Drug-Induced Anaphylaxis in Children.

Drug-induced anaphylaxis in children is less common than in adults and primarily involves beta-lactams and nonsteroidal anti-inflammatory drugs. Epidemiological studies show variable prevalence, influenced by age, gender, and atopic diseases. The pathophysiology includes IgE-mediated reactions and non-IgE mechanisms, like cytokine release reactions. We address drug-induced anaphylaxis in children, focusing on antibiotics, nonsteroidal anti-inflammatory drugs, neuromuscular blocking agents, and monoclonal antibodies. Diagnosis combines clinical criteria with in vitro, in vivo, and drug provocation tests. The immediate management of acute anaphylaxis primarily involves the use of adrenaline, coupled with long-term strategies, such as allergen avoidance and patient education. Desensitization protocols are crucial for children allergic to essential medications, particularly antibiotics and chemotherapy agents.

IgE to cyclophilins in pollen-allergic children: Epidemiologic, clinical, and diagnostic relevance of a neglected panallergen.

BACKGROUND: Cyclophilins are ubiquitous panallergens whose epidemiologic, diagnostic, and clinical relevance is largely unknown and whose sensitization is rarely examined in routine allergy practice. OBJECTIVE: We investigated the epidemiologic, diagnostic, and clinical relevance of cyclophilins in seasonal allergic rhinitis and its comorbidities. METHODS: We examined a random sample of 253 (25%) of 1263 Italian children with seasonal allergic rhinitis from the Panallergens in Pediatrics (PAN-PED) cohort with characterized disease phenotypes. Nested studies of sensitization prevalence, correlation, and allergen extract inhibition were performed in patients sensitized to birch pollen extract but lacking IgE to Bet v 1/2/4 (74/1263) or with highest serum level of IgE to Bet v 1 (26/1263); and in patients with sensitization to various extracts (ragweed, mugwort, pellitory, Plantago, and plane tree), but not to their respective major allergenic molecule, profilins, and polcalcins. IgE to cyclophilin was detected with recombinant Bet v 7, and extract inhibition tests were performed with the same rBet v 7. RESULTS: IgE to rBet v 7 was detected in 43 (17%) of 253 patients. It was associated with asthma (P < .028) and oral allergy syndrome (P < .017) in univariate but not multivariate analysis adjusted for IgE to profilins (Phl p 12), PR-10s (Bet v 1), and lipid transfer proteins (Pru p 3). IgE to rBet v 7 was also highly prevalent (47/74, 63%) among patients with unexplained sensitization to birch pollen extract. In patients with unexplained sensitization to ragweed, mugwort, pellitory, Plantago and plane tree pollen, the levels of IgE to those extracts correlated with the levels of IgE to rBet v 7, and they were also significantly inhibited by rBet v 7 (inhibition range 45%-74%). CONCLUSIONS: IgE sensitization to cyclophilin is frequent in pollen-allergic patients living in temperate areas and can produce "false" positive outcomes in skin prick and IgE tests to pollen extracts. Molecular diagnostic guidelines should include this panallergen family.

IgE to cross-reactive carbohydrate determinants (CCD) in childhood: Prevalence, risk factors, putative origins.

