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Abstract Drug hypersensitivity reactions are common in children. Risk factors predisposing to IgE-mediated drug allergies and delayed drug reactions are a matter of debate. Gender, age, previous reactions to the same drug or to another drug, reduced drug metabolism, chronic diseases, polypharmacy, drug doses are linked with the onset of hypersensitivity reactions in some children. Novel advances in genetic polymorphisms can rapidly change the approach to the prevention of reactions since gene testing can be a useful screening test for severe cutaneous adverse reactions. Viral infections may act as cofactors in susceptible individuals. Polypharmacy, high doses, repeated doses and parental route of administration are also risk factors. Clinicians should take into account risk factors to allow the risk–benefit balance to be maintained.

Several studies have shown the effects of e-cigarettes in adults. Nowadays, few data are available in the pediatric population. This study aims to assess the relationship between asthma exacerbations and home exposure to e-cigarettes. We conducted a pilot, retrospective, monocenter, observational study. Demographic and clinical data were collected, including number of asthma exacerbations, need for rescue therapy and/or therapeutic step-up, and Asthma Control Test (ACT) and children-Asthma Control Test (c-ACT) scores. The cohort consisted of 54 patients (5–17 years old), divided into two groups: A, including patients exposed to e-cigarette aerosols; B, including unexposed patients. The statistical analysis showed no relevant variation in the number of asthma symptomatic days and need for rescue therapy in group A versus group B (p = 0.27 and 0.19, respectively). There were no statistically significant variations when also considering the number of patients who needed a therapeutic step-up (p = 0.3). The mean values of ACT and c-ACT were, respectively, 17.2 ± 7.6 and 18.3 ± 5.6 in group A and 19.6 ± 3.8 and 14.6 ± 5.8 in group B (p = 0.3 and 0.4, respectively). Although we did not find a statistically significant correlation between second-hand e-cigarette exposure and asthma exacerbations, our findings suggest that asthmatic children exposed second-hand to e-cigarettes may have increased risk of asthma symptomatic days. Future research is warranted.

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.

Background: Despite the increasing interest in biologics for the management of allergic diseases, sparse real-world data are still available in the pediatric population. This study aimed to evaluate the early real-life efficacy and safety of omalizumab for patients with moderate-to-severe asthma and chronic spontaneous urticaria (CSU), and Dupilumab for patients with moderate-to-severe atopic dermatitis (AD). Methods: A prospective study enrolling children aged 6–18 years was designed to assess the efficacy and safety of biologic drugs at 16 weeks of treatment (T1). The effectiveness was measured using validated questionnaires (ACQ-5 for asthma, UAS7 for CSU, and EASI score for AD). Secondary outcome measures included reductions in inhaled corticosteroid (ICS) dosages, asthma-related hospitalizations/exacerbations, and quality of life (QoL) indicators (iNRS, sNRS, DLQI/cDLQI) for CSU and AD. Safety was expressed according to the descriptions of adverse events provided by EMA and FDA. Results: The study cohort consisted of eighteen children (mean age 12.9 ± 3.4 years). The omalizumab treatment significantly reduced ACQ-5 and UAS7 scores (p = 0.002 and p < 0.001, respectively). In patients with asthma, decreased ICS dosage and hospitalization/exacerbation rates were observed. QoL parameters significantly improved in CSU and AD patients. No severe adverse events were reported for either treatment. Conclusions: Our findings validate omalizumab and dupilumab as effective and safe therapeutic options for managing moderate-to-severe allergic diseases in children and adolescents.

Background: Allergic rhinitis (AR) is the most common chronic allergic disease in children. Several studies have shown an association between attention deficit hyperactivity disorder (ADHD) and allergies, especially AR. Patients with ADHD usually have poor therapeutic adherence, and untreated AR symptoms may worsen the quality of life of patients. Methods: The aim of our study was to analyse therapeutic adherence in patients with ADHD and AR and estimate the impact of the adherence on ADHD symptoms. Total Nasal Symptoms Score (TNSS), Paediatric or Adolescent Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ 6–12 years; ARQLQ 13–17 years), Swanson, Nolan, and Pelham version IV scale (SNAP-IV), and Medication Assessment Questionnaire (MGL MAQ) were recorded. Results: In the AR-ADHD group, a positive correlation between TNSS and SNAP-IV subscales was found: worse AR symptoms were related to a negative effect on ADHD scores. AR-ADHD patients with better ADHD therapeutic adherence showed higher AR symptoms and higher oppositional defiant disorder scores in the SNAP-IV questionnaire. Conclusions: Our results suggest that better adherence to AR therapy (oral antihistamines and/or intranasal corticosteroids, INCS) is associated with a reduction in inattention symptoms in children with ADHD. This data could prove to be fundamental for the psychic outcome of these patients.

