Salvatore Barberi

A new protocol for specific oral tolerance induction in children with IgE-mediated cow's milk allergy.

IgE-mediated cows milk allergy (CMA) is a heavy burden for patients, particularly for children and their families. Allergen avoidance represents the only therapeutic option, but oral desensitization protocols have been suggested. Because of the long duration and complexity of these protocols we examined the feasibility of an oral tolerance induction protocol using a weekly up-dosing schedule. Children with IgE-mediated food allergy to milk, confirmed by a double-blind placebo-controlled food challenge, were recruited. Six of them were randomized to double-blind desensitization with milk or soy formula as placebo. Seven patients underwent the protocol in open fashion. The desensitization schedule started with one drop of whole CM diluted 1:25 every week. The dose was doubled weekly until the 18th week to achieve an intake of 200 mL in approximately 4 months. Of the 13 children enrolled, 10 children received CM and 3 control children received soy formula. Full tolerance (200 mL of milk) was achieved in 7 children; in 2 children this therapeutic approach failed, because severe reactions occurred during the procedure. One patient achieved a partial tolerance (64 mL of milk). The three control children receiving placebo still showed a positive food challenge at the end of the study. A weekly up-dosing oral tolerance induction could be a viable alternative to traditional protocols for children with IgE-mediated CMA.

Epigenetic Effects of Human Breast Milk

A current aim of nutrigenetics is to personalize nutritional practices according to genetic variations that influence the way of digestion and metabolism of nutrients introduced with the diet. Nutritional epigenetics concerns knowledge about the effects of nutrients on gene expression. Nutrition in early life or in critical periods of development, may have a role in modulating gene expression, and, therefore, have later effects on health. Human breast milk is well-known for its ability in preventing several acute and chronic diseases. Indeed, breastfed children may have lower risk of neonatal necrotizing enterocolitis, infectious diseases, and also of non-communicable diseases, such as obesity and related-disorders. Beneficial effects of human breast milk on health may be associated in part with its peculiar components, possible also via epigenetic processes. This paper discusses about presumed epigenetic effects of human breast milk and components. While evidence suggests that a direct relationship may exist of some components of human breast milk with epigenetic changes, the mechanisms involved are still unclear. Studies have to be conducted to clarify the actual role of human breast milk on genetic expression, in particular when linked to the risk of non-communicable diseases, to potentially benefit the infant’s health and his later life.

Nutritional management and follow up of infants and children with food allergy: Italian Society of Pediatric Nutrition/Italian Society of Pediatric Allergy and Immunology Task Force Position Statement

Although the guidelines on the diagnosis and treatment of food allergy recognize the role of nutrition, there is few literature on the practical issues concerning the nutritional management of children with food allergies.This Consensus Position Statement focuses on the nutritional management and follow-up of infants and children with food allergy.It provides practical advices for the management of children on exclusion diet and it represents an evidence-based consensus on nutritional intervention and follow-up of infants and children with food allergy.Children with food allergies have poor growth compared to non-affected subjects directly proportional to the quantity of foods excluded and the duration of the diet. Nutritional intervention, if properly planned and properly monitored, has proven to be an effective mean to substantiate a recovery in growth.Nutritional intervention depends on the subject’s nutritional status at the time of the diagnosis.The assessment of the nutritional status of children with food allergies should follow a diagnostic pathway that involves a series of successive steps, beginning from the collection of a detailed diet-history.It is essential that children following an exclusion diet are followed up regularly.The periodic re-evaluation of the child is needed to assess the nutritional needs, changing with the age, and the compliance to the diet.The follow- up plan should be established on the basis of the age of the child and following the growth pattern.

Adherence to sublingual immunotherapy in preschool children.

