Montserrat Alvaro

Baseline specific IgE levels are useful to predict safety of oral immunotherapy in egg-allergic children.

Oral immunotherapy (OIT) is a promising treatment for food allergy but dose‐related reactions are common.

Cow's milk protein allergy. A multi-centre study: clinical and epidemiological aspects

BACKGROUND Due to the age when it becomes apparent and the treatment needed, cows milk proteins (CMP) allergy requires an accurate diagnosis to avoid labelling infants falsely as allergic and subjecting them to unnecessary diets. The objective of this multi-centre study carried out at the Allergy Units of 14 Childrens Hospitals was to discover the epidemiological, clinical and evolutionary characteristics of cows milk protein allergy (CMPA). METHODS AND RESULTS Infants suspected of CMPA who attended allergy clinics at the hospitals taking part during the study period were studied and a detailed clinical history was collected on all of them. Prick tests were done with cows milk and its proteins and specific IgE anti-bodies were determined by means of CAP with the same allergens as the Prick test. The challenge test with cows milk was carried out unless contraindicated by the diagnostic protocol. Two different challenge regimens were used: one of them carried out in 3 days and the other in one day. 409 infants with suspected CMPA were included and the diagnostic challenge test was performed on 286 patients (70 %) and not carried out on 123, as it was not indicated according to the protocol. IgE-mediated allergy was confirmed in 234 infants (58 %) and in 15 (4 %) non-IgE-mediated hypersensitivity was diagnosed. The two challenge regimens were equally secure. The average age when the reaction to cows milk formula took place was 3.5 months (10 days-10 months). The symptoms appeared in the first week of introduction in 95 % of cases and appeared in 60 % with the first feeding with the formula. The most frequent clinical signs were cutaneous in 94 % of cases and the majority of cases appeared within 30 minutes of the feed. 99 % had been breast fed and 44 % had received some cows milk supplement during the lactation period. Sensitization to egg not given in the feed was noted in 30 % and to beef in 29 %, being well tolerated in all of these. CONCLUSIONS Carrying out an appropriate diagnostic protocol in infants attending for suspected CMPA allows allergy to be ruled out in a high percentage of cases.

Tolerance to egg proteins in egg‐sensitized infants without previous consumption

Egg‐sensitized infants who have never eaten egg may react at first ingestion. We sought to determine the association between skin prick test (SPT) and specific IgE (sIgE) to egg proteins (EP) and oral food challenge (OFC) outcomes to find cut‐off points which can diagnose egg allergy.

Allergen-specific immunotherapy: Update on immunological mechanisms

UNLABELLED Immunotherapy selectively modulates the allergen-specific immune response. It involves the gradual administration of increasing amounts of allergen for the purpose of inducing protective immunological changes and it is the only curative approach for specific type I allergy. AIM Description of the allergic inflammation.- Comprehension of the early cellular changes after specific immunotherapy has been initiated. Exposure of the mechanisms involved in tolerance induction by regulatory T cells (Treg) with the inhibition of the Th2 responses. Comprehension of IL-10 and transforming growth factor (TGF- ) roles. Explanation of specific IgE, IgG and IgA changes. Description of the suppression of inflammatory responses during immunotherapy.

Asymptomatic LTP sensitisation is common in plant-food allergic children from the Northeast of Spain.

BACKGROUND The sensitisation profile at molecular level in plant-food allergy is complex. Several allergens may be involved, with different potential for severe reactions. lipid transfer proteins (LTP) are considered the most relevant plant-food allergens in adults in Mediterranean countries, but less is known in children. AIM To describe the clinical pattern and sensitisation profile of children with plant-food allergy and LTP sensitisation from Northeast Spain. METHODS Children with history of immediate reaction to plant-food(s), positive skin-prick-test to the culprit plant-food(s) and specific-IgE to plant-food LTPs were analysed. RESULTS 130 children were included. 69.2% (90/130) had reacted to ≥2 taxonomically unrelated plant-foods. Peach, walnut, hazelnut and peanut were most frequently involved. Reactions severity ranged from anaphylaxis (45.4%, 59/130) to oral symptoms only. Sensitisation to a particular plant-food LTP not always caused clinical symptoms with that plant-food; 69% (40/58) and 63% (17/27) of peach- and walnut-tolerant subjects had positive rPru p 3 and nJug r 3 specific IgE, respectively. 65.4% (85/130) of children were also sensitised to storage proteins, which was associated to anaphylaxis and nut allergy. However, 60% of patients without nuts/seeds allergy were sensitised to storage proteins. Specific-IgE levels to LTPs and/or storage proteins were not useful to predict allergy (vs. tolerance) to peach, walnut, peanut or hazelnut. CONCLUSIONS Sensitisation to LTP and/or storage proteins without clear clinical significance is relatively common. Prospective longitudinal studies are required to evaluate the relevance of these silent sensitisations over time. Caution is required when interpreting the results of molecular-based diagnostic tools in clinical practice.

A 10% liquid immunoglobulin preparation for intravenous use (Privigen®) in paediatric patients with primary immunodeficiencies and hypersensitivity to IVIG.

