The role of the atopy patch test in the diagnostic work-up of non-IgE gastrointestinal food allergy in children: a systematic review.

The "Atopy Patch Test" (APT) has been proposed as a diagnostic tool for food allergies (FA), especially in children with FA-related gastrointestinal symptoms. However, its diagnostic accuracy is debated, and its usefulness is controversial. The aim of this systematic review was to evaluate the APT diagnostic accuracy compared with the diagnostic gold standard, i.e., the oral food challenge (OFC), in children affected by non-IgE mediated gastrointestinal food allergies, including the evaluation in milk allergic subgroup. Both classical non-IgE mediated clinical pictures and food induced motility disorders (FPIMD) were considered. The search was conducted in PubMed and Scopus from January 2000 to June 2022 by two independent researchers. The patient, intervention, comparators, outcome, and study design approach (PICOS) format was used for developing key questions, to address the APT diagnostic accuracy compared with the oral food challenge (OFC). The quality of the studies was assessed by the QUADAS-2 system. The meta-analysis was performed to calculate the pooled sensitivity, specificity, DOR (diagnostic odds ratio), PLR (positive likelihood ratio), and NLR (negative likelihood ratio) with their 95% confidence intervals (CI). Out of the 457 citations initially identified via the search (196 on PubMed and 261 on Scopus), 37 advanced to full-text screening, and 16 studies were identified to be included in the systematic review. Reference lists from relevant retrievals were searched, and one additional article was added. Finally, 17 studies were included in the systematic review. The analysis showed that APT has a high specificity of 94% (95%CI: 0.88-0.97) in the group of patients affected by FPIMD. Data showed a high pooled specificity of 96% (95% CI: 0.89-0.98) and the highest accuracy of APT in patients affected by cow's milk allergy (AUC = 0.93).      Conclusion: APT is effective in identifying causative food in children with food-induced motility disorders.  What is Known: • Atopy patch test could be a useful diagnostic test for diagnosing food allergy, especially in children with food allergy-related gastrointestinal symptoms. What is New: • Atopy patch test may be a useful tool in diagnosing non IgE food allergy, especially in children with food-induced gastrointestinal motility disorders and cow's milk allergy.

Developments in pediatrics in 2020: choices in allergy, autoinflammatory disorders, critical care, endocrinology, genetics, infectious diseases, microbiota, neonatology, neurology, nutrition, ortopedics, respiratory tract illnesses and rheumatology.

In this article, we describe the advances in the field of pediatrics that have been published in the Italian Journal of Pediatrics in 2020. We report progresses in understanding allergy, autoinflammatory disorders, critical care, endocrinology, genetics, infectious diseases, microbiota, neonatology, neurology, nutrition, orthopedics, respiratory tract illnesses, rheumatology in childhood.

Component-Resolved Diagnosis of Hazelnut Allergy in Children.

Hazelnuts commonly elicit allergic reactions starting from childhood and adolescence, with a rare resolution over time. The definite diagnosis of a hazelnut allergy relies on an oral food challenge. The role of component resolved diagnostics in reducing the need for oral food challenges in the diagnosis of hazelnut allergies is still debated. Therefore, three electronic databases were systematically searched for studies on the diagnostic accuracy of specific-IgE (sIgE) on hazelnut proteins for identifying children with a hazelnut allergy. Studies regarding IgE testing on at least one hazelnut allergen component in children whose final diagnosis was determined by oral food challenges or a suggestive history of serious symptoms due to a hazelnut allergy were included. Study quality was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Eight studies enrolling 757 children, were identified. Overall, sensitivity, specificity, area under the curve and diagnostic odd ratio of Cor a 1 sIgE were lower than those of Cor a 9 and Cor a 14 sIge. When the test results were positive, the post-test probability of a hazelnut allergy was 34% for Cor a 1 sIgE, 60% for Cor a9 sIgE and 73% for Cor a 14 sIgE. When the test results were negative, the post-test probability of a hazelnut allergy was 55% for Cor a 1 sIgE, 16% for Cor a9 sIgE and 14% for Cor a 14 sIgE. Measurement of IgE levels to Cor a 9 and Cor a 14 might have the potential to improve specificity in detecting clinically tolerant children among hazelnut-sensitized ones, reducing the need to perform oral food challenges.