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

Background: Insufficient data are available on the long-term “real-life” safety profile of omalizumab in children. This study evaluated the long-term safety of omalizumab in a pediatric cohort with severe asthma or chronic spontaneous urticaria (CSU). Methods: A monocentric, prospective study evaluated the long-term safety of omalizumab in patients aged 6–18 years. Each patient completed the standardized MedDRA questionnaire to identify adverse events (AEs). Results: In total, 23 patients, median age 15 (14–18) years, affected by severe asthma (60.8%) or CSU (39.2%), treated with omalizumab for 2 (1–4) years were enrolled. The most common AEs belong to the system organ class (SOC) of general disorders and administration-site conditions (37.17%). Skin and subcutaneous tissue problems represent the second most frequently reported AEs (24.35%). Central nervous system and musculoskeletal disorders were quite frequent (15.38% and 8.97%, respectively). Other adverse events were tachycardia (5.12%), vertigo and abdominal pain (2.60% and 3.86%, respectively), and dry eye (1.3%). Only one patient reported herpes virus infection during treatment (1.3%). No cases of anaphylaxis, hemopathies, uronephropathies, respiratory, psychiatric, hepatobiliary, or oncological pathologies were reported. Conclusions: Long-term “real-life” treatment with omalizumab in children appears well tolerated. Its safety and efficacy profile makes omalizumab an excellent alternative in severe asthma and CSU in children.

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.

Food allergy is a potentially life-threatening condition and a significant public health concern worldwide. The current management includes food avoidance and use of emergency medications. The growing prevalence of food allergy drives research towards specific allergen immunotherapy (AIT), which represents a potential disease-modifying approach. AIT consists of the progressive administration of amounts of the offending allergen in order to induce food desensitisation, creating an increase in reaction threshold with regular exposure to the allergen. AIT can be performed through oral, sublingual, epicutaneous, and subcutaneous routes. The target is to achieve post desensitisation effectiveness: a long-lasting condition allowing patients to introduce food without reactions, even after a period of discontinuation of the offending food.

Abstract Thyroid cancer (TC) in childhood is a rare disease characterized by an excellent prognosis. Thyroid nodules in children, although less common than in adults, have a greater risk of malignancies, particularly in those cases associated with anamnestic, clinical and ultrasonographic risk factors. Among the factors, which have been found to be linked with an increased relative risk of TC in children, an important role seems to be possibly played by an underlying nodular Hashimoto’s thyroiditis (HT) and by the serum levels of TSH. Aim of this Commentary was to specifically address this last point. According to the available pediatric literature on the relationships between these risk factors and phenotypical expression of TC in children, it is possible to conclude that: 1) It is not completely clarified if HT per se predisposes to malignancy or if it represents an incidental histologic finding in cases with TC or if it may be the result of an immune response against tumoral cells. 2) It is unclear whether phenotypic expression of TC is more severe in the cases with associated HT but normal TSH serum levels. 3) Persistently elevated TSH levels play an independent role as predictors of the likelihood of TC, especially in children but also in adults. 4) Patients with nodular HT and subclinical hypothyroidism need to be treated with Levothyroxine in order to prevent the development of both TC and severe thyroid dysfunctions.

Abstract The aim of this guidance is to provide recommendations to clinicians and other interested parties on chronic urticaria in children. The Italian Society for Pediatrics (SIP), the Italian Society for Allergy and Immunology (SIAIP), the Italian Society for Pediatric dermatology (SIDerP) convened a multidisciplinary panel that prepared clinical guidelines for diagnosis and management of chronic urticaria in childhood. Key questions on epidemiology, natural history, diagnosis, and management were developed. The literature was systematically searched and evaluated, recommendations were rated and algorithms for diagnosis and treatment were developed. The recommendations focus on identification of diseases and comorbidities, strategies to recognize triggering factors, improvement of treatment by individualized care.

