Hypersensitivity reactions to vaccines in children: from measles to SARS-CoV-2.

Allergic individuals at risk for hypersensitivity reactions to measles vaccine marketed for a long time are well established. On the other hand, risk factors for hypersensitivity reactions to the new mRNA COVID-19 vaccines currently include a history of allergy, allergy to excipient of the vaccine, or hypersensitivity reactions to the first dose of COVID-19 vaccine. In the last two cases, the recipient should be assessed by an allergist before vaccination to share a decision on the choice of vaccination. Studies on skin testing accuracy and desensitization protocols to the COVID-19 vaccines and the efficacy of potential alternatives in patients with confirmed hypersensitivity reactions to the first COVID-19 vaccine are necessary to improve the safety of COVID-19 vaccines.

The history of the drug-induced enterocolitis syndrome.

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.

Radiocontrast Media Hypersensitivity Reactions in Children.

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.

Hypersensitivity reactions to proton pump inhibitors in childhood.

Hypersensitivity reactions (HRs) to proton pump inhibitors (PPIs) are mainly described in adults. Anyway, increased use of PPIs in childhood has been observed in recent years. In the literature, only case reports are published on children. Most of the PPI HRs are IgE-mediated. Skin test concentrations and allergy workup protocols used for adults are also applied in children. This study underlies that multicentric pediatric studies focusing on PPI reactions in children are needed.

Epidemiology of rare allergic diseases in children.

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.

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.

Component-Resolved Diagnosis in Food Allergies.

Component-resolved diagnostics (CRD) in food allergies is an approach utilized to characterize the molecular components of each allergen involved in a specific IgE (sIgE)-mediated response. In the clinical practice, CRD can improve diagnostic accuracy and assist the physician in many aspects of the allergy work-up. CRD allows for discriminatory co-sensitization versus cross-sensitization phenomena and can be useful to stratify the clinical risk associated with a specific sensitization pattern, in addition to the oral food challenge (OFC). Despite this, there are still some unmet needs, such as the risk of over-prescribing unnecessary elimination diets and adrenaline auto-injectors. Moreover, up until now, none of the identified sIgE cutoff have shown a specificity and sensitivity profile as accurate as the OFC, which is the gold standard in diagnosing food allergies. In light of this, the aim of this review is to summarize the most relevant concepts in the field of CRD in food allergy and to provide a practical approach useful in clinical practice.

Evaluating children with suspected allergic reactions to vaccines for infectious diseases.

BACKGROUND: Vaccines often contain potentially allergenic material in addition to pathogen-specific immunogens that may induce allergic reactions. Parents and physicians often suspect that adverse reactions to vaccines are allergic in etiology. The concern that some of the substances contained in vaccines may trigger an anaphylactic reaction may lead to a low vaccination adherence with emergence of infectious disease epidemics. OBJECTIVE: To provide practical suggestions for managing children suspected to have an allergic reaction to a vaccine. METHODS: Information was obtained from a search of guidelines and relevant studies on allergic reactions to vaccines for infectious diseases. RESULTS: True allergic reactions elicited by a vaccine are rare. Skin testing to the vaccine and to its components may identify the triggering agent. Graded dosing desensitization is helpful in children sensitized to the offending vaccine. CONCLUSION: All children with a suspected allergic reaction to a vaccine should be carefully evaluated by routine allergy tests. When it is necessary, further immunization should be given under strict medical surveillance, which ensures that every child can safely complete the vaccination schedule.

Matrix effect on baked egg tolerance in children with IgE-mediated hen's egg allergy.

BACKGROUND: Children with IgE-mediated hen's egg allergy (IgE-HEA) often tolerate baked egg within a wheat matrix. OBJECTIVE: To evaluate the influence of wheat matrix and the effects of little standardized cooking procedures on baked egg tolerance. METHODS: Fifty-four children with IgE-HEA were enrolled. They underwent prick-by-prick (PbP) tests and open oral food challenges (OFC) performed with baked HE within a wheat matrix (a home-made cake, locally called ciambellone), baked HE without a wheat matrix (in the form of an omelet, locally named frittata) and boiled HE. Three months after passing ciambellone OFC, parents were asked to answer a survey. RESULTS: About 88% of children tolerated ciambellone, 74% frittata, and 56% boiled HE. Negative predictive value of PbP performed with ciambellone, frittata, and boiled HE was 100%. No IgE-mediated adverse reactions were detected at follow-up carried out by the survey. CONCLUSIONS: Wheat matrix seemed to be relevant only in few cases. If our results will be confirmed by larger studies, a negative PbP with ciambellone, frittata, or boiled HE will allow patients with IgE-HEA to eat these foods without undergoing OFC. Moreover, our study showed that very strict standardized cooking procedures do not seem to be essential, to guarantee tolerance toward baked HE.

Risk factors for drug hypersensitivity reactions in children.

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.

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.

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.

Elimination Diets in Lactating Mothers of Infants with Food Allergy.

Breastfeeding is the most important nutrition source for infants. However, managing breastfed infants with signs and symptoms related to food allergy can be difficult. Many studies have shown the presence of different food allergens in breast milk, but the clinical role of these antigens in human milk is still much debated. Milk is the main suspect in exclusively breastfed infants with signs and symptoms attributable to food allergy, even if other foods may be responsible. This narrative review analyzes the recommendations provided by international guidelines to determine the diagnosis and management of IgE-mediated and non-IgE-mediated food allergies in exclusively breastfed infants. Dietary restrictions in lactating mothers of infants with suspected FA are usually not necessary. Only in the very few cases where significant allergy signs and symptoms occur in the infant during exclusive breastfeeding should the lactating mother follow an elimination diet for the suspected food for a short period.

Pediatric idiopathic anaphylaxis: practical management from infants to adolescents.

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.

Imported allergens in Italy: an emerging issue.

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.