Drug-induced enterocolitis syndrome (DIES) is the term used to describe reactions occurring after drug exposure. It is a non-IgEmediated hypersensitivity reaction, characterized by symptoms that typically resemble those of FPIES (food protein-induced enterocolitis syndrome). It is a rare and probably underestimated entity, since very few cases have been reported in literature so far. To date, seven cases of DIES have been described, four in children, [1][2][3][4] one in an 18-year-old male patient, 5 and two in adult patients. 6,7 In 2014, Novembre et al 1 described the case of a 6-year-old girl who developed gastrointestinal symptoms of vomiting, diarrhea, pallor, and lethargy 2 hours after a drug provocation test (DPT) with amoxicillin (AMX). As the clinical and laboratory features, that is, vomiting, neutrophilia, methemoglobinemia (MethHb), and need for intravenous fluid support, resembled those of FPIES, the term DIES was proposed for the first time. In the following, five other cases of DIES have been reported, summarized in Table 1.

A food allergy is an immunoglobulin E (IgE)-mediated hypersensitive reaction to food, which consists in the appearance of allergic symptoms; it can vary from common urticaria to even fatal anaphylaxis. The prevalence of food allergies has been increasing in the past twenty years and it represents a major public health problem in industrialized countries. The mechanism that leads to food allergies is the lack of immunologic and clinical tolerance to food allergens. The diagnosis of IgE-mediated food allergies is based on the combined use of a detailed medical history, in-vivo, and in-vitro research of specific IgE, the elimination diet, and the double-blind placebo-controlled food challenge. The only currently available treatment for allergies is the strict elimination diet. This type of attitude, which we could define as “passive”, does not overcome the risk of accidental reactions due to involuntary intake of the culprit food. For food allergy management, an “active” approach is urgently needed, such as specific allergen immunotherapy, which is currently under development and only used for research purposes. This article aims to give an updated review of IgE-mediated food allergies in pediatric populations in terms of epidemiology, pathogenesis, prevention, diagnosis, and management.

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Background: Severe cutaneous adverse reactions (SCARs) are delayed-type hypersensitivity reactions to drugs including as follows: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN) and Acute Generalized Exanthematous Pustulosis (AGEP). Incidence, triggers and management of SCARs have not been investigated in large-scale epidemiological studies on children.Objective: The aim of our study was to collect epidemiological, clinical and aetiological data from children with SCARs referred to our tertiary care paediatric hospital of Florence.Methods: From 2010 to 2018 charts of children with diagnosis of SCAR were reviewed, and data collected during the acute phase and/or the subsequent allergy evaluation. Patients underwent patch tests, intradermal tests and lymphocyte transformation tests. All children were investigated for infectious diseases.Results: Incidence of SCARs in hospitalized children was 0.32% over a 9-year period.Fifty-four children were enrolled (31 M; 23 F; median age 6.5 years): 17 cases of DRESS, 30 SJS, 3 TEN, 2 AGEP, 1 linear immunoglobulin A bullous disease (LABD) and 1 pemphigus. Twenty-eight out of 54 patients underwent drug allergy investigations, and 50% of them resulted positive. Combining clinical history and results of allergy work-up, 74% SCARs seem to be caused by drugs, 18.6% by both drugs and infections, 3.7% by infections, and 3.7% remained idiopathic. No deaths occurred. Conclusions:In this study, SCARs incidence is in line with literature data. Drugs were most commonly the leading cause. Management of SCARs requires cooperation among professional figures for an early diagnosis and a prompt treatment. Mortality rate seems to be lower in children. K E Y W O R D Sacute generalized exanthematous pustulosis, aetiopathogenesis, children, drug reaction with eosinophilia and systemic symptoms, hypersensitivity drug reactions, lymphocyte | 65

Background and objective: Drug Hypersensitivity Reactions (DHRs) are considered adverse effects of medications that resemble allergy symptoms. The reported positive clinical history of pediatric drug reactions is about 10%, however, after allergy investigations, only a small percent is confirmed as hypersensitivity. The aim of this study was to analyze the clinical history, allergy work-up results and sensitization profile of children and adolescents referred to our Allergy Unit for suspected DHRs. Methods: The study evaluated data related to a group of children with a positive history of drug reactions during a two-year period. The allergy work-up consisted of in vivo and in vitro tests, in accordance with the recommendations of the ENDA/EAACI guidelines. Results: Data from a group of 637 patients [348 M (54.6%); 289 F (45.4%)] were retrospectively analyzed. Beta lactams (BLs) were the most common drugs involved in the reported clinical history, followed by non-steroidal antiinflammatory drugs (NSAIDs). Severe cutaneous adverse reactions (SCARs) were most frequently observed during BL treatment. The confirmation of BL hypersensitivity was higher for immediate reactions (IRs) [9.4%; 5.1% through positive skin tests (STs) and 5.5% through drug provocation test (DPT)] compared to nonimmediate reactions (non-IRs) (8.1%; 2.2% through STs and 6.2% through DPT). A higher number of positive results was obtained for BLs and macrolides when the tests were performed within 12 months after the index reaction (p < 0.05). During DPTs with amoxicillin-clavulanic acid, four hypersensitivity reactions (including one anaphylaxis) occurred despite negative STs. Conclusion: Our data demonstrated that only 9.1% of patients resulted in being positive to allergy tests which is in line with the data in literature. An allergy work-up is mandatory for excluding suspected hypersensitivity.

Introduction: Acute generalized exanthematous pustulosis (AGEP) is a generalized, non-follicular sterile pustular rash, categorized as a severe cutaneous adverse reaction, which usually has a favorable prognosis. In a majority of cases (90%), AGEP is drug induced and different drugs are reported as cause of AGEP. Hydroxychloroquine (HCQ) is an antimalarial drug that is also used in some dermatologic and rheumatic diseases due to its immunosuppressive actions. Some cases of AGEP induced by HCQ are reported in literature but only in adults. Materials, Methods and Results: We describe the first case of AGEP caused by HCQ in a child affected by juvenile Sjögren syndrome. After withdrawal of HCQ and subsequent administration, the patient experienced the same cutaneous reaction. An allergy work-up was performed and patch test showed an ectopic flare of AGEP eruption. Conclusion: Our patient represents the first pediatric case of AGEP to HCQ, posing such a drug as a possible trigger also in children. Therefore, an accurate drug medical history is mandatory in order to rule out potential drug reactions when facing a sudden rash.

Oral Immunotherapy (OIT), a promising allergen-specific approach in the management of Food Allergies (FA), is based on the administration of increasing doses of the culprit food until reaching a maintenance dose. Each step should be adapted to the patient, and OIT should be considered an individualized treatment. Recent studies focused on the standardization and identification of novel biomarkers in order to correlate endotypes with phenotypes in the field of FA.