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.

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.

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.

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.

Drugs and Vaccines Hypersensitivity in Children with Mastocytosis.

Mastocytosis, a heterogeneous mastcell disease, include three different entities: cutaneous mastocytosis, systemic mastocytosis (SM) and mast-cell sarcoma. Tryptase levels can differentiate cutaneous mastocytosis from SM. In mastocytosis, quick onset drug hypersensitivity reactions (DHRs) that are facilitated by mastcell mediators, are investigated in adults. Due to the limited number of children with mastcell disease and increased serum tryptase levels, the role of drugs in this age group is less studied. In this review, we critically assessed relevant papers related with immediate DHRs in children with mastocytosis and discuss practical issues of the management. In childhood mastocytosis, anaphylaxis is frequently idiopathic, and elevated level of basal tryptase, and high burden of disease may increase the risk. Among drugs, antibiotics, NSAIDs and opioids can potentially induce anaphylaxis, anyway avoidance should be recommended only in case of previous reactions. Moreover, vaccinations are not contraindicated in patients with mastocytosis. The risk of severe systemic reactions after drugs intake seems to be extremely low and in general lower in children than in adults. Anyway, studies on this topic especially focusing on children, are missing to state final recommendations.

Tailored therapies for primary immunodeficiencies.

Primary immunodeficiency disorders (PIDs) are rare inherited monogenic disorders of the immune system, characterized by an increased risk of infection, immune dysregulation and malignancies. To date, more than 420 PIDs have been identified. The recent introduction of high throughput sequencing technologies has led to identifying the molecular basis of the underlying aberrant immune pathway, and candidate targets to develop precision treatment, aimed at modifying the clinical course of the disease. In PID, targeted therapies are especially effective to manage immune dysregulation and autoimmunity, also reducing the incidence of side effects compared to conventional treatments, sparing the use of steroids and immunosuppressive drugs. Moreover, in the last years, the approach of conventional treatments such as immunoglobulin replacement therapies has evolved and the indication has expanded to new diseases, leading to individualized strategies to both improve infection control and quality of life.  Similarly, the new advent of gene therapy in selected PIDs has introduced the benefit to correct the immunological defect, reducing at the same time the complications related to the hematopoietic stem cell transplantation. Here, we illustrate the most recent findings on tailored treatments for PIDs.

Non-invasive biomarkers of eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is an emerging allergen-mediated disease characterized by symptoms of esophageal dysfunction and eosinophilic inflammation. EoE diagnosis requires 15 eosinophils per high power field (eos/HPF) in tissue biopsies endoscopically obtained. The need for several endoscopies to monitoring the disease and the absence of validated non-invasive biomarkers or tools are the main reasons for the significant burden on affected patients and the healthcare system. There is a critical need for non-invasive or minimally invasive biomarkers. In the last years, several efforts have been made to identify potential biomarkers for diagnosing and monitoring the disease that we summarized in this review. The future of EoE is exciting from both a diagnostic and therapeutic standpoint. Further research is required to confirm phenotypes and histological or serological biomarkers to provide a novel endotype classification based on different cytokine or genetic signatures relevant to precision medicine.

Inter-society consensus for the use of inhaled corticosteroids in infants, children and adolescents with airway diseases.

BACKGROUND: In 2019, a multidisciplinary panel of experts from eight Italian scientific paediatric societies developed a consensus document for the use of inhaled corticosteroids in the management and prevention of the most common paediatric airways disorders. The aim is to provide healthcare providers with a multidisciplinary document including indications useful in the clinical practice. The consensus document was intended to be addressed to paediatricians who work in the Paediatric Divisions, the Primary Care Services and the Emergency Departments, as well as to Residents or PhD students, paediatric nurses and specialists or consultants in paediatric pulmonology, allergy, infectious diseases, and ear, nose, and throat medicine. METHODS: Clinical questions identifying Population, Intervention(s), Comparison and Outcome(s) were addressed by methodologists and a general agreement on the topics and the strength of the recommendations (according to the GRADE system) was obtained following the Delphi method. The literature selection included secondary sources such as evidence-based guidelines and systematic reviews and was integrated with primary studies subsequently published. RESULTS: The expert panel provided a number of recommendations on the use of inhaled corticosteroids in preschool wheezing, bronchial asthma, allergic and non-allergic rhinitis, acute and chronic rhinosinusitis, adenoid hypertrophy, laryngitis and laryngospasm. CONCLUSIONS: We provided a multidisciplinary update on the current recommendations for the management and prevention of the most common paediatric airways disorders requiring inhaled corticosteroids, in order to share useful indications, identify gaps in knowledge and drive future research.

Childhood Obesity and Respiratory Diseases: Which Link?

