IgE-Mediated and Non-IgE-Mediated Fish Allergy in Pediatric Age: A Holistic Approach-A Consensus by Diagnostic Commission of the Italian Society of Pediatric Allergy and Immunology.

Fish is one of the "big nine" foods triggering allergic reactions. For this reason, fish allergens must be accurately specified on food labels. Fish allergy affects less than 1% of the world population, but a higher prevalence is observed in pediatric cohorts, up to 7%. Parvalbumin is the main fish allergen found in the muscles. In childhood, sensitization to fish allergens occurs most frequently through the ingestion of fish, rarely transcutaneously or by inhalation. Fish allergy symptoms usually appear within two hours of the allergen contact. The diagnosis begins with the collection of the history. If it is suggestive of fish allergy, prick tests or the measurement of serum-specific IgE should be performed to confirm the suspicion. The oral food challenge is the gold standard for the diagnosis. It is not recommended in case of a severe allergic reaction. It is important to make a differential diagnosis with anisakiasis or scombroid poisoning, which have overlapping clinical features but differ in pathogenesis. Traditionally, managing fish allergy involves avoiding the triggering species (sometimes all bony fish species) and requires an action plan for accidental exposures. The present review will analyze IgE- and non-IgE-mediated fish allergy in children from epidemiology, pathogenesis to clinical features. Moreover, clinical management will be addressed with a particular focus on potential nutritional deficiencies.

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.

A two-week summer program promoting physical activity: quality of life assessment in Italian children.

Physical activity (PA) can be associated with better health-related quality of life (HRQoL). This study aimed to assess HRQoL before and after a two-week summer program promoting PA in Italian school-aged children. Participants were recruited during the Giocampus summer2017 (Parma, Italy), from June to July. Before (T0) and after (T1) the program, children and one of their parents answered the Kindl questionnaire. For each domain, least-square mean changes (LSmc) at T1 were derived from linear regression models stratified by responder and adjusted for child gender, age group, time spent in PAs and HRQoL score of the responder at T0. 350 children (7-13 years, 52% males) and 342 parents answered the questionnaire at both T0 and T1. At T1, the HRQoL score of the children significantly improved in the emotional (LSmc 2.9, p<0.001), self-esteem (LSmc 3.3, p<0.001), family (LSmc 4.2, p<0.001) and friend (LSmc 3.1, p<0.001) domains. Parents reported significantly more improvement in self-esteem than children (LSmc 6.7 vs 3.3, p=0.012). Children spending more time in PA reported significantly more improvement in self-esteem than those doing less PA (LSmc 4.4 [p<0.001] vs 2.2 [p=0.181]). A short summer program promoting PA may improve HRQoL in the general population of school-aged children.

Role of in vitro testing in food allergy.

Oral food challenges remain the gold standard for the diagnosis of food allergy. Nevertheless, the allergy workup is based on the presence of a clinical history, which is evocative of an immune-allergic reaction, and the first assessment is usually the performance of skin prick tests. Based on these results, allergists are used to evaluate the presence of serum-specific IgE, which are today the most commonly prescribed in vitro test for the evaluation of a possible food allergy. Other in vitro tests include the basophil activation test, that is becoming more and more employed by clinicians and not only by researchers, and the evaluation of serum IgG4, which is still an issue of debate in the allergy community. The present paper reviews the use of these in vitro tests for the diagnosis of food allergy.

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.

New insights into food protein-induced enterocolitis in children.

Food protein-induced enterocolitis syndrome (FPIES) represents a non-IgE-mediated food allergic disorder with delayed gastrointestinal symptoms that may evolve in a medical emergency. Clinically, FPIES can be distinguished into acute and chronic phenotypes. FPIES is mainly diagnosed in infancy however the onset at older ages is being progressively described. The pathogenetic mechanism underlying FPIES remains mainly unexplained, but an alteration of food-specific T-cell response has been proposed. The diagnosis of FPIES is primarily clinical, since there are not available specific biomarkers. Oral food challenge (OFC) is the gold standard for diagnosing FPIES or excluding the onset of tolerance to the triggering food. Management of FPIES includes an acute phase treatment and a maintenance therapy with the strict food avoidance until challenge, in order to prevent new attacks and avoid nutritional alterations. Acute management requires hydration that can be performed orally or intravenously according to clinical status. Long-term management of FPIES is based on the avoidance of the culprit food(s) and supervised introduction of other high-risk foods if never taken before among infants before 12 months of age. There is a compelling need of future achievements in FPIES research for the definition of underlying disease pathogenesis and potential therapeutic point of care.

