iii) possibility of tolerating fish other than the offending fish. Adverse reactions with shellfish are possible. [ABSTRACT FROM AUTHOR]

Background Vernal keratoconjunctivitis ( VKC) is a chronic sight-threatening ocular disease. Topical cyclosporine A (Cyc) has been widely administered as a steroid-sparing drug, although in about 7-10% of cases, it has been ineffective. The purpose of this study was to evaluate the efficacy of 0.1% topical tacrolimus (Tcr) in patients with severe VKC who failed to respond to 1% Cyc eyedrops. Methods Consecutive patients with severe, Cyc-resistant VKC were enrolled in a double-blind, comparative, crossover ( DBCO) trial; all patients were treated with 1% Cyc in one eye and 0.1% Tcr in the other eye for 3 wk. After a washout period of 7 days, patients were instructed to cross over the medications for three additional weeks. Objective ocular score, subjective score, and quality-of-life questionnaires (Qo LQ) were collected during the trial. Blood samples were drawn to assess several safety parameters. Results Thirty patients have been enrolled (mean age 9.05 ± 2.12 yr). In each of the two phases of the DBCO trial, a significant improvement in objective and subjective scores was observed in the eyes treated with 0.1% Tcr (p < 0.001). Likewise, the quality of life significantly improved despite only half the eyes being successfully treated. Serum creatinine and blood parameters were constantly within the normal range, and both blood Cyc and Tcr concentrations remained below the lowest detectable levels. Conclusions Topical Tcr is very effective and safe in the short term for patients suffering from severe VKC resistant to topical Cyc. [ABSTRACT FROM AUTHOR]

Hemophilia B is a rare X-linked recessive disorder with plasma factor IX (FIX) deficiency. 1-3% of patients treated with exogenous FIX-containing products develop inhibitors (i.e. polyclonal high affinity immunoglobulins) that neutralize the procoagulant activity of a specific coagulation factor. Although the incidence of inhibitors in hemophilia B patients is low, most are “high titer” and frequently associated with the development of severe allergic or anaphylactic reactions. Immune tolerance induction as a strategy for inhibitor eradication was first described in 1984. Unfortunately, the overall reported success of immune tolerance induction in FIX deficiency with inhibitors is approximately 25-40%. We report the case of a 2-year-old boy with hemophilia B severe FIX deficiency (<1%), inhibitor antibodies to FIX development, and a history of adverse reactions to FIX infusions, who underwent a successful desensitization and immune tolerance induction with a daily FIX infusion. With this regimen the inhibitor titer decreased with effective bleeding prevention. [ABSTRACT FROM AUTHOR]

The article presents a case study of a four-year-old boy with severe atopic dermatitis (AD). Topics include the patient's history of persistent rhinitis and milk/egg-induced anaphylaxis, efficacy of omalizumab therapy against AD, and the potential role of house dust mites (HDM) allergy in AD severity.

No Abstract. [ABSTRACT FROM AUTHOR]

Non-steroidal anti-inflammatory drugs are suspected to cause drug hypersensitivity very frequently in paediatric patients. In this article, we describe the first case of anaphylaxis to flurbiprofen in a child and provide insight into the possibility of severe reactions and even anaphylaxis to over-the-counter flurbiprofen. Finally, the importance of a rigorous allergy work-up in reaching a confident diagnosis and providing the patient with a safe alternative is shown. [ABSTRACT FROM AUTHOR]