Prevalence of childhood obesity is progressively increasing, reaching worldwide levels of 5.6% in girls and of 7.8% in boys. Several evidences showed that obesity is a major preventable risk factor and disease modifier of some respiratory conditions such as asthma and Obstructive Sleep Apnea Syndrome (OSAS). Co-occurrence of asthma and obesity may be due to common pathogenetic factors including exposure to air pollutants and tobacco smoking, Western diet, and low Vitamin D levels. Lung growth and dysanapsis phenomenon in asthmatic obese children play a role in impaired respiratory function which appears to be different than in adults. Genes involved in both asthma and obesity have been identified, though a gene-by-environment interaction has not been properly investigated yet. The identification of modifiable environmental factors influencing gene expression through epigenetic mechanisms may change the natural history of both diseases. Another important pediatric respiratory condition associated with obesity is Sleep-Disordered Breathing (SDB), especially Obstructive Sleep Apnea Syndrome (OSAS). OSAS and obesity are linked by a bidirectional causality, where the effects of one affect the other. The factors most involved in the association between OSAS and obesity are oxidative stress, systemic inflammation, and gut microbiota. In OSAS pathogenesis, obesity's role appears to be mainly due to mechanical factors leading to an increase of respiratory work at night-time. However, a causal link between obesity-related inflammatory state and OSAS pathogenesis still needs to be properly confirmed. To prevent obesity and its complications, family education and precocious lifestyle changes are critical. A healthy diet may lead to an improved quality of life in obese children suffering from respiratory diseases. The present review aimed to investigate the links between obesity, asthma and OSAS, focusing on the available evidence and looking for future research fields.

Mast Cell Activation Disorders.

Background and Objectives: Mast cell disorders comprise a wide spectrum of syndromes caused by mast cells' degranulation with acute or chronic clinical manifestations. Materials and Methods: In this review article we reviewed the latest findings in scientific papers about mast cell disorders with a particular focus on mast cell activation syndrome and mastocytosis in pediatric age. Results: Patients with mast cell activation syndrome have a normal number of mast cells that are hyperreactive upon stimulation of various triggers. We tried to emphasize the diagnostic criteria, differential diagnosis, and therapeutic strategies. Another primary mast cell disorder is mastocytosis, a condition with a long-known disease, in which patients have an increased number of mast cells that accumulate in different regions of the body with different clinical evolution in pediatric age. Conclusions: Mast cell activation syndrome overlaps with different clinical entities. No consensus was found on biomarkers and no clearly resolutive treatment is available. Therefore, a more detailed knowledge of this syndrome is of fundamental importance for a correct diagnosis and effective therapy.

Tuberculosis and TNF-α inhibitors in children: how to manage a fine balance.

Since the introduction of biologic response modifiers (BRMs) in the management of children affected by the immune-mediated inflammatory disease, these patients substantially improved their quality of life. BRMs are generally well tolerated and effective in most children and adolescents refractory to conventional immunosuppressive therapy. On the other hand, patients receiving BRMs, especially TNF-α inhibitors, display an increased risk of primary infections or reactivations, i.e. due to Mycobacterium tuberculosis. M. tuberculosis can cause severe disease with consequent short- and long-term morbidity in children on anti-TNF-α treatment. The present paper analyses the increased risk of reactivation of latent tuberculosis infection (LTBI) or de novo TB infection in children treated with TNF-α inhibitors, with the purpose to provide recommendations for screening strategies and safety monitoring of paediatric patients. Special attention is also given to the currently available TB screening tools (IGRAs and TST) and their utility in the diagnosis of LTBI before starting the biologic therapy and during the treatment. Finally, the paper analyses the suggested TB-preventing therapies to adopt in these children and the correct timing to overlap anti-TB and anti-TNF-a treatment.

Update in Primary Immunodeficiencies.

Primary immunodeficiencies (PIDs) are inherited disorders classically characterized by increased susceptibility to infections. Nevertheless, in the last two decades, genomic analysis (such as NGS) coupled with biochemical and cellular studies led to a more accurate definition for a growing number of novel genetic disorders associated with PIDs. This revealed new aspects of the immune system and its function and regulation within these diseases. In particular, it has been clarified that the clinical features of PIDs are much broader that originally thought and extend beyond an increased susceptibility to infections. More specifi- cally, immune dysregulation is very often described in novel characterized PIDs and can lead to multiple autoimmune diseases, lymphoproliferation and malignancies. If not promptly diagnosed, these could negatively impact patient's prognosis. The aim of this review is to increase the awareness of recently discovered PIDs, characterized predominantly by immune dysregulation phenotypes. Findings highlighted in this review  suggest screening for immunodeficiency in patients with lymphoproliferation or early onset/multiple autoimmune diseases. Prompt diagnosis would potentially allow most successful treatment and clinical outcome for patients with PIDs.