BACKGROUND: IgE antibodies to cross-reactive carbohydrate determinants (CCD) are usually clinically irrelevant but they can be a cause of false positive outcomes of allergen-specific IgE tests in vitro. Their prevalence and levels have been so far cross-sectionally examined among adult allergic patients and much less is known about their origins and relevance in childhood. METHODS: We examined CCD with a cross-sectional approach in 1263 Italian pollen allergic children (Panallergen in Paediatrics, PAN-PED), as well as with a longitudinal approach in 612 German children (Multicenter Allergy Study, MAS), whose cutaneous and IgE sensitization profile to a broad panel of allergen extracts and molecules was already known. The presence and levels of IgE to CCD were examined in the sera of both cohorts using bromelain (MUXF3) as reagent and a novel chemiluminescence detection system, operating in a solid phase of fluorescently labelled and streptavidin-coated paramagnetic microparticles (NOVEOS, HYCOR, USA). RESULTS: IgE to CCD was found in 22% of the Italian pollen allergic children, mainly in association with an IgE response to grass pollen. Children with IgE to CCD had higher total IgE levels and were sensitized to more allergenic molecules of Phleum pratense than those with no IgE to CCD. Among participants of the German MAS birth cohort study, IgE to CCD emerged early in life (even at pre-school age), with IgE sensitization to group 1 and 4 allergen molecules of grasses, and almost invariably persisted over the full observation period. CONCLUSIONS: Our results contribute to dissect the immunological origins, onset, evolution and risk factors of CCD-sIgE response in childhood, and raise the hypothesis that group 1 and/or 4 allergen molecules of grass pollen are major inducers of these antibodies through an antigen-specific, T-B cell cognate interaction.

Local Anesthetic Hypersensitivity Reactions in Pediatric Patients: Recognition and Management.

Local anesthetics (LAs) are commonly used in all medical specialties, particularly in association with surgery, obstetrics, dentistry, and emergency departments. Most individuals, starting from young children, are exposed to LAs during life. LA hardly induces adverse events when used in recommended doses and with proper injection techniques. However, immediate anaphylactic reactions to LA injections may be a rare but life-threatening manifestation. A comprehensive report of the event and performing a specialist examination are crucial to prevent further episodes. The diagnosis should be based on history, medical records, skin and challenge tests.

Fish Allergy and Related Conditions in Children: A Review.

Fish allergy is the important food allergies in childhood, often persisting into adulthood. It can cause severe hypersensitivity reactions, including fatal anaphylaxis; furthermore, avoiding-fish diet has negative nutritional and psychological effects. Recent research studies focus on epitope structures and aim to develop sensitive and specific diagnostic tools, which have a better correlation with clinical reactions. Protocols with hypoallergenic parvalbumin or other recombinant antigens are also under study and will likely lead to new immunotherapy protocols. IgE-mediated fish allergy differs substantially from other forms of immunological adverse reactions to fish, such as Food Protein-Induced Enterocolitis Syndrome and eosinophilic esophagitis. In addition, fish ingestion can cause non-immunological adverse reactions, such as in the case of scombroid poisoning, anisakiasis and toxic poisoning. This review aims to summarize the characteristics of the main immunological and non-immunological fish reactions, analyzing the epidemiology, clinical manifestations, diagnosis and therapy, with a particular focus on clinical management.

Cold Anaphylaxis in Children: Italian Case Series and Review of the Literature.

Chronic urticaria (CU) is one of the most common skin disorders worldwide. Among the inducible subgroup of CU, cold urticaria (ColdU) can affect both children and adults and is the only type associated with the risk of anaphylaxis without cofactors. In the scientific literature, data about cold anaphylaxis (ColdA) are poor, especially at pediatric age, and little is known about risk factors associated with the onset of systemic reactions and about the criteria for prescribing adrenaline auto-injectors (AAIs) in these patients. We describe the clinical characteristics and management of a case series of 21 patients with a history of ColdA, and we compare them with the pediatric case reports and case series published so far. On the basis of the scientific literature and of our case series of patients, we suggest that AAI should be prescribed to all high-risk patients: those with urticaria caused by cold-water immersion, oropharyngeal reactions, and with a previous history of systemic symptoms or anaphylaxis.

Maintenance Therapy for Children and Adolescents with Asthma: Guidelines and Recommendations from the Emilia-Romagna Asthma (ERA) Study Group.