Editor, Specific immunotherapy is the only effective causal treatment that can modify the natural history of respiratory allergy (1). This effect is important in children, where a secondary prevention is desirable. Sublingual administration (SLIT) is accepted as a valid therapeutic option (2), and children represent an ideal population for SLIT, because of the good safety profile (2). Nonetheless, as per all chronic treatments, adherence is essential, but no data are available in preschool children. We assessed the adherence to SLIT in children aged <6 yrs and analyzed the factors possibly affecting adherence itself. Children (age, 3–6 yrs) referred for respiratory diseases (bronchial asthma and/or rhinitis) and eligible for SLIT were enrolled. None had food allergy (possible confounding factor), and respiratory symptoms had to be present at least in the previous 6 months. The diagnosis of allergic asthma/ rhinitis was made according to guidelines (3, 4). Patients receiving SLIT were stratified according to age: group A (3£ yrs <4.0), group B (4.0£ yrs <5.0), group C (5.0£ yrs <6.0). All the procedures involved standard clinical approaches; thus, the study was simply notified to the Ethical Committee of the University of Messina, and all parents provided written informed consent. Children were followed up during the 2-yr observation period with 3-month regular visits. SLIT extracts were from Stallergénes, Lofarma, ALK– Abellò, Allergopharma. Parents were allowed to choose drops or tablets, and SLIT was given according to manufacturers’ recommendations. The administration technique was checked by pediatricians, using a placebo. Specific diary cards to assess the adherence (pre-compiled list), side effects, and reasons for discontinuation/temporary interruption of SLIT (free answers) were given to parents and collected at each visit. The time and reasons for interruption/discontinuation were carefully recorded. The remaining vials/tablets were checked at control visits. If >80% of the scheduled doses were taken, the patient was considered adherent. One hundred and fifty children (3–5.9 yrs, 86 boys) received SLIT for respiratory allergy (76% drops and 24% tablets). All suffered from allergic asthma and/or rhinitis from at least 6 months, and all received standard medications (antihistamines, intranasal corticosteroids, inhaled corticosteroids, bronchodilators). Mite SLIT accounted for 89.4% of prescriptions. Overall, 46% of 150 children discontinued SLIT. The percentage of discontinuations during the first year was significantly higher in group A than in groups B (52% vs. 18%, v = 12.7, p = 0.035) and C (52% vs. 13%, v 2 = 17.33, p = 0.032), whereas during the second year, there was no difference between groups (v 2 > 0.5). The reasons for discontinuation, as determined by parents’ interviews, are summarized in Table 1. The most common cause for withdrawal in group A was the subjective discomfort in keeping under the tongue drops/tablets, or children’s refusal, without apparent side effects. The refusal was generally attributed to unpleasant taste. For groups B and C, withdrawals were attributed to ineffectiveness, or to family problems, not better defined. All withdrawals occurred during the first 3 months of treatment in group A, and within the first 6 months in the other groups. In those patients who did not discontinue SLIT, short interruptions (all <5 days), as a

Omalizumab in Children

Omalizumab is a recombinant humanized monoclonal antibody that reduces levels of circulating immunoglobulin E (IgE) and expression of IgE high-affinity receptors on mast cells and basophils, interrupting the subsequent allergic inflammatory cascade. Current indications for treatment with omalizumab in pediatric patients are clearly defined and are confined to moderate-to-severe uncontrolled allergic asthma and chronic spontaneous urticaria (CSU). Any other prescription can only be off label. Data available from clinical trials conducted in children suggest that omalizumab is clinically effective and generally well tolerated. Given its mechanism of action, recent reports have suggested its possible clinical use in other IgE-mediated disorders, such as allergic rhinitis, food allergy, and anaphylaxis. In recent years, several studies have also investigated the possible applications of omalizumab in a number of non IgE-mediated diseases. The aim of the present review is to assess all applications of omalizumab as therapy in the pediatric population. The approved indications—allergic asthma and CSU—are reviewed. Moreover, further potential applications of omalizumab are discussed in both IgE-mediated and non-IgE-mediated diseases.

Adenoids in children: Advances in immunology, diagnosis, and surgery.

Adenoids are strategically located for mediating local and regional immune functions as they are exposed to antigens from both the outside air and the alimentary tract. Recurrent or chronic respiratory infections can induce histomorphological and functional changes in the adenoidal immunological barrier, sometimes making surgical treatment necessary. Our aim in this review is to summarize the crucial points about not only the immunological histopathology of adenoidal tissue, especially in patients with adenoid hypertrophy, but also the most common and useful diagnostic techniques and surgical options. Clin. Anat. 27:346–352, 2014.