Non-IgE- or Mixed IgE/Non-IgE-Mediated Gastrointestinal Food Allergies in the First Years of Life: Old and New Tools for Diagnosis.

non-IgE and mixed gastrointestinal food allergies present various specific, well-characterized clinical pictures such as food protein-induced allergic proctocolitis, food protein-induced enterocolitis and food protein-induced enteropathy syndrome as well as eosinophilic gastrointestinal disorders such as eosinophilic esophagitis, allergic eosinophilic gastroenteritis and eosinophilic colitis. The aim of this article is to provide an updated review of their different clinical presentations, to suggest a correct approach to their diagnosis and to discuss the usefulness of both old and new diagnostic tools, including fecal biomarkers, atopy patch tests, endoscopy, specific IgG and IgG4 testing, allergen-specific lymphocyte stimulation test (ALST) and clinical score (CoMiss).

Best practices, challenges and innovations in pediatrics in 2019.

This paper runs through key progresses in epidemiology, pathomechanisms and therapy of various diseases in children that were issued in the Italian Journal of Pediatrics at the end of last year. Novel research and documents that explore areas such as allergy, critical care, endocrinology, gastroenterology, infectious diseases, neonatology, neurology, nutrition, and respiratory tract illnesses in children have been reported. These observations will help to control childhood illnesses.

Safety, Efficacy, and Preventive Role of Subcutaneous and Sublingual Allergen Immunotherapy for the Treatment of Pediatric Asthma.

Allergen-specific immunotherapy is currently the only treatment with the potential to modify and prevent progression of allergic asthma in children. In clinical practice, it is available in two forms: subcutaneous immunotherapy and sublingual immunotherapy. Trials and meta-analyses showed both the safety and the short- and long-term benefits of allergen-specific immunotherapy in asthmatic children. However, its use and role in asthma remains controversial, since studies are largely heterogeneous. This is mainly due to the lack of consensus on the optimal primary outcome to be considered for clinical trials evaluating the efficacy of allergen-specific immunotherapy in asthma. Therefore, well-conducted researchis needed using standardized and validated tools to evaluate key outcomes in asthmatic children.

Summation anaphylaxis: A challenging diagnosis.

Anaphylaxis is the most severe of allergic reactions. The most frequent triggers of anaphylaxis in childhood are food, insect venom, drugs, exercise, etc. In some cases, the presence of more than one trigger is necessary for the allergic reaction, while one trigger alone is tolerated. This rare condition is called summation anaphylaxis (SA). Food-dependent exercise-induced anaphylaxis is the most well-known SA. However, SA may also occur with the association between food and/or exercise plus one or more of the following other cofactors, such as drugs, especially non-steroidal anti-inflammatory (NSAID), alcohol, infections, temperature variation, and menstrual cycle. SA can explain some cases of idiopathic anaphylaxis, as well as cases of an apparent breakdown in a previously acquired tolerance for food, or finally, when faced with a suggestive clinical history of food allergy or exercise anaphylaxis and the provocation test is negative. In these situations, a more careful clinical history looking for other cofactors is necessary.

Urticaria in childhood.

Histaminergic urticaria-angiodema is a common complaint in children. According to clinical criteria, it is classified as acute and chronic urticaria. A further clinical classification relies on triggering factors. We focus on diagnosis and therapeutic strategies. We report the main progresses in the field and issues that remain to be understood.

Use of Sublingual Immunotherapy for Aeroallergens in Children with Asthma.

Asthma is a heterogeneous disease that in children is often allergen-driven with a type 2 inflammation. Sublingual immunotherapy represents an important progress in the use of personalized medicine in children with allergic asthma. It is a viable option for house dust mite-driven asthma and in subjects with the asthma associated with allergic rhinitis. The use and indications for isolated asthma caused by other allergens are still controversial owing to heterogeneity of commercially available products and methodological limitations of studies in children. Nevertheless, most studies and meta-analyses found the efficacy of sublingual immunotherapy. Sublingual immunotherapy is safe but cannot be recommended in children with uncontrolled asthma.

Primary Prevention of Allergic Diseases: The Role of Early Exposure to Cow's Milk Formula.