Hormones may play a role in the pathophysiology of vernal keratoconjunctivitis (VKC). An increased incidence of thyroid autoantibodies was recently observed in VKC, although there were no data on thyroid function. Two hundred and eighty-eight patients (202 males, 86 females; range 5.5 to 16.9 years) with VKC were evaluated and compared with 188 normal age- and sex-matched subjects. In all subjects, serum concentrations of free T4, TSH, thyroperoxidase, thyroglobulin, and TSHr autoantibodies were evaluated. In VKC, the family history of thyroid diseases showed no significant differences compared to the controls (9.4 versus 8.6%), whereas the family history of autoimmune diseases was significantly higher (13.2% versus 6.3%; P < 0.05). Subclinical hypothyroidism was diagnosed in 6.6% (versus 1.6% of the controls; P < 0.05) and overt hypothyroidism in 0.7% (versus 0.0% of the controls; P = NS). Finally, 5.2% of patients were positive for thyroid autoantibodies, which were significantly higher with respect to the controls (0.5%, P < 0.05). In the patients positive for thyroid autoantibodies, 80% showed a sonography pattern that suggested autoimmune thyroiditis. Thyroid function and autoimmunity abnormalities are frequently present in children with VKC. Children with VKC should be screened for thyroid function and evaluated for thyroid autoimmunity. [ABSTRACT FROM AUTHOR]

Mori F, Pucci N, Rossi ME, de Martino M, Azzari C, Novembre E. Oral desensitization to milk: how to choose the starting dose! Pediatr Allergy Immunol 2010: 21: e450–e453. © 2009 John Wiley & Sons A/S A renewed interest in oral desensitization as treatment for food allergy has been observed in the last few years. We studied a novel method based on the end point skin prick test procedure to establish the starting dose for oral desensitization in a group of 30 children higly allergic to milk. The results (in terms of reactions to the first dose administered) were compared with a group of 20 children allergic to milk as well. Such control group started to swallow the same dose of 0.015 mg/ml of milk. None reacted to the first dose when administered according to the end point skin prick test. On the other side, ten out of 20 children (50%) from the control group showed mild allergic reactions to the first dose of milk. In conclusion the end point skin prick test procedure results safe and easy to be performed in each single child in order to find out the starting dose for oral desensitization to milk, also by taking into account the individual variability. [ABSTRACT FROM AUTHOR]

Sublingual-specific immunotherapy (SLIT) is considered as a valid treatment of respiratory allergies. However, there are few data on large sample size regarding its clinical role in ‘real life’ in term of reduction of symptoms, rescue medications and prevention of asthma in patients suffering from allergic rhinitis (AR) especially in children. We performed a multicenter, case–control study to evaluate the effect of SLIT in children (age 6–18 yr) with intermittent or persistent AR. 171 children (27% girls and 73% boys) with AR due to seasonal or perennial allergens were enrolled in a multicenter case–control study. Cases (n = 90) were defined as patients with intermittent (64%) or persistent (36%) AR who were treated for at least two consecutive years with specific SLIT with the related allergen extracts (SLITone® ALK-Abellò). Controls (n = 81) were defined as sex-age- and type of allergen matched AR children who were never treated with specific immunotherapy and had no asthmatic symptoms at the beginning of observation period. Main outcomes of the study were the rhinoconjunctivitis symptom score (SS) (sneezing, rhinorrea, nasal itch, congestion, ocular itch and watery eyes) with a ranging scale from 0 (=no symptoms) to 3 (=severe symptoms) and the medication score (MS) evaluating symptomatic drug intake (antihystamine and inhaled corticosteroids). SS and MS were evaluated at the end of the observational period in relation with the period, considering the last 12 months, in which patients suffered the highest symptoms levels (i.e., peak of relevant pollen season (seasonal AR) or during the period of maximum allergen exposure in case of perennial AR). Secondary outcome of the study was the development of asthma symptoms during the observation period. SS (mean ± SD) was 4.5 ± 2.5 in cases and 9.0 ± 3.0 in controls (−50%) (p = 0.0001). MS (mean ± SD) was 2.5 ± 1.9 and 3.6 ± 2.1 in the case and control groups, respectively (−31%) (p = 0.0001). At the end of the observation period asthma symptoms were present in 14 subjects in the case group (15%) and in 20 children (24%) in the control group (p = 0.13). New skin sensitizations appeared in 6% of cases (n = 2) and in 36% (n = 12) of the controls (p = 0.001). The EFESO trial shows that a 2-yr once daily SLIT treatment in children with intermittent or persistent AR is associated with lower symptom and medication scores in comparison with subjects treated with symptomatic drugs only. [ABSTRACT FROM AUTHOR]