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.

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.

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.

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.

An oesophageal spring.

Oesophageal foreign bodies (OFBs) are a relatively common emergency in young children. OFBs are complicated by significant morbidity and mortality because their ingestion often occurs without witnesses, leading to a delay in diagnosis and treatment. We report an occult OFB in an 11-month-old infant who initially presented without any specific respiratory symptoms, mimicking a respiratory infection. Worsening of the patient's cough, which did not show any improvement, despite treatment, and progressive onset of gastrointestinal manifestations (dysphagia, vomiting, and drooling) led to the diagnosis of an OFB (metallic spring). The complex and long-term clinical course of the patient highlights the need of promptly recognizing the presence of an occult OFB. This is because rapid diagnosis and treatment are essential for preventing severe and sometimes irreversible complications.