BACKGROUND The objective of this study was to evaluate safety and efficacy of Privigen®, a 10% intravenous immunoglobulin (IVIG), in a particular group of paediatric patients (highly sensitive to previous IVIG infusion) affected with Primary Immunodeficiencies (PID). MATERIAL AND METHODS Patients (n=8) from 3 to 17 years old diagnosed of PID who often suffered from adverse events related to the infusion to previous IVIG were switched to Privigen® in an open protocol. Data were prospectively collected regarding Privigen® administration: infusion, safety and efficacy. In parallel, data on safety and tolerance were retrospectively collected from medical charts regarding the previous 10% IVIG product used. RESULTS 50% of the patients required premedication with previous IVIG. At the end of the study none required premedication with Privigen®. The infusion rate was lower than that recommended by the manufacturer. All patients had suffered through adverse events during previous IVIG infusion being severe in three patients and recurrent in the rest. With Privigen® only three patients suffered from an adverse event (all cases were milder than previous related). Trough levels of IgG remained stable. None suffer from any episode of bacterial infection. CONCLUSION The present work shows that Privigen® was safe in a group of hypersensitive paediatric patients who did not tolerate the administration of a previous 10% liquid IVIG by using a particular infusion protocol slower than recommended. The number of adverse effects was smaller than published, and all cases were mild. No premedication was needed. Privigen® was also effective in this small group.

Food protein–induced enterocolitis syndrome to fish and egg usually resolves by age 5 years in Spanish children

Food proteineinduced enterocolitis syndrome to fish and egg usually resolves by age 5 years in Spanish children Marta Vazquez-Ortiz, MD, PhD*, Adrianna Machinena, MD*, Olga Dominguez, MD, Montserrat Alvaro, MD, PhD, Katty Calvo-Campoverde, MD, María Teresa Giner, MD, Rosa Jiménez-Feijoo, MD, PhD, Jaime Lozano, MD, Mònica Piquer, MD, Marcia Dias, MD, María del Mar Folqué, MD, and Ana María Plaza, MD, PhD

Evidence in immunotherapy for paediatric respiratory allergy: Advances and recommendations. Document of the Immunotherapy Working Group of the Spanish Society of Pediatric Clinical Immunology and Allergology (SEICAP)

Allergic respiratory diseases are major health problems in paediatric population due their high level of prevalence and chronicity, and to their relevance in the costs and quality of life. One of the most important risk factors for the development of airway diseases in children and adolescents is atopy. The mainstays for the treatment of these diseases are avoiding allergens, controlling symptoms, and preventing them through sustained desensitization by allergen immunotherapy (AIT). AIT is a treatment option that consists in the administration of increasing amounts of allergens to modify the biological response to them, inducing long-term tolerance even after treatment has ended. This treatment approach has shown to decrease symptoms and improve quality of life, becoming cost effective for a large number of patients. In addition, it is considered the only treatment that can influence the natural course of the disease by targeting the cause of the allergic inflammatory response. The aim of this publication is to reflect the advances of AIT in the diagnosis and treatment of allergic respiratory diseases in children and adolescents reviewing articles published since 2000, establishing evidence categories to support the strength of the recommendations based on evidence. The first part of the article covers the prerequisite issues to understand how AIT is effective, such as the correct etiologic and clinical diagnosis of allergic respiratory diseases. Following this, the article outlines the advancements in understanding the mechanisms by which AIT achieve immune tolerance to allergens. Administration routes, treatment regimens, dose and duration, efficacy, safety, and factors associated with adherence are also reviewed. Finally, the article reviews future advances in the research of AIT.

Usefulness of the ratio total IgE / specific IgE (sIgE) to predict tolerance in children allergic to cow's milk proteins (CMP)

Background Cow’s milk (CM) IgE-mediated allergy is the most common food allergy in children. It affects 2 - 3% of the general population. About 80% of children allergic to CMP reach natural tolerance in the third year of life. It remains difficult to decide when it is time to attempt a controlled food challenge (CFC) to reintroduce CM in their diets. Objectives. To evaluate if the ratio total IgE / CM sIgE or total IgE / casein sIgE can be more useful than the single measurement of sIgE to predict tolerance in our patients, and to determine the highest sensitivity cut-off point. Methods Retrospective, observational study. The medical records of 178 patients allergic to CM with CFC performed between January 2010 and December 2011 were reviewed. Clinical data, skin prick tests (SPT), total IgE, CM sIgE and casein sIgE at baseline and at the time of the CFC were recorded. These measures were compared between groups of tolerant and nontolerant patients using the nonparametric Mann-Whitney. ROC curves were performed to evaluate predictive values of tolerance for total IgE, CM sIgE, casein sIgE and ratios (total IgE / CM sIgE; total IgE / casein sIgE).

Allergic reactions due to cow’s milk (CM) doses and triggering factors in 40 CM anaphylactic children during maintenance phase of specific oral tolerance induction (SOTI) treatment to CM in our unit

Results Median age: 10.6 years. Median maintenance period: 1.5 years. CM-IgE before SOTI: 101 KU/L. Median threshold dose at oral food challenge before SOTI: 2.5 ml. Median current daily CM dose: 200 ml. Allergic reactions to CM: 29 children have had reactions, as follows: A) Non anaphylactic reactions: 15 children. 8 children suffer daily from mild symptoms (4, mouth itching; 1, abdominal pain; 1, hives; 2, rhinitis) and 4 children from mild asthma 2-3/week, with no triggers associated. 6 children had 1 to 6 mild respiratory or digestive symptoms related to trigger factors. B) 20 children have suffered from anaphylactic reactions, 50% of which are related to trigger factors. 14 patients had skin and respiratory involvement (rank: 65 to 1 episodes). 3 children had skin and digestive symptoms (rank: 4 to 1 episodes). 3 children, respiratory and digestive (rank:13 to 1 episodes). 7 children received epinephrine (39 doses). Number of children reacting to CM because of the following trigger factors: fasting, 5; exercise, 8 (66 episodes); lying, 12 (16 episodes); tiredness, 3; stress, 3; asthma exacerbation, 4; infection, 6. 9 children reacted to goat’s or sheep’s cheese and 4 to cow’s cheese. 7 children have reduced in 10 to 75% their daily milk doses because of allergic reactions. 2 children withdrew SOTI during the maintenance period due to intense and frequent reactions.