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

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 radiocontrast media seem to be rare in children. Furthermore, the use of radiocontrast media in children remains quite safe in terms of the severity of reactions. Since pediatric guidelines are lacking, the diagnostic workup employed in adults could be adapted to children, taking into account that results have not yet been validated in this age group. Specific protocols for risk stratification and management of severe reactions have been proposed so far.

Abstract Drug hypersensitivity reactions (DHRs) in childhood are mainly caused by betalactam or non-betalactam antibiotics, and non-steroidal anti-inflammatory drugs (NSAIDs). Laboratory tests for identifying children who are allergic to drugs have low diagnostic accuracy and predictive value. The gold standard to diagnose DHR is represented by the drug provocation test (DPT), that aims of ascertaining the causative role of an allergen and evaluating the tolerance to the suspected drug. Different protocols through the administration of divided increasing doses have been postulated according to the type of drug and the onset of the reaction (immediate or non immediate reactions). DPT protocols differ in doses and time interval between doses. In this position paper, the Italian Pediatric Society for Allergy and Immunology provides a practical guide for provocation test to antibiotics and NSAIDs in children and adolescents.

Abstract Aim of this commentary is to analyze the relationships between genotypic bases and phenotypic expression of congenital “multiple pituitary hormone deficiency” (MPHD) syndrome and to indicate some reliable criteria for selecting the patients who should undergo genetic analyses in order to clarify the etiology of their disorder. On the basis of the most recent reports on this topic, it is possible to infer that: 1) in only few patients with congenital MPHD it is possible to detect a causative gene mutation; 2) therefore, it is fundamental to define some criteria for selecting the patients who should undergo genetic analyses; 3) such inclusion criteria should be based on the overall evaluation of hormonal clinical and neuroradiological phenotype; 4) it is crucial to consider whether the cases are sporadic or familial, since the probability of finding a causative gene mutation is distinctly higher in familial cases; 5) for PROP1 gene it is also important to consider the geographical origin of the patients, because this mutation is much more frequent in some ethnic groups.

Abstract Aim of this commentary is to report the main peculiarities that have been found to characterize the phenotypic expression of autoimmune thyroid diseases (AITDs) in children with Down’s syndrome (DS). According to recent reports, DS children are, per se, more exposed to the risk of both Hashimoto’s thyroiditis (HT) and Graves’ disease (GD), irrespective of other concomitant risk factors, such as female gender and family antecedents for AITDs. In the context of extra-thyroidal autoimmune disorders, the ones that preferentially aggregate with AITDs in DS children are alopecia areata and vitiligo. Another peculiar aspect, in DS children, is that HT presents with a more severe biochemical picture, which furtherly deteriorates over time. By contrast, GD does not demonstrate a more severe clinical and biochemical picture with respect to that generally observed in patients without DS. Finally, DS children might be at higher risk of progressing from HT toward GD over time.

Abstract ᅟ Aim of this commentary is to summarize the salient literature views on the relationships between presentation and evolution patterns of thyroid function in children with Hashimoto’s thyroiditis (HT). According to the most recent reports, children with HT and subclinical hypothyroidism (SH) are more prone to the risk of developing severe thyroid dysfunctions over time, if compared to those presenting with euthyroidism. In contrast, children presenting with HT and either overt or subclinical hyperthyroidism are incline to exhibit a definitive resolution of the hyperthyroid phase within some months, although there is a wide variability between the different individuals. The natural history of frank hypothyroidism in the children with HT has never been investigated so far, since in these cases an immediate onset of replacement treatment is mandatory. Conclusions 1) a deterioration of thyroid status over time may be observed especially in the children presenting with SH, but also in those presenting with euthyroidism; 2) a definitive resolution of the hyperthyroid phase is generally observed in those presenting with either overt or subclinical hyperthyroidism.

The COVID-19 pandemic is the most challenging global health crisis of our times. Vaccination against COVID-19 plays a key role to control the current pandemic situation. The risk of allergic reactions to new COVID-19 vaccines is low. However, there is a debate on the safety in allergic patients following post marketing findings by different agencies. Our aim is to understand from current experiences whether children with cow’s milk or food allergy are at higher risk than a general population for allergic reactions to COVID-19 vaccines. Current data indicate that patients with a history of allergy to cow’s milk or other foods, even if severe, should receive COVID-19 vaccine in a setting with availability of treatments for anaphylactic reactions and under medical supervision. Recipients should be discharged after a protracted observation period of 30 min if no reaction developed.