Asthma is the most frequent chronic disease of childhood, affecting up to 20% of children worldwide. The main guidelines on asthma maintenance therapy in pediatrics suggest different approaches and describe different stages of asthma to determine the most appropriate treatment. This project aims to summarize the most recent evidence regarding maintenance therapy for asthma in children and adolescents. A multidisciplinary panel of experts was asked clinical questions regarding the treatment of children and adolescents with asthma. Overall, 10 clinical questions were addressed, and the search strategy included accessing electronic databases and a manual search of gray literature published in the last 25 years. After data extraction and narrative synthesis of results, recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. Results showed that the choice of medication depends on the severity of the child's asthma, phenotype, age, preference, and individual factors. In addition to medications, the identification of comorbidities and modifiable factors is crucial to obtaining good control. Asthma in children is heterogeneous, and its evolution varies over time. Since most recommendations for asthma management in childhood are extrapolated from clinical studies performed in adults, more clinical trials specifically designed for young children should be conducted.

Year 2022: exploring COVID-19 pandemic in children.

COVID-19 pandemics is rapidly changing. In this article, we review progresses published in the Italian Journal of Pediatrics in 2022. More data on clinical pictures, prevention strategies and active management in children have been provided. The continued evolution of knowledge has driven transformations in the clinical approach to the disease and allowed key advancements in the care of children with COVID-19.

Advances for pediatricians in 2022: allergy, anesthesiology, cardiology, dermatology, endocrinology, gastroenterology, genetics, global health, infectious diseases, metabolism, neonatology, neurology, oncology, pulmonology.

The last year saw intensive efforts to advance knowledge in pediatric medicine. This review highlights important publications that have been issued in the Italian Journal of Pediatrics in 2022. We have chosen papers in the fields of allergy, anesthesiology, cardiology, dermatology, endocrinology, gastroenterology, genetics, global health, infectious diseases, metabolism, neonatology, neurology, oncology, pulmonology. Novel valuable developments in epidemiology, pathophysiology, prevention, diagnosis and treatment that can rapidly change the approach to diseases in childhood have been included and discussed.

Anti-inflammatory and biologic drugs for atopic dermatitis: a therapeutic approach in children and adolescents.

Atopic dermatitis (AD) is a chronic inflammatory disease with a heterogeneous pathogenesis correlated with dysregulation of the immune system and a prevalence of the T2-mediated immune pathway. Recent understanding of the pathogenesis of AD has allowed the development of new drugs targeting different mechanisms and cytokines that have changed the treatment approach. The aim of this review is to update knowledge on the standard of care and recent advancements in the control of skin inflammation. In light of recent guidelines, we report on the clinical efficacy of novel treatments, with special attention to situations where biologics and small molecules are involved.

Are Babies Born Preterm High-Risk Asthma Candidates?

Among preterm infants, the risk of developing asthma is a matter of debate. This review discusses the state of the art of poorly understood prematurity-associated asthma. Impaired pulmonary function is common in children born prematurely. Preterm infants are prone to developing viral respiratory tract infections, bronchiolitis in the first year of life, and recurrent viral wheezing in preschool age. All of these conditions may precede asthma development. We also discuss the role of both atopic sensitization and intestinal microbiome and, consequently, immune maturation. Diet and pollution have been considered to better understand how prematurity could be associated with asthma. Understanding the effect of factors involved in asthma onset may pave the way to improve the prediction of this asthma phenotype.

IgE Mediated Shellfish Allergy in Children-A Review.

Shellfish is a leading cause of food allergy and anaphylaxis worldwide. Recent advances in molecular characterization have led to a better understanding of the allergen profile. High sequence homology between shellfish species and between shellfish and house dust mites leads to a high serological cross-reactivity, which does not accurately correlate with clinical cross-reactions. Clinical manifestations are immediate and the predominance of perioral symptoms is a typical feature of shellfish allergy. Diagnosis, as for other food allergies, is based on SPTs and specific IgE, while the gold standard is DBPCFC. Cross-reactivity between shellfish is common and therefore, it is mandatory to avoid all shellfish. New immunotherapeutic strategies based on hypoallergens and other innovative approaches represent the new frontiers for desensitization.