Early molecular biomarkers predicting the evolution of allergic rhinitis and its comorbidities: A longitudinal multicenter study of a patient cohort.

BACKGROUND: Pollen-related seasonal allergic rhinoconjunctivitis (SAR) is a very frequent pediatric disease in Westernized countries. Risk factors and disease phenotypes have been thoroughly examined in several cross-sectional studies. By contrast, only a few studies have examined disease evolution in patient cohorts. We investigated predictive biomarkers of disease evolution in a large cohort of children with SAR. METHODS: During 2015-2017 (follow-up), we re-examined 401 patients from those enrolled in 2009-2011 (baseline) by the "Panallergens in Pediatrics" study, a large multicenter survey of Italian children with SAR. Information on clinical history (standard questionnaire, AllergyCARD®; TPS, Italy) and skin prick tests for inhalant and foods extracts (ALK-Abelló, Hørsholm, Denmark) was acquired as at baseline visit. Evolution in clinical and sensitization data of patients was analyzed over time, as well as their association with the main baseline characteristics and atopy risk factors. RESULTS: The average age of participants was 10.4 ± 3.4 years at baseline and 16.2 ± 3.6 years at follow-up. SAR persisted in 93.3% of patients at follow-up and became more frequently associated with asthma (from 36.7% at baseline to 48.6% at follow-up) and oral allergy syndrome (OAS, from 23.4% to 37.7%). Compared to baseline, the prevalence of skin sensitization to some pollens (Phleum pratense, Corylus avellana, Platanus acerifolia, Artemisia vulgaris) and vegetables (hazelnut, wheat, and apple) significantly decreased at follow-up. Earlier onset of SAR and polysensitization at baseline were associated with incident asthma at follow-up. The presence at baseline of serum IgE to the following allergen molecules was identified as biomarkers of clinical evolution: (a) Phl p 1, for persistence of SAR; (b) Phl p 5, for persistence of both rhinitis and asthma; (c) Pru p 3, for new onset of asthma; (d) Bet v 1, for persistence of OAS. CONCLUSIONS: Seasonal allergic rhinoconjunctivitis is clinically heterogeneous in its evolution from childhood to adolescence. The detection of serum IgE to specific molecules (Phl p 1, Phl p 5, Bet v 1, Pru p 3) may be useful as biomarkers to predict SAR persistence and future onset of comorbidities, such as asthma and/or OAS.

Pollen-Food Allergy Syndrome: A not so Rare Disease in Childhood.

Seasonal allergic rhinoconjunctivitis (SAR) affects millions of people worldwide, particularly in childhood and adolescence. Pollen food allergy syndrome (PFAS) is a common adverse reaction occurring few minutes after the consumption of vegetable foods in patients with pollen-induced SAR. PFAS has rarely been investigated in the pediatric population, as it has been mainly examined as an adult disease. Recent studies suggested that PFAS might be more frequent in childhood than previously recognized. The present review aims to give an overview of the epidemiology, pathophysiology, diagnosis, management and prognosis of PFAS in children with SAR-induced by pollens.

Hazardous Medications in Children with Egg, Red Meat, Gelatin, Fish, and Cow's Milk Allergy.

Childhood food allergies are a growing public health problem. Once the offending food allergens have been identified, a strict elimination diet is necessary in treatment or prevention of most of the allergic reactions. Accidental food ingestion can lead to severe anaphylaxis. Food- derived substances can be used in medications at various stages of the manufacturing process. In this review, the possible roles of medications which may contain egg, red meat, gelatin, and fish allergens on allergic reactions in children with food allergy were evaluated.

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.

Food allergy and atopic dermatitis: Prediction, progression, and prevention.

The rising burden of allergic diseases in childhood requires a compelling need to identify individuals at risk for atopy very early in life or even predict the onset of food allergy and atopic dermatitis since pregnancy. The development and clinical phenotypes of atopic diseases in childhood depend on a complex interaction between genetic and environmental factors, such as allergen exposure, air pollution, and infections. Preventive strategies may include avoidance measures, diet supplements, and early complementary food introduction. Overall, the management of allergic diseases has been improving to date toward a patient's tailored approach. This review will cover the current understanding of risk factors, prediction, and management of food allergy and atopic dermatitis in childhood and discuss how these may contribute to the modification of the natural history of food allergy and atopic dermatitis.