Aim of this mini review was to analyze the main variables which should be taken into account when the decision regarding a possible treatment with L-T4 has to be considered for a child with subclinical hypothyroidism (SH). The indications of periodical monitoring and vigilance have been also discussed. It was inferred that therapy should be recommended for children with underlying Hashimoto's thyroiditis and progressive deterioration of thyroid status over time, particularly in the cases with goiter and hypothyroid symptoms and in those with associated Turner syndrome or Down's syndrome and/or other autoimmune diseases. Treatment might also be recommended for children with proatherogenic metabolic abnormalities. Treatment is not advisable in children with idiopathic and mild SH, no goiter, no hypothyroid symptoms and negative anti-thyroid autoantibodies. In the absence of any therapeutic intervention, clinical status and thyroid function tests should be periodically monitored, in order to individuate the children who might benefit from treatment. It has been suggested that children with a persistent mild elevation of TSH, who are not treated with L-T4, should undergo biochemical monitoring of thyroid function and re-assessment of clinical status every 6 months. After 2 years with stable thyroid function tests, the interval between monitoring can be extended.

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.

Context: Asthma is the most common inflammatory disease of the airways in children. The term problematic asthma is used to describe children with chronic symptoms or acute severe exacerbations, or both, not responding to standard asthma therapy. Case Presentation: We describe the case of a 5 years old girl with a history of recurrent respiratory infections and asthma since the first months of life, with a poor response to conventional therapies (antibiotics, high dose corticosteroids combined with long-acting β2 agonists and oral leukotriene-receptor antagonists). In some cases she needed hospitalization for the important respiratory engagement and radiological findings of pulmonary consolidations, predominantly localized to the right lung. Computed tomography angiography (CTA), described a mild tracheobronchomalacia caused by the right innominate artery compression and a dense tissue mediastinal extrinsic compression of the main bronchus of the middle lobe, defined a Middle Lobe Syndrome (MLS). Evidence Acquisition: MLS is defined as a recurrent or chronic collapse or infection of the middle lobe of the right lung. There is often a history of multiple treatments with antibiotics and anti-asthmatic drugs for ‘‘recurrent pneumonia’’ or ‘‘asthma’’, as in our patient. Chest X-ray is the first-line diagnostic tool, especially on the lateral view. CT-scan and bronchoscopy are considered useful for diagnosis or treatment. Treatment depends on etiology of MLS. Conclusion: In case of severe asthma symptoms co-morbidities must be evaluated. MLS is frequently unrecognized in children and thinking of it is a prerequisite for diagnosis, especially when recurrent respiratory infections or asthma symptoms are predominantly localized to the right lung.

AbstractChildhood immunisation is one of the greatest public health successes of the last century. Vaccines contain an active component (the antigen) which induces the immune response. They may also contain additional components such as preservatives, additives, adjuvants and traces of other substances. This review provides information about risks of hypersensitivity reactions to components of vaccines. Furthermore, recommendations to avoid or reduce reactions to vaccine components have been detailed.

IntroductionThe Health Assessment Questionnaire (HAQ) has been translated into many languages and it has been classified as the predictor of disability and medical costs, however, the psychometric properties of the HAQ have never been studied in a population with neurological disease. The purpose of this study was the evaluation of the psychometric properties of HAQ in a population of individuals with multiple sclerosis (MS).Materials and MethodsThis cross-sectional study was conducted with patients diagnosed with MS. The evaluation tools administered were the 36-item short form health survey (SF–36) to evaluate the health state of the patients and HAQ and to evaluate the limitations of the activities of daily living (ADL).ResultsA total of 34 patients were included in this study. Cronbach's alpha assessed the internal consistency of the HAQ, and it is equal to 0.94. The study revealed some significant correlations between the dimensions of the SF-36 and the sub-categories of the HAQ using Pearson's Correlation Coefficient. Significant correlations emerged between the demographic and clinical characteristics of patients and the subcategories of HAQ.DiscussionThe HAQ is a valid and reliable tool to assess the limitations of the activities of daily living, and it could provide for the healthcare and rehabilitation sector with an additional evaluation tool.