Giorgio Longo

IgE-mediated food allergy in children

Food allergy is a serious health issue affecting roughly 4% of children, with a substantial effect on quality of life. Prognosis is good for the most frequent allergens with almost all children outgrowing their allergy. However, the long-term implications for disease burden are substantial for children with persistent allergies (eg, peanuts, tree nuts, fish, and shellfish) and for those with high concentrations of milk, egg, and wheat IgE. Antigen avoidance has been the time-honoured approach both for prevention and treatment. However, findings from studies done in the past 5 years show that early contact with food can induce tolerance and desensitisation to foods. We review the epidemiology, natural history, and management of food allergy, and discuss the areas of controversy and future directions in research and clinical practice.

Fatal allergy as a possible consequence of long-term elimination diet

Urticaria is a commondisorder that affects as many as 20% of the population at some point during their lifetime. Factors believed to cause or aggravate urticaria include drugs, foods, additives, connective tissue disorders and infections. It is well established that hepatitis B virus causes urticaria (1). Whether hepatitis C infection causes urticaria or not is still debated. There have been conflicting reports both in favour of (2,3) and against (4,5) hepatitis C virus (HCV) causing urticaria. Kanazawa and colleagues (2) reported a positive relationship between hepatitis C and urticaria. Nineteen of 79 patients tested were found to be positive for HCV. Subsequent studies however did not confirm such an association (4,5). We describe here a case of chronic intermittent urticaria caused by HCV. A 49-year-old Caucasian man presented with a typical history of recurrent urticaria of several months duration. There were no clues in the history apart from promiscuity, and all routine screening investigations were negative apart from an approximately three times raised alanine aminotransferase (ALT). In view of a history of multiple sexual partners and raised ALT, hepatitis serology was requested. Hepatitis C antibody was reported to be positive by both enzymelinked immunosorbent assay (ELISA) and microparticle enzyme immune assay. Results of ELISA for hepatitis B were negative.We conclude that HCV infection may have caused urticaria in this patient. There does not appear to be any clearcut evidence to affirm or refute a direct link between chronic urticaria and HCV infection in the literature. We suggest that HCV status should be checked in patients presenting with urticaria in areas with a high prevalence. It may not be cost-effective to perform routine screening forHCVwhere the prevalence of this infection is low, but should be considered where the history or laboratory tests suggest this possibility. Further studies are needed to establish any definite association, possible aetiopathogenic role and the cost implications of screening and therapy of HCV in chronic urticaria.

Microbiota in Healthy Skin and in Atopic Eczema

The Italian interest group (IG) on atopic eczema and urticaria is member of the Italian Society of Allergology and Immunology. The aim of our IG is to provide a platform for scientists, clinicians, and experts. In this review we discuss the role of skin microbiota not only in healthy skin but also in skin suffering from atopic dermatitis (AD). A Medline and Embase search was conducted for studies evaluating the role of skin microbiota. We examine microbiota composition and its development within days after birth; we describe the role of specific groups of microorganisms that colonize distinct anatomical niches and the biology and clinical relevance of antimicrobial peptides expressed in the skin. Specific AD disease states are characterized by concurrent and anticorrelated shifts in microbial diversity and proportion of Staphylococcus. These organisms may protect the host, defining them not as simple symbiotic microbes but rather as mutualistic microbes. These findings reveal links between microbial communities and inflammatory diseases such as AD and provide novel insights into global shifts of bacteria relevant to disease progression and treatment. This review also highlights recent observations on the importance of innate immune systems and the relationship with normal skin microflora for the maintenance of healthy skin.

Autoimmunity in atopic dermatitis: Biomarker or simply epiphenomenon?

The idea that a mechanism of autoimmunity could play a role in the pathogenesis of atopic dermatitis gained support from the observation that patients with atopic dermatitis display IgE reactivity to a variety of human protein antigens, several of which have been characterized at molecular level. A broad spectrum of at least 140 IgE‐binding self‐antigens associated with atopic dermatitis has been demonstrated; they might promote, perpetuate, or both, skin inflammation by binding IgE antibodies or activating specific T cells. Even if the presence of autoreactivity seems to be associated with the severity of the disease and may be used as a parameter reflecting chronic tissue damage, at the state of art the role of autoimmunity in atopic dermatitis is far from clear. Data from the literature show that the use of autoantibodies as biomarkers of atopic dermatitis are still limited by the evidence that the epiphenomenon of autoreactivity is detectable only in a percentage of patients and that the involved self‐allergens often are not the same; further longitudinal case‐control studies are needed to investigate and to clarify the pathogenethic role of autoimmunity in the course of atopic dermatitis.

Food Allergy: From the of Loss of Tolerance Induced by Exclusion Diets to Specific Oral Tolerance Induction

The prevalence of food allergy and anaphylaxis in children is reported to be increasing in recent years. Evidence suggests that exposure to large doses of antigen might produce a suppression of the specific IgE response, so that the continuous contact with high doses of antigens favours the maintenance of tolerance In the same way loss of contact with allergen in children with specific IgE reactivity may favour a loss of tolerance with development of systemic reactions, while a progressive new contact with allergen may favour a specific tolerance induction. We hypothesize that widespread and uncontrolled use of elimination diets for atopic dermatitis may have played a role in the increase of allergy and anaphylaxis. Specific oral tolerance induction may be a possible therapeutic strategy. The article review food allergies caused by exclusion diet and also discuss recent patents related to the field.

Food protein-induced enterocolitis syndrome caused by fish and/or shellfish in Italy.