Long-term growth hormone therapy in mitochondrial cytopathy

Objective: To describe in a 5-year-old Caucasian male with mitochondrial cytopathy, a biochemical growth hormone (GH) deficiency associated with normal GH biological activity as evaluated by Nb2 cell bioassay and normal serum IGF-I and IGFBP3 values increasing slightly after GH administration. Method: Serum GH concentrations were measured with a commercial immunofluorometric assay and with a biological assay, which uses the Nb2 cell line. Serum IGF-I and IGFBP3 concentrations were measured with RIA. Results: The GH-supplementary therapy was initially effective in terms of growth gain, but no therapeutic benefit was observed over a long period of time. Conclusion: In patients suffering from mitochondrial cytopathy, short stature seems to be attributed more to a disease-related inadequate protein substrate than to the non-classical GH deficiency.

Differences in Serum GH Cut-Off Values for Pharmacological Tests of GH Secretion Depend on the Serum GH Method Clinical Validation from the Growth Velocity Score during the First Year of Treatment

Background: The serum GH cut-off value for pharmacological tests of GH secretion (PhT GH) depends on the type of test and also on the method used for determining serum GH. Cut-off serum GH values as different as 5–10 ng/ml, have been reported, and have been validated biochemically. We have used the growth velocity (GV)-standard deviation score (SDS) during the first year of treatment with rhGH to validate these cut-offs on a biological basis. Methods: Fifty pre-pubertal patients with short stature (height ≤–2 SDS and GV ≤–1.2 SDS) were studied. GH deficiency (GHD) was diagnosed in 39 patients, on the basis of clinical and auxological parameters and on the serum concentration of IGF-1, and non-GHD in the other 11 patients. Two PhT GH (arginine and clonidine) were carried out in the 50 patients. Serum GH was determined by two different methods: one detecting most of serum GH isoforms, named Total GH (HGH Bio-Tech, MAIA Clone), and another one, only detecting the 22 kDa GH, named 22K GH (GH-22K IFMA, Wallac). Results: Basal data: all patients with GHD and with non-GHD had maximal serum GH response (MaxR) values below and above the cut-off, respectively, for the serum Total GH and 22K GH. The mean 22K GH/Total GH ratio was similar to previous publications. Post-rhGH treatment data: the two groups improved their height SDS during the first year of treatment, particularly patients with GHD. A receiver-operator curve was used to define the best threshold for post-treatment GV-SDS that separates GHD from non-GHD patients. This value was 1.91 GV-SDS. A negative correlation between first year treatment GV-SDS and pre-treatment serum GH MaxR was found for the two assays (p < 0.001). Then, the best cut-off GV-SDS, previously calculated with the receiver-operator curve (1.91 SDS) was used to interpolate the corresponding serum GH values, as determined by the two methods. For Total GH, the value was 10.8 ng/ml, and for 22K GH, it was 5.4 ng/ml. Conclusion: The cut-off values calculated by biological means to separate GHD from non-GHD were remarkably similar to those calculated biochemically (10.0 and 4.8 ng/ml, respectively) for Total and 22K GH. This is a biological validation for using different cut-off values, appropriate for each assay, to diagnose GHD.

Current recommendations and emerging options for the treatment of allergic rhinitis

Allergic rhinitis (AR) is one of the most common diseases and represents a global health problem, currently affecting up to 30% of the general population, with a continuously increasing prevalence and significant comorbidities and complications. The aim of this review is to provide an update on AR treatment, with a focus on current therapies defined by AR and its impact on asthma guidelines and with a particular emphasis on new and future therapeutic perspectives.

Atopic dermatitis: recent insight on pathogenesis and novel therapeutic target.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. It affects infancy, but it is also highly prevalent in adults and it is one of the disease burdens for the patients and their families. Nowadays, AD is recognized as a heterogenous disease with different subtypes with variable clinical manifestations which is affected by the impairments of the skin barrier. The severity of AD dictates the level of treatment. Current AD treatment focuses on restoration of the barrier function, mainly through the use of moisturizers and corticosteroids to control the inflammation, topical calcineurin inhibitors, and immunosuppresive drugs in the most severe cases. However, targeted disease-modifying therapies are under investigation. The most recent findings on the skin microbial dysbiosis is a promising future direction for the development of new treatments. We need to improve the understanding of the complex microbiome-host interactions, the role of autoimmunity, the comparative effectiveness of therapies and the ways to appropriately implement the educational strategies.