The burden of atopic disorders is continuously worsening worldwide, especially in childhood. Therefore, risk factors and preventive measures have been called into question. The age when infants introduce complementary foods, varies greatly according to traditional habits, clinical practice recommendations, and breastfeeding duration. It is still debated the impact of early exposure to cow's milk on the increase of allergic diseases, mainly food allergy, and atopic dermatitis. Many factors may play a role in this potential link, such as genetic variation, parental atopy, infant feeding regimens. Recent evidences suggest that the early introduction of complementary foods (up to 6 months of age), including cow's milk, could prevent the development of food allergies. So, several countries included this new approach into feeding guidelines. Our review will focus on the influence of early exposure to cow's milk formula on the development of allergic diseases. Some trials found that cow's milk supplementation in the first days of life could even increase the development of IgE sensitization and food allergies. Other trials did not show any efficacy on prevention of allergic disorders. Further studies are needed to understand the prospective for allergy prevention related to optimal timing of cow's milk formula introduction.

Advances in paediatrics in 2019: current practices and challenges in allergy, endocrinology, gastroenterology, public health, neonatology, nutrition, nephrology, neurology, respiratory diseases and rheumatic diseases.

We highlight the main developments that have been published during the first semester of the last year in the Italian Journal of Pediatrics. We have carefully chosen information from numerous exciting progresses issued in the Journal in the field of allergy, endocrinology, gastroenterology, neonatology, nutrition, nephrology, neurology, public health, respiratory diseases and rheumatic diseases. The impact on the care of patients has been placed in the broader context of studies that appeared in other journals. We think that many observations can be used directly to upgrade management of patients.

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.

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.

COVID-19 and food allergy in children.

In children with food allergy the visits should be limited to those that are unequivocally needed on clinical basis. Food challenge can be performed in selected situations, taking a more detailed history to make sure that patients provide whatever information we need. The maintenance of a safe diet can be hampered by several factors. Nutritional supplementation may be necessary.

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.

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.

Allergic reactions to cow's milk proteins in medications in childhood.

INTRODUCTION: Cow's milk is a frequent trigger of allergic reactions in childhood. Cow's milk proteins can be present in pharmaceutical excipients. METHODS: We have analyzed paediatric literature on allergic reactions to cow's milk proteins in medication, focusing on the different routes of administration (inhaled, parental and oral). RESULTS: Dry-powder inhalers may contain lactose as excipient. Lactose can be rarely contaminated with milk proteins and it may induce allergic reactions in patients with cow's milk allergy. Case reports have described immediate hypersensitivity reactions to methylprednisolone sodium succinate 40 mg injection, a formulation that contains lactose as excipient. Some cases of anaphylaxis after receiving diphteria-tetanus-pertussis vaccine injection in children allergic to milk have been reported. Cow's milk proteins can be detected also in oral polio vaccine, certain probiotics and lactulose syrup. CONCLUSIONS: We suggest caution in administration of pharmaceuticals containing milk allergens in children allergic to milk.

Disturbed eating behavior in pre-teen and teenage girls and boys with type 1 diabetes.

AIM: To investigate Disturbed Eating Behavior (DEB) and eating patterns in the context of a teenage population with T1D. METHODS: DEB was investigated using Eating Disorder Examination (EDE) test by a psychologist. Questions regarding insulin dosage manipulation or omission to obtain decrease in weight were added. Specific behavioral items from the EDE were used to define DEB: Objective Binge-eating, Self-induced Vomiting for weight control; the use of Diuretics, Laxatives or Insulin Omission for weight loss. Some EDE items provided information about four composite subscales which assesse Restraint, Eating concern, Shape concern and Weight concern. RESULTS: Shape and Weight concern showed significantly higher scores than those observed in the other two subscales (p=0.021). Average scores of each subscale resulted significantly higher in girls than in boys as well as in teen than in pre-teen participants. Objective binge eating (20%) and insulin dosage omission or reduction (17.6%) were the most common DEB (p<0.03). Forty-one percent of participants reported to consume three, 25% four and 34% five meals daily. A significantly lower proportion of females than males resulted to consume breakfast and mid-afternoon snacks. CONCLUSIONS: Findings from this study suggest that caregivers working in pediatric diabetes units should be alert in order to discover some DEB such as medication omission and binge-eating, all indicative symptoms of dissatisfaction of the body and psychological distress in diabetes management.