Severe Pemphigus Vulgaris Resistant to Conventional Therapies and with Hypersensitivity to Rituximab in a 12-Year-Old Child.

Pemphigus vulgaris (PV) is a rare, potentially lethal blistering disease typically occurring in adulthood and characterized by autoantibodies directed against mucocutaneous desmosomal proteins. Clinically, flaccid vesicles, bullae and erosions after breakage are the main clinical features. According to the literature, the incidence of PV is rare in the pediatric population, ranging from 1 to 4% of reported cases. We describe an interesting case of a 12-year-old boy with severe PV that was referred to our university hospital for a mucocutaneous disease resistant to anti-infective therapy. Following the appearance of bullous lesions on the skin, antibody screening for autoimmune diseases showed positivity for PV and corticosteroid therapy was started. In view of the numerous adverse effects, we decided to set up biological therapy with rituximab, which was interrupted due to the onset of an urticarial reaction. Further second-line therapies were therefore attempted, with only a partial response. For this reason, a desensitizing therapy with rituximab was decided, thus allowing a clear improvement in the clinical picture and quality of life of the patient. To the best of our knowledge, this is the first report of a child with severe PV resistant to conventional therapies and with an urticarial reaction to rituximab. This case highlights that despite PV being extremely rare in the pediatric population, this diagnosis should not be entirely discounted. In case of severe clinical manifestations, rituximab represents a valid option in children and desensitization tests should be recommended in the presence of hypersensitivity to this drug.

Current knowledge on the effects of environmental contaminants in early life nutrition.

Breast milk represents the optimal source of feeding for newborns, in terms of nutritional compounds and as it provides immunological, metabolic, organic, and neurological well-being. As a complex biological fluid, it consists not only of nutritional compounds but also contains environmental contaminants. Formulas through production, contact with bottles and cups, and complementary feeding can also be contaminated. The current review focuses on endocrine-disrupting chemicals, and made-man xenoestrogens present in the environment and both commonly present in food sources, agricultural practices, packaging, consumer products, industry, and medical care. These contaminants are transferred by passive diffusion to breast milk and are delivered during breastfeeding. They mainly act by activating or antagonizing hormonal receptors. We summarize the effects on the immune system, gut microbiota, and metabolism. Exposure to endocrine-disrupting chemicals and indirect food additives may induce tissue inflammation and polarize lymphocytes, increase proinflammatory cytokines, promote allergic sensitization, and microbial dysbiosis, activate nuclear receptors and increase the incidence of allergic, autoimmune, and metabolic diseases. Breast milk is the most important optimal source in early life. This mini-review summarizes current knowledge on environmental contaminants and paves the way for strategies to prevent milk contamination and limit maternal and infant exposure during pregnancy and the first months of life.

Inhaled Short-Acting Beta Agonist Treatment-Associated Supraventricular Tachycardia in Children: Still a Matter of Concern in Pediatric Emergency Departments?

Inhaled selective short-acting ß-2 agonists (SABA), such as salbutamol, are the rescue treatment of choice for the relief of symptoms of acute asthma exacerbations: one of the leading causes of pediatric emergency department admission and hospitalization. Cardiovascular events, including supraventricular arrhythmias, are the most frequent side effects reported with inhaled SABA in children with asthma and are the main reason for a continuing debate about their safety, despite their widespread use. Although supraventricular tachycardia (SVT) is the most common potentially serious dysrhythmia in children, the incidence and risk factor of SVT after SABA administration is currently unknown. We here reported three cases and conducted a review of the literature in an attempt to gain insight into this issue.

Natural History of Hazelnut Allergy and Current Approach to Its Diagnosis and Treatment.