The study describes the demographic features, culprit foods, clinical features and outcomes for children presenting with acute fish and/or shellfish food protein‐induced enterocolitis syndrome (FPIES) in four Italian paediatric allergy centres.

Prevalence of celiac disease in patients with severe food allergy

The association between food allergy and celiac disease (CD) is still to be clarified. We screened for CD 319 patients with severe food allergy (IgE > 85 kU/l against food proteins and a history of severe allergic reactions) who underwent specific food oral immunotherapy (OIT), together with 128 children with mild allergy who recovered without OIT, and compared the prevalence data with our historical data regarding healthy schoolchildren. Sixteen patients (5%) with severe allergy and one (0.8%) with mild allergy tested positive for both genetic and serological CD markers, while the prevalence among the schoolchildren was 1%. Intestinal biopsies were obtained in 13/16 patients with severe allergy and in the one with mild allergy, confirming the diagnosis of CD. Sufferers from severe food allergy seem to be at a fivefold increased risk of CD. Our findings suggest that routine screening for CD should be recommended in patients with severe food allergy.

The Dietary Paradox in Food Allergy: Yesterday's Mistakes, Today's Evidence and Lessons for Tomorrow

During the last decades the prevalence of food allergy has significantly increased among children and antigen avoidance still remains the standard care for the management of this condition. Most reactions are IgE-mediated with a high risk of anaphylaxis requiring emergency medications in case of inadvertent ingestion. Recent studies showed that continuous administration of the offending food, rather than an elimination diet, could promote the development and maintenance of oral tolerance. Indeed, intestinal transit of food proteins and their interaction with gut-associated lymphoid tissue (GALT) is the essential prerequisite for oral tolerance. On the contrary, low-dose cutaneous exposure to environmental foods in children with atopic dermatitis and altered skin barrier facilitates allergic sensitization. The timing and the amount of cutaneous and oral exposure determine whether a child will have allergy or tolerance. Furthermore, previous preventive strategies such as the elimination diet during pregnancy and breastfeeding, prolonged exclusive breastfeeding and delayed weaning to solid foods did not succeed in preventing the development of food allergy. On the other hand, there could be an early narrow window of immunological opportunity to expose children to allergenic foods and induce natural tolerance. Finally, the gradual exposure to the offending food through special protocols of specific oral tolerance induction (SOTI) may be a promising approach to a proactive treatment of food allergy.

Specific oral tolerance induction in children with very severe cow-milk allergy

The prevalence of food allergy is high in early childhood and it seems to be increasing [1]. The prognosis is good in most cases, with gradual recovery over time [2]. The tolerance is antigen dependent and develops progressively, in many cases by 6 years of age. The only current option is strict food avoidance. In recent years, a limited volume of evidence regarding the efficacy of specific oral tolerance induction (SOTI) has been reported [3–10]. We have recently published a study proving the feasibility of SOTI in patients affected by very severe cow-milk allergy, with interesting results [11]. We selected patients with very severe food allergy, over the age of 6 years, presenting severe reactions after the ingestion of only trace amounts of antigen or even after skin contact or smell inhalation. For these children, the risk of fatal reactions is real [12] and increases with the child’s age, in conjunction with reduced parental control over their diet [13]. For them, we have set up a SOTI protocol: the first step taking place in a hospital, with quick increases in dosage during a 10-day period, eventually followed by a slow rising phase at home. The protocol was evaluated in 60 children that tested positive during a challenge to very small amounts of milk. A total of 30 children were subjected to SOTI, while 30 were kept on a milkfree diet. After 1 year, 11 out of 30 children (36%) in the treatment group tolerated large volumes of milk, 16 (54%) could take limited amounts (5–150 ml) and three (10%) were not able to complete the protocol because of reactions. In the diet group, the challenge performed after 1 year was positive in all 30 cases. The total number of reactions in the treatment group during the study was high and four patients required intramuscular adrenaline. In this experience, SOTI was effective in a significant percentage of cases and was perceived as an important improvement in the quality of life for these patients. The number of reactions to milk was significant, and data are still needed to estimate the risk of fatal or near-fatal events in these subjects and to confirm the safety of this intervention that should, therefore, be restricted to highly defined assistance settings.

Cooking influence in tolerance acquisition in egg-induced acute food protein enterocolitis syndrome

BACKGROUND Few studies on the age of resolution of Food Protein Induced Enterocolitis Syndrome (FPIES) induced by solid foods are available. In particular, for FPIES induced by egg, the mean age of tolerance acquisition reported in the literature ranges from 42 to 63 months. OBJECTIVE We have assessed whether the age of tolerance acquisition in acute egg FPIES varies depending on whether the egg is cooked or raw. METHODS We conducted a retrospective and multicentric study of children with diagnosis of acute egg FPIES seen in 10 Italian allergy units between July 2003 and October 2017. The collected data regarded sex, presence of other allergic diseases, age of onset of symptoms, kind and severity of symptoms, cooking technique of the ingested egg, outcome of the allergy test, age of tolerance acquisition. RESULTS Sixty-one children with acute egg FPIES were enrolled, 34 (56%) males and 27 (44%) females. Tolerance to cooked egg has been demonstrated by 47/61 (77%) children at a mean age of 30.2 months. For 32 of them, tolerance to raw egg has been demonstrated at a mean age of 43.9 months. No episodes of severe adverse reaction after baked egg ingestion have been recorded. CONCLUSIONS It is possible to perform an OFC with baked egg, to verify the possible acquisition of tolerance, at about 30 months of life in children with acute egg FPIES.