Preschool Wheezing: Trajectories and Long-Term Treatment.

Wheezing is very common in infancy affecting one in three children during the first 3 years of life. Several wheeze phenotypes have been identified and most rely on temporal pattern of symptoms. Assessing the risk of asthma development is difficult. Factors predisposing to onset and persistence of wheezing such as breastfeeding, atopy, indoor allergen exposure, environmental tobacco smoke and viral infections are analyzed. Inhaled corticosteroids are recommended as first choice of controller treatment in all preschool children irrespective of phenotype, but they are particularly beneficial in terms of fewer exacerbations in atopic children. Other therapeutic options include the addition of montelukast or the intermittent use of inhaled corticosteroids. Overuse of inhaled steroids must be avoided. Therefore, adherence to treatment and correct administration of the medications need to be checked at every visit.

Hypersensitivity Reactions to Monoclonal Antibodies in Children.

Biologic drugs are widely used in pediatric medicine. Monoclonal antibodies (mAbs) in particular are a therapeutic option for rheumatic, autoinflammatory and oncologic diseases. Adverse drug reactions and hypersensitivity reactions (HSR) to mAbs may occur in children. Clinical presentation of HSRs to mAbs can be classified according to phenotypes in infusion-related reactions, cytokine release syndrome, both alpha type reactions and type I (IgE/non-IgE), type III, and type IV reactions, all beta-type reactions. The aim of this review is to focus on HSRs associated with the most frequent mAbs in childhood, with particular attention to beta-type reactions. When a reaction to mAbs is suspected a diagnostic work-up including in-vivo and in-vitro testing should be performed. A drug provocation test is recommended only when no alternative drugs are available. In selected patients with immediate IgE-mediated drug allergy a desensitization protocol is indicated. Despite the heavy use of mAbs in childhood, studies evaluating the reliability of diagnostic test are lacking. Although desensitization may be effective in reducing the risk of reactions in children, standardized pediatric protocols are still not available.

Report on advances for pediatricians in 2018: allergy, cardiology, critical care, endocrinology, hereditary metabolic diseases, gastroenterology, infectious diseases, neonatology, nutrition, respiratory tract disorders and surgery.

This review reported notable advances in pediatrics that have been published in 2018. We have highlighted progresses in allergy, cardiology, critical care, endocrinology, hereditary metabolic diseases, gastroenterology, infectious diseases, neonatology, nutrition, respiratory tract disorders and surgery. Many studies have informed on epidemiologic observations. Promising outcomes in prevention, diagnosis and treatment have been reported. We think that advances realized in 2018 can now be utilized to ameliorate patient care.

Management of the child with allergy to non-antibiotic drugs.

Non-steroidal anti-inflammatory drugs, perioperative drugs, radio contrast media and chemotherapeutics drugs are, after the non-antibiotic drugs, the drugs most commonly responsible for allergic reactions in children. Management is different depending on the drug involved.

Drug desensitization in allergic children.

Drug allergy is an increasing problem worldwide, affecting all populations and races, children and adults, and for which diagnosis and treatment are not well standardized yet. Besides classical treatments, new drugs have been developed, especially for patients suffering from malignancies and chronic inflammatory diseases, that specifically target the cause of the disease. For those patients requiring such molecules, it is sometimes difficult to find an alternative drug when hypersensitivity reactions occur. Desensitization is therefore the best option whenever no alternative therapy is available but also when alternative treatments are considered therapeutically inferior and or more toxic. Despite its clinical success, little is known about the mechanisms and molecular targets of drug desensitization. Desensitization protocols use a gradual dose escalation to allow the safe administration of a treatment to which a patient previously presented a hypersensitivity reaction. The procedure requires special training and coordination of an allergy team, including physicians, nurses, and pharmacists, working together to safely and successfully implement desensitization protocols when appropriate. There is no difference in desensitization protocol between adults and children, except for the final cumulative dose of the administered drug.

Pediatric drug hypersensitivity: which diagnostic tests?

Along with the anamnesis and clinical evaluation, diagnostic tests are one of the mainstream key points in the evaluation and management of drug hypersensitivity reactions (DHR). A wide knowledge gap, both in diagnosis and management of pediatric DHR, must be filled.  Only a few published studies evaluated sensitivity and specificity of skin and in vitro tests in children. However, selected case series show that diagnostic work-up for adults could be useful, with some limitations, in pediatric age. Indeed, despite improvement in in vivo and in vitro diagnosis, drug provocation test remains the gold standard in pediatric age, too. Unmet needs in children include multi-centric studies on incidence of DHR, utility and feasibility of in vivo and in vitro diagnostic tests and specifically dedicated guidelines for the diagnosis and management of DHR in children.