Asthma and allergic rhinitis in childhood: what's new.

Novel approaches are currently offered for the diagnostic workup and therapeutic management of allergic rhinitis and asthma. New predictive biomarkers of allergy and asthma are available. Primary and secondary prevention, earlier intervention, and modification of the natural history of allergic rhinitis and asthma are being intensively investigated. This review highlights advances in the understanding of the etiology, diagnosis, and management of atopic airway diseases in childhood, as well as prenatal and early-life risk factors and strategies for prevention.

Diagnostic accuracy of patch test in children with food allergy.

BACKGROUND: The gold standard test for confirming whether a child has clinical hypersensitivity reactions to foods is the oral food challenge. Therefore, there is increasing interest in simpler diagnostic markers of food allergy, especially in children, to avoid oral food challenge. The goal of this study was to assess the diagnostic accuracy of atopy patch test in comparison with oral food challenge. METHODS: We investigated 243 children (mean age, 51 months) referred for evaluation of suspected egg or cow's milk allergy. Skin prick test and atopy patch test were carried out, and after a 2 weeks elimination diet, oral food challenge was performed. RESULTS: Two hundred and forty-three children underwent OFC to the suspected food. We found clinically relevant food allergies in 40 (65%) children to egg and in 22 (35%) to cow's milk. The sensitivity of skin prick test for both milk and egg was 92%, specificity 91%, positive predictive value 35%, and negative predictive value of 93%. Sensitivity, specificity, positive predictive value, and negative predictive value of atopy patch test for both milk and egg were 21%, 73%, 20%, and 74%, respectively. CONCLUSION: Our study suggests that there is insufficient evidence for the routine use of atopy patch test for the evaluation of egg and cow's milk allergy. OFC remains gold standard for the diagnosis of egg and milk allergy even in the presence of high costs in terms of both time and risks during application.

Why do some Children Get Sick with Recurrent Respiratory Infections?

Respiratory tract infections (RTI) represent a frequent condition, particularly among preschool children, with an important burden on the affected children and their families. It has been estimated that recurrent RTIs affect up to 25% of children during the first 4 years of life. These infections are mainly caused by viruses and are generally self-limiting. Social and environmental factors have been studied in determining the incidence of recurrent RTIs and the mostly recognized are precocious day care attendance, tobacco exposure and pollution. Primary immune defects, local anatomical factors, and genetic disorders such as primary ciliary dyskinesia or cystic fibrosis, may be also involved in recurrent RTIs of a subgroup of children, typically characterized by more severe and chronic symptoms. However, there is increasing awareness that RTIs have a complex pathophysiology and that some underrecognized factors, including genetic susceptibility to infections, low levels of some micronutrients, and respiratory microbiota might shape the probability for the child to develop RTIs. The sum (i.e. the number) of these factors may help in explaining why some children get sick for RTIs whilst other not. In some children iatrogenic factors, including improper use of antibiotics and NSAIDS or glucocorticoids might also aggravate this condition, further weakening the host's immune response and the possibly of establishing a "vicious circle". The present review aims to focus on several possible factors involved in influencing RTIs and to propose a unifying hypothesis on pathophysiological mechanisms of unexplained recurrent RTIs in children.

Nutritional and Psychosocial Impact of Food Allergy in Pediatric Age.

Treatment of IgE-mediated food allergy involves avoiding the food causing the allergic reaction. In association, an action plan for allergic reactions is indicated, sometimes including self-injectable adrenaline. In addition to these dietary and medical implications, there are two equally important ones: nutritional and psychosocial. From a nutritional point of view, it is known that children suffering from food allergy have a growth delay in height and weight compared to their non-allergic peers. Specifically, this condition is directly related to the specific food excluded from the diet, the number of foods excluded and the duration of the elimination diet. From a psychosocial point of view, the child often cannot eat the foods other guests eat. Children with food allergy may perceive an aura of parental anxiety around their mealtime and may be afraid that what they eat could have harmful consequences for their health. Furthermore, children's and their parents' quality of life appears to be affected. The need to manage the allergy and the nutritional and psychosocial problems positions the pediatric nutritionist and the child neuropsychiatrist as support figures for the pediatric allergist in managing the child with food allergy.

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.