Hazelnut allergy is the most prevalent type of nut allergy in Europe, with symptoms that can range from mild, such as hives and itching, to severe, such as anaphylaxis, particularly in patients who are sensitized to highly stable allergens, such as storage proteins. Compared to other types of food allergies, allergies to tree nuts, including hazelnuts, tend to persist throughout life. Although symptoms can appear in early childhood, they often continue into adulthood, with a minority of cases improving during adolescence. Currently, there is no curative treatment available for hazelnut allergy, and patients must adhere to a restrictive diet and carry autoinjective epinephrine. However, oral allergen immunotherapy (AIT) is a promising treatment option. Patients can be categorized based on their risk for severe reactions using various clinical, in vivo, and in vitro tests, including component-resolved diagnosis and oral food challenge. This review aims to provide an overview of the current knowledge of the natural history of hazelnut allergy and new approaches for its diagnosis and management.

New insights in pediatrics in 2021: choices in allergy and immunology, critical care, endocrinology, gastroenterology, genetics, haematology, infectious diseases, neonatology, neurology, nutrition, palliative care, respiratory tract illnesses and telemedicine.

In this review, we report the developments across pediatric subspecialties that have been published in the Italian Journal of Pediatrics in 2021. We highlight advances in allergy and immunology, critical care, endocrinology, gastroenterology, genetics, hematology, infectious diseases, neonatology, neurology, nutrition, palliative care, respiratory tract illnesses and telemedicine.

Risk Factors Affecting Development and Persistence of Preschool Wheezing: Consensus Document of the Emilia-Romagna Asthma (ERA) Study Group.

Wheezing at preschool age (i.e., before the age of six) is common, occurring in about 30% of children before the age of three. In terms of health care burden, preschool children with wheeze show double the rate of access to the emergency department and five times the rate of hospital admissions compared with school-age asthmatics. The consensus document aims to analyse the underlying mechanisms involved in the pathogenesis of preschool wheezing and define the risk factors (i.e., allergy, atopy, infection, bronchiolitis, genetics, indoor and outdoor pollution, tobacco smoke exposure, obesity, prematurity) and the protective factors (i.e., probiotics, breastfeeding, vitamin D, influenza vaccination, non-specific immunomodulators) associated with the development of the disease in the young child. A multidisciplinary panel of experts from the Emilia-Romagna Region, Italy, addressed twelve key questions regarding managing preschool wheezing. Clinical questions have been formulated by the expert panel using the PICO format (Patients, Intervention, Comparison, Outcomes). Systematic reviews have been conducted on PubMed to answer these specific questions and formulate recommendations. The GRADE approach has been used for each selected paper to assess the quality of the evidence and the degree of recommendations. Based on a panel of experts and extensive updated literature, this consensus document provides insight into the pathogenesis, risk and protective factors associated with the development and persistence of preschool wheezing. Undoubtedly, more research is needed to improve our understanding of the disease and confirm the associations between certain factors and the risk of wheezing in early life. In addition, preventive strategies must be promoted to avoid children's exposure to risk factors that may permanently affect respiratory health.

Hypersensitivity to Intravenous Iron Preparations.

Intravenous iron is widely used for the treatment of iron deficiency anemia when adherence to oral iron replacement is poor. Acute hypersensitivity reactions during iron infusions are very rare but can be life threatening. Major risk factors for hypersensitivity reactions include a previous reaction to an iron infusion, a fast iron infusion rate, multiple drug allergies, atopic diseases, high serum tryptase levels, asthma, and urticaria. The management of iron infusions requires meticulous observation, and, in the event of an adverse reaction, prompt recognition and severity-related interventions by well-trained medical and nursing staff. Avoidance of IV iron products in patients with iron hypersensitivity reactions may not be considered as a standard practice.

The year 2021 in COVID-19 pandemic in children.

In this article, the developments in the field of COVID-19 pandemic published in the Italian Journal of Pediatrics in 2021 are reflected. We describe progresses in SARS-CoV-2 transmission route, clinical presentation, diagnosis, treatment, and access to health care facilities in children. They led to substantial changes in